Characterization of Undiscovered miRNA Involved in Tumor Necrosis Factor Alpha-Induced Atrophy in Mouse Skeletal Muscle Cell Line.

Muscular atrophy is a complex catabolic condition that develops due to several inflammatory-related disorders, resulting in muscle loss. Tumor necrosis factor alpha (TNF-α) is believed to be one of the leading factors that drive inflammatory response and its progression. Until now, the link between inflammation and muscle wasting has been thoroughly investigated, and the non-coding RNA machinery is a potential connection between the candidates. This study aimed to identify specific miRNAs for muscular atrophy induced by TNF-α in the C2C12 murine myotube model. The difference in expression of fourteen known miRNAs and two newly identified miRNAs was recorded by next-generation sequencing between normal muscle cells and treated myotubes. After validation, we confirmed the difference in the expression of one novel murine miRNA (nov-mmu-miRNA-1) under different TNF-α-inducing conditions. Functional bioinformatic analyses of nov-mmu-miRNA-1 revealed the potential association with inflammation and muscle atrophy. Our results suggest that nov-mmu-miRNA-1 may trigger inflammation and muscle wasting by the downregulation of LIN28A/B, an anti-inflammatory factor in the let-7 family. Therefore, TNF-α is involved in muscle atrophy through the modulation of the miRNA cellular machinery. Here, we describe for the first time and propose a mechanism for the newly discovered miRNA, nov-mmu-miRNA-1, which may regulate inflammation and promote muscle atrophy.

Serum Calprotectin - a NET Product - as a Biomarker of Disease Activity in Patients with Systemic Lupus Erythematosus: A Single-Center Case-Control Study from Poland.

BACKGROUND Calprotectin (S100A8/A9 or myeloid-related protein 8/14) is a heterodimeric S100 complex expressed in leukocytes. Calprotectin participates in development of the inflammatory response by binding to receptors for advanced glycation end-products (RAGE) and Toll-like receptors (TLR). The clinical activity of systemic lupus erythematosus (SLE) is evaluated using the Systemic Lupus International Collaborating Clinics (SLICC) criteria and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This Polish single-center case-control study aimed to evaluate serum levels of calprotectin as a rapid diagnostic biomarker of SLE (59 patients with SLE were compared with 52 healthy controls). MATERIAL AND METHODS Calprotectin concentration was measured with the use of enzyme-linked immunosorbent assay (ELISA). The SLE activity of the patients was assessed by the SLEDAI scale. Statistical analysis of the results was carried out using MedCalc 15.8 software. P<0.05 was considered statistically significant. RESULTS A significantly higher concentration of calprotectin was found in the study group compared to the control group (medians: 3.11 vs 2.45 ng/ml; P=0.0013). We found that calprotectin has high sensitivity (89.83%) and specificity (53.85%) in differentiating between SLE patients and healthy volunteers. We found that calprotectin has very high sensitivity (100%) and specificity (82.46%) in detection of patients with moderate and severe SLE assessed using SLEDAI. CONCLUSIONS Consistent with previous studies, serum calprotectin level was revealed to have potential as a rapid diagnostic biomarker of disease activity in patients with SLE.

High Level of Irisin as a Marker of Malnutrition in Head and Neck Cancer Patients Subjected to Radiotherapy.

BACKGROUND Head and neck cancers (HNC) are the 7th most prevalent neoplasms in the world. In 50% of these patients, body weight loss and malnutrition are observed before the beginning of therapy. It is known that an important role in the pathomechanism of malnutrition and cachexia is played by the development of inflammation, degradation of muscle fibers, and browning of white adipose tissue (WAT). It was demonstrated that even a slight increase in irisin concentration leads to browning of WAT. MATERIAL AND METHODS The study group consisted of 50 patients with HNC. The nutritional status of the patients was assessed by the Nutritional Risk Score 2002 (NRS 2002) and Subjective Global Assessment (SGA) scales. Using bioelectrical impedance analysis (BIA), the parameters fat mass (FM) and fat-free mass (FFM) were obtained. RESULTS Higher irisin values (1.57 vs 1.18 [ng/ml], P=0.0004) were observed in patients with higher nutritional risk (≥3) evaluated according to the NRS scale. In patients assessed as B or C on the SGA scale, higher values of irisin concentration (1.38 vs 1.07 [ng/ml], P=0.0139) were noted. It was also observed that the level of irisin before treatment was negatively correlated (rho=-0.30, p=0.0350) with FM% and was positively correlated (rho=0.30, p=0.0340) with FFM% in BIA measurements performed after the 7th cycle of RTH. CONCLUSIONS Based on these results, we conclude that patients with malnutrition tend to have higher irisin values compared to normally nourished patients. A high level of irisin may be a useful marker of malnutrition in patients with HNC.

TNF-α Induced Myotube Atrophy in C2C12 Cell Line Uncovers Putative Inflammatory-Related lncRNAs Mediating Muscle Wasting.

BACKGROUND: Muscle atrophy is a complex catabolic condition developing under different inflammatory-related systemic diseases resulting in wasting of muscle tissue. While the knowledge of the molecular background of muscle atrophy has developed in recent years, how the atrophic conditions affect the long non-coding RNA (lncRNAs) machinery and the exact participation of the latter in the mediation of muscle loss are still unknown. The purpose of the study was to assess how inflammatory condition developing under the tumor necrosis factor alpha (TNF-α) treatment affects the lncRNAs' expression in a mouse skeletal muscle cell line. MATERIALS AND METHOD: A C2C12 mouse myoblast cell line was treated with TNF-α to develop atrophy, and inflammatory-related lncRNAs mediating muscle loss were identified. Bioinformatics was used to validate and analyze the discovered lncRNAs. The differences in their expression under different TNF-α concentrations and treatment times were investigated. RESULTS: Five lncRNAs were identified in a discovery set as atrophy related and then validated. Three lncRNAs, Gm4117, Ccdc41os1, and 5830418P13Rik, were selected as being significant for inflammatory-related myotube atrophy. Dynamics changes in the expression of lncRNAs depended on both TNF-α concentration and treatment time. Bioinformatics analysis revealed the mRNA and miRNA target for selected lncRNAs and their putative involvement in the molecular processes related to muscle atrophy. CONCLUSIONS: The inflammatory condition developing in the myotube under the TNF-α treatment affects the alteration of lncRNAs' expression pattern. Experimental and bioinformatics testing suggested the prospective role of lncRNAs in the mediation of muscle loss under an inflammatory state.

AA genotype of PLIN1 13041A>G as an unfavourable predictive factor of malnutrition associated with fat mass loss in locally advanced head and neck cancer male patients treated with radiotherapy.

INTRODUCTION: Malnutrition is a frequently diagnosed condition in head and neck cancer (HNC) patients after radiation therapy (RTH). Malnutrition causes adipose tissue dysfunction associated with intensified lipolysis and disruption of the activity of mechanisms that protect adipose tissue against this process, which include the protective function of perilipin. MATERIAL AND METHODS: The purpose of this study was the evaluation of the predictive value of 13041A>G PLIN1 polymorphism in the development of malnutrition related to adipose tissue loss in a group of 80 patients with locally advanced HNC treated by means of radical radiation therapy. RESULTS: After the completion of RTH, men with AA genotype had significantly lower fat mass (FM compared to men with G haplotype; FM: 13.84 ± 6.36 kg and 19.06 ± 6.30 kg (p = 0.009). In consequence of RTH, the AA genotype carriers lost an average of 37.01% adipose tissue mass and patients with GA and GG genotypes lost 12.82 and 0.31% (p = 0.035), respectively. AA genotype was also associated with higher chance of ≥ 10%, ≥ 20% and ≥ 30% FM loss in the course of RTH (OR = 13.78; 5.78; 2.28). CONCLUSIONS: The evaluation of such molecular factors as SNP 13041A>G may have higher predictive value in the development of malnutrition associated with severe loss of fat mass than the subjective scales, e.g., SGA and NRS-2002. The presence of AA genotype on men with HNC before RTH may facilitate earlier nutritional intervention and supportive treatment aimed at limiting or preventing body mass and fat mass loss during the applied treatment.

Serum brain-derived neurotrophic factor (BDNF) concentration predicts polyneuropathy and overall survival in multiple myeloma patients.

Brain-derived neurotrophic factor (BDNF) is a protein with a potent influence on several aspects of neuronal and blood vessel functions. However, its prognostic potential and functional role in multiple myeloma (MM) remain largely unknown. In this study, we investigated the influence of BDNF on the risk of chemotherapy-induced peripheral neuropathy (CIPN) and clinical outcome. Study group consisted of 91 newly-diagnosed MM patients treated with bortezomib and/or thalidomide-based chemotherapy. Detection of BDNF in serum was performed using ELISA. Polyneuropathy was assessed according to the CTCAE Criteria v5. We observed that BDNF concentration correlated with the severity of polyneuropathy (P = 0·0463). Higher BDNF values were noted in patients who responded to treatment (P = 0·0326), and BDNF proved to be a useful marker to predict lack of response after eight cycles of treatment (sensitivity - 100%, specificity - 61·5%, P = 0·0142). Moreover this marker showed significant diagnostic usefulness in diagnosis of CIPN (sensitivity - 76%, specificity - 71·43%; area under the curve (AUC)= 0·77, 95%, confidence interval (CI): 0·64-0·88; P < 0·0001). Low BDNF was an independent, unfavourable prognostic factor associated with reduced overall survival (OS) (hazard ratio (HR) = 2·79, P = 0·0470). In conclusion, BDNF level may play a prognostic role and constitute a useful biomarker in predicting CIPN in MM patients.

The relationship between TNF-α gene promoter polymorphism (- 1211 T > C), the plasma concentration of TNF-α, and risk of oral mucositis and shortening of overall survival in patients subjected to intensity-modulated radiation therapy due to head and neck cancer.

PURPOSE: Radiotherapy (RTH) usually combined with chemotherapy (C-RTH) is the main method of treatment in head and neck cancer (HNC). The most common complication of RTH is oral mucositis (OM). At a certain stage of RTH, it occurs in almost all patients, often lead to discontinuation of treatment. Tumour necrosis factor alpha (TNF-α) is a cytokine secreted during inflammatory process accompanying RTH and the development of cancer itself. Single nucleotide polymorphism (SNP) of the TNF-α promoter region can potentially affect the function or expression of this cytokine, and thus modulate the risk of occurrence and intensity of OM and shortening of overall survival (OS). METHODS: The study group consisted of 62 patients with HNC in whom intensity-modulated radiation therapy (IMRT) technique was applied. The plasma TNF-α level was assessed using the ELISA Kit. Genotyping was performed using a real-time PCR method. RESULTS: HNC patients with the CC genotype of TNF-α (- 1211 T > C) have higher TNF-α plasma concentrations than those with T allele (10.70 vs 9.62 ng/ml). Patients with the 3rd degree of OM have significantly higher TNF-α levels after 5th (10.40 vs 9.45 ng/ml) and 7th (10.32 vs 9.60 ng/ml) week of RTH. CC genotype was related to a higher risk of 3rd degree OM development in the last weeks of RTH (5th, OR = 7.33; 7th, OR = 23.15). CONCLUSIONS: High TNF-α plasma concentration and CC genotype of TNF-α are related to the higher risk of more severe OM in patients irradiated due to HNC. High TNF-α plasma concentration and CC genotype of TNF-α are independent prognostic factors for patients subjected to RTH due to HNC.

Polymorphisms in the promotor region of the CRBN gene as a predictive factor for peripheral neuropathy in the course of thalidomide-based chemotherapy in multiple myeloma patients.

Thalidomide is commonly used in treatment of multiple myeloma (MM). This study aimed to analyse the influence of clinical and molecular factors - single nucleotide polymorphisms (SNPs) of the CRBN gene: rs6768972 and rs1672753, on the risk of adverse effects (AEs) of thalidomide-based chemotherapy in patients with MM. The study group included 82 patients receiving CTD (thalidomide, cyclophosphamide, dexamethasone) as first line treatment. The intensity of haematological and non-haematological AEs was assessed according to the Common Terminology Criteria for Adverse Events v4.03. Multivariate analysis showed that patients with the CRBN CC genotype (rs1672753) had more than a 14-fold higher risk of peripheral polyneuropathy compared to patients with other variants of the investigated SNP [odds ratio (OR) = 14·29]. Carriers of this genotype were burdened with significantly (about 17-fold) higher risk of diarrhoea during treatment (OR = 16·67). The presence of CRBN AA (rs6768972) or TT (rs1672753) genotypes was associated with about 333-fold and 250-fold lower risk of constipation in the course of therapy (OR = 0·003; OR = 0·004, respectively). Selected CRBN SNPs may be useful in assessing the probability of AEs in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with MM.

Reasons for diagnostic delays of axial spondyloarthritis.

OBJECTIVE: Introduction: The probability of development of axial spondyloarthritis (axSpA) is estimated to be above 90% among patients with chronic back pain, presence of HLA B27 antigen and positive family history of ankylosing spondylitis (AS), psoriasis, reactive arthritis, inflammatory bowel disease or uveitis. The nonradiographic axSpA and ankylosing spondylitis diseases' activity has a comparable impact on the patients' quality of life and from the practical point of view the approach to treatment of each of them is the same. The aim: The attempt to identify the reasons of diagnostic delays of AS among patients hospitalized in the Rheumatology and Connective Tissue Diseases Department in Lublin and to suggest the ways of improving the accuracy of diagnostic track among other healthcare providers than rheumatologists. PATIENTS AND METHODS: Material and methods: We performed a retrospective analysis of the records of 82 patients' with the established diagnosis of AS, hospitalized in the Rheumatology and Connective Tissue Diseases Department in Lublin in 2000-2019, and of 45 years of age and older. RESULTS: Results: From among 82 patients (28 women and 54 men) the diagnosis of AS after 45 years of age was established in 25 patients (10 women and 15 men) - group t, and in the other 57 patients (group n) the diagnosis was established before 45 years of age. On average the age at the time of diagnosis in the whole group (t+n) was 40,7±10,2 (18-76) years, the age at the beginning of inflammatory back pain (age of axial symptoms) was 30,9±8,5 (13-51) years and the diagnostic delay (period between first axial symptoms and diagnosis establishment) was 9,75±9,5 (0-46) years. We did not find any statistically significant associations between sex and age at the moment of diagnosis, age of the beginning of axial symptoms and the time of diagnostic delay. There was no significant difference of incidence of enthesitis, uveitis, arthritis, prevalence of family history of spondyloarthritis and CRP level between group t and n. Antigen HLA B27 was more frequently present in group t. CONCLUSION: Conclusions: Instead of the recognition progress and worldwide popularization of knowledge about axSpA, the diagnostic delays in this field are still estimated to last many years, the patients are looking for other specialists' help, and they can be not knowledgeable of the inflammatory back pain criteria. Currently, HLA B27 antigen and C-reactive protein are the two most commonly used biomarkers for diagnostic and disease activity monitoring purposes of axSpA and magnetic resonance is the only "imaging biomarker". The presence of extra-axial symptoms does not improve the diagnostic sensitivity.

[Uwarunkowania opóznienia rozpoznan osiowych spondyloartropatii zapalnych].

OBJECTIVE: Wstep: Prawdopodobienstwo rozwoju osiowej postaci spondyloartropatii zapalnej (axSpA) wynosi ponad 90% u chorych z przewleklym bólem kregoslupa, obecnym antygenem HLA B27 i dodatnim wywiadem rodzinnym w kierunku zesztywniajacego zapalenia stawów kregoslupa (ZZSK), luszczycy, reaktywnego zapalenia stawów, chorób zapalnych jelit lub zapalenia blony naczyniowej oka. Aktywnosc choroby w postaci nieradiologicznej axSpA i ZZSK podobnie wplywa na jakosc zycia a z praktycznego punktu widzenia podejscie do leczenia jest jednakowe. Cel pracy: Próba identyfikacji przyczyn spóznionych rozpoznan ZZSK wsród chorych hospitalizowanych w Klinice Reumatologii i Ukladowych Chorób Tkanki Lacznej w Lublinie oraz sugestie dotyczace poprawy sciezki diagnostycznej, zwlaszcza wsród lekarzy innych specjalnosci niz reumatolodzy. PATIENTS AND METHODS: Material i metody: Retrospektywnej analizie poddano historie chorób 82 pacjentów z ustalonym rozpoznaniem ZZSK hospitalizowanych w Klinice Reumatologii i Ukladowych Chorób Tkanki Lacznej w Lublinie w latach 2000-2019, którzy ukonczyli 45. rok zycia. RESULTS: Wyniki: Sposród 82 chorych (28 kobiet i 54 mezczyzn) rozpoznanie ZZSK po 45. roku zycia postawiono u 25 chorych (10 kobiet i 15 mezczyzn) - grupa t (30,4%), u pozostalych 57 chorych (grupa n) rozpoznanie ustalono przed 45. rokiem zycia. Sredni wiek w chwili rozpoznania w calej grupie (t+n) wynosil 40,7±10,2 (18-76) roku, wiek, w którym pojawil sie zapalny ból kregoslupa (wiek objawów osiowych) wynosil 30,9±8,5 (13-51) roku a opóznienie rozpoznania (okres od pojawienia sie objawów osiowych do ustalenia rozpoznania) 9,7±9,5 (0-46) roku. Nie stwierdzono istotnych statystycznie zaleznosci miedzy plcia a wiekiem w chwili rozpoznania, wiekiem pojawienia sie objawów osiowych i opóznieniem rozpoznania. Nie zaobserwowano istotnych zaleznosci miedzy czestoscia wystepowania zapalenia przyczepów sciegnistych, blony naczyniowej oka, stawów obwodowych, chorób z kregu spondyloartropatii zapalnych w rodzinie oraz stezenia CRP miedzy grupa t i n. Antygen HLA B27 czesciej obecny byl w grupie t. CONCLUSION: Wnioski: Mimo postepu w diagnostyce i wiekszego upowszechniania wiedzy na temat spondyloartropatii zapalnych, opóznienia w rozpoznaniu tych chorób sa wieloletnie, poniewaz pacjenci bardzo czesto poszukuja pomocy u innych specjalistów, którzy moga byc niezaznajomieni z kryteriami bólu zapalnego kregoslupa. W chwili obecnej jedynymi biomarkerami wykorzystywanymi w diagnostyce i monitorowaniu aktywnosci spondyloartropatii zapalnych jest odpowiednio obecnosc antygenu HLA B27 i stezenie CRP a jedynym "biomarkerem obrazowym" jest rezonans magnetyczny. Wystepowanie objawów pozaosiowych nie poprawia czulosci diagnostycznej.

[Autoimmune diseases with the presence of anti-ku antibodies - analysis of three cases]. / Choroby autoimmunologiczne z obecnoscia przeciwcial anty-ku na podstawie analizy trzech przypadków klinicznych.

a-Ku are rare antibodies, which are reported in course of connective tissue diseases. Their prevalence ranges from 0 to 10% , 2%, on average. The main symptoms associated with the presence of a-Ku antibodies include: myositis, arthritis, Raynaud`s phenomenon and skin lesions. The above features are often defined as autoimmune clinical syndrome associated with a-Ku antibodies. In recent years, three cases with the presence of a-Ku antibodies were observed at the Department of Rheumatology and Connective Tissue Diseases. Case 1, a 77-year-old man, with the diagnosis of mixed connective tissue disease according to Raynaud`s phenomenon, myositis, arthritis and presence of a-ribonucleoprotein antibodies. Moreover, secondary Sjögren syndrome (SS) and myasthenia gravis were diagnosed. Case 2, a 56-year-old woman with longstanding history of Raynaud`s phenomenon, sclerodactyly, myositis and arthritis. Based on clinical manifestations and additional tests, systemic sclerosis and myositis were diagnosed. Case 3, a 46-year-old woman with SS diagnosis, long-standing history of Raynaud`s phenomenon, arthralgia and polyneuropathy. Moreover, HCV infection with the presence of cryoglobulin was confirmed. The presence of a-Ku antibodies in high titers was found in all cases. The clinical conditions improved after steroid and immunosuppressive therapy. In conclusion, clinical syndromes with the presence of a-Ku antibodies are associated with a wide range of non-specific symptoms, regarding muscle, joint and skin involvement, in particular. The conditions are more often diagnosed in the elderly; in the majority of cases, they are characterized by mild courses, good response to steroid therapy and good prognosis.

[Prediction of response to TNF-α inhibitors treatment with use of swollen to tender joint count ratio (STR)]. / Prognozowanie odpowiedzi na zastosowanie leczenia inhibitorami TNF-α z wykorzystaniem wskaznika stawów stawów obrzeknietych do bolesnych (STR).

INTRODUCTION: STR is swollen to tender joint count ratio. The aim of this study was to determine the usefulness of STR in predicting response to treatment with biological agents in patients with RA. MATERIAL AND METHODS: The study included 27 biologically naive patients treated with TNF inhibitors: infliximab (6), etanercept (10), adalimumab (5) and certolizumab (6). STR index was assessed at baseline and after 3 and 9 months (m) . Patients due to the STR value were divided into two groups: group1 with value of STR < 1 and group 2 with value of STR ≥ 1. Group 1 included 18 patients (17 F, 1 M). Group 2 consisted of 9 persons (7 F 2 M). RESULTS: At the beginning of the observation the average values for the group 1 were: the number of swollen joints (SJ) 6/28 (2-14), the number of tender joints (TJ) 11/28 (5-21), STR 0.46 (0.2-0.9), CRP 27.8 mg/I (1-130.2), DAS28 4.95 (4.03-7.56), disease activity VAS 50 mm (20-75), ESR 35 (8-95). In group 1, the DAS28 improved after 3 months on average - 1.68 (0.08-3.91) and ESR decreased about 16 mm. On the assessment after 9 months of treatment DAS 28 improved on average - 2.89 (0.74-5.17); ESR dropped by 21 mm compared to the baseline. At the beginning of the observation average values for group 2 were: SJ 13/28 (8-19), TJ 19 (4-15), STR 1.48 (1-2.5), CRP 19.27 (7.7-32.1), DAS28 5.75 (5.25-6.47), disease activity - VAS 57 mm (47-66), ESR 25 (14-41). After 3 months of treatment DAS28 reduced on average - 2.52 (1.97-3.71), ESR decreased circa 11 mm. Six patients from group 2 were evaluated after 9 months of treatment. There was observed improvement both in DA528 on average 3.28 (1.86-3.95) and ESR, which dropped by 10 mm. Patients with >1 STR achieved greater improvement in DAS28 after 3 m (p=0.0395) and after 9 months (Ns) compared to patients with STR <1. However, decrease of ESR was higher both after 3 and 9 months in patients with STR <1. CONCLUSIONS: We conclude that the STR may be useful in predicting response to treatment with TNF inhibitors.

The Relationship between miR-5682 and Nutritional Status of Radiotherapy-Treated Male Laryngeal Cancer Patients.

BACKGROUND: Nutritional deficiencies are frequently observed in patients with head and neck cancer (HNC) undergoing radiation therapy. microRNAs (miRNAs) were found to play an important role in the development of metabolic disorders throughout regulation of genes involved in inflammatory responses. This study aimed to explore the correlation between pre-treatment miR-5682 expression and parameters reflecting nutritional deficits in laryngeal cancer (LC) patients subjected to radiotherapy (RT). METHODS: Expression of miR-5682 was analyzed in plasma samples of 56 male LC individuals. Nutritional status of LC patients was assessed using anthropometric and laboratory parameters, bioelectrical impedance analysis (BIA) and clinical questionnaires. RESULTS: A high expression of miR-5682 was associated with significantly lower values of BMI, fat mass, fat-free mass and plasma albumin at selected periods of RT course. miR-5682 allowed us to distinguish between patients classified with both SGA-C and low albumin level from other LC patients with 100% sensitivity and 69.6% specificity (AUC = 0.820; p < 0.0001). Higher expression of studied miRNA was significantly associated with shorter median overall survival (OS) in LC patients (HR = 2.26; p = 0.008). CONCLUSIONS: analysis of miR-5682 expression demonstrates a potential clinical utility in selection of LC patients suffering from nutritional deficiencies developing as a consequence of RT-based therapy.

IL1B Polymorphism (rs1143634) and IL-1ß Plasma Concentration as Predictors of Nutritional Disorders and Prognostic Factors in Multiple Myeloma Patients.

BACKGROUND: Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35-71% of MM patients. Interleukin 1 beta (IL-1ß) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1ß in the assessment of the risk of nutritional disorders and prognosis in patients with MM. METHODS: In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1ß ELISA kit was used to determine IL-1ß concentration in plasma samples. RESULTS: Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1ß in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1ß plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). CONCLUSIONS: Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1ß may be useful in the assessment of the risk of cachexia and prognosis in patients with MM.

The TT Genotype of the KIAA1524 rs2278911 Polymorphism Is Associated with Poor Prognosis in Multiple Myeloma.

BACKGROUND: The KIAA1524 gene encodes an oncoprotein, CIP2A, which inhibits the phosphorylation of the Akt kinase B, stabilizes the c-Myc protein, and, through that, promotes cancerogenesis. An increase in CIP2A expression has been observed in numerous solid tumors and hematologic malignancies, including multiple myeloma (MM). The aim of our study was to evaluate the clinical impact of the functional single nucleotide polymorphisms (SNP) of the KIAA1524 gene (rs2278911, 686C > T) in MM patients. METHODS: The study group consisted of 128 patients with de novo MM. EDTA venous blood samples were collected prior to the treatment. The SNPs were analyzed by Real-Time PCR with the use of specific Taqman probes. RESULTS: Multivariable analysis revealed that variables independently associated with shorter progression-free survival (PFS) included thrombocytopenia, delTP53 and IGH/CCND1 translocation and the TT genotype of the KIAA1524 gene (686C > T) (median PFS: 6 vs. 25 months; HR = 7.18). On the other hand, autologous haematopoietic stem cell transplantation (AHSCT) was related to a lower risk of early disease progression. Moreover, light chain disease, International Staging System (ISS) 3, poor performance status, hypoalbuminemia, IGH/FGFR3 translocation and the TT genotype of the KIAA1524 gene (686C > T) were independent prognostic factors associated with shorter overall survival (OS) (median OS: 8 vs. 45 months; HR = 7.08). CONCLUSION: The evaluation of the SNP 686C > T of the KIAA1524 gene could be used as a diagnostic tool in MM patients at risk of early disease progression and death.

Does Human Papillomavirus Infection Influence the Frequency and Severity of Nutritional Disorders in Head and Neck Cancer?

BACKGROUND: About 87% of head and neck cancer (HNC) patients (mostly oropharyngeal cancer-OPC) are infected with human papillomavirus (HPV). Recent studies have demonstrated a significant correlation between HPV infection and nutritional disorders in HNC patients. Therefore, we formed a hypothesis that nutritional disorders or their severity in HNC patients may be associated with the occurrence of HPV infection due to known molecular differences in involved tissue. This literature review aimed to evaluate the influence of HPV infection on the occurrence and severity of nutritional disorders in HNC patients. MATERIALS AND METHODS: The PubMed database was used to search papers with the keywords "HPV", "HNC", and "nutritional disorders" in different variants and combinations. CONCLUSIONS: The data available in the discussed papers indicate, among other things, that HPV-positive patients may be at higher risk of malnutrition, critical weight loss, and necessity for gastrostomy after radiotherapy or chemoradiotherapy (C-RT). It should be highlighted that despite some studies demonstrating positive results, currently available data regarding the influence of HPV infection on the occurrence and severity of nutritional disorders in HNC remain limited and inconclusive, and thus further research on this issue is warranted.

TNFRSF1A Gene Polymorphism (−610 T > G, rs4149570) as a Predictor of Malnutrition and a Prognostic Factor in Patients Subjected to Intensity-Modulated Radiation Therapy Due to Head and Neck Cancer

Background: Malnutrition is a nutritional disorder observed in 52% of patients with head and neck cancer (HNC). Malnutrition is frequently related to the increased level of proinflammatory cytokines. In turn, ongoing inflammation is associated with increased catabolism of skeletal muscle and lipolysis. Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that plays a pivotal role in the development of malnutrition and cachexia in cancer patients. The aim of the study was to assess the relationship between a functional single-nucleotide polymorphism (SNP) −610 T > G (rs4149570) of the TNFRSF1A gene and the occurrence of nutritional disorders in patients subjected to RT due to HNC. Methods: The study group consisted of 77 patients with HNC treated at the Oncology Department of the Medical University in Lublin. Genotyping of the TNFRSF1A gene was performed using capillary electrophoresis (Genetic Analyzer 3500). Results: Multivariable analysis revealed that the TT genotype of the TNFRSF1A gene (−610 T > G) was an independent predictor of severe malnutrition (odds ratio­OR = 5.05; p = 0.0350). Moreover, the TT genotype of this gene was independently related to a higher risk of critical weight loss (CWL) (OR = 24.85; p = 0.0009). Conclusions: SNP (−610 T > G) of the TNFRSF1A may be a useful marker in the assessment of the risk of nutritional deficiencies in HNC patients treated with intensity-modulated radiotherapy (IMRT).

Circulating Serum MiRNA-8074 as a Novel Prognostic Biomarker for Multiple Myeloma.

MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16-3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie-Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high ß2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20-7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients.

High miR-511-3p Expression as a Potential Predictor of a Poor Nutritional Status in Head and Neck Cancer Patients Subjected to Intensity-Modulated Radiation Therapy.

Nutritional deficiencies, including malnutrition and its irreversible type cachexia, are often observed in patients with head and neck cancer (HNC). Among the various factors contributing to the occurrence of these disorders, inflammation seems to be crucial. The potential regulatory properties of miR-511-3p, e.g., post-translational alteration of expression of genes with protein products that are involved in inflammation, may be related to nutritional deficiencies observed in HNC patients. Therefore, the aim of our study was to assess the correlation between pretreatment miR-511-3p expression and nutritional status in patients undergoing radiotherapy (RT) due to HNC. In our retrospective study, 60 consecutively admitted patients treated with intensity-modulated radiotherapy (IMRT) due to advanced HNC were enrolled. The analysis of miR-511-3p expression was performed using real-time PCR. Significantly higher expression of miR-511-3p was observed in well-nourished patients compared to patients with moderate or severe malnutrition (p = 0.0001). Pretreatment expression of miR-511-3p may be a useful biomarker of nutritional deficiencies in patients subjected to IMRT due to HNC.

The Usefulness of Extended Inflammation Parameters and Systemic Inflammatory Response Markers in the Diagnostics of Autoimmune Hepatitis.

(1) Introduction: Autoimmune hepatitis (AIH) is a chronic disease. A persistent autoimmune reaction in the liver is significantly related to the systemic inflammatory response. Extended Inflammation Parameters (EIP) can be used to assess the activation of immune cells such as activated neutrophils (NEUT-RI and NEUT-GI) and activated lymphocytes (RE-LYMP and AS-LYMP) in the phase of active inflammation. The role of the systemic inflammatory response markers should also be emphasised, especially: NLR, PLR, and RLR, which have recently been widely studied as markers in autoimmune skin diseases or liver diseases. (2) Materials and Methods: The study included 30 patients with AIH and 30 healthy volunteers. The parameters of the EIP group (RE-LYMP, AS-LYMP, NEUT-RI, NEUT-GI), calculated haematological indices Red Blood Cell Distribution Width-to-Platelet Ratio (RPR), Mean Platelet Volume-to-Platelet Ratio (MPR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Red Blood Cell Distribution Width-to-Lymphocyte Ratio (RLR), and selected blood morphological and biochemical indices were analysed. The aim of the study was to assess the usefulness of the EIP and systemic inflammatory response markers in the diagnostics of AIH. (3) Results: Compared to the controls, the patients with AIH showed significantly higher EIP values: NEUT-RI (48.05 vs. 43.30), NEUT-GI (152.65 vs. 147.40), RE-LYMP (0.07 vs. 0.03), and the inflammatory response markers: MPR (0.05 vs. 0.04), RPR (0.07 vs. 0.05), and NLR (2.81 vs. 1.42. Among the examined markers, EIP has significant diagnostic potential: NEUT-RI (AUC = 0.86), NEUT-GI (AUC = 0.80), and RE-LYMP (AUC = 0.78), and so do calculated haematological indices, i.e., MPR (AUC = 0.75), PLR (AUC = 1.00), and RLR (AUC = 1.00) Moreover, the importance of NEUT-GI (AUC = 0.89), MPR (AUC = 0.93), PLR (AUC = 0.86), RPR (AUC = 0.91), and FIB-4 (AUC = 0.83) in the detection of liver fibrosis in the course of AIH has also been proven. (4) Conclusions: EIP and systemic inflammatory response markers may turn out to be useful in detecting AIH and in looking for features of already developed liver cirrhosis in its course.