Optimization of diagnostic and therapeutic management in patients with stage III non-small cell lung cancer — experience of the centers in Poznań

Lung cancer is one of the most frequently diagnosed malignancies, with one of the worst prognoses. Non-small cell lung cancer (NSCLC) is the dominant histological type, accounting for 85% of cases. In Poland, in more than one-third of patients, NSCLC is diagnosed at stage III. One of the most effective methods of radical treatment in such cases is concurrent radiochemotherapy. However, in Poland the percentage of patients eligible for this type of therapy is quite low, due to delayed diagnosis, lack of reference centers, long qualification process for treatment, and ineffective treatment organization. This article discusses the optimization of therapeutic management in patients with stage III NSCLC based on the experience of centers in Poznań (the Greater Poland Cancer Center and Greater Poland Center for Pulmonology and Thoracic Surgery). Some modifications include introduction of a surgery qualification form, urgent early evaluation using combined positron emission tomography (PET)/computed tomography (CT) and invasive mediastinum evaluation, and initial qualification for radiochemotherapy (with the setting of dates) already during diagnostics. These activities led to the multiplication of the number of patients qualified for concurrent radiochemotherapy

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Compensatory effect of TNFα on low natural killer activity in the elderly.

Regulatory effect of CD25, an activation antigen the α subunit of interleukin 2 receptor (IL2R) on the activity of natural killer (NK) cells was studied in fifty elderly (57-70 years old) and fifty young people (19-35 years old). Cytotoxic NK activity was assessed by 51Cr release assay, the levels of interleukin 2 (IL2) and tumour necrosis factors α (TNFα) were measured using bioassays and expression of CD16 and CD25 proteins by flow cytometry. Low NK activity in the elderly was associated with decline of full health, lowered serum concentration of IL2 and increased production of TNFα during NK reaction. Inhibition of TNFα activity by anti-TNF monoclonal antibody suppressed exclusively NK activity of low NK responders. Moreover, stimulation in vitro of blood mononuclear cells, with TNFα induced in the elderly low NK responders a significantly higher increase of the CD25 expression on the surface of NK cells as compared with that in the elderly high responders. Since the CD25 molecule constitutes a subunit of the high affinity receptor, binding IL2 to immunocompetent cells, its increased expression on NK cells of low NK responders would enable them to bind even low amounts of the endogenous IL2 available in this group of the elderly. Thus, an overproduction of TNFα seems to be a mechanism compensating, in the non-fully healthy elderly, for the decreased IL2 production, promoting efficient cytotoxic reaction

Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis) By-Products

Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides. The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated. Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction. At a protein concentration of 44 µg/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At the low protein concentration of only 11 µg/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids. The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods

Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis) By-Products

Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides. The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated. Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction. At a protein concentration of 44 µg/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At the low protein concentration of only 11 µg/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids. The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods

Normal Lung Tissue CT Density Changes after Volumetric-Arc Radiotherapy (VMAT) for Lung Cancer

Radiation-induced lung injury remains a significant toxicity in thoracic radiotherapy. Because a precise diagnosis is difficult and commonly used assessment scales are unclear and subjective, there is a need to establish quantitative and sensitive grading methods. The lung tissue density change expressed in Hounsfield units (HUs) derived from CT scans seems a useful numeric surrogate. The study aimed to confirm a dose-response effect on HU value changes (ΔHU), their evolution in time, and the impact of selected clinical and demographic factors. We used dedicated, self-developed software to register and analyze 120 pairs of initial and follow-up CT scans of 47 lung cancer patients treated with dynamic arc radiotherapy. The differences in HU values between CT scans were calculated within discretized dose-bins limited by isodose lines. We have proved the dose-effect relationship, which is well described with a sigmoid model. We found the time evolution of HU changes to suit a typical clinical presentation of radiation-induced toxicity. Some clinical factors were found to correlate with ΔHU degree: planning target volume (PTV), V35 in the lung, patient’s age and a history of arterial hypertension, and initial lung ventilation intensity. Lung density change assessment turned out to be a sensitive and valuable method of grading post-RT lung toxicity

Optymalizacja postępowania diagnostyczno-terapeutycznego u chorych na niedrobnokomórkowego raka płuca w III stadium zaawansowania — doświadczenia ośrodków w Poznaniu

Rak płuca jest jednym z najczęściej diagnozowanych i najgorzej rokujących nowotworów złośliwych. Dominującym typem histologicznym (85% chorych) jest typ niedrobnokomórkowy. W Polsce u ponad jednej trzeciej chorych z wymienionym nowotworem w momencie rozpoznania stwierdza się III stopień zaawansowania. Wówczas jedną z najskuteczniejszych metod leczenia radykalnego jest jednoczesna radiochemioterapia. Jednak w Polsce odsetek chorych poddawanych jednoczesnej radiochemioterapii wynosi zaledwie kilkanaście procent. Przyczy wspomnianej sytuacji obejmują opóźnienia diagnostyki, brak ośrodków referencyjnych, długi proces kwalifikowania chorych do leczenia oraz niewłaściwy sposób organizacji leczenia. Niniejszy artykuł omawia działania optymalizujące postępowanie terapeutyczne u chorych na niedrobno komórkowego raka płuca w III stadium na podstawie doświadczeń ośrodków poznańskich (Wielkopolskie Centrum Onkologii oraz Wielkopolskie Centrum Pneumonologii i Torakochirurgii). Wprowadzono kartę kwalifikacji do zabiegu operacyjnego, pilną wczesną ocenę z wykorzystaniem badania pozytonowej emisyjnej tomografii w fuzji w komputerową tomografią i inwazyjną ocenę śródpiersia, wstępną kwalifikację chorych do radiochemioterapii (ustalenie terminów) już w toku diagnostyki. Działania te doprowadziły do zwielokrotnienia liczby chorych zakwalifikowanych do jednoczesnej radiochemioterapii.Rak płuca to jeden z najczęściej diagnozowanych i najgorzej rokujących nowotworów złośliwych. Dominujący (85% chorych) jest histologiczny typ niedrobnokomórkowy. W Polsce u ponad jednej trzeciej chorych z wymienionym nowotworem w momencie rozpoznania stwierdza się III stopień zaawansowania. Wówczas jedną z najskuteczniejszych metod leczenia radykalnego jest jednoczesna radiochemioterapia. W Polsce odsetek chorych poddawanych jednoczesnej radiochemioterapii wynosi jednak zaledwie kilkanaście procent. Wśród przyczyn wspomnianej sytuacji znajdują się opóźnienia diagnostyki, brak ośrodków referencyjnych, długi proces kwalifikowania chorych do leczenia oraz niewłaściwy sposób organizacji leczenia. W niniejszym artykule omówiono działania optymalizujące postępowanie terapeutyczne u chorych na niedrobnokomórkowego raka płuca w III stadium na podstawie doświadczeń ośrodków poznańskich (Wielkopolskie Centrum Onkologii oraz Wielkopolskie Centrum Pneumonologii i Torakochirurgii). Wprowadzono kartę kwalifikacji do zabiegu operacyjnego, pilną wczesną ocenę z wykorzystaniem badania pozytonowej emisyjnej tomografii w fuzji w komputerową tomografią i inwazyjną ocenę śródpiersia, wstępną kwalifikację chorych do radiochemioterapii (ustalenie terminów) już w toku diagnostyki. Działania te doprowadziły do zwielokrotnienia liczby chorych zakwalifikowanych do jednoczesnej radiochemioterapii

Effect of Different Blood-Pressure-Lowering Regimens on the Blood Pressure Control among Hypertensive Patients Treated in Hospital Conditions

Background. Scientific references lack sufficient amount of data on analyses of the reasons for hospital admissions or assessment of efficacy of arterial hypertension treatment at hospitals. Objectives. The aim of the study was to evaluate the efficacy of antihypertensive drug therapy on the blood pressure control among hospitalized hypertensive patients. Methodology. A cross-sectional retrospective study consisted of 204 patients aged 18–65 years admitted to the hospital due to hypertension between January 2018 and December 2018. The study was based on analysis of electronic records, obtained from the medical database of the selected healthcare facility. Results. As a result of the treatment applied at the hospital, 65.19% of the patients achieved the desired degree of blood pressure normalization (≤130/80 mmHg). Vast majority of the patients during their stay at the ward would receive three or more hypertensive drugs (63.73%). The most frequently prescribed antihypertensive drug combinations included bitherapies such as diuretics + ACEI and ACEI + β-blockers and tritherapy such as diuretics + β-blockers and calcium channel antagonists and diuretics + ACEI and ARBs. The highest blood-pressure lowering effects were observed among patients receiving combination therapy of a ACEI, a diuretic, and a ARBs. Tritherapy induced a significant mean reduction of inpatients`s SBP compared with bitherapy (p=0.0001). Conclusion. During their hospital stay, vast majority of patients (65.19%) achieved normal values of blood pressure, mostly owing to combined treatment with several hypertensive drugs. Efficacy of the most frequently used combinations of hypertensive drugs in normalizing arterial pressure varies