The role of parathyroid hormone and vitamin D serum concentrations in patients with cardiovascular diseases

25-hydroxyvitamin D (25(OH)D) plays a crucial role in human homeostasis. Its deficiency (vitamin D deficiency-VDD), being common in European population, combined with elevated concentration of parathyroid hormone (PTH), represents a vicious cycle of mechanisms leading to heart failure (HF). Despite several papers published in that field, the effect of VDD and PTH concentration on cardiovascular system remains unequivocal; thus, the aim of the study was to compare these data among HF and non-HF patients being prospectively enrolled into the study during hospital stay in the cardiology ward. Patients with HF had higher PTH concentration (85.0 ± 52.6 versus 64.5 ± 31.7, p = 0 02) compared to non-HF patients. Mean PTH values were associated with the clinical status expressed by the New York Heart Association class (NYHA class) (“0”-66.04, "I"-56.57, "II"-72.30, "III"-85.59, and "IV"-144.37 pg/ml, p = 0 00004). Interestingly, neither 25(OH)D (31.5 versus 29.7 ng/ml, p = ns) nor phosphorus (P) (1.23 versus 1.18 mmol/l, p = ns) nor total calcium (Ca2+) concentration (2.33 versus 2.37 mmol/l, p = ns) differed among the groups. Reassuming PTH serum concentration in contrary to 25(OH)D, P and Ca2+ are significantly raised among the patients with HF and shows significant relationship with the clinical status expressed by the NYHA class

Pernicious anaemia and endocrine glands antibodies

Introduction: The aim of the study was to determine the frequency of occurrence of antibodies participating in the development of endocrine diseases in patients with autoimmune haematopoietic disease, thus documenting the potential suitability of specific diagnostic and screening tests. Material and methods: The study group consisted of 124 persons (men and women) with newly diagnosed pernicious anaemia (PA) and a control group (C) of 41 healthy people. Antibodies against: intrinsic factor (IFAb), gastric parietal cells (APCA), thyroid peroxidase (TPOAb), thyroglobulin (TgAb), adrenal cortex (AdrenalAb), and pituitary anterior lobe (PituitaryAb) were determined in the blood. Results: 1. The risk of the presence of antibodies against endocrine glands in patients with PA can be classified in order: TPOAb and/or TgAb — 41.1%, TPOAb — 36.3%, TgAb — 25.0%, TPOAb and TgAb — 20.2%, AdrenalAb — 1.6%, PituitaryAb — 0.8%. 2. TPOAb and/or TgAb (mainly TPOAb) are more frequently present in patients with PA, who have IFAb and/or APCA. This correlation is most evident in patients with simultaneous occurrence of IFAb and APCA. 3. Among patients with PA, the simultaneous presence of antibodies IFAb and/or APCA with TPOAb and/or TgAb antibodies is most likely in women over 45 years of age. 4. In group C, 12% had at least one of two antithyroid antibodies (TgAb twice as often as TPOAb), and 2.4% had both. AdrenalAb and PituitaryAb are not found in healthy persons. Conclusions: In patients with PA, a screening for autoimmune thyroid disease is justified, which should first involve the determination of TPOAb (further TgAb) in the blood. The assessment of antithyroid antibodies should be recommended primarily to patients with PA, who have IFAb and/or APCA, and in particular those with concurrent IFAb and APCA

Leczenie celowane chorego na zaawansowanego czerniaka z następową immunoterapią

Czerniak jest nowotworem złośliwym wywodzącym się z neuroektodermalnych komórek melanocytarnych dotyczącym przede wszystkim skóry, ale także gałki ocznej (najczęściej naczyniówki) oraz błon śluzowych. Zapadalność na czerniaka wykazuje tendencję wzrostową. Przerzuty odległe czerniaka wiążą się z niepomyślnym rokowaniem, jednak w ciągu ostatnich 5 lat nastąpił istotny postęp w leczeniu chorych na czerniaka w stadium rozsiewu. Przedstawiono przypadek chorej, u której po progresji w trakcie immunoterapii z zastosowaniem inhibitorów BRAF i MEK, w drugiej linii leczenia zastosowano przeciwciało monoklonalne przeciw PD-1 — pembrolizumab, uzyskując stabilizację choroby

The efficacy and safety of ipilimumab in patients with advanced cutaneous or mucosal melanoma

Introduction. Ipilimumab is a monoclonal antibody registered for the treatment of patients with unresectable or metastatic melanoma. Studies have shown prolongation of overall survival in patients treated with ipilimumab. Adverse events related to excessive stimulation of the immune system may occur during treatment. The aim of this paper was to analyse the results of treatment with the use of ipilimumab, which were achieved in one institution in the frame of a therapeutic program established in Poland. Materials and methods. Forty-seven patients (27 men, 20 women) were treated from April 2014 to February 2015 with ipilimumab in a dose of 3 mg/kg of body weight after failure of one previous systemic line of treatment. Median age at the beginning of the treatment was 54 years (range 18–73). Nineteen patients (40%) had BRAF mutation. Thirty patients received chemotherapy as first-line treatment prior to ipilimumab, 14 patients were given vemurafenib, and three patients were treated in clinical trials. Performance status 0 or 1 was found in 15 patients and 32 patients, respectively. Five patients (10.6%) had asymptomatic brain metastases. Twenty-four (51%) patients had metastatic disease with three or less organs involved, whereas 23 (49%) patients had metastases in more than three organs. Lactate dehydrogenase (LDH) activity and neutrophil count was elevated at the beginning of treatment in 40% and 30% of patients, respectively. Results. Thirty-five patients (74%) completed four doses of treatment. Four patients (8.5%) had partial response to the treatment, 12 patients (25.5%) had stable disease (SD) for three or more months, and 31 (66%) had progressive disease. Sixteen patients (34%) had clinical benefit from the treatment (PR + SD). Median progression-free survival (PFS) time was two months. Median overall survival (OS) time was 7.5 months. Increased LDH activity at the beginning of treatment and elevated neutrophil count significantly influenced overall survival of patients (p = 0.005 and p = 0.01, respectively). After progression on ipilimumab 25 patients (53%) received further lines of systemic treatment. Conclusions. This analysis confirms the efficacy of ipilimumab in some patients with advanced melanoma in second-line systemic therapy. A limited proportion of patients obtain long lasting control of the disease after use of ipilimumab with good tolerance to the treatment. There is a need to determine predictive factors of response to treatment for better selection of patients.Introduction. Ipilimumab is a monoclonal antibody registered for the treatment of patients with unresectable or metastatic melanoma. Studies have shown prolongation of overall survival in patients treated with ipilimumab. Adverse events related to excessive stimulation of the immune system may occur during treatment. The aim of this paper was to analyse the results of treatment with the use of ipilimumab, which were achieved in one institution in the frame of a therapeutic program established in Poland. Materials and methods. Forty-seven patients (27 men, 20 women) were treated from April 2014 to February 2015 with ipilimumab in a dose of 3 mg/kg of body weight after failure of one previous systemic line of treatment. Median age at the beginning of the treatment was 54 years (range 18–73). Nineteen patients (40%) had BRAF mutation. Thirty patients received chemotherapy as first-line treatment prior to ipilimumab, 14 patients were given vemurafenib, and three patients were treated in clinical trials. Performance status 0 or 1 was found in 15 patients and 32 patients, respectively. Five patients (10.6%) had asymptomatic brain metastases. Twenty-four (51%) patients had metastatic disease with three or less organs involved, whereas 23 (49%) patients had metastases in more than three organs. Lactate dehydrogenase (LDH) activity and neutrophil count was elevated at the beginning of treatment in 40% and 30% of patients, respectively. Results. Thirty-five patients (74%) completed four doses of treatment. Four patients (8.5%) had partial response to the treatment, 12 patients (25.5%) had stable disease (SD) for three or more months, and 31 (66%) had progressive disease. Sixteen patients (34%) had clinical benefit from the treatment (PR + SD). Median progression-free survival (PFS) time was two months. Median overall survival (OS) time was 7.5 months. Increased LDH activity at the beginning of treatment and elevated neutrophil count significantly influenced overall survival of patients (p = 0.005 and p = 0.01, respectively). After progression on ipilimumab 25 patients (53%) received further lines of systemic treatment. Conclusions. This analysis confirms the efficacy of ipilimumab in some patients with advanced melanoma in second-line systemic therapy. A limited proportion of patients obtain long lasting control of the disease after use of ipilimumab with good tolerance to the treatment. There is a need to determine predictive factors of response to treatment for better selection of patients

Association of microRNAs and pathologic response to preoperative chemotherapy in triple negative breast cancer: preliminary report

Triple negative breast cancer (TNBC) has caught the attention of oncologists worldwide because of poor prognosis and paucity of targeted therapies. Gene pathways have been widely studied, but less is known about epigenetic factors such as microRNAs (miRNAs) and their role in tailoring an individual systemic and surgical approach for breast cancer patients. The aim of the study was to examine selected miRNAs in TNBC core biopsies sampled before preoperative chemotherapy and the subsequent pathologic response in mastectomy or breast conservation specimens. Prior to treatment, core needle biopsies were collected from 11 female patients with inoperable locally advanced TNBC or large resectable tumors suitable for down-staging. In all 11 TNBC core biopsies we analyzed 19 miRNAs per sample: 512, 190, 200, 346, 148, 449, 203, 577, 93, 126, 423, 129, 193, 182, 136, 135, 191, 122 and 222 (miRCURY LNA™ Universal RT microRNA polymerase chain reaction Custom Pick & Mixpanels). The Wilcoxon signed-rank test was used to compare related samples. Ingenuity pathway analysis was used to evaluate potential functional significance of differentially expressed miRNAs. Statistical analysis showed that 3 of 19 miRNAs differed in relation to pathologic response i.e. good versus poor. These differences failed to reach statistical significance, although a trend was observed (p = 0.06). Among these miRNAs, we identified—miR-200b-3p, miR-190a and miR-512-5p. In summary, our results indicate that higher miR-200b-3p, higher miR-190a and lower miR-512-5p expression levels in core biopsies sampled from TNBC patients may be associated with better pathologic response to chemotherapy and the increased feasibility of breast conserving surgery in these patients. Although these results were from a small cohort, they provide an important basis for larger, prospective, multicenter studies to investigate the potential role of miRNAs in neoadjuvant setting

Copeptin as a Prognostic Marker in Acute Chest Pain and Suspected Acute Coronary Syndrome

: Background. In patients admitted with chest pain and suspected acute coronary syndrome (ACS), it is crucial to early identify those who are at higher risk of adverse events. The study aim was to assess the predictive value of copeptin in patients admitted to the emergency department with chest pain and nonconclusive ECG. Methods. Consecutive patients suspected for an ACS were enrolled prospectively. Copeptin and high-sensitive troponin T (hs-TnT) were measured at admission. Patients were followed up at six and 12 months for the occurrence of death and major adverse cardiac and cerebrovascular events (MACCE). Results. Among 154 patients, 11 patients died and 26 experienced MACCE. Mortality was higher in copeptin-positive than copeptin-negative patients with no difference in the rate of MACCE. Copeptin reached the AUC 0.86 (0.75-0.97) for prognosis of mortality at six and 0.77 (0.65-0.88) at 12 months. It was higher than for hs-TnT and their combination at both time points. Copeptin was a strong predictor of mortality in the Cox analysis (HR14.1 at six and HR4.3 at 12 months). Conclusions. Copeptin appears to be an independent predictor of long-term mortality in a selected population of patients suspected for an ACS. The study registration number is ISRCTN14112941

The efficacy and safety of ipilimumab in patients with advanced cutaneous or mucosal melanoma

Wstęp. Ipilimumab jest przeciwciałem monoklonalnym zarejestrowanym do leczenia chorych z rozpoznaniem czerniaka w stadium nieoperacyjnym lub uogólnienia. W badaniach wykazano wydłużenie czasu całkowitego przeżycia u chorych leczonych ipilimumabem. Lek ten charakteryzuje się toksycznością wynikającą z nadmiernej aktywacji układu odpornościowego. Celem badania była analiza wyników leczenia ipilimumabem chorych leczonych w jednym ośrodku w ramach obowiązującego w Polsce programu lekowego. Materiały i metody. Od kwietnia 2014 do lutego 2015 roku w Klinice Nowotworów Tkanek Miękkich, Kości i Czerniaków (KNTMKiCz) ipilimumabem w dawce 3 mg/kg masy ciała leczono 47 chorych (27 mężczyzn, 20 kobiet) z rozpoznaniem przerzutowego czerniaka po niepowodzeniu pierwszej linii leczenia systemowego. Mediana wieku w momencie rozpoczęcia leczenia wyniosła 54 lata (zakres 18–73). U 19 chorych (40%) stwierdzono mutacje w genie BRAF. Chemioterapii poddano wcześniej 30 chorych, 14 osób otrzymało w pierwszej linii leczenia wemurafenib i 3 osoby brały udział w badaniu klinicznym. Stan sprawności 0 i 1 według Eastern Cooperative Oncology Group (ECOG) stwierdzono — odpowiednio — u 15 i 32 chorych. Pięciu (10,6%) chorych miało bezobjawowe przerzuty do ośrodkowego układu nerwowego. U 24 (51%) chorych stwierdzono rozsiew do mniej niż 3 narządów, a u 23 (49%) osób przerzuty występowały w większej liczbie narządów. Aktywność dehydrogenazy mleczanowej (LDH) w momencie rozpoczęcia leczenia była podwyższona u 19 chorych (40%), natomiast liczba neutrofilów — u 14 chorych (30%). Wyniki. Pełne 4 dawki leczenia otrzymało 35 osób (74%). U 4 chorych (8,5%) stwierdzono częściową odpowiedź na leczenia (PR), u 12 (25,5%) wystąpiła stabilizacja choroby (SD) wynosząca 3 lub więcej miesięcy, a u 31 (66%) odnotowano progresję choroby (PD). Kliniczną korzyść (PR + SD) stwierdzono u 16 (34%) chorych. Mediana czasu przeżycia wolnego od progresji choroby (PFS) wyniosła 2 miesiące, a mediana czasu całkowitego przeżycia (OS) osiągnęła 7,5 miesiąca. Znamienny wpływ na OS miała wyjściowa aktywność LDH (p = 0,005) i podwyższona liczba neutrofilów (p = 0,01). Kolejne linie leczenia po wystąpieniu PD podczas leczenia ipilimumabem otrzymało 25 chorych (53%). Wnioski. Przeprowadzona analiza potwierdza skuteczność ipilimumabu w paliatywnym leczeniu drugiej linii u ograniczonego odsetka chorych na zaawansowane czerniaki. Zastosowanie leku u części chorych pozwala na uzyskanie długotrwałej kontroli choroby przy dość dobrej tolerancji leczenia. Konieczne jest określenie czynników predykcyjnych odpowiedzi w celu optymalnego doboru chorych do leczenia.Introduction. Ipilimumab is a monoclonal antibody registered for the treatment of patients with unresectable or metastatic melanoma. Studies have shown prolongation of overall survival in patients treated with ipilimumab. Adverse events related to excessive stimulation of the immune system may occur during treatment. The aim of this paper was to analyse the results of treatment with the use of ipilimumab, which were achieved in one institution in the frame of a therapeutic program established in Poland. Materials and methods. Forty-seven patients (27 men, 20 women) were treated from April 2014 to February 2015 with ipilimumab in a dose of 3 mg/kg of body weight after failure of one previous systemic line of treatment. Median age at the beginning of the treatment was 54 years (range 18–73). Nineteen patients (40%) had BRAF mutation. Thirty patients received chemotherapy as first-line treatment prior to ipilimumab, 14 patients were given vemurafenib, and three patients were treated in clinical trials. Performance status 0 or 1 was found in 15 patients and 32 patients, respectively. Five patients (10.6%) had asymptomatic brain metastases. Twenty-four (51%) patients had metastatic disease with three or less organs involved, whereas 23 (49%) patients had metastases in more than three organs. Lactate dehydrogenase (LDH) activity and neutrophil count was elevated at the beginning of treatment in 40% and 30% of patients, respectively. Results. Thirty-five patients (74%) completed four doses of treatment. Four patients (8.5%) had partial response to the treatment, 12 patients (25.5%) had stable disease (SD) for three or more months, and 31 (66%) had progressive disease. Sixteen patients (34%) had clinical benefit from the treatment (PR + SD). Median progression-free survival (PFS) time was two months. Median overall survival (OS) time was 7.5 months. Increased LDH activity at the beginning of treatment and elevated neutrophil count significantly influenced overall survival of patients (p = 0.005 and p = 0.01, respectively). After progression on ipilimumab 25 patients (53%) received further lines of systemic treatment. Conclusions. This analysis confirms the efficacy of ipilimumab in some patients with advanced melanoma in second-line systemic therapy. A limited proportion of patients obtain long lasting control of the disease after use of ipilimumab with good tolerance to the treatment. There is a need to determine predictive factors of response to treatment for better selection of patients.

Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1

Functional SNPs selected for the study. Table S2. Restriction fragment analysis for BRCA1 mutations. Table S3. Oxidative stress parameters in breast cancer cases according to treatment. (DOCX 31 kb

Aktywność transkrypcyjna genów TGFbeta1 i ich receptorów w gruczole tarczowym

  Introduction: Determination of gene-candidates’ profile expression responsible for fibrosis, immunosuppression, angiogenesis, and neoplasia processes in the pathogenesis of thyroid gland disease. Material and methods: Sixty-three patients underwent thyroidectomy: 27 with non-toxic nodular goitre (NG), 22 with toxic nodular goitre (TNG), six with papillary cancer (PTC), and eight with Graves’ disease (GD). In thyroid tissues, transcriptional activity of TGFbeta1 and its receptors TGFbetaRI, TGFbetaRII, and TGFbetaRIII genes were assessed using RT-qPCR (Reverse Transcriptase Quantitative Polymerase Chain Reaction). Molecular analysis was performed in tissues derived from GD and from the tumour centre (PTC, NG, TNG) and from peripheral parts of the removed lobe without histopathological lesions (tissue control). Control tissue for analysis performed in GD was an unchanged tissue derived from peripheral parts of the removed lobe of patients surgically treated for a single benign tumour. Results/Conclusions: Strict regulation observed among transcriptional activity of TGFb1 and their receptor TGFbetaRI-III genes in control tissues is disturbed in all pathological tissues – it is completely disturbed in PTC and GD, and partially in NG and TNG. Additionally, higher transcriptional activity of TGFb1 gene in PTC in comparison with benign tissues (NG, GD) and lower expression of mRNA TGFbRII (than in TNG, GD) and mRNA TGFbetaRIII than in all studied benign tissues (NG, TNG, GD) suggests a pathogenetic importance of this cytokine and its receptors in PTC development. In GD tissue, higher transcriptional activity of TGFbetaRII and TGFbetaRIII genes as compared to other pathological tissues was observed, indicating a participation of the receptors in the pathomechanism of autoimmune thyroid disease (AITD). TGFbeta1 blood concentrations do not reflect pathological processes taking place in thyroid gland. (Endokrynol Pol 2016; 67 (4): 375–382)    Wstęp: Wyznaczenie profilu ekspresji genów-kandydatów odpowiedzialnych za procesy włóknienia, immunosupresji, angiogenezy, nowotworzenia w patogenezie chorób gruczołu tarczowego. Materiał i metody: W grupie badanej było 63 chorych poddanych tyreoidektomii: 27 z wolem guzkowym nietoksycznym (NG), 22 z wolem guzkowym toksycznym (TNG), 6 z rakiem brodawkowatym (PTC), 8 z chorobą Gravesa-Basedowa (GD). W tkankach tarczycy oceniono ilościowo aktywność transkrypcyjną genów TGFb1 i jego receptorów TGFbetaRI, TGFbetaRII, TGFbetaRIII metodą RT-qPCR (ilościową reakcją łańcuchową polimerazy z udziałem odwrotnej transkryptazy). Analizę molekularną wykonano w tkankach pochodzących od GD i z centrum zmiany guzowatej (PTC, NG, TNG) oraz z obwodowych części usuniętego płata w których nie stwierdzono zmian histopatologicznych (tkanka kontrolna). Tkankę kontrolną dla analizy wykonanej u chorych z GD stanowiła niezmieniona tkanka tarczycy pochodząca z obwodowych części usuniętego płata chorych operowanych z powodu pojedynczego łagodnego guza. Wyniki/Wnioski: Obserwowana ścisła regulacja pomiędzy aktywnością transkrypcyjną genów TGFb1 i jego receptorów TGFbetaRI-III w tkankach kontrolnych ulega zaburzeniu we wszystkich tkankach patologicznych – całkowitemu w PTC i GD, częściowemu w NG i TGN. Dodatkowo, większa aktywność transkrypcyjna TGFbeta1 w PTC w porównaniu z tkankami łagodnymi (NG, GD) oraz mniejsza ekspresja mRNA TGFbRII (niż w TNG, GD) i mRNA TGFbetaRIII w porównaniu z łagodnymi tkankami (NG, TNG, GD) sugeruje patogenetyczne znaczenie tej cytokiny i jej receptorów w rozwoju PTC. W tkance GD, zwraca uwagę większa aktywność transkrypcyjna genów TGFbetaRII i TGFbetaRIII w porównaniu do innych tkanek patologicznych wskazując na udział tych receptorów w patomechanizmie autoimmunologicznej choroby tarczycy (AITD). Stężenia TGFbeta1 we krwi nie odzwierciedlają procesów patologicznych zachodzących w gruczole tarczowym. (Endokrynol Pol 2016; 67 (4): 375–382)