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Predictors of Short-term LAMA Ineffectiveness in Treatment Naive Patients with Moderate to Severe COPD
No full textBACKGROUND: No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients.
METHODS: A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium). Short-term treatment ineffectiveness was assessed as a composite measure comprising COPD exacerbations, need for additional treatment, and no improvement in functional parameters, e.g. 6‑min walking test (6MWT), body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV1), and as single components.
RESULTS: Treatment ineffectiveness was significantly associated with baseline hemoglobin level, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale and BODE index (p = 0.002). Incident exacerbation during the follow-up was associated with baseline bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (p < 0.001), and change in treatment with leukocyte count, 6MWT desaturation and fatigue (p < 0.001). No improvement in 6MWT was associated with baseline CAT score, body mass index, mMRC, fatigue, 6MWT and BODE index (p = 0.002). No improvement in BODE index was associated with leukocyte count, serum interleukin 8 (IL-8) and BALF albumin levels (p < 0.001); and no improvement in FEV1 with CAT score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha) level (p < 0.001).
CONCLUSION: Our results suggest that there is a possibility to identify predictors of short-term tiotropium ineffectiveness in patients with moderate to severe COPD
Dietary habits of patients with inflammatory bowel diseases (IBD) from Eastern Croatia
No full textUvod: Prehrana ima važnu ulogu u životu i liječenju bolesnika s upalnim bolestima crijeva (UBC). Cilj istraživanja bio je utvrditi prehrambene navike oboljelih od UBC-a s područja istočne Hrvatske, te njihovo poimanje istih u kontekstu smanjenja simptoma bolesti.
Ispitanici i metode: U presječno istraživanje, provedeno na području istočne Hrvatske u razdoblju od siječnja do lipnja 2016. godine, bilo je uključeno 296 bolesnika oboljelih od UBC-a prosječne dobi 50,1 ± 15,0 godina; 53,7% muškaraca i 46,3% žena; 29,4% oboljelih od Crohnove bolesti, te 70,6% oboljelih od ulceroznog kolitisa. Anonimni anketni upitnik korišten je za utvrđivanje sociodemografskih osobina oboljelih, te njihovih prehrambenih navika.
Rezultati: Istraživanje je pokazalo kako 78,7% oboljelih dnevno konzumira 2-3 obroka, te kako 87,5% oboljelih nije promijenilo broj dnevnih obroka nakon obolijevanja od UBC. Prije postavljanja dijagnoze UBC-a 5,1% oboljelih, kao najzastupljeniju namirnicu u prehrani izdvojilo je meso, a nakon postavljene dijagnoze 0,7% oboljelih. Među oboljelima je bilo 34,5% onih koji kao pomoćno sredstvo u kontroli simptoma svoje bolesti, uz standardnu terapiju koriste i neki oblik posebnog prehrambenog režima.
Zaključak: Dijetoterapija je značajno pomoćno sredstvo u kontroli simptoma UBC-a, pri čemu temelj dijete predstavlja osobno iskustvo oboljeloga, te uklanjanje nepoželjnih namirnica iz prehrane, sukladno istom.Introduction: Nutrition plays an important role in the life and treatment of patients with inflammatory bowel disease (IBD). The aim of this study was to determine the dietary habits of patients with IBD from Eastern Croatia, and their perception of the same in the context of reducing the symptoms of the disease
Patients and Methods: This cross-sectional study was conducted in Eastern Croatia in the period from January to June 2016. The study included 296 patients with IBD whose average age was 50.1 ± 15.0 years; 53.7% men and 46.3% women; 29.4% of patients with Crohn's disease and 70.6% of patients with ulcerative colitis. An anonymous questionnaire was used to determine the socio-demographic characteristics of patients and their eating habits.
Results: The study showed that 78.7% of patients daily consume 2-3 servings and that 87.5% of patients did not change the number of daily meals after they had been diagnosed with IBD. Before the diagnosis of the IBD 5.1% of patients reported that meat is the most frequent foodstuff in their diet while after the diagnosis of the IBD 0.7% of patients reported meat as the most frequent foodstuff in their diet. Among the patients there were 34.5% of those who used some form of special dietary regime as an adjunct to control the symptoms of their illness along with standard therapy.
Conclusion: Dietotherapy is a significant complementary therapy in controlling the symptoms of IBD, whereby the basis for the implementation of a special nutrition regime is a personal experience of particular patients and removal of undesirable foodstuff from his or her diet in accordance with the mentioned experience
The Inhibitory Effect of Flavonoid Aglycones on the Metabolic Activity of CYP3A4 Enzyme
No full textFlavonoids are natural compounds that have been extensively studied due to their positive effects on human health. There are over 4000 flavonoids found in higher plants and their beneficial effects have been shown in vitro as well as in vivo. However, data on their pharmacokinetics and influence on metabolic enzymes is scarce. The aim of this study was to focus on possible interactions between the 30 most commonly encountered flavonoid aglycones on the metabolic activity of CYP3A4 enzyme. 6β-hydroxylation of testosterone was used as marker reaction of CYP3A4 activity. Generated product was determined by HPLC coupled with diode array detector. Metabolism and time dependence, as well as direct inhibition, were tested to determine if inhibition was reversible and/or irreversible. Out of the 30 flavonoids tested, 7 significantly inhibited CYP3A4, most prominent being acacetin that inhibited 95% of enzyme activity at 1 µM concentration. Apigenin showed reversible inhibition, acacetin, and chrysin showed combined irreversible and reversible inhibition while chrysin dimethylether, isorhamnetin, pinocembrin, and tangeretin showed pure irreversible inhibition. These results alert on possible flavonoid–drug interactions on the level of CYP3A4
Falsely Elevated Serum Oestradiol due to Exemestane Therapy
No full textIn this study, we present a case of falsely elevated oestradiol (E2) concentration, determined by two immunoassays, in a breast cancer patient receiving exemestane therapy. The positive bias of immunochemical measurements was revealed
using liquid chromatography tandem mass spectrometry which showed undetectable E2 concentration. The discrepancy
is expected to be a consequence of the structural resemblance of E2 and exemestane sharing the same steroidal backbone. Inaccurate laboratory findings in therapy monitoring, as in this case, may lead to unnecessary changes of therapy
Povezanost koštane mineralne gustoće i sastavnica metaboličkog sindroma u postmenopauzalnih žena sa šećernom bolešću tipa 2
No full textDiabetes mellitus type 2 is associated with greater bone mineral density (BMD) due to obesity, although rapid bone loss observed over time could be explained by elevated chronic inflammation. The objective of this study was to investigate the relationship between central adiposity and hyperinsulinemia, as well as inflammation markers with vertebral and femoral BMD and bone turnover markers in postmenopausal women with type 2 diabetes. Femoral and vertebral BMD, osteocalcin, pyrilinks D, beta-CrossLaps (B-CTx), insulin, C-reactive protein (CRP), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) were measured in 114 postmenopausal female patients with diabetes type 2. The patients of similar age, HbA1c levels and diabetes duration were divided into 2 groups based on their body mass index (BMI) values: lower or equal to 27 kg/m2(31 patients) and higher than 27 kg/m2(83 patients). Lower levels of osteocalcin (p=0.001), B-CTx (p=0.000007) and pyrilinks D (p=0.0365), and higher femoral BMD (p=0.00006), insulin level (p=0.0002), PAI-1 (p=0.00000) and CRP (p=0.002) were found in the overweight group. There were no significant differences in vertebral BMD and fibrinogen. Osteocalcin and B-CTx showed inverse correlation, and femoral BMD positive correlation with waist circumference, insulin level and PAI-1. This suggests that abdominal obesity and hyperinsulinemia as components of the metabolic syndrome could increase femoral BMD by lowering bone rate. In addition, the only inflammation marker linked with femoral BMD was PAI-1, which is associated with increased mineralization of cortical bone in mouse models.Šećerna bolest tipa 2 povezana je s većom koštanom mineralnom gustoćom (bone mineral density, BMD) zbog debljine, iako se zamijećeni ubrzani gubitak koštane mase tijekom vremena može objasniti prisustvom kronične upale. Cilj ovoga istraživanja bio je utvrditi povezanost biljega koštane pregradnje i koštane gustoće s centralnom debljinom, hiperinzulinemijom kao i upalnim biljezima u postmenopauzalnih žena sa šećernom bolešću tipa 2. U 114 ispitanica izmjerena je koštana gustoća kralježnice i kuka, određeni su osteokalcin, pirilinks D, beta-CrossLaps (B-CTx), inzulin, C-reaktivni protein (CRP), fibrinogen i inhibitor aktivatora plazminogena-1 (PAI-1). Ispitanice slične dobi, podjednakog trajanja dijabetesa te HbA1c bile su podijeljene u dvije skupine prema indeksu tjelesne mase (ITM): niži ili jednaki 27 kg/m2(31 ispitanica) te veći od 27 kg/m2 (83 ispitanice). Niže vrijednosti osteokalcina (p=0,001), B-CTx (p=0,000007) i pirilinksa D (p=0,0365) te više vrijednosti košane gustoće kuka (p=0,00006), inzulina (p=0,0002), PAI-1 (p=0,0000) i CRP (p=0,002) utvrđene su u skupini s prekomjernom tjelesnom težinom. Nije bilo statistički značajne razlike u koštanoj gustoći kralježnice i vrijednosti fibrinogena. Osteokalcin i B-CTx su negativno korelirali, dok je BMD kuka bio u pozitivnoj korealciji s opsegom struka, inzulinom i PAI-1. Ovi rezultati upućuju na to da sastavnice metaboličkog sindroma, centralna debljina i hiperinzulinemija utječu na povećanje koštane gustoće kuka inhibirajući koštanu pregradnju. Jedini upalni biljeg povezan s BMD kuka bio je PAI-1 koji povećava mineralizaciju kortikalne kosti na mišjem modelu
Anemia, Hypoalbuminemia, and Elevated Troponin Levels as Risk Factors for Respiratory Failure in Patients With Severe Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Invasive Mechanical Ventilation
No full textAim: to determine in-hospital and post-discharge mortality, readmission rates, and predictors of invasive mechanical ventilation (IMV) in patients treated at intensive care unit (ICU) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD).
Methods: a retrospective observational cohort study included all patients treated at a respiratory ICU for AECOPD during one year. A total of 62 patients (41 men) with mean age 68.4 ± 10.4 years were analyzed for outcomes including in-hospital and post-discharge mortality, readmission rates, and IMV. Patients’ demographic, hematologic, biochemical data and arterial blood gas (ABG) values were recorded on admission to hospital. Mean duration of followup time was 2.4 years. Results: of 62 patients, 7 (11.3%) died during incident hospitalization and 21 (33.9%) died during the follow-up. The overall 2.4-year mortality was 45.2%. Twenty nine (46.8%) patients were readmitted due to AECOPD. The average number of readmissions was 1.2. Multivariate analysis showed that blood pH, bicarbonate levels, low albumin, low serum chloride, and low hemoglobin were significant predictors of IMV during incident hospitalization (P < 0.001 for the overall model fit).
Conclusion: high in-hospital and post-discharge mortality and high readmission rates in our patients treated due to AECOPD at ICU indicate that these patients represent a high risk group in need of close monitoring. Our results suggested that anemia, hypoalbuminemia, and elevated troponin levels were risk factors for the need of IMV in severe AECOPD. Identification of such high-risk patients could provide the opportunity for administration of an appropriate and timely treatment
Antioxidant Pre-treatment Reduces the Toxic Effects of Oxalate on Renal Epithelial Cells in a Cell Culture Model of Urolithiasis
No full textUrolithiasis is characterized by the formation and retention of solid crystals within the urinary tract. Kidney stones are mostly composed of calcium oxalate, which predominantly generates free radicals that are toxic to renal tubular cells. The aim of the study is to explore possible effects of antioxidant pre-treatment on inhibition of oxidative stress. Three cell lines were used as in vitro model of urolithiasis: MDCK I, MDCK II and LLC-PK1. Oxidative stress was induced by exposure of cells to sodium oxalate in concentration of 8 mM. In order to prevent oxidative stress, cells were pre-treated with three different concentrations of l-arginine and vitamin E. Oxidative stress was evaluated by determining the expression of superoxide dismutase (SOD), osteopontin (OPN), and by the concentration of glutathione (GSH). In all three cell lines, pre-treatment of antioxidants increased cell survival. Positive correlation of SOD and OPN expression as well as GSH concentration was observed in all groups of cells. Our results indicate that an antioxidant pre-treatment with l-arginine and vitamin E is able to hamper oxalate-induced oxidative stress in kidney epithelial cells and as such could play a role in prevention of urolithiasi
Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes
No full textBACKGROUND: Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec.
METHODS: We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-to-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-adjusted secondary outcome.
RESULTS: Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups.
CONCLUSIONS: Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529 .
Mood Disorders in Adult Asthma Phenotypes
No full textOBJECTIVE: Studies show high comorbidity of mood disorders in asthma. As asthma is a highly heterogeneous disease with different phenotypes it can be expected that there is a difference in this association with different asthma phenotypes. The aim of our cross-sectional study was to assess the association of specific asthma phenotypes with anxiety and/or depression and their impact on asthma control.
METHODS: A cross-sectional study in 201 consecutive adult outpatients with asthma (≥18 years of age) was conducted. Each patient underwent physical examination, detailed medical history, Hospital Anxiety and Depression Scale, Asthma Control Questionnaire, Asthma Control Test, together with measurements of lung function and fraction of exhaled nitric oxide. Phenotypes were assessed using cluster analysis, and a multivariate analysis was used to identify associations of mood disorders with different phenotypes.
RESULTS: Five asthma phenotypes were identified: allergic (AA, 43.8%), aspirin-exacerbated respiratory disease (AERD, 21.9%), late-onset (LOA, 18.9%), obesity-associated (OAA, 10.0%), and respiratory infections associated asthma (RIAA, 5.5%). A multivariate analysis showed a significant association of anxiety with LOA and comorbid hypertension (LOA, odds ratio (OR) = 2.12; hypertension, OR = 2.37, p = 0.012), and depression with AA, RIAA, hypertension, and ACQ score (AA, OR = 6.07; RIAA, OR = 4.73; hypertension, OR = 5.67; ACQ, OR = 1.87; p < 0.001). Comorbid anxiety/depression was associated with AA, LOA, RIAA, hypertension, and ACQ score (AA, OR = 10.15; LOA, OR = 2.98; RIAA, OR = 6.29; hypertension, OR = 5.15; ACQ, OR = 1.90; p < 0.001.
CONCLUSION: Mood disorders were significantly associated with AA, LOA, and infection-associated asthma, together with comorbid hypertension and the level of asthma control
Nodular Lymphoid Hyperplasia Complicated with Ileal Burkitt's Lymphoma in an Adult Patient with Selective IgA Deficiency
No full textINTRODUCTION: Primary lymphomas of the small intestine are rare. Burkitt's lymphoma (BL) occurs sporadically in adults. Nodular lymphoid hyperplasia (NLH) is a rare disorder characterized by diffuse nodular lesions, which represent hyperplastic lymphoid follicles, and it is often associated with immunodeficiency syndromes.
PRESENTATION OF CASE: We present a 38-year-old male patient in a state of surgical emergency, suspected of Crohn's disease, who had an unusual combination of NLH and BL of the proximal ileum. Furthermore, retrospectively analyzed documentation revealed selective IgA deficiency.
DISCUSSION: Association between NLH and intestinal lymphomas in patients with immunodeficiency syndromes was indicated before. This case report supports the notion on NLH as a transition state between immunodeficiency and intestinal lymphomas.
CONCLUSION: This is one of the first case reports which presents the combination of NHL and BL. The awareness of the existence of this rare combination, especially in young adult males, can improve the diagnostic accuracy and the treatment management