Predictors of Worsening of Patients' Quality of Life Six Months After Coronary Artery Bypass Surgery

Abstract Background: The possibility to predict the change in (the) quality of life after coronary artery bypass surgery (CABG) being unclear, the aim was to evaluate the change of quality of life and predictors of worsening of quality of life in patients six months after CABG. Methods: We studied 208 consecutive patients, who underwent elective CABG. The Nottingham Health Profile Questionnaire part 1 was used as the model for quality of life determination. The questionnaire contains 38 subjective statements divided into six sections: physical mobility, social isolation, emotional reaction, energy, pain, and sleep. We distributed the questionnaire to all patients before CABG and six months after CABG. One hundred ninety‐two patients filled in the postoperative questionnaire. Results: The comparison between mean preoperative and postoperative scores showed an improvement in all sections of quality of life (p < 0.001). New York Heart Association functional class was significantly improved after CABG (2.23 ± 0.65 vs. 1.58 ± 0.59, p<0.001). Independent predictors of patients worsened by CABG were as follows: female gender in the pain section (p = 0.002; OR = 4.27; CI 1.74–10.47), diabetes mellitus in the physical mobility section (p = 0.003; OR = 8.09; CI 2.04–32.09), low ejection fraction in the physical mobility (p = 0.047; OR = 0.73; CI 0.56–0.95) and emotional reaction (p = 0.03; OR = 0.86; CI 0.60–0.93) sections, and postoperative complications in the social isolation (p = 0.002; OR = 4.63; CI 1.79–11.99), sleep (p = 0.03; OR = 2.71; CI 1.12–6.51), and pain (p = 0.005; OR = 3.39; CI 1.45–7.97) sections. Conclusion: The predictive factors for quality of life worsening six months after CABG are female gender, diabetes mellitus, low ejection fraction, and the presence of postoperative complications.     

Health Care Providers’ Advice on Lifestyle Modification in the US Population: Results from the NHANES 2011-2016

Objective

Health care providers are encouraged to prescribe lifestyle modifications for preventing and managing obesity and associated chronic conditions. However, the pattern of lifestyle advice provision is unknown. We investigate the prevalence of advised lifestyle modification according to weight status and chronic conditions in a US nationally representative sample.

Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate

Intramembrane proteolysis is a core regulatory mechanism of cells that raises a biochemical paradox of how hydrolysis of peptide bonds is accomplished within the normally hydrophobic environment of the membrane. Recent high-resolution crystal structures have revealed that rhomboid proteases contain a catalytic serine recessed into the plane of the membrane, within a hydrophilic cavity that opens to the extracellular face, but protected laterally from membrane lipids by a ring of transmembrane segments. This architecture poses questions about how substrates enter the internal active site laterally from membrane lipid. Because structures are static glimpses of a dynamic enzyme, we have taken a structure-function approach analyzing >40 engineered variants to identify the gating mechanism used by rhomboid proteases. Importantly, our analyses were conducted with a substrate that we show is cleaved at two intramembrane sites within the previously defined Spitz substrate motif. Engineered mutants in the L1 loop and active-site region of the GlpG rhomboid protease suggest an important structural, rather than dynamic, gating function for the L1 loop that was first proposed to be the substrate gate. Conversely, three classes of mutations that promote transmembrane helix 5 displacement away from the protease core dramatically enhanced enzyme activity 4- to 10-fold. Our functional analyses have identified transmembrane helix 5 movement to gate lateral substrate entry as a rate-limiting step in intramembrane proteolysis. Moreover, our mutagenesis also underscores the importance of other residue interactions within the enzyme that warrant further scrutiny.     

Survival analysis of 314 episodes of sepsis in medical intensive care unit in university hospital: impact of intensive care unit performance and antimicrobial therapy

Aim

To evaluate epidemiology of sepsis in medical intensive care unit (ICU) in an university hospital, and the impact of ICU performance and appropriate empirical antibiotic therapy on survival of septic patients.

Methods

Observational, partly prospective study conducted over 6 years assessed all patients meeting the criteria for sepsis at ICU admission at the Sisters of Mercy Hospital in Zagreb. Clinical presentation of sepsis was defined according to 2001 International Sepsis Definitions Conference. Demographic data, admission category, source of infection, severity of sepsis, ICU or hospital stay and outcome, ICU performance, and appropriateness of empirical antibiotic therapy were analyzed.

Results

The analysis included 314 of 5022 (6.3%) patients admitted to ICU during the study period. There were 176 (56.1%) ICU survivors. At the ICU admission, sepsis was present in 100 (31.8%), severe sepsis in 89 (28.6%), and septic shock in 125 (39.8%) patients with mortality rates 17%, 33.7%, 72.1%, respectively. During ICU treatment, 244 (77.7%) patients developed at least one organ dysfunction syndrome. Of 138 (43.9%) patients who met the criteria for septic shock, 107 (75.4) were non-survivors (P<0.001). Factors associated with in-ICU mortality were acquisition of sepsis at another department (odds ratio [OR] 0.06; 95% confidence interval [CI], 0.02-0.19), winter season (OR 0.42; 0.20-0.89), limited mobility (OR 0.28; 0.14-0.59), ICU length of stay (OR 0.82; 0.75-0.91), sepsis-related organ failure assessment (SOFA) score on day 1 (OR 0.80; 0.72-0.89), history of global heart failure (OR 0.33; 0.16-0.67), chronic obstructive pulmonary disease (COPD)-connected respiratory failure (OR 0.50; 0.27-0.93), septic shock present during ICU treatment (OR 0.03; 0.01-0.10), and negative blood culture at admission (OR 2.60; 0.81-6.23). Microbiological documentation of sepsis was obtained in 235 (74.8%) patients. Urinary tract infections were present in 168 (53.5%) patients, followed by skin or soft tissue infections in 58 (18.5%) and lower respiratory tract infections in 44 (14.0%) patients. Lower respiratory tract as focus of sepsis was connected with worse outcome (P<0.001). Empirical antibiotic treatment was considered adequate in 107 (60.8%) survivors and 42 (30.4%) non-survivors. Patients treated with adequate empirical antibiotic therapy had significantly higher survival time in hospital (log-rank, P = 0.001).

Conclusion

The mortality rate of sepsis was unacceptably high. The odds for poor outcome increased with acquisition of sepsis at another department, winter season, limited mobility, higher SOFA score on day 1, history of chronic global heart failure, COPD-connected respiratory failure, and septic shock present during ICU treatment, whereas longer ICU length of stay, positive blood culture, and adequate empirical antibiotic therapy were protective factors.Sepsis is a systemic response of the host to infectious stimuli, which consists of clinical, hemodynamic, biochemical, and inflammatory components (1,2). When an organ system begins to fail because of sepsis, the condition is considered severe and is one of the leading causes of death in the critically ill, with the mortality rate of 28-55% (3). The death rates in some subgroups of patients with sepsis-induced organ failure have decreased, even though there is no specific therapy (2). The reduced mortality may be due to changes in the definition of sepsis, better detection and treatment of the underlying infection, or improved supportive care (4). Effective treatment of organ failure is essential because the average risk of death increases by 15-20% with failure of each additional organ (5). The host response is perhaps as important as the site of infection or the type of microorganism causing sepsis. The lung is the most common site of infection, followed by abdominal and urinary tract organs (6). Positive blood cultures are accepted as the evidence of serious infection, but they are positive in only 30% of patients (6). Antimicrobial drugs are necessary, but not sufficient for the treatment of sepsis. Around 10% of the patients do not receive prompt antibiotic therapy for causative pathogen, and their mortality rate is 10-15% higher than in those who receive immediate, appropriate antibiotic therapy (5). The adequacy of initial empirical antimicrobial treatment is crucial in terms of outcome, although early mortality rate is unaffected by the appropriate empirical antibiotic therapy (7). The application of proven medical and technological interventions in a standard therapeutical algorithm is important in everyday performance of intensive care unit (ICU) (8). Since epidemiology and surveillance data significantly differ between medical and surgical ICU patients (9), each ICU has to assess its own epidemiological data and establish critical pathways for the management and treatment of patients with sepsis (10).Our aim was to evaluate the epidemiology of sepsis syndrome in the medical ICU at University Hospital and the impact of ICU performance and adequate empirical antibiotic therapy on the outcome in patients with sepsis.     

Ergonovine-Induced Changes of Coronary Artery Diameter in Patients with Nonsignificant Coronary Artery Stenosis

BACKGROUND AND PURPOSE: Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease. PATIENTS AND METHODS: 105 patients (46 male, 59 female, mean age 52 +/- 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured. RESULTS: There was a significant negative correlation between resting MLD and LDL cholesterol (r = -0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]). CONCLUSION: In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.     

Comparison of the suppressing capecitabine and 5-fluorouracil effects on the pronounce of inflammatory cells score in the induction of episcleral fibrosis after trabeculectomy

BACKGROUND/AIM: Trabeculectomy is a filtering antiglaucoma surgery performed to facilitate the formation of a drainage channel for the aqueous humor from the anterior chamber of the eye to the subconjunctival space making a collector, filtering cushion of the eyeliquid. The cause of unfavourable outcome of trabeculectomy is episcleral fibrosis which leads to the obstruction of the drainage channel Inflammatory reaction is an initial, but, also, the key event in the process of fibrosis and directly proportional to it A successful medicamentous suppression of inflammation could stop fibrosis. Arccordingly, the aim of this study was to comparatively evaluate suppressing effects of capecitabine and 5-fluoroaracil upon inflammation, an initial fibrosis process after trabeculectomy. METHODS: This study was performed on an experimental animal model, namely 2 4 rabbits (48 eyes), which were exposed to artificial cause of the tissue changes analogous to human subclinical inflammation. During the trabeculectomy, a 5% solution of 5-fluoroaracil was applied to the right eye sclera of a rabbit, while 2% solution of kapecitabine was applied to the left eye sclera, thus making possible to evaluate the effects of different drugs to the same animal. Two weeks after the surgery the subconjunctival - episcleral tissue cuts were analyzed. Semiquantitative histologic test was used to compare the cellular elements of inflammatory (fibroblasts, mononuclears, plasmocytes, eosinophiles), as well as fibrosing (colagen, reticulin fibers) process, and, based on the differences in histopathologic score, suppressive efficacy of 5-fluoroaracil and kapecitabine was evaluated and compared between the groups of the treated tissues. The results were shown as mean values +/- standard deviation. RESULTS: A statistically significantly lower score was revealed in the initial inflammatory cells - mononudears and plasmocytes in the group of the tissues treated with kapecitabine, while there was no differences between the groups in the score of fibroblasts and colagen fibers. CONCLUSION: The suppression of the initial episcleral fibrosis process obtained by kapecitabine was more significant as compared to the suppression obtained by 5-fluoroaracil, thus providing more favorable outcome of the trabeculectomy.     

The safety of enoxaparine use in elderly with acute myocardial infarction

BACKGROUND/AIM: Enoxaparin (ENOX), the low-molecular-weight heparin, used in acute myocardial infarction (AMI) could lead to hemorrhage. The aim of this study was to determine wether bleeding was more often in AMI patients older than 65 or 75 years who receive ENOX or unfractionated heparin (UFH). METHODS: Among the patients with AMI hospitalized during three successive months receiving ENOX or UFH, three group of parameters were investigated: demographic, ischemic and bleeding TIMI criteria. RESULTS: Among 85 hospitalized patients with signs of AIM, there were 35 (41.2%) old 65 years or less, 32 (38.5) old 66-75 years and 18 (21.2%) older than 75 years. In AMI elderly patients, according to the received ENOX/UFH: ischemic complication (18.2 vs. 21.4%) were insignificantly lower and the number of lethal outcomes (18.2 vs. 17.8%) were insignificantly more often in ENOX group; represented only by one patient (age beyond 75 years), major and non-major bleeding events occurred only in UFH group. CONCLUSION: The ENOX usage in AMI in patients older than 65 years did not show any significant difference in efficacy and bleeding rate comparing to UFH.     

Cloning and characterization of the biosynthetic gene cluster for kutznerides

Kutznerides, actinomycete-derived cyclic depsipetides, consist of six nonproteinogenic residues, including a highly oxygenated tricyclic hexahydropyrroloindole, a chlorinated piperazic acid, 2-(1-methylcyclopropyl)-glycine, a beta-branched-hydroxy acid, and 3-hydroxy glutamic acid, for which biosynthetic logic has not been elucidated. Herein we describe the biosynthetic gene cluster for the kutzneride family, identified by degenerate primer PCR for halogenating enzymes postulated to be involved in biosyntheses of these unusual monomers. The 56-kb gene cluster encodes a series of six nonribosomal peptide synthetase (NRPS) modules distributed over three proteins and a variety of tailoring enzymes, including both mononuclear nonheme iron and two flavin-dependent halogenases, and an array of oxygen transfer catalysts. The sequence and organization of NRPS genes support incorporation of the unusual monomer units into the densely functionalized scaffold of kutznerides. Our work provides insight into the formation of this intriguing class of compounds and provides a foundation for elucidating the timing and mechanisms of their biosynthesis.