Bács-Kiskun Megyei Kórház

To evaluate the associations between pregnancy-associated plasma protein A (PAPP-A) levels and pregnancy-associated conditions, perinatal outcomes, and placental histopathology. This retrospective, single-center cohort analysis included cases of preterm and term deliveries from pregnancies complicated by preeclampsia and fetal growth restriction or gestational hypertension. A correlation analysis was performed to assess the relationship between PAPP-A levels and neonatal parameters, the prevalence of various pregnancy complications, and placental and birth weight percentiles and ratios. Associations between placental histopathological entities and PAPP-A were explored in different subgroups defined by PAPP-A multiple of the median (MoM) ranges. Potential associations between PAPP-A levels and placental capillarization were also investigated. A total of 74 pregnancies were investigated. PAPP-A levels were significantly lower in cases involving cesarean section (P = 0.002), preterm birth (P = 0.030), and/or preeclampsia (P = 0.002). Among the preeclamptic cases, early-onset preeclampsia was associated with a significantly lower PAPP-A level (P < 0.001). No significant associations were identified between first-trimester PAPP-A levels and placental weight percentile, birth weight percentile, villous capillarization, or the percentage of intact terminal villi; however, correlations were found between low PAPP-A levels and placental weight-to-birth weight ratios of < 1:8 (Kruskal-Wallis test P = 0.004; Spearman's correlation P = 0.011). PAPP-A levels were also significantly lower in the presence of distal villous hypoplasia (P < 0.001), accelerated villous maturation (P < 0.001), or avascular villi (P < 0.001) in the placenta. Lower PAPP-A levels may represent an early marker of pathological placentation in the background of preeclampsia and fetal growth restriction-especially in early-onset cases-which are characterized by villous underdevelopment and a non-branching villous tree pattern on placental histopathology. From a clinical translation perspective, PAPP-A levels may serve as a potential early indicator of pregnancies that warrant close monitoring during clinical management.

We evaluated the common histopathological characteristics of preeclampsia (PE) and fetal growth restriction (FGR), and demonstrated the major differences of the three groups of 1/PE with FGR, 2/PE without FGR and 3/FGR without PE. Placental slides were studied retrospectively. Predominantly FGR- and PE-associated lesions were identified. Gestational age at the time of delivery (GATD) and diagnosis-to-delivery time (DTDT) were also examined. Decidual arteriopathies, maternal hypertension and obesity were more common in PE, and villous capillarization was significantly lower in FGR. We found that only villous infarction and chorangiosis had a connection with GATD. Villous infarction and chorangiosis were associated with DTDT >80 days, while placental changes leading to decreased villous capillarization was associated with DTDT <30 days. Despite several common histopathological characteristics, placental histopathological profile of PE with FGR, PE without FGR and FGR without PE have remarkable differences, indicating histological background of their distinguished prognosis. Inadequate vascular development and decidual vasculopathies are characteristic in PE, while the undercapillarization of placental villous tree and villitis of unknown etiology leading to placental damage are characteristic of FGR. The dynamic equilibrium of different entities determines global placental function, and manifestation of FGR and/or PE.

The turnover intention of elderly care workers affects the quality and costs of social care, worker overload and associated health risks. Preventing the turnover and job-related stress of elderly care workers is essential to effectively support the elderly and ensure high-quality care. This study investigated the relationship between fear of COVID-19 and turnover intention, and job-related stress through burnout. A cross-sectional survey was conducted in Hungary with 269 elderly care workers. Data collection tools included a self-designed demographic questionnaire, the Turnover Intention Scale (TIS-6), Maslach Burnout Inventory (MBI-HSS), Effort-Reward Imbalance (ERI) and Fear of COVID-19 Scale (FCV-19). Indirect effects of fear of COVID-19 were observed on the turnover intention (B = 0.092, p = .008), ER ratio (B = 0.009, p = .007), effort (B = 0.070, p = .007), and overcommitment (B = 0.093, p = .006) via emotional exhaustion. Additionally, fear of COVID-19 negatively influenced overcommitment (B = - 0.043, p = .017) through depersonalization. The models explained 26.3% of the variance in effort (R² = 0.263), 3.4% in reward (R² = 0.034), 23.9% in overcommitment (R² = 0.239), and 25.8% in the ER ratio (R² = 0.258). The mediating role of emotional exhaustion and depersonalization in the relationship between pandemic-related fear and turnover intention and job-related stress underscores the need for targeted interventions in Hungary's elderly care sector. These should focus on early detection of burnout symptoms, especially emotional exhaustion, and implement systematic strategies such as regular monitoring, stress management training, supportive supervision, and team-based peer support to mitigate the impact of chronic occupational stress. The study protocol was registered on ClinicalTrials.gov before the start of the study, on 02/08/2022 (identifier: NCT05487157).

Abstract Improving adaptive potentials of crops to extreme environments is a key objective in breeding programs. Application of phenotyping platforms has become an integral component of maize breeding. This study presents a comprehensive analysis of 14 maize pre-breeding hybrids using an automated phenotyping system in a greenhouse setting. Maize plants were cultivated in plexiglass columns under controlled water conditions, maintaining soil water content at 60% (control) and 30% (drought stress). A strong correlation ( r = 0.70) was observed between manually measured plant biomass (g) and estimated biovolume (kilopixel). Based on the reduction in biomass under drought stress, the hybrids were classified into three categories: Tolerant I, Tolerant II, and Sensitive groups. Hybrids in the Sensitive group demonstrated the highest productivity under control conditions. Also, high correlation ( r = 0.60) was detected between plant height and biomass. Analysis of a large set of photosynthetic fluorescence markers revealed their negative correlations with biomass under drought conditions. Therefore, these parameters have limited applicability in identifying drought-tolerant genotypes. Through an in-depth analysis of growth-related shoot and root traits of young maize hybrid plants, the hybrid PG6 has been identified as a promising candidate for further development in ongoing breeding programs.

Of breast cancers, the triple-negative subtype (TNBC) is characterized by aggressive behavior, poor prognosis and limited treatment options due to its high molecular heterogeneity. Since insufficient programmed cell death response is a major hallmark of cancer, here we searched for apoptosis-related biomarkers of prognostic potential in TNBC. The expression of the pro-apoptotic caspase 8, cytochrome c, caspase 3, the anti-apoptotic BCL2 and the caspase-independent mediator, apoptosis-inducing factor-1 (AIF1; gene AIFM1) was tested in TNBC both in silico at transcript and protein level using KM-Plotter, and in situ in our clinical TNBC cohort of 103 cases using immunohistochemistry. Expression data were correlated with overall survival (OS), recurrence-free survival (RFS) and distant metastasis-free survival (DMFS). We found that elevated expression of the executioner apoptotic factors AIF1 and caspase 3, and of BCL2, grants significant OS advantage within TNBC, both at the mRNA and protein level, particularly for chemotherapy-treated vs untreated patients. The dominantly cytoplasmic localization of AIF1 and cleaved-caspase 3 proteins in primary TNBC suggests that chemotherapy may recruit them from the cytoplasmic/mitochondrial stocks to contribute to improved patient survival in proportion to their expression. Our results suggest that testing for the expression of AIF1, caspase 3 and BCL2 may identify partly overlapping TNBC subgroups with favorable prognosis, warranting further research into the potential relevance of apoptosis-targeting treatment strategies.

In metastatic colorectal cancer (mCRC), improvements in survival from combining leucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) with bevacizumab have come at the risk of increased rates of high-grade toxicities. Trilaciclib is indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients receiving standard-of-care chemotherapy for extensive-stage small cell lung cancer. Patients with untreated mCRC were randomly assigned 1:1 to trilaciclib (n = 164) or placebo (n = 162) prior to FOLFOXIRI/bevacizumab for up to 12 cycles (induction), followed by trilaciclib or placebo prior to fluorouracil/leucovorin/bevacizumab (maintenance). Co-primary endpoints were duration of severe (grade 4) neutropenia (DSN) in cycles 1-4 and occurrence of severe neutropenia (SN) during induction. Secondary endpoints included antitumor efficacy, survival, and safety. The study met its co-primary endpoints. Administering trilaciclib prior to FOLFOXIRI/bevacizumab resulted in significant reductions in DSN in cycles 1-4 vs placebo (mean, 0.1 vs 1.3 days; P < .001) and occurrence of SN during induction (1.3% vs 19.7%; adjusted relative risk [96% CI] = 0.07 [0.0 to 0.3]; P < .001). Grade 3/4 adverse events, including neutropenia, diarrhea, and leukopenia, were less frequent with trilaciclib vs placebo (64.8% vs 73.1%). Trilaciclib was associated with fewer chemotherapy dose reductions and delays and with reduced administration of supportive therapies, compared with placebo. Objective response rate (41.6% vs 57.1%; P = .009) and median progression-free survival (10.3 vs 13.1 months; P < .001) were significantly lower with trilaciclib vs placebo. Administering trilaciclib prior to FOLFOXIRI/bevacizumab protected the neutrophil lineage from the effects of chemotherapy-induced myelosuppression. However, antitumor efficacy endpoints favored placebo. ClinicalTrials.gov: NCT04607668.

Simple SummaryPostoperative adjuvant chemotherapy generally improves survival in patients with breast cancer. However, adjuvant chemotherapy does not benefit all patients. There are considerations and guidelines that guide us as to whether or not chemotherapy is recommended to a particular patient. The decision is based on clinicopathologic features and may be aided by multigene assays. The Oncotype DX test is used worldwide. It makes the recommendation more accurate; however, there are possibilities to refine the process to make a more accurate decision. We investigated how we could move forward in recommending adjuvant chemotherapy.Background: The use of the Oncotype DX test reduces the rate of adjuvant chemotherapy recommendations. Few in-depth analyses have been performed on this decision-making process. Methods: We retrospectively analyzed patient data based on available Oncotype DX test results (RS) irrespective of nodal status at a single center. We collected recommendations from six oncologists, first without RS (pre-RS) and then with RS results (post-RS). We investigated changes in recommendations, agreement between oncologist decisions, and the effect of different National Comprehensive Cancer Network (NCCN) recommendation categories (for, against, and considering chemotherapy). Results: Data from 201 patients were included in the analysis. Recommendation of chemotherapy decreased by an average of 39.5%. Agreement improved substantially with RS, with a kappa value pre-RS of 0.37 (fair agreement) and post-RS of 0.75 (substantial agreement). Discordance remained substantial in cases where the NCCN recommendations considered chemotherapy only (32%). Pre-RS consensus against chemotherapy predicted low RS results (50 out of 51 patients). Post-RS consensus was highest in the NCCN chemotherapy recommendation group. Conclusions: The Oncotype DX test substantially improves decision accuracy in recommending adjuvant chemotherapy. It may be further improved with a consensus decision. In the case of pre-RS consensus against chemotherapy, the test can be spared.

The aim of this prospective pilot study was to compare culture and microbiome results of the removed tonsils of patients with assumed distant focal disease (11 patients) and those who underwent a tonsillectomy, due to other reasons, such as recurrent tonsillitis, tonsil stones or snoring (nine patients). Aerobic culture was carried out for samples taken from the surface of the tonsils by swabs before tonsillectomy for all 20 patients. The squeezed detritus and the tissue samples of removed tonsils, taken separately for the right and left tonsils, were incubated aerobically and anaerobically. The microbiome composition of tissue samples of removed tonsils was also evaluated. Based on the culture results of the deep samples Staphylococcus aureus was the dominating pathogen, besides a great variety of anaerobic and facultative anaerobic bacteria present in the oral microbiota in those patients who underwent tonsillectomy due to distant focal diseases. Microbiome study of the core tissue samples showed a great diversity on genus and species level among patients of the two groups however, S. aureus and Prevotella nigrescens were present in higher proportion in those, whose tonsils were removed due to distant focal diseases. Our results may support previous findings about the possible triggering role of S. aureus and P.nigrescens leading to distant focal diseases. Samples taken by squeezing the tonsils could give more information about the possible pathogenic/triggering bacteria than the surface samples cultured only aerobically.