Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group.

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.

Blood pressure in preterm infants with bronchopulmonary dysplasia in the first three months of life.

BACKGROUND: Neonatal hypertension is common in preterm infants with bronchopulmonary dysplasia (BPD). Our study aimed to examine blood pressure variation in the first three months of life in preterm BPD patients. METHODS: We conducted a retrospective, single-centre study at the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We collected blood pressure data from 26 preterm infants (born at < 30 weeks gestation) with moderate or severe BPD over three years (2019-2021). We calculated the BPD group's daily average blood pressure values and used previously defined normal blood pressure values from a preterm patient group born at < 30 weeks gestation as a reference. We used 19,481 systolic, diastolic and mean blood pressure measurement data separately to calculate daily average blood pressures. RESULTS: We found a statistically significant correlation between the blood pressure values of the BPD patient group and the reference data. The difference between the blood pressure curve of the group with BPD and that of the reference group was also statistically significant. We also analysed individual patients' daily average blood pressure values and found that 11 patients (42%) had hypertensive blood pressure values for three or more days within the first 90 days of life. Within this group, our statistical analysis showed a 25% chance of acute kidney injury. CONCLUSION: The blood pressure of the BPD group not only correlated with but also significantly differed from the reference data. Hypertension lasting three or more days occurred more frequently in patients with acute kidney injury accompanied by BPD.

Oligoclonal gammopathy: An analysis of 253 cases.

BACKGROUND: Oligoclonal gammopathy (OG) is a rare disorder of the lymphoid system that is characterized by the presence of at least 2 distinct monoclonal proteins in a patient's serum or urine. The biological and clinical characteristics of this disease are as yet poorly understood. OBJECTIVES: The study aimed to assess whether there are significant differences between patients with OG regarding the developmental history (i.e., OG diagnosed at the first presentation compared to OG that has developed in patients with an original monoclonal gammopathy) and the number of monoclonal proteins (2 compared to 3). Moreover, we attempted to determine when secondary oligoclonality develops following the original diagnosis of monoclonal gammopathy. MATERIAL AND METHODS: Patients were analyzed with regard to their age at diagnosis, sex, serum monoclonal proteins, and underlying hematological disorders. Multiple myeloma (MM) patients were additionally evaluated for their Durie-Salmon stage and cytogenetic alterations. RESULTS: Patients with triclonal gammopathy (TG: n = 29) did not differ significantly from patients with biclonal gammopathy (BG: n = 223) (p = 0.81) in terms of age at diagnosis and the dominant diagnosis (MM was the most common diagnosis (65.0% and 64.7%, respectively)). In both cohorts, myeloma patients were mainly classified to the Durie-Salmon stage III. In the TG cohort, there was a higher proportion of males (69.0%) than among patients with BG (52.5%). Oligoclonality developed at various times after diagnosis (up to 80 months in the investigated cohort). However, the occurrence of new cases was higher during the initial 30-month period following the diagnosis of monoclonal gammopathy. CONCLUSIONS: There are only small differences between patients with primary compared to secondary OG, between BG and TG, and most patients have a combination of IgGκ+IgGλ. Oligoclonality could develop at any time after the diagnosis of monoclonal gammopathy, but it happens more frequently during the first 30 months, with advanced myeloma being the most prevalent underlying disorder.

Autoimmune cytopenias in patients with malignant lymphoma: A multicenter report by the Polish Lymphoma Research Group.

BACKGROUND: Autoimmune cytopenias (ACs), including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA) and autoimmune granulocytopenia, are rare complications observed in lymphoma patients. They may appear before, during or after lymphoma diagnosis, whether the patients had disease progression or not. OBJECTIVES: This study aims to correlate ACs with lymphoma type, disease course and prognosis. We performed a multicenter retrospective analysis of adult patients with malignant lymphoma and ACs coexistence diagnosed and treated in centers aligned with the Polish Lymphoma Research Group (PLRG). MATERIAL AND METHODS: The analysis covers the years 2016-2022 and included 51 patients comprised of 23 women and 28 men. Of these, 35 patients were diagnosed with AIHA, 15 patients with ITP and 1 patient with both AIHA and ITP. RESULTS: The most common type of lymphoma was Hodgkin lymphoma (HL) (12 patients) and diffuse large B-cell lymphoma (DLBCL) (14 patients). At the time of diagnosis, 31 (61%) of patients had stage 4 of HL or DLBCL, according to Ann Arbor classification. In total, the response to treatment was evaluated in 50 patients, with 25 being in complete remission and 6 in partial remission. We observed that B cell symptoms (p = 0.036), bone marrow involvement (p = 0.073), splenomegaly (p = 0.025), and more than 2 lines of treatment were more common in AIHA compared to ITP patients. Conversely, eucopenia (p = 0.056) and ACs without lymphoma progression (p = 0.002) were more often diagnosed in ITP patients. CONCLUSIONS: In the study group, relapsed and refractory disease was observed more often, and shorter overall survival (OS) was noted in patients with DLBCL. We found that AC is associated with a worse prognosis in comparison to the general population of lymphoma patients. There were no differences in response to AC therapy. To have more accurate data, a larger group, as part of a multicenter study, should be evaluated.

Clinical features, etiology, and survival in patients with restrictive cardiomyopathy: A single-center experience.

BACKGROUND: Numerous prognostic factors have been proposed for cardiac amyloidosis (CA). The knowledge about other subtypes of restrictive cardiomyopathy (RCM) is scant. AIMS: This study aimed to elucidate the etiology and prognostic factors of RCM as well as assess cardiac biomarkers: high-sensitive troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and soluble suppression of tumorigenicity 2, as mortality predictors in RCM. METHODS: We enrolled 36 RCM patients in our tertiary cardiac department. All patients were screened for CA. Genetic testing was performed in 17 patients without CA. RESULTS: Pathogenic or likely pathogenic gene variants were found in 86% of patients, including 5 novel variants. Twenty patients died, and 4 had a heart transplantation during the study. Median overall survival was 29 months (8-55). The univariate Cox models analysis indicated that systolic and diastolic blood pressure, GDF-15, hs-TnT, NT-proBNP, left ventricular stroke volume, the ratio of the transmitral early peak velocity (E) estimated by pulsed wave Doppler over the early mitral annulus velocity (e'), tricuspid annulus plane systolic excursion, early tricuspid valve annular systolic velocity, the presence of pulmonary hypertension, and pericardial effusion influenced survival (P <0.05). A worse prognosis was observed in patients with GDF-15 >1316 pg/ml, hs-TnT >42 ng/l, NT-proBNP >3383 pg/ml, and pericardial effusion >3.5 mm (Kaplan-Meier analysis, log-rank test, P <0.001). CONCLUSIONS: Genetic testing should be considered in every RCM patient where light-chain amyloidosis has been excluded. Survival remains poor regardless of etiology. Increased concentrations of GDF-15, hs-TNT, NT-proBNP, and pericardial effusion are associated with worse prognosis. Further studies are warranted.

Determination of Tiamulin Concentration in Sow Milk and in Sera of Suckling Piglets.

Although modern analytical methods developed for monitoring antibiotics in several biological matrices are easily available, none of them have been applied to evaluate the transfer of tiamulin into sow milk. Therefore, this work was intended to analyse the concentrations of tiamulin in milk samples collected from lactating sows during and after a treatment consisting of three consecutive intramuscular applications of the antibiotic. The second aim of this investigation was to determine tiamulin concentrations in serum samples obtained from suckling piglets ingesting milk contaminated with the compound. Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) was used to quantify the analyte in both matrices. Our investigation proved tiamulin was transmitted into the milk of lactating sows. The mean concentration of the antibiotic among samples collected 3 h after administration was 1043 µg/L. The mean level of tiamulin on days 1 and 2 was 876 µg/L and 902 µg/L, respectively. The highest mean concentration of the antibiotic (1061 µg/L) was observed in samples collected on day 3. The mean concentration of the antibiotic in serum samples collected from 3-day-old piglets was 22.2 µg/L. The association between their body weight and serum tiamulin concentration was not statistically significant (p = 0.456).

Steady-State and Time-Resolved Fluorescence Study of Selected Tryptophan-Containing Peptides in an AOT Reverse Micelle Environment.

The aim of this study was to demonstrate the utility of time-resolved fluorescence spectroscopy in the detection of subtle changes in the local microenvironment of a tryptophan chromophore in a confined and crowded medium of AOT reverse micelles, which mimic biological membranes and cell compartmentalization. For this purpose, fluorescence properties of L-tryptophan and several newly synthesized tryptophan-containing peptides in buffer and in an AOT reverse micelle medium were determined. It was shown that insertion of tryptophan and its short di- and tripeptides inside micelles led to evident changes in both the steady-state emission spectra and in fluorescence decay kinetics. The observed differences in spectral characteristics, such as a blue shift in the emission maxima, changes in the average fluorescence lifetime, and the appearance of environmental-dependent fluorescent species, showed the utility of time-resolved fluorescence spectroscopy as a sensitive tool for detecting subtle conformational modifications in tryptophan and its peptides induced by changes in polarity, viscosity, and specific interactions between chromophores and water molecules/polar groups/ions that occur inside reverse micelles.

Outcome of Second Primary Malignancies Developing in Multiple Myeloma Patients.

BACKGROUND: There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs. RESULTS: 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger (p = 0.05) and more frequently had a prior AutoHCT (p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, p = 0.037) predicted longer OS. CONCLUSIONS: With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.

Isothiocyanates as Tubulin Polymerization Inhibitors-Synthesis and Structure-Activity Relationship Studies.

Among the various substances that interfere with the microtubule formation process, isothiocyanates (ITCs) are the group of compounds for which the binding mode and mechanism of action have not yet been explained. To better understand the structure-activity relationship of tubulin-isothiocyanate interactions, we designed and synthesized a series of sixteen known and novel, structurally diverse ITCs, including amino acid ester-derived isothiocyanates, bis-isothiocyanates, analogs of benzyl isothiocyanate, and phosphorus analogs of sulforaphane. All synthesized compounds and selected natural isothiocyanates (BITC, PEITC, AITC, and SFN) were tested in vitro to evaluate their antiproliferative activity, tubulin polymerization inhibition potential, and influence on cell cycle progression. The antiproliferative activity of most of the newly tested compounds exceeded the action of natural isothiocyanates, with four structures being more potent as tubulin polymerization inhibitors than BITC. As a confirmation of anti-tubulin activity, the correlation between polymerization inhibition and cell cycle arrest in the G2/M phase was observed for the most active compounds. In light of the biological results indicating significant differences in the impact of structurally diverse isothiocyanate on tubulin polymerization, in silico analysis was conducted to analyze the possible mode of isothiocyanate-tubulin binding and to show how it can influence the polymerization reaction.

Investigation of 29 Antimicrobial Compounds in Soil Using Newly Developed UHPLC-MS/MS Method.

While the prudent and reasonable use of veterinary antimicrobial agents in food-producing animals is necessary, researchers over the decades have shown that these antimicrobial agents can spread into the environment through livestock manure and wastewater. The analysis of the occurrence of antimicrobial compounds in soil samples is of a great importance to determine potential impacts on human and animal health and the environment. In this study, an affordable, rugged and simple analytical method has been developed for the determination of twenty-nine antimicrobial compounds from five different classes (tetracyclines, fluoro(quinolones), macrolides, sulfonamides and diaminopirimidines). Liquid-liquid extraction (LLE) with extract filtration combined with ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was the best strategy for the simultaneous determination of all analytes. The developed method was validated according to the Commission Implementing Regulation (EU) 2021/808. The limit of detections (LODs) ranged from 0.5 to 2.0 µg/kg, while the limit of quantitation (LOQ) was established at 1.0 to 20.0 µg/kg. The developed method was successfully applied for the determination of antimicrobial residues in one hundred and eighteen soil samples obtained from four European countries (Austria, Czech Republic, Estonia and Portugal). Doxycycline in the concentration levels of 9.07 µg/kg-20.6 µg/kg was detected in eight of the analysed samples. Samples were collected from areas where natural fertilizers (swine or cow manure) were applied. Our method can be efficiently used to monitor anti-microbial compounds in soil samples.

[Abdominal and cranial ultrasound screenings in our Neonatal Intensive Care Unit]. / Hasi és agyi ultrahang-szurovizsgálatok Neonatális Intenzív Centrumunkban.

INTRODUCTION: Previously, all admitted neonates to our tertiary Neonatal Unit, University of Szeged, had a cranial and abdominal ultrasound performed as part of their care. OBJECTIVE: To analyze the findings and to evaluate the effectiveness of the universal ultrasound screening. METHOD: Results of cranial and abdominal ultrasound imaging performed in our Unit between 1st January 2014 and 31st December 2015 were analyzed retrospectively. Abnormalities found during the screening scans were studied further and assessed until discharge and during the first 2 years. All imagings were performed by a radiologist. RESULTS: During the examined 2 years, 579 neonates were admitted (gestational age mean 34.2 weeks [23-41, SD ± 4.04]), abdominal ultrasound was performed in 562 (97%) and cranial ultrasound in 560 (97%) babies, on the 3.6th day of life at an average (0-18, SD ± 2.24). Of all abdominal ultrasound scans, 87% (n = 488) was carried out as screening, and the found abnormalities in 140 (29%) of the cases: renal pelvic dilatation (n = 67 [47.9%]), free abdominal fluid (n = 17 [12.1%]), echogenic kidneys (n = 13 [9.3%]), congenital abnormalities of the kidney and urinary tract (n = 9 [6.4%]), abnormalities of the liver, bile system, adrenal gland [n = 14 [10%]). The screening identified 4 (0.8%) neonates with renal abnormilaties requiring surgical correction. In regards of renal abnormalities, we observed male (p = 0.18) and left sided (p = 0.54) predominance. Screening cranial ultrasound was performed in 65% (n = 362) of all neonates, discovering 51 (14%) anomalies: plexus chorioideus cyst (n = 21 [41%]), plexus chorioideus hemorrhage (n = 9 [17.6%]), mild ventricular asymmetry (n = 8 [15.7%]), subependymal hemorrhage (n = 5 [9.8%]), abnormalities of the periventricular area (n = 4 [7.8%]), colpocephaly, hydrocephalus externus, echogenic meninx and thalamic nodule [n = 1-1 (1.9-1.9%)]. CONCLUSION: Abdominal ultrasound screening discovered renal abnormalities and umbilical line complications as clinically relevant findings. However, a small number of renal abnormalities identified by screening required surgical intervention. Further studies are needed to identify possible risk groups to develop more efficient screening strategy to decrease the number of screened babies for 1 relevant finding (number to screen). Cranial ultrasound screening did not identify any abnormalities that needed intervention. We can not recommend universal cranial ultrasound screening based on our results. Orv Hetil. 2023; 164(31): 1222-1230.

The Real-World Evidence on the Fragility and Its Impact on the Choice of Treatment Regimen in Newly Diagnosed Patients with Multiple Myeloma over 75 Years of Age.

Fragility scales are intended to help in therapeutic decisions. Here, we asked if the fragility assessment in MM patients ≥ 75 years old qualified for treatment by the local physician correlates with the choice of treatment: a two- or three-drug regimens. Between 7/2018 and 12/2019, we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in completely dependent. Patients with more than three comorbidities made up 26.9% (53 patients). Thus, according to the Palumbo calculator, 43 patients were in the intermediate fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received three-drug regimens and 20.3% (40) received two-drug regimens. In each ECOG group, more than three out of four patients received three-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received three-drug regimens. Out of 53 patients with at least four comorbidities, 71.7% received three-drug regimens, and the rest received two-drug regimens. Thirty-four patients from the intermediate fit group (79.0%), and 123 (79.9%) from the frail group received three-drug regimens. Early mortality occurred in 25 patients (12.7%). No one discontinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with triple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations, which brings into question the clinical utility of current fragility scales in everyday practice.

Analysis of Aminoglycoside Antibiotics: A Challenge in Food Control.

Aminoglycosides are a widely used group of antibiotics in veterinary medicine. However, misuse and abuse of these drugs can lead to residues in the edible tissues of animals. Due to the toxicity of aminoglycosides and the exposure of consumers to the emergence of drug resistance, new methods are being sought to determine aminoglycosides in food. The method presented in this manuscript describes the determination of twelve aminoglycosides (streptomycin, dihydrostreptomycin, spectinomycin, neomycin, gentamicin, hygromycin, paromomycin, kanamycin, tobramycin, amikacin, apramycin, and sisomycin) in thirteen matrices (muscle, kidney, liver, fat, sausages, shrimps, fish honey, milk, eggs, whey powder, sour cream, and curd). Aminoglycosides were isolated from samples with extraction buffer (10 mM NH4OOCH3, 0.4 mM Na2EDTA, 1% NaCl, 2% TCA). For the clean-up purpose, HLB cartridges were used. Analysis was performed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) with a Poroshell analytical column and a mobile phase of acetonitrile and heptafluorobutyric acid. The method was validated according to Commission Regulation (EU) 2021/808 requirements. Good performance characteristics were obtained for recovery, linearity, precision, specificity, and decision limits (CCα). This simple and high-sensitivity method can determine multi-aminoglycosides in various food samples for confirmatory analysis.

Epidemiology of multiple myeloma in Poland in the years 2008-2017.

Introduction: Multiple myeloma is the third most common blood cancer in Europe and accounts for approx. 10-15% of these cancers. The objective of this study was to determine the incidence, prevalence, mortality and survival in multiple myeloma (ICD code: C90.0) patients in Poland in the years 2008-2017. Material and methods: The analysis used the data on healthcare services provided to patients with multiple myeloma defined with the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) code C90.0 and reported by healthcare entities to the National Health Fund (NFZ). Results: In 2009, the C90.0 incidence per 100,000 inhabitants was 6.4, while in 2017 it was 8.3. The prevalence in the same period increased by 76%, from 13.6/100,000 to 23.9/100,000. The mortality to prevalence ratio gradually decreased from 78% in 2008 to 22.8% in 2017. The 1-year, 3-year and 5-year survival rates in patients with this diagnosis made in the years 2009 and 2013 were 70.5%, 51.5% and 40.2% versus 78.4%, 60.3% and 48.3%, respectively. Conclusions: The incidence and prevalence of multiple myeloma and survival rates in Poland were continuously increasing in the studied period. These trends may result from the aging of Polish society, better recognisability of multiple myeloma and/or improved access to increasingly more effective therapies in Poland. The impact of these factors on the epidemiology of multiple myeloma requires further studies.

Oscillometric arterial blood pressure in haemodynamically stable neonates in the first 2 weeks of life.

BACKGROUND: We aimed to provide data on the normal blood pressure of haemodynamically stable neonates. Our study uses retrospective, real-life oscillometric blood pressure measurement values to determine the expected blood pressure in different gestational age, chronological age and birth weight groups. We also investigated the effect of antenatal steroid on neonatal blood pressure. METHODS: Our retrospective study (2019-2021) was carried out in the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We involved 629 haemodynamically stable patients and analysed 134,938 blood pressure values. Data were collected from electronic hospital records of IntelliSpace Critical Care Anesthesia by Phillips. We used the PDAnalyser program for data handling and the IBM SPSS program for statistical analysis. RESULTS: We found a significant difference between the blood pressure of each gestational age group in the first 14 days of life. The systolic, diastolic and mean blood pressure rise are steeper in the preterm group than in the term group in the first 3 days of life. No significant blood pressure differences were found between the group with a complete antenatal steroid course and those who received incomplete steroid prophylaxis or did not receive antenatal steroids. CONCLUSION: We determined the average blood pressure of stable neonates and obtained normative data by percentiles. Our study provides additional data on how blood pressure varies with gestational age and birth weight. A higher resolution version of the Graphical abstract is available as Supplementary information.

Analysis of Antimicrobials in Muscle and Drinking Water in Terms of Reducing the Need of Antimicrobial Use by Increasing the Health and Welfare of Pig and Broiler.

Antimicrobial residues may pose harmful effects on the health of consumers. At the same time, an adequate quality of drinking water for animals is one of the important element to ensure animal welfare and food without antibacterials. The presented study is aimed at estimating the residue levels of antibacterial compounds, such as penicillins, cephalosporin, macrolides, tetracyclines, quinolones, sulphonamides, aminoglycosides, diaminopirymidines, pleuromutilines and lincosamides in meat and on-farm drinking water samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS), as a part of a surveillance system on pig and broiler farms within the project Healthy Livestock. A total of 870 samples of muscle from pig and broiler, as well as 229 water samples were analysed for antibiotic residues. Samples were collected from farms in EU countries in two steps, before and after implementation of a tailor-made health plan. In muscle samples, the detected concentrations of doxycycline in the post-intervention step (15.9-70.8 µg/kg) were lower than concentrations in the pre-intervention step (20.6-100 µg/kg). In water samples, doxycycline in an average concentration of 119 µg/L in the pre- and 23.1 µg/L in the post-intervention step, as well as enrofloxacin at concentrations of 170 µg/L in the pre- and 1.72 µg/L in the post-intervention step were quantified. Amoxicillin was only present before intervention. The obtained results confirm the effectiveness of the intervention actions. The concentrations of antibiotics in muscles and water were lower after implementation of a health plan on the farms.

Safety and efficacy of autologous stem cell transplantation in dialysis-dependent myeloma patients-The DIADEM study from the chronic malignancies working party of the EBMT.

The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.

Interactions of naturally occurring compounds with antimicrobials.

Antibiotics are among the most often used medications in human healthcare and agriculture. Overusing these substances can lead to complications such as increasing antibiotic resistance in bacteria or a toxic effect when administering large amounts. To solve these problems, new solutions in antibacterial therapy are needed. The use of natural products in medicine has been known for centuries. Some of them have antibacterial activity, hence the idea to combine their activity with commercial antibiotics to reduce the latter's use. This review presents collected information on natural compounds (terpenes, alkaloids, flavonoids, tannins, sulfoxides, and mycotoxins), of which various drug interactions have been observed. Many of the indicated compounds show synergistic or additive interactions with antibiotics, which suggests their potential for use in antibacterial therapy, reducing the toxicity of the antibiotics used and the risk of further development of bacterial resistance. Unfortunately, there are also compounds which interact antagonistically, potentially hindering the therapy of bacterial infection. Depending on its mechanism of action, each compound can behave differently in combination with different antibiotics and when acting against various bacterial strains.

Two Faces of the Screened Bottom Boards-An Ambiguous Influence on the Honey Bee Winter Colony Loss Rate.

We conducted a citizen science survey on the winter honey bee colony losses in Poland from 2017/18 to 2019/20 to determine the influence of the use of screened bottom boards on the winter colony losses due to various causes. A total of 1035 beekeepers with 40,003 colonies reported valid data. The overall winter colony loss rate ranged from 10.7% to 13.9%, and in every year, the overall winter colony loss rate was higher than 10% (which is considered as acceptable in Poland). The study reveals that the use of screened bottom boards was associated with reduced overall loss rate. However, the nature of this relationship was not the same in terms of all types of colony losses: while the use of screened bottom boards was associated with a reduced mortality rate (management-related colony loss rate due to dead colonies) in which the empty hives were observed (colony depopulation syndrome, CDS), it was associated with an increased mortality rate in which the lack of food was observed (starvation). Given that in our study the role of CDS in the overall colony loss rate was 2.5-fold higher than the role of starvation, the final influence of the use of screened bottom boards on the overall colony loss rate turned out to be beneficial. Given the well-known beneficial role of screened bottom boards in varroosis control, they are highly recommended in beekeeping practices in Poland.

Isothiocyanates (ITCs) 1-(Isothiocyanatomethyl)-4-phenylbenzene and 1-Isothiocyanato-3,5-bis(trifluoromethyl)benzene-Aldehyde Dehydrogenase (ALDH) Inhibitors, Decreases Cisplatin Tolerance and Migratory Ability of NSCLC.

One of the main treatment modalities for non-small-cell lung cancer (NSCLC) is cisplatin-based chemotherapy. However, the acquisition of cisplatin resistance remains a major problem. Existing chemotherapy regimens are often ineffective against cancer cells expressing aldehyde dehydrogenase (ALDH). As such, there is an urgent need for therapies targeting ALDH-positive cancer cells. The present study compares the anticancer properties of 36 structurally diverse isothiocyanates (ITCs) against NSCLC cells with the ALDH inhibitor disulfiram (DSF). Their potential affinity to ALDH isoforms and ABC proteins was assessed using AutoDockTools, allowing for selection of three compounds presenting the strongest affinity to all tested proteins. The selected ITCs had no impact on NSCLC cell viability (at tested concentrations), but significantly decreased the cisplatin tolerance of cisplatin-resistant variant of A549 (A549CisR) and advanced (stage 4) NSCLC cell line H1581. Furthermore, long-term supplementation with ITC 1-(isothiocyanatomethyl)-4-phenylbenzene reverses the EMT phenotype and migratory potential of A549CisR to the level presented by parental A549 cells, increasing E-Cadherin expression, followed by decreased expression of ABCC1 and ALDH3A1. Our data indicates that the ALDH inhibitors DSF and ITCs are potential adjuvants of cisplatin chemotherapy.