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Background/Aim: Bioelectrical Impedance Analysis is a method that evaluates body composition, useful in assessing the nutritional status of cancer patients. The analysis of its indicators may be helpful in predicting clinical course. The aim of the study was to evaluate the following body composition parameters: fat mass (FM), fat-free mass (FFM), skeletal muscle mass (SMM), muscle mass index (MMI), visceral fat (VF) and body mass index (BMI) measured before and after surgery in patients with gastrointestinal cancer and to determine the relationship between body composition and the course of treatment. Patients and Methods: The study included 125 patients, aged 65-68, operated on due to gastric, pancreatic or colorectal cancer. Body composition was assessed with electrical bioimpedance before and on the fifth postoperative day. The severity of complications was assessed with the Clavien-Dindo classification. Results: In the whole group of patients, the percentage of FM, VF, and BMI levels measured before surgery were significantly higher in curative surgery patients in comparison to palliative surgery patients, p

Objectives The study aimed to examine the number of unnecessary medical procedures and healthcare costs with the use of the educational intervention in Poland. Methods Secondary data were collected between 2014 and 2015. Analysis of events and cost per patient revealed significant variability and overutilization of diagnostics and other services by physicians practicing in a network of private outpatient clinics in Poland. To reduce unjustified referrals and costs, a 2-year educational intervention was carried out, which included printed evidence-based practice recommendations and quarterly verification of the results from each of the 617 participating physicians. We analyzed the effects of the intervention on the number of medical events and costs with 17 diagnoses generating the highest costs. Results After 2 years of the intervention, the number of medical events per patient decreased by over 20% compared to baseline, primarily in orthopedics (by 31%-37%). Moreover, the healthcare costs per patient decreased by about 18% at the end of the intervention. Patient satisfaction remained high during the intervention. Conclusions Intervention based on evidence-based practice reduced both the number of unnecessary medical procedures and healthcare costs in the outpatient setting, while not affecting patient satisfaction.

Human β-defensin 3, HBD-3, is a 45-residue antimicrobial and immunomodulatory peptide that plays multiple roles in the host defense system. In addition to interacting with cell membranes, HBD-3 is also a ligand for melanocortin receptors, cytokine receptors and voltage-gated potassium channels. Structural and functional studies of HBD-3 have been hampered by inefficient synthetic and recombinant expression methods. Herein, we report an optimized Fmoc solid-phase synthesis of this peptide using an orthogonal disulfide bonds formation strategy. Our results suggest that utilization of an optimized resin, coupling reagents and pseudoproline dipeptide building blocks decrease chain aggregation and largely improve the amount of the target peptide in the final crude material, making the synthesis more efficient. We also present an alternative synthesis of HBD-3 in which a replacement of a native disulfide bridge with a diselenide bond improved the oxidative folding. Our work enables further biological and pharmacological characterization of HBD-3, hence advancing our understanding of its therapeutic potential.

Summary Aim Home parenteral nutrition (HPN) is one of the most demanding medical therapies as it is the only option for patients for intestinal failure (IF). No unequivocal policy on how to start and progress with HPN has ever been presented. The IF Center at the Stanley Dudrick's Memorial Hospital in Skawina is one of the biggest centers in Poland, celebrating its twentieth birthday last year. It offered the unique chance to present how to create and grow the IF center, increasing the quality of care. The above became the aim of this study. Methods A retrospective analysis of all medical records of HPN patients from the University Hospital and Stanley Dudrick's Memorial Hospital in Skawina. Patient profile, clinical course and treatment outcomes were assessed. The evolution of all aspects of HPN is presented. A brief historical perspective has been added to better illustrate the center's growth and transformation. Results 608 patients (363 female, 245 male, mean age 55.55 year) from all over Poland were treated between December 1999 and December 2019. The most frequent indication for HPN was mechanical obstruction (277, 45.7%), followed by short bowel syndrome (SBS, 208, 34.3%) and intestinal fistula (46, 7.59%). The most common primary disease was cancer (n = 267), followed by mesenteric ischemia (n = 104), and surgical complications (n = 62). 314 patients (51.8%) died. 73 (12.04%) were successfully weaned off PN. The catheter infection rate reached 0.39/1000 catheter days. Conclusions the founding of the HPN center and its further development is possible provided that there is team of dedicated people, supported by hospital base. The real growth opportunity is guaranteed by the reimbursement. It is necessary to adapt to the changing circumstances.

OBJECTIVE To evaluate impact of directing patients with back pain for first visit to a physiotherapist on sick leaves, healthcare utilization, and patient satisfaction. METHODS Pre-post intervention study of 70,138 patients treated in Poland for back pain: 27,034 before the care pathway redesign and 43,104 after. RESULTS After the redesign, all per-patient measures (mean ± SD) significantly decreased over the 12-month follow-up: sick leaves number from 0.32 ± 0.87 to 0.29 ± 0.86, sick leaves days from 2.78 ± 11.56 to 2.56 ± 11.25, doctors' visits from 2.02 ± 1.70 to 1.51 ± 1.63, diagnostic imaging services from 0.63 ± 0.79 to 0.43 ± 0.71 and rehabilitation services from 7.55 ± 14.90 to 4.70 ± 12.61.The Net Promoter Score was higher for physiotherapist (83), than for orthopedists (59), primary care (74), or neurologists (67). CONCLUSIONS Involving physiotherapists early in the back pain care may result in benefits for patients and healthcare organizations.

This study evaluated the association between religiosity and binge drinking in early adolescence. A cross-sectional study was conducted with adolescents aged 10-13 from Belo Horizonte, Brazil. Stratified random sampling was performed considering the administrative district and school year. Adolescents filled an AUDIT-C form, containing questions about religiosity and binge drinking by parents and their best friends. Adolescents’ caregivers answered a form regarding socioeconomic issues. Descriptive analysis, univariate, and multivariate logistic regression were performed. A total of 650 adolescents participated in the study. The frequency of binge drinking was 13.7%. In the adjusted model, religiosity was not associated with binge drinking. The covariates associated were the age of 12-13 years (OR: 1.94; CI95%: 1.06-3.56; p=0.030), maternal binge drinking (OR: 3.12; CI95%: 1.76-5.52; p

Introduction: The development of pneumonia in patients treated in intensive care wards is influenced by numerous factors resulting from the primary health condition and co-morbidities. The aim of this study is the determination of the correlation between nutritional status disorders and selected risk factors (type of injury, epidemiological factors, mortality risk, inflammation parameters, age, and gender) and the time of pneumonia occurrence in patients mechanically ventilated in intensive care wards. Material and method: The study included 121 patients with injuries treated in the intensive care ward who had been diagnosed with pneumonia related to mechanical ventilation. The data were collected using the method of retrospective analysis of patients’ medical records available in the electronic system. Results: Ventilator-associated pneumonia (VAP) occurred more frequently in patients over 61 years of age (40.4%), men (67.8%), after multiple-organ injury (45.5%), and those with a lower albumin level (86%), higher CRP values (83.5%), and leukocytes (68.6%). The risk of under-nutrition assessed with the NRS-2002 system was confirmed in the whole study group. The statistical analysis demonstrated a correlation between the leukocytes level (p = 0.012) and epidemiological factors (p = 0.035) and the VAP contraction time. Patients infected with Staphylococcus aureus had 4% of odds for the development of late VAP in comparison to Acinetobacter baumannii (p < 0.001), whereas patients infected by any other bacteria or fungi had about four times lower odds of the development of late VAP in comparison to Acinetobacter baumannii (p = 0.02). Patients with results in APACHE from 20 to 24 and from 25 to 29 had 13% and 21%, respectively, odds of the development of late VAP in comparison to patients with APACHE II scores ranging from 10 to 19 (respectively, p = 0.006; p = 0.028). Conclusions: The development of VAP is impacted by many factors, the monitoring of which has to be included in prophylactics and treatment.

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments.

Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton’s tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and

In this paper, the techniques used to study the function of mitochondrial potassium channels are critically reviewed. The majority of these techniques have been known for many years as a result of research on plasma membrane ion channels. Hence, in this review, we focus on the critical evaluation of techniques used in the studies of mitochondrial potassium channels, describing their advantages and limitations. Functional analysis of mitochondrial potassium channels in comparison to that of plasmalemmal channels presents additional experimental challenges. The reliability of functional studies of mitochondrial potassium channels is often affected by the need to isolate mitochondria and by functional properties of mitochondria such as respiration, metabolic activity, swelling capacity, or high electrical potential. Three types of techniques are critically evaluated: electrophysiological techniques, potassium flux measurements, and biochemical techniques related to potassium flux measurements. Finally, new possible approaches to the study of the function of mitochondrial potassium channels are presented. We hope that this review will assist researchers in selecting reliable methods for studying, e.g., the effects of drugs on mitochondrial potassium channel function. Additionally, this review should aid in the critical evaluation of the results reported in various articles on mitochondrial potassium channels.

In patients scheduled for surgery, nutritional disorders worsen during the perioperative period, which is often a risk factor for postoperative complications. The aim of the study was to determine relationship between the preoperative nutritional status of elderly people with stomach, pancreatic and colon cancer and the incidence of postoperative complications and the length of hospital stay. The study included 143 patients with gastrointestinal cancer, aged 65–68, qualified for surgery. Mini Nutritional Assessment, body mass index questionnaires and medical records were used. Malnutrition was found in 9.8%, and a risk of malnutrition in 53.5% of the respondents. Body mass index showed overweight in 28% and obesity in 14% of the patients. Complications occurred in all types of nutritional status, the most common were those requiring intensive care unit treatment (36.8%), pancreatic and biliary fistulas (29.4%) and surgical site infections (58.2%). Gastric cancer patients at risk of malnutrition stayed longer in the hospital. Postoperative complications and longer hospital stays were observed more frequently in cases of overweight, obesity, malnutrition and its risk. Disturbances in the nutritional status, in the form of malnutrition and its risk, as well as overweight and obesity, determined more frequent occurrence of postoperative complications and longer hospital stay.

INTRODUCTION. Dental caries is a transmissible chronic disease of dental hard tissues. To monitor the course of carious process, age reference groups were designated which are subject to regular dental check-ups. The groups include children aged 6, 12, and 18 years as well as adults at the age of 35-44 and 55-64 years. AIM. The aim of the study was to evaluate the state of dentition and effectiveness of treatment among children and adolescents in the reference groups aged 6, 12, and 18 years from the town of Skierniewice and its region in the years 2017-2020. MATERIAL AND METHODS. The study included 385 children and adolescents from the reference groups. Dental examination was carried out in the dental office of the Ogrodowa Medical Centre in Skierniewice. Dental caries intensity expressed by the the DMFT index, and its particular components, D, M, and F (D– the mean number of teeth with caries (decayed), M– teeth extracted (missing), and F– filled) as well as the dental caries treatment index DTI (F/(D+F)) were determined according to sex. RESULTS. Distribution of the DMFT index components was very similar in children aged 6 years and in 18-year-old adolescents. The D component constituted half the DMF index (50.7% in 6-year-olds and 52.4% in 18-year-olds), the M component values were lowest (16.1% and 12.3%, respectively) while the F component accounted for slightly more than 1/3 of the whole value (33.2% and 35.3%, respectively). In 12-year-olds, the D component value was 68.4% of the DMF index, the M component accounted for only a few percent (4.5%) and the F component was 27.1%. The DTI value was 0.40 for 6-year-olds and 18-year-olds and appeared to be significantly higher than in the group of 12-year-olds (0.3). CONCLUSIONS. There is an urgent need for monitoring the dental status, professional caries prevention, and conservative treatment of teeth in children and adolescents of the Skierniewice region.

Background: Acalabrutinib is a selective, covalent Bruton tyrosine-kinase inhibitor with activity in chronic lymphocytic leukaemia. We compare the efficacy of acalabrutinib with or without obinutuzumab against chlorambucil with obinutuzumab in patients with treatment-naive chronic lymphocytic leukaemia. Methods: ELEVATE TN is a global, phase 3, multicentre, open-label study in patients with treatment-naive chronic lymphocytic leukaemia done at 142 academic and community hospitals in 18 countries. Eligible patients had untreated chronic lymphocytic leukaemia and were aged 65 years or older, or older than 18 years and younger than 65 years with creatinine clearance of 30–69 mL/min (calculated by use of the Cockcroft-Gault equation) or Cumulative Illness Rating Scale for Geriatrics score greater than 6. Additional criteria included an Eastern Cooperative Oncology Group performance status score of 2 or less and adequate haematologic, hepatic, and renal function. Patients with significant cardiovascular disease were excluded, and concomitant treatment with warfarin or equivalent vitamin K antagonists was prohibited. Patients were randomly assigned (1:1:1) centrally via an interactive voice or web response system to receive acalabrutinib and obinutuzumab, acalabrutinib monotherapy, or obinutuzumab and oral chlorambucil. Treatments were administered in 28-day cycles. To reduce infusion-related reactions, acalabrutinib was administered for one cycle before obinutuzumab administration. Oral acalabrutinib was administered (100 mg) twice a day until progressive disease or unacceptable toxic effects occurred. In the acalabrutinib-obinutuzumab group, intravenous obinutuzumab was given on days 1 (100 mg), 2 (900 mg), 8 (1000 mg), and 15 (1000 mg) of cycle 2 and on day 1 (1000 mg) of cycles 3–7. In the obinutuzumab-chlorambucil group, intravenous obinutuzumab was given on days 1 (100 mg), 2 (900 mg), 8 (1000 mg), and 15 (1000 mg) of cycle 1 and on day 1 (1000 mg) of cycles 2–6. Oral chlorambucil was given (0·5 mg/kg) on days 1 and 15 of each cycle, for six cycles. The primary endpoint was progression-free survival between the two combination-therapy groups, assessed by independent review committee. Crossover to acalabrutinib was allowed in patients who progressed on obinutuzumab-chlorambucil. Safety was assessed in all patients who received at least one dose of treatment. Enrolment for this trial is complete, and the study is registered at ClinicalTrials.gov, NCT02475681. Findings: Between Sept 14, 2015, and Feb 8, 2017, we recruited 675 patients for assessment. 140 patients did not meet eligibility criteria, and 535 patients were randomly assigned to treatment. 179 patients were assigned to receive acalabrutinib-obinutuzumab, 179 patients were assigned to receive acalabrutinib monotherapy, and 177 patients were assigned to receive obinutuzumab-chlorambucil. At median follow-up of 28·3 months (IQR 25·6–33·1), median progression-free survival was longer with acalabrutinib-obinutuzumab and acalabrutinib monotherapy, compared with obinutuzumab-chlorambucil (median not reached with acalabrutinib and obinutuzumab vs 22·6 months with obinutuzumab, hazard ratio [HR] 0·1; 95% CI 0·06–0·17, p

Mitochondria are intracellular organelles, which play a crucial role in the generation of ATP. Mitochondria are surrounded by a double membrane, consisting of a smooth outer membrane (OMM) and a markedly folded inner mitochondrial membrane (IMM). Mitochondrion that has been stripped of its outer membrane, leaving the inner membrane intact is called mitoplast. There is a number of different transport proteins located in the inner mitochondrial membrane including ion channels that mediate fluxes of potassium, calcium, and chloride ions. These channels regulate the mitochondrial membrane potential, respiration, and production of reactive oxygen species. The stability of mitoplasts offers the possibility of measuring the activity of ion channels from IMM using the patch-clamp technique. Electrophysiological measurements of currents through ion channels in the IMM permit discovery of unique properties of these channels with the aim of new specific pharmacological therapies. In this chapter, we describe the isolation of mitochondria, preparation of mitoplast for patch-clamp recordings and single-mitoplast PCR experiments, which can be helpful in mastering the technique of recording the activity of mitochondrial ion channels.

Background It is known that job satisfaction has an important impact on efficacy or burnout syndrome of medical personnel. Many studies have concerned job satisfaction among critical care nurses. Not as many have focused on anesthesia nurses working in operating theaters. In Poland, anesthesia and intensive care is a combined specialty for nurses. However, nurses work in an intensive care unit (ICU) or in an operating room (OR), and very rarely in both settings. We would like to compare satisfaction between ICU and OR nurses. Methods It was a multicenter cross-sectional study. 406 nurses from thirteen hospitals participated in this study. All respondents filled in the questionnaire that contained fifteen Likert-like questions reflecting different aspects of job satisfaction. Demographic data were also collected. Results We did not find a significant difference between ICU and OR nurses in the overall job satisfaction. Furthermore, the type of hospital did not significantly influence satisfaction of our study participants. The most important factor which differentiated the level of satisfaction among nurses was the region of Poland in which they worked. Interestingly, nurses who worked in ICUs were significantly younger in comparison to their colleagues from ORs. Conclusion The results of our study suggest that the region of the country in which nurses work might play a very important role in their satisfaction.

Background We wished to examine treatment and outcome patterns in older diffuse large B-cell lymphoma (DLBCL) patients, with a focus on the effect of route-to-diagnosis to outcome. Methods Data were extracted from Public Health England’s National Cancer Registration and Analysis Service between 2013 and 2015 included route-to-diagnosis, disease characteristics and survival for 9186 patients ≥65 years. Systemic Anti-Cancer Therapy data identified front-line regimens, cycles and doses. Results Route-to-diagnosis were emergency (34%), NHS urgent cancer pathway (rapid haemato-oncologist review n = 4392). 313 patients received R-miniCHOP (7% of R-CHOP). For all patients, 3-year overall survival (OS) for 65–79 years was 57% and for ≥80 years was 32%. Three-year OS for R-CHOP-treated patients diagnosed via emergency presentation was 54% (adjusted hazard ratio (HR) 1.63, p p Conclusions Our comprehensive population analysis is the first to show that the NHS urgent cancer pathway is associated with a superior survival after adjusting for multiple confounders. Equivalent survival for R-CHOP and R-mini-CHOP was demonstrated in those ≥80 years.

Gamma rays and electrons with kinetic energy up to 10 MeV are routinely used to sterilize biomaterials. To date, the effects of irradiation upon human acellular dermal matrices (hADMs) remain to be fully elucidated. The optimal irradiation dosage remains a critical parameter affecting the final product structure and, by extension, its therapeutic potential. ADM slides were prepared by various digestion methods. The influence of various doses of radiation sterilization using a high-energy electron beam on the structure of collagen, the formation of free radicals and immune responses to non-irradiated (native) and irradiated hADM was investigated. The study of the structure changes was carried out using the following methods: immunohistology, immunoblotting, and electron paramagnetic resonance (EPR) spectroscopy. It was shown that radiation sterilization did not change the architecture and three-dimensional structure of hADM, however, it significantly influenced the degradation of collagen fibers and induced the production of free radicals in a dose-dependent manner. More importantly, the observed effects did not disrupt the therapeutic potential of the new transplants. Therefore, radiation sterilization at a dose of 35kGy can ensure high sterility of the dressing while maintaining its therapeutic potential.

There is a Blood Commentary on this article in this issue., Key Points Both watch-and-wait and treated CLL patients have high mortality rates when admitted for COVID-19. Receiving a BTKi for CLL at COVID-19 diagnosis severe enough to require hospitalization did not influence case fatality rate in this study., Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median Cumulative Illness Rating Scale score was 8 (range, 4-32). Thirty-nine percent were treatment naive (“watch and wait”), while 61% had received ≥1 CLL-directed therapy (median, 2; range, 1-8). Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly Bruton tyrosine kinase inhibitors (BTKi’s; n = 68/90 [76%]). At a median follow-up of 16 days, the overall case fatality rate was 33%, though 25% remain admitted. Watch-and-wait and treated cohorts had similar rates of admission (89% vs 90%), intensive care unit admission (35% vs 36%), intubation (33% vs 25%), and mortality (37% vs 32%). CLL-directed treatment with BTKi’s at COVID-19 diagnosis did not impact survival (case fatality rate, 34% vs 35%), though the BTKi was held during the COVID-19 course for most patients. These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess severe acute respiratory syndrome coronavirus 2 infection risk, these data should be validated independently, and randomized studies of BTKi’s in COVID-19 are needed to provide definitive evidence of benefit., Visual Abstract

Aim: Patients on parenteral nutrition (PN) are prone to inflammation. This may aggravate an existing proinflammatory state and become a critical factor in the development of liver dysfunction (LD). Intravenous fish oil may attenuate this inflammatory state, but data on its use in adults are scarce. The aim of this study was to investigate the effects of adding a pure fish oil intravenous lipid emulsion (ILE) into short- and long-term PN in patients either at risk of, or with existing, inflammation. Methods: A retrospective analysis of 61 patients (32 female, 29 male, mean age 51.5 &plusmn, 12.6 years) who received all-in-one PN, including amino acids, glucose, and lipids supplemented with pure fish oil ILE, was performed. Pure fish oil ILE (Omegaven&reg, Fresenius Kabi, Bad Homburg, Germany) was used along with the standard ILE to reach a fish oil dose of 0.4&ndash, 0.5 g fish oil/kg/d. Diagnoses were chronic intestinal failure (CIF, n = 20), Crohn&rsquo, s disease (CD, n = 22), and ulcerative colitis (UC, n = 19). The observation period was 12 months for CIF and 21 days for UC and CD. Results: A reduction in inflammation was noticeable in all patients and became statistically significant in CD (hsCRP p &lt, 0.0001, ESR p = 0.0034, procalcitonin p = 0.0014, Il-6 p = 0.001) and UC groups (hsCRP and ESR p &lt, 0.0001, Il-6 p = 0.0001, TNF-&alpha, p = 0.0113). In the CIF group, the total bilirubin concentration (p = 0.2157) and aspartate transaminase SGOT (p = 0.1785) did not vary over time. Conclusions: PN with pure fish oil ILE reduces some inflammatory parameters in IBD and maintains liver function parameters in CIF patients. Fish oil might become a valuable ingredient in both short- and long-term PN in patients at risk of liver dysfunction.

Potassium channels have been discovered in the inner mitochondrial membrane of various cells. These channels can regulate the mitochondrial membrane potential, the matrix volume, respiration and reactive species generation. Therefore, it is believed that their activation is cytoprotective in various tissues. In our study, the single-channel activity of a large-conductance calcium-activated potassium channel (mitoBKCa) was measured by the patch-clamp technique on mitoplasts derived from mitochondria isolated from human glioma U-87 MG cells. Here, we show for the first time that mechanical stimulation of mitoBKCa channels results in an increased probability of channel opening. However, the mechanosensitivity of mitoBKCa channels was variable with some channels exhibiting no mechanosensitivity. We detected the expression of mechanosensitive BKCa-STREX exon in U-87 MG cells and hypotesize, based on previous studies demonstrating the presence of multiple BKCa splice variants that variable mechanosensitivity of mitoBKCa could be the result of the presence of diverse BKCa isoforms in mitochondria of U-87 MG cells. Our findings indicate the possible involvement of the mitoBKCa channel in mitochondria activities in which changes in membrane tension and shape play a crucial role, such as fusion/fission and cristae remodeling.

TO THE EDITOR: The term “clonal B cell lymphocytosis of marginal zone origin” (CBL-MZ)[1][1],[2][2] has recently been suggested for asymptomatic individuals whose routine blood count shows a persistent modest lymphocytosis that is usually accompanied by bone marrow involvement. This

Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell cancer exhibiting a wide spectrum of disease courses and treatment responses. Molecular characterization of RNA and DNA from CLL cases has led to the identification of important driver mutations and disease subtypes, but the precise mechanisms of disease progression remain elusive. To further our understanding of CLL biology we performed isobaric labeling and mass spectrometry proteomics on 14 CLL samples, comparing them with B-cells from healthy donors (HDB). Of 8694 identified proteins, ∼6000 were relatively quantitated between all samples (q

Curcumin (CUR) is a natural compound that exhibits anti-inflammatory, anti-bacterial, and other biological properties. However, its application as an effective drug is problematic due to its poor oral bioavailability, solubility in water, and poor absorption from the gastrointestinal tract. The aim of this work is to synthesize monocarbonyl analogs of CUR based on the 9-methyl-9-azabicyclo[3.2.1]nonan-3-one (pseudopelletierine, granatanone) scaffold to improve its bioavailability. Granatane is a homologue of tropane, whose structure is present in numerous naturally occurring alkaloids, e.g., l-cocaine and l-scopolamine. In this study, ten new pseudopelletierine-derived monocarbonyl analogs of CUR were successfully synthesized and characterized by spectral methods and X-ray crystallography. Additionally, in vitro test of the cytotoxicity and anti-inflammatory properties of the synthesized compounds were performed.

The alarming raise of multi-drug resistance among human microbial pathogens makes the development of novel therapeutics a priority task. In contrast to conventional antibiotics, antimicrobial peptides (AMPs), besides evoking a broad spectrum of activity against microorganisms, could offer additional benefits, such as the ability to neutralize toxins, modulate inflammatory response, eradicate bacterial and fungal biofilms or prevent their development. The latter properties are of special interest, as most antibiotics available on the market have limited ability to diffuse through rigid structures of biofilms. Lipidation of AMPs is considered as an effective approach for enhancement of their antimicrobial potential and in vivo stability, however, it could also have undesired impact on selectivity, solubility or the aggregation state of the modified peptides. In the present work, we describe the results of structural modifications of compounds designed based on cationic antimicrobial peptides DK5 and CAR-PEG-DK5, derivatized at their N-terminal part with fatty acids with different lengths of carbon chain. The proposed modifications substantially improved antimicrobial properties of the final compounds and their effectiveness in inhibition of biofilm development as well as eradication of pre-formed 24 h old biofilms of Candida albicans and Staphylococcus aureus. The most active compounds (C5-DK5, C12-DK5 and C12-CAR-PEG-DK5) were also potent against multi-drug resistant Staphylococcus aureus USA300 strain and clinical isolates of Pseudomonas aeruginosa. Both experimental and in silico methods revealed strong correlation between the length of fatty acid attached to the peptides and their final membranolytic properties, tendency to self-assemble and cytotoxicity.

Volumetric Modulated Radiotherapy (VMAT) implementation requires additional Quality Assurance (QA) tests to assure stable machine performance especially in terms of dynamic parameters synchronization. The lack of a twin machine for TrueBeam led us to the investigation of backup workflow with Clinacs 2300C/D. These Clinacs were upgraded to make them VMAT-enabled. This study aimed to compare long-term VMAT performance QA on 3 accelerators: TrueBeam (TB) and 2 Clinacs (V4 and V5). All VMAT test plans were provided by Varian. The test set consisted of initial and advanced tests. Initial tests were intended to check the gravity effect on Multileaf Collimator (MLC) and dosimetry system. As the results of these tests were correct and there was visual inspection applied for MLC positioning accuracy analysis, they were not presented in the paper. We focused on 2 advanced tests: dose rate vs gantry speed and dose rate vs MLC speed. The idea of the advanced test was to compare segments irradiated with the same fluence but different dose rate, gantry speed or MLC speed. Test sets were irradiated weekly on average for 12 months. These tests were analysed following Varian procedures and criteria using in-house-developed software. Apart from that we calculated correlation between all segments pairs and performed profile analysis. According to Varian criteria, all tests for TrueBeam were very well within the tolerances. Dose rate vs gantry speed tests for Clinacs were within allowed limits while as many as 28% and 6% of dose rate vs MLC speed tests failed for Clinacs V4 and V5, respectively. The profile analysis revealed tests for which the difference between measured and planned dose was over 3% and still met the criteria. The correlation analysis showed that VMAT plans on TrueBeam were irradiated repeatably because all segments were strongly correlated. There was no correlation between the segment with the highest MLC speed and the other segments on Clinacs in dose rate vs MLC speed test. This segment was irradiated randomly. TrueBeam is more reliable than upgraded Clinacs 2300C/D for VMAT performance. That is why in our centre the one of upgraded Clinac that performed tests better served only as a backup machine for VMAT technique, and the second one was excluded from clinical use for this technique.

Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with chemotherapy trials representing an invaluable resource to explore disease-related/genetic features contributing to long-term outcomes. In 499 LRF CLL4 cases, a trial with >12 years follow-up, we employed targeted resequencing of 22 genes, identifying 623 mutations. After background mutation rate correction, 11/22 genes were recurrently mutated at frequencies between 3.6% (NFKBIE) and 24% (SF3B1). Mutations beyond Sanger resolution (KRAS mutations principally composed of these low VAF variants. Firstly, employing orthogonal approaches to confirm TP53 mutations, we assessed the clinical impact of TP53 clonal architecture. Whilst ≥ 12% VAF TP53mut cases were associated with reduced PFS and OS, we could not demonstrate a difference between TP53 mutations and either wild type or ≥12% VAF TP53mut cases. Secondly, we identified biallelic BIRC3 lesions (mutation and deletion) as an independent marker of inferior PFS and OS. Finally, we observed that mutated MAPK-ERK genes were independent markers of poor OS in multivariate survival analysis. In conclusion, our study supports using targeted resequencing of expanded gene panels to elucidate the prognostic impact of gene mutations.

Cel pracyCelem niniejszej pracy jest poznanie opinii młodzieży w wieku 16-19 lat, uczęszczającej do warszawskich publicznych liceów ogólnokształcących, na temat efektywności profilaktyki samobójstw.MetodaPopulacja badana objęła młodzież, która w roku 2015 była w wieku 16-19 lat (M = 17,29; SD = 0,94). Respondenci uczęszczali do ośmiu warszawskich publicznych liceów ogólnokształcących z ośmiu różnych dzielnic. Badanie było reprezentatywne. W badaniu uczestniczyło 1439 respondentów – 821 dziewcząt (57,1%) i 592 chłopców (41,1%). Badanie przeprowadzono metodą PAPI. Kwestionariusz zawierał 34 pytania.WynikiRespondenci najczęściej nie wiedzieli czy w Polsce istnieje zorganizowany system zapobiegania samobójstwom (42,0%), ale duża część respondentów (39,7%) miała świadomość, że taki system w Polsce nie istnieje. Respondenci uważali działalność szkoły (46,7%), Kościoła (38,3%) i policji (55,9%) za nieskuteczną, jednostek opieki zdrowotnej (47,7%) i mediów (46,6%) za mało skuteczne, natomiast rodzinę (70,9%) za skuteczną w zakresie zapobiegania samobójstwom. Osoby, które upatrują znaczącą rolę kościoła równocześnie wskazują na znaczący udział rodziny w zapobieganiu samobójstwom, a w znacznie mniejszym stopniu innych z wymienionych instytucji.Wnioski1. Ponad 1/3 badanej młodzieży zdaje sobie sprawę, iż w Polsce nie istnieje zintegrowany system zapobiegania samobójstwom. 2. Najważniejszą rolę w prewencji zachowań autodestrukcyjnych, w opinii licealistów, pełni rodzina. 3. Istnieje potrzeba większego zaangażowania szkół, Kościoła, policji, jednostek służby zdrowia oraz mediów w edukację i uświadamianie młodzieży w kwestii profilaktyki zachowań autodestrukcyjnych.

Venetoclax is a BCL2 inhibitor with activity in relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). We conducted a multi-centre retrospective analysis of 105 R/R CLL patients who received venetoclax pre-National Health Service commissioning. The median age was 67 years and median prior lines was 3 (range: 1–15). 48% had TP53 disruption. At ≥2 lines, 60% received a Bruton Tyrosine Kinase inhibitor (BTKi) and no prior phosphoinositide 3-kinase inhibitor (Pi3Ki), 25% received a Pi3Ki and no prior BTKi, and 10% received both. Patients discontinued B cell receptor inhibitor (BCRi) because of toxicity in 44% and progression in 54%. Tumour lysis syndrome risk was low, intermediate or high in 27%, 25%, and 48% respectively. Overall response was 88% (30% complete response [CR]). The overall response rate was 85% (CR 23%) in BTKi-exposed patients, 92% (CR 38%) in Pi3Ki-exposed patients and 80% (CR 20%) in both (P = 0·59). With a median follow-up of 15·6 months, 1-year progression-free survival was 65·0% and 1-year overall survival was 75·1%. Dose reduction or temporary interruption did not result in an inferior progression-free or discontinuation-free survival. Risk of progression or death after stopping a prior BCRi for progression was double compared to those stopping for other reasons (predominantly toxicity) (Hazard Ratio 2·01 P = 0·05). Venetoclax is active and well tolerated in R/R CLL post ≥1 BCRi. Reason(s) for stopping BCRi influences venetoclax outcomes.

The use of home enteral or parenteral nutrition has been a necessary step in the optimization of nu tritional support in patients who, due to several diseases, fail to meet their nutritional requirements by oral feeding. This article presents the recommendations of the Chilean Pediatric Society Nutritio nal Branch, aimed at health teams that treat pediatric patients who require enteral feeding for a long time. The general objective is to provide guidelines for the proper management of these patients. It describes the ideal conformation of the health team for the care and follow-up of those patients, the program admission criteria, and its evaluation method over time. In addition, it describes general characteristics of enteral feeding, routes of administration, available enteral formulas, complications, and patient follow-up.

Cel pracyCelem niniejszej pracy jest poznanie opinii młodzieży w wieku 16-19 lat, uczęszczającej do warszawskich publicznych liceów ogólnokształcących, na temat czynników ryzyka samobójstw.MetodaPopulacja badana objęła młodzież, która w roku 2015 była w wieku 16-19 lat (M = 17,29; SD = 0,94). Respondenci uczęszczali do ośmiu warszawskich publicznych liceów ogólnokształcących z ośmiu różnych dzielnic. Badanie było reprezentatywne. W badaniu uczestniczyło 1439 respondentów – 821 dziewcząt (57,1%) i 592 chłopców (41,1%). Badanie przeprowadzono metodą PAPI. Kwestionariusz zawierał 34 pytania podzielone na trzy bloki- dotycząc epidemiologii, czynników ryzyka i profilaktyki zachowań samobójczych.WynikiWedług 37,0% badanych głównym problemem występującym w rodzinie, który może stać się czynnikiem ryzyka popełnienia samobójstwa jest brak zrozumienia przez rodziców. Badani uważali, że konflikty z rówieśnikami stanowią sytuacje związane ze szkołą, które mogą stać się przyczyną powstania myśli samobójczych (48,6%). Ponad połowa badanych (59,1%) uważała, że odrzucenie przez osoby bliskie i ważne stanowi główny czynnik związany z poczuciem osamotnienia, mogący być przyczyną aktu samobójczego.Wnioski1. Istotnym elementem w prewencji zachowań autodestrukcyjnych młodych osób powinien być trening rodzicielski w zakresie okazywania zrozumienia i akceptacji swoim dzieciom. 2. Wskazane jest prowadzenie zajęć, doskonalących umiejętności psychospołeczne młodzieży, w szczególności zdolności rozwiązywania problemów interpersonalnych, w celu zmniejszenia liczby konfliktów z rówieśnikami, występujących w środowisku szkolnym.

Recently, gaseous signaling molecules, such as carbon monoxide (CO), nitric oxide (NO), and hydrogen sulfide (H2S), which were previously considered to be highly toxic, have been of increasing interest due to their beneficial effects at low concentrations. These so-called gasotransmitters affect many cellular processes, such as apoptosis, proliferation, cytoprotection, oxygen sensing, ATP synthesis, and cellular respiration. It is thought that mitochondria, specifically their respiratory complexes, constitute an important target for these gases. On the other hand, increasing evidence of a cytoprotective role for mitochondrial potassium channels provides motivation for the analysis of the role of gasotransmitters in the regulation of channel function. A number of potassium channels have been shown to exhibit activity within the inner mitochondrial membrane, including ATP-sensitive potassium channels, Ca2+-activated potassium channels, voltage-gated Kv potassium channels, and TWIK-related acid-sensitive K+ channel 3 (TASK-3). The effects of these channels include the regulation of mitochondrial respiration and membrane potential. Additionally, they may modulate the synthesis of reactive oxygen species within mitochondria. The opening of mitochondrial potassium channels is believed to induce cytoprotection, while channel inhibition may facilitate cell death. The molecular mechanisms underlying the action of gasotransmitters are complex. In this review, we focus on the molecular mechanisms underlying the action of H2S, NO, and CO on potassium channels present within mitochondria.

Objectives Intravenous lipid emulsions (ILE) are an essential component of parenteral nutrition (PN); however, pure soybean oil emulsion is considered a risk factor for intestinal failure–associated liver disease (IFALD). Limited data are available on the effect of different ILEs on the liver during long-term PN, and to our knowledge, no study has evaluated outcomes beyond 12 mo. Therefore, the aim of the present study was to assess the influence of mixed ILEs on liver function during long-term PN. Methods A randomized, open-label clinical trial was performed at the Intestinal Failure Center in Skawina, Poland. Sixty-seven patients (35 F, 32 M; mean age, 53.2 years) receiving home parenteral nutrition (HPN) due to stable chronic intestinal failure (CIF) were randomized to receive one of the following three ILEs: medium/long-chain triacylglycerides (MCT/LCT), olive oil/soybean oil (OO/SO), or a combination of SO/MCT/OO/fish oil (FO) (SMOFlipid). Patients were followed for 5 y. Liver function was assessed clinically and with biochemical parameters (total bilirubin, serum glutamyl oxalate transaminase, serum glutamyl pyruvate transaminase, γ-glutamyl transpeptidase, and alkaline phosphatase) at baseline and after 24 and 60 mo. Results The most common etiology for CIF was vascular, followed by Crohn's disease, surgical complications, and radiation enteritis. HPN was effective in improving nutritional status and was associated with low rates of catheter infections and clinical complications. No significant differences were observed between groups in median concentrations serum glutamyl oxalate transaminase, serum glutamyl pyruvate transaminase, γ-glutamyl transpeptidase, or alkaline phosphatase at 24 or 60 mo. A significant reduction in median bilirubin concentration was observed in the SMOFlipid group at 60 mo compared with baseline (6.8 umol/L; interquartile range, 5.2–8.5 versus 7.7 umol/L; interquartile range, 4.9–12.4; P = 0.0138). Conclusions Mixed ILEs are safe and effective for use in patients on long-term HPN. A multicomponent ILE with FO can provide additional benefits in terms of liver function during long-term HPN.

Disease progression in IGHV-M CLL with 'good-risk' cytogenetics is frequently associated with co-evolution of 'poor risk' driver mutations and DNA methylation changes.Drug resistance in IGHV-M CLL may be consequent upon the emergence of an IGHV-U cloneThe biological features of IGHV-M CLL responsible for disease progression are still poorly understood. We undertook a longitudinal study close to diagnosis, pre-treatment and post relapse in thirteen patients presenting with cMBL or Stage A disease and good risk biomarkers (IGHV-M genes, no del(17p) or del(11q) and low CD38 expression) who nevertheless developed progressive disease, of whom ten have required therapy. Using cytogenetics, FISH, genome-wide DNA methylation and copy number analysis together with whole exome, targeted deep- and Sanger sequencing, at diagnosis we identified mutations in established CLL driver genes in nine (69%), non-coding mutations (PAX5 enhancer region) in three, and genomic complexity in two patients. Branching evolutionary trajectories predominated (n=9/13), revealing intra-tumoural epi- and genetic heterogeneity and sub-clonal competition prior to therapy. Of the patients subsequently requiring treatment, two had sub-clonal TP53 mutations that would not be detected by standard methodologies, three qualified for the very-low risk category defined by integrated mutational and cytogenetic analysis and yet had established or putative driver mutations and one patient developed progressive, therapy-refractory disease associated with the emergence of an IGHV-U clone. These data suggest that extended genomic and immunogenetic screening may have clinical utility in patients with apparent good risk disease.Leukemia accepted article preview online, 05 February 2016. doi:10.1038/leu.2016.10.

Introduction Hepatitis A (HA) is caused by infection with the hepatitis A virus (HAV). The differential etiological diagnosis of acute hepatitis is based on a positive result of the serological test detecting IgM class anti-HAV. For epidemiological studies on past infection and seroprevalence of HAV in populations, the tests measuring IgG class anti-HAV or total anti-HAV are used. Since the 1990s, specific prophylaxis is possible by vaccination against HA. In Poland, vaccination is recommended and in majority is performed at own cost. Material and methods Database was obtained from electronic medical records of the 2 major private health care providers networks (Luxmed and Medicover) operating in Poland. During a 3-year period (2013-2015), 1,124 persons with unknown status of anti-HA vaccination were tested for the presence of total anti-HAV. Objective. The aim of the study was to evaluate the seroprevalence of anti-HAV among working professionals in Poland. Results Anti-HAV were detected in 603 (53.6%) persons, while 521 (46.3%) tested negative. The study group was divided into 2 subgroups: 25-44 and 45-64-years-old. For detailed statistical analysis, the presence of anti-HAV was considered as a dependent variable, and its predictors were gender, age and the year of the test performance. The presence of anti-HAV was significantly more prevalent in older age group. The lack of specific antibodies was more prevalent in younger age group. Conclusions Results of the study show increasing susceptibility to HAV infection in the younger age group, compared with the older age group of corporate professional employees in large cities in Poland. Since the epidemiological situation of HA is currently changing with increasing number of symptomatic cases of HA, it is suggested that employers might consider including an additional procedure of vaccination against HA into their private health insurance portfolio.

Immunomodulating enteral nutrition in the perioperative period may reduce postoperative complications in cancer patients. Little is known if this effect translates to the better survival. The aim of study was to assess the impact of postoperative immunomodulating enteral nutrition on postoperative complications and survival of gastric cancer patients.A group of 98 gastric cancer patients was randomly assigned for postoperative immunomodulating enteral nutrition n = 44 (Reconvan, Fresenius Kabi, Bad Homburg, Germany), or standard enteral nutrition n = 54 (Peptisorb, Nutricia, Schipol, The Netherlands). Postoperative complications, mortality, 6-mo and 1-yr survival were analyzed.The overall postoperative morbidity did not differ between the groups. The rate of pulmonary complications (excluding pneumonia) was significantly lower in immunomodulation group (0% vs 9.3%, p = 0.044), as well as 60-day mortality (0% vs. 11.1%, p = 0.037). There was no difference in 6-mo and 1-yr survival between the groups.Postoperative immunomodulating enteral nutrition may reduce respiratory complications and postoperative mortality in comparison to standard enteral nutrition. Despite this effect, it did not improve 6-mo and 1-yr survival in immunomodulation group. Probably the beneficial effect of immunomodulating enteral nutrition is too weak to be significant in such a number of patients.

Aim Intravenous lipid emulsion (ILE) can become a risk factor for intestinal failure associated liver disease (IFALD). Many ILEs are commercially available, however, a direct comparison of their impact on liver has, to our knowledge, never been performed. The aim of the study was to analyse that clinical problem during long term parenteral nutrition (PN). Methods A randomized, controlled clinical trial was performed at the Intestinal Failure Center in Skawina, Poland. Sixty-seven patients (37 F, 30 M, mean age 53.9 years) enrolled in home parenteral nutrition (HPN) due to stable chronic intestinal failure (CIF) were randomized to receive one the following for 12 months: long-chain triglycerides (LCT), medium/long-chain triglycerides, olive oil/LCT (OO/LCT) and a mix of LCT/MCT/OO/fish oil. Clinical evaluation and biochemical tests (total bilirubin, SGOT, SGTP, GGPT, alkaline phosphatase) were performed at enrolment and after 6 and 12 months. Results the most common reason for intestinal failure (IF) was short bowel due to mesenteric ischaemia, followed by Crohn's disease, surgical complications and radiation enteritis. PN stabilized liver parameters in all patients. No essential fatty acids deficiency was diagnosed. All four ILEs demonstrated comparable influence on liver in all study periods. The only exception was the decrease in total bilirubin concentration after 12 months (28.1 ± 25.3 vs 11.1 ± 4.5, p = 0.0023) and GGTP (222.5 ± 205.8 vs 146.6 ± 197.7, p = 0.0079) when OO/LCT was in use. Conclusions All four ILEs tested may be safe even during long-term parenteral nutrition. OO/LCT may be more effective than the others, but more studies in the field are needed.

Histopathological features and determinants of liver disease progression were analyzed in 42 treatment-naïve children (mean age: 10.7 ±3.7) with chronic hepatitis C (14/42 infected vertically and 26/42 horizontally). Histopathological evaluation was performed according to Knodell's modified system. Predictors of necroinflammation and fibrosis were identified using linear regression analyses. Most children presented with mild necroinflammation and fibrosis (mean grade 4.3 ±2.7, mean staging 1.2 ±0.8), irrespective of the mode of transmission. Vertically infected children were younger than those infected horizontally (8.6 ±2.5 vs. 11.5 ±3.7 years, p = 0.02). Alanine and aspartate aminotransferase (ALT and AST) levels were associated with necroinflammation (p = 0.003 and p = 0.01 for ALT and AST, respectively) and fibrosis (p = 0.01 and p = 0.04, respectively). Other positive independent predictors of fibrosis included duration of infection (p = 0.03) and body mass index (BMI) z-score (p = 0.03). Children with chronic hepatitis C presented with mild liver changes over a decade after the infection, irrespective of the mode of transmission. Since fibrosis is a time-dependent process, progression of the liver disease in vertically infected children may occur at a younger age compared to patients infected horizontally. Aminotransferase levels were associated with necroinflammation and fibrosis. Longer duration of infection and a higher BMI z-score were associated with more severe fibrosis.

Mitochondrial ATP-regulated potassium channels are present in the inner membrane of the mitochondria of various cells. In the present study, we show for the first time mitochondrial ATP-regulated potassium channels in human dermal fibroblast cells. Using the patch-clamp technique on the inner mitochondrial membrane of fibroblasts, we detected a potassium channel with a mean conductance equal to 100 pS in symmetric 150 mM KCl. The activity of this channel was inhibited by a complex of ATP/Mg 2+ and activated by potassium channel openers such as diazoxide or BMS 191095. Channel activity was inhibited by antidiabetic sulfonylurea glibenclamide and 5-hydroxydecanoic acid. The influence of substances modulating ATP-regulated potassium channel activity on oxygen consumption and membrane potential of isolated fibroblast mitochondria was also studied. Additionally, the potassium channel opener diazoxide lowered the amount of superoxide formed in isolated fibroblast mitochondria. Using reverse transcriptase-PCR, we found an mRNA transcript for the KCNJ1(ROMK) channel. The presence of ROMK protein was observed in the inner mitochondrial membrane fraction. Moreover, colocalization of the ROMK protein and a mitochondrial marker in the mitochondria of fibroblast cells was shown by immunofluorescence. In summary, the ATP-regulated mitochondrial potassium channel in a dermal fibroblast cell line have been identified.

Cancer is one of the most common cause of death nowadays. Thorough knowledge of the mechanisms of tumorigenesis and invasiveness of tumor cells is crucial for the development of molecular targeted therapies, which are believed to be future treatment of this type of diseases. Proteolytic enzymes are one of the factors involved in the development of cancer cells, very often used as markers of tumor progression. In this paper we describe the role of enzymes termed proprotein convertases (PCs) in pathogenesis and progress of cancer diseases. Furthermore, we indicate potential directions for the development of therapeutic strategies designed based on PCs inhibitors.Choroby nowotworowe są jedną z najczęstszych przyczyn zgonów w dzisiejszych czasach. Gruntowne poznanie mechanizmów nowotworzenia oraz inwazyjności komórek nowotworowych są kluczowe dla opracowania terapii celowanych molekularnie, w których upatruje się przyszłości leczenia tego typu schorzeń. Jednym z czynników zaangażowanych w rozwój komórek nowotworowych są enzymy proteolityczne, będące często markerami progresji nowotworów. W niniejszej pracy opisana została rola enzymów z rodziny konwertaz probiałkowych (PCs) w patogenezie oraz rozwoju chorób nowotworowych. Ponadto, wskazano możliwe kierunki rozwoju strategii terapeutycznych zaprojektowanych w oparciu o inhibitory PCs.

Demographic changes in contemporary society require implementation of proper perioperative care of elderly patients due to an increased risk of perioperative complications in this group. Preoperative assessment of health status identifies risks and enables preventive interventions, improving outcomes of surgical treatment. The Comprehensive Geriatric Assessment contains numerous diagnostic tests and consultations, which is expensive and difficult to use in everyday practice. The development of a simplified model of perioperative assessment of elderly patients will help identifying the group of patients who require further diagnostic workup.The aim of the study is to evaluate the usefulness of the tests used in a proposed model of perioperative risk assessment in elderly patients.In a group of 178 patients older than 64 years admitted for surgical procedures, a battery of tests was performed. The proposed model of perioperative risk assessment included: Charlson Comorbidity Index, ADL (activities of daily living), TUG test (timed "up and go" test), MNA (mini nutritional assessment), AMTS (abbreviated mental test score), spirometry measurement of respiratory muscle strength (Pimax, Pemax). Distribution of abnormal results of each test has been analysed.The Charlson Index over 6 points was recorded in 10.1% of patients (15.1% in cancer patients). Abnormal result of the TUG test was observed in 32.1%. The risk of malnutrition in MNA test has been identified in 29.7% (39.2% in cancer patients).Abnormal test results at the level of 10-30% indicate potential diagnostic value of Charlson Comorbidity Index, TUG test and MNA in the evaluation of perioperative risk in elderly patients.

Background Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population. Methods Subjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays. Results Nineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance (P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously associated with PBC and PSC, respectively. The SNP, rs35730843, mapping to the POLR2G gene promoter (P = 1.2 × 10-5, OR = 0.39) demonstrated the highest effect size, and was protective for PBC, whereas for PSC respective SNPs were: rs13191240 in the intron of ADGRB3 gene (P = 0.0095, OR = 0.2) and rs3822659 (P = 0.0051, OR = 0.236) along with rs9686714 (P = 0.00077, OR = 0.2), both located in the WWC1 gene. Conclusions Our cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients. However, further functional studies are warranted to understand the roles of these newly identified variants in the development of the two disorders. Electronic supplementary material The online version of this article (doi:10.1186/s12920-016-0239-9) contains supplementary material, which is available to authorized users.

Objective The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done. Methods Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN). In all patients, short- and long-term (5 y) survival was analyzed. Results Analysis of the overall survival time did not reveal differences between groups ( P = 0.663). Until the end of the third month, however, there were nine deaths in the standard enteral nutrition group and no deaths in the EEN group (16.7% versus 0.0%, P = 0.004). The univariate analyses suggested that the EEN group may have lower risk, especially during the first year after intervention. A significant reduction in the risk of death was seen during the early period after surgery (first 6 mo) in the EEN group in stage IV patients (hazard ratio = 0.25, P = 0.049). The use of enriched enteral diet did not influence, however, the risk of dying when patients were analyzed together. Conclusions The study does not support the beneficial effect of enriched enteral nutrition in long-term survival; however, the positive impact on the stage IV patients suggests the need for further, more detailed studies.

Only scarce data on liver steatosis in children with chronic hepatitis B and C (CHB and CHC) are available. The objective of this study was to evaluate the prevalence, predictors, and impact of hepatic steatosis on children with CHB and CHC. A total of 78 patients aged 11.5 ± 3.4 years were included: 30 (38%) had CHB, and 48 (62%) had CHC. Steatosis was scored on a 5-point scale, as follows: absent; minimal (≤5% hepatocytes affected), mild (6–33%), moderate (34–66%), and severe (>66%). Stepwise logistic regression was used to determine the factors associated with steatosis and moderate-to-severe steatosis. Steatosis was observed in 4/30 (13%) patients with CHB and 13/48 (27%) patients with CHC (P = 0.17). Moderate-to-severe steatosis was observed in 6/78 (8%) patients: 1/30 (3%) had CHB and 5/48 (10%) had CHC (P = 0.40). The body mass index (BMI) z-score was positively associated with the presence of steatosis in children with CHB (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.02–10.64). In CHC, steatosis occurred more frequently in patients with hepatitis C virus genotype 3 compared with other genotypes (P = 0.002). In patients with non-3 genotype hepatitis C virus, steatosis was associated with the stage of fibrosis (OR = 3.35, 95% CI: 1.01–11.07) and inversely associated with the duration of infection (OR = 0.74, 95% CI: 0.55–0.97). Moderate-to-severe steatosis was positively associated with the BMI z-score (OR = 3.62, 95% CI: 1.22–10.75) and stage of fibrosis (OR = 3.89, 95% CI: 1.05–14.47). Steatosis is a common finding in children with chronic viral hepatitis. It is associated with metabolic factors in CHB, whereas in patients with CHC, metabolic and viral factors may have a combined effect, leading to more advanced grades of steatosis in children with higher BMI z-scores. Moderate-to-severe steatosis is a predictor of advanced fibrosis in children with CHC.