Physical function endpoints in cancer cachexia clinical trials: Systematic Review 1 of the cachexia endpoints series

In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia

Appetite and dietary intake endpoints in cancer cachexia clinical trials: Systematic Review 2 of the cachexia endpoints series

There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40–628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials

The role of open-air inhalatoria in the air quality improvement in spa towns

Objectives: The present study was aimed at evaluating microbiological contamination of air in Ciechocinek and Ino­wro­cław – Polish lowland spa towns. Additionally, the impact of open-air inhalatoria on the quality of air was evaluated. Material and Methods: Air samples were collected seasonally in the urban areas, in the recreation areas and in the vicinity of inhalatoria in both towns using impaction. The numbers of mesophilic bacteria, staphylococci, hemolytic bacteria and actinomycetes were determined on media according to the Polish Standard PN-86/Z-04111/02. The number of moulds was determined on media according to the Polish Standard PN-86/Z-04111/03. Results: While the highest numbers of microorganisms were noted at the sites located in the urban areas, the lowest numbers were noted in the vicinity of the open-air inhalatoria. In all the investigated air samples the values of bioaerosol concentrations were below the recommended TLVs (≤ 5000 CFU×m–3 for both bacteria and fungi in outdoor environments). Location of the sampling site was invariably a decisive factor in determining the number of microorganisms in the air. Conclusions: The aerosol which is formed in the open-air inhalatoria has a positive influence on microbiological air quality. Owing to a unique microclimate and low air contamination, Ciechocinek and Inowrocław comply with all necessary requirements set for health resorts specializing in treating upper respiratory tract infections

The Significance of Microbial Transformation of Nitrogen Compounds in the Light of Integrated Crop Management

Nitrogen (N) is widely distributed in the lithosphere, hydrosphere, atmosphere and biosphere. It is a basic component of every plant cell as well as microorganisms, as a component of proteins, nucleic acids and chlorophyll. It enters soil with organic and mineral fertilizers, plant and animal residues and biological nitrogen fixation. There are various forms of nitrogen in soil, and this element is usually transformed by microorganisms. The transformation of nitrogen compounds (ammonification, nitrification and immobilization) is significantly influenced by climatic conditions and the physicochemical properties of soil. Microbial mineralization of nitrogen organic matter results in the enrichment of soil with this element, which is necessary to generate a yield. The amount of nitrogen entering soil through the mineralization of crop residues ranges from 15 to 45 kg N/ha in cereal residues and from 80 to 144 kg N/ha in winter rape residues. Biological nitrogen fixation can increase the nitrogen content in soil by 30–50 kg/ha/year. In recent decades, the mismanagement of mineral fertilizers has drastically changed the natural balance of the nitrogen cycle. Every year huge amounts of nitrogen compounds enter the aquatic ecosystems and cause their eutrophication. That is why it is important to have adequate knowledge of sustainable fertilization so as to practice integrated crop management

Environmental Factors Affecting the Mineralization of Crop Residues

The aim of this article is to present the issues related to the significance of microorganisms in the mineralization of crop residues and the influence of environmental factors on the rate of this process. Crop residues play a very important role in agriculture because they can be used both as an environment-friendly waste management strategy and as a means of improving soil organic matter. The inclusion of crop residues in the soil requires appropriate management strategies that support crop production and protect the quality of surface water and groundwater. Crops need nutrients for high yields; however, they can only absorb ionic forms of elements. At this point, the microorganisms that convert organically bound nitrogen, phosphorus, and sulfur into soluble NH4+, NO3−, H2PO4−, HPO42−, and SO42− ions are helpful. Mineralization is the transformation of organic compounds into inorganic ones, which is a biological process that depends on temperature, rainfall, soil properties, the chemical composition of crop residues, the structure and composition of microbial communities, and the C:N ratio in soil after the application of plant matter. An adjustment of the values of these factors enables us to determine the rate and direction of the mineralization of crop residues in soil

Effect of metformin therapy on protein oxidation end products (AOPPs) and lipocalin2 (NGAL) levels in diabetic patients with vascular complications

Celem pracy była ocena wpływu farmakoterapii metforminą na poziomy końcowych produktów utleniania białek (AOPPs) oraz lipokaliny 2 (NGAL) u pacjentów z cukrzycą z powikłaniami naczyniowymi. W osoczu pacjentów badano także stężenia interleukiny 6 (IL-6).Do napisania pracy wykorzystano analizę dostępnej literatury oraz badania własne przeprowadzone w laboratorium Zakładu Cytobiologii Katedry Farmakobiologii Wydziału Farmaceutycznego Uniwersytetu Jagiellońskiego Collegium Medicum w Krakowie. Praca skupia się na wykonaniu oznaczeń stężeń AOPPs, NGAL i IL-6 w osoczu pacjentów.W wyniku przeprowadzonych badań stwierdzono, że u pacjentów z cukrzycą i powikłaniami naczyniowymi stężenia AOPPs, NGAL i IL-6 są wyższe niż u pacjentów bez cukrzycy.Zaobserwowano, że leczenie metforminą u pacjentów z cukrzycą typu 2 wiąże się z poprawą kontroli cukrzycy, a także aktywacją stresu oksydacyjnego wyrażonego AOPPs, wraz z układem antyoksydacyjnym. W badaniach wykazano najniższe stężenie lipokaliny 2/NGAL w osoczu pacjentów stosujących monoterapię metforminą. Podobne wyniki zaobserwowano w przypadku cytokiny prozapalnej IL-6.Terapia metforminą może zapewnić znaczną ochronę przed diabetologicznymi powikłaniami naczyniowymi, związanymi ze stanem zapalnym w cukrzycy i z aktywacją interakcji neutrofili z śródbłonkiem naczyniowym.The aim of the study was to evaluate the effect of metformin pharmacotherapy on the levels of Advanced Oxidation Protein Products (AOPPs) and lipocalin 2 (NGAL) in diabetic patients with vascular complications. Interleukin 6 (IL-6) levels in patients' plasma were also tested.An analysis of the available literature and research done in the Cytobiology Department of the Pharmacobiology Department, at the Medical College of Jagiellonian University in Krakow, were used to write the thesis. The work is focused on the determination of AOPPs, NGAL and IL-6 concentrations in the plasma of patients.As a result of the research, it was found that the concentrations of AOPPs, NGAL and IL-6 in samples from patients with diabetes and vascular complications, were higher than in non-diabetic subjects.In the study the lowest plasma levels of lipocalin 2/NGAL in patients receiving metformin monotherapy was found. Similar results were obtained with the pro-inflammatory cytokine IL-6.Metformin therapy can provide significant protection against diabetic vascular complications associated with inflammation in diabetes and the activation of neutrophil-vascular endothelial interactions

Introduction to Bacterial Anhydrobiosis: A General Perspective and the Mechanisms of Desiccation-Associated Damage

Anhydrobiosis is the ability of selected organisms to lose almost all water and enter a state of reversible ametabolism. Such an organism dries up to a state of equilibrium with dry air. Unless special protective mechanisms exist, desiccation leads to damage, mainly to proteins, nucleic acids, and membrane lipids. A short historical outline of research on extreme dehydration of living organisms and the current state of research are presented. Terminological issues are outlined. The role of water in the cell and the mechanisms of damage occurring in the cell under the desiccation stress are briefly discussed. Particular attention was paid to damage to proteins, nucleic acids, and membrane lipids. Understanding the nature of the changes and damage associated with desiccation is essential for the study of desiccation-tolerance mechanisms and application research. Difficulties related to the definition of life and the limits of life in the scientific discussion, caused by the phenomenon of anhydrobiosis, were also indicated