Liquid chromatography-tandem mass spectrometry methods for quantification of total and free antibiotic concentrations in serum and exudate from patients with post-sternotomy deep sternal wound infection receiving negative pressure wound therapy.

BACKGROUND: Systemically administered antibiotics are thought to penetrate the wounds more effectively during negative pressure wound therapy (NPWT).To test this hypothesis total and free antibiotic concentrations were quantified in serum and wound exudate. METHODS: UHPLC-MS/MS methods were developed and validated for the determination of ceftazidime, cefepime, cefotaxime, cefuroxime, cefazolin, meropenem, oxacillin, piperacillin with tazobactam, clindamycin, ciprofloxacin, sulfamethoxazole/trimethoprim (cotrimoxazole), gentamicin, vancomycin, and linezolid. The unbound antibiotic fraction was obtained by ultrafiltration using a Millipore Microcon-30kda Centrifugal Filter Unit. Analysis was performed on a 1.7-µm Acquity UPLC BEH C18 2.1 × 100-mm column with a gradient elution. RESULTS: The validation was performed for serum, exudates and free fractions. For all matrices, requirements were met regarding linearity, precision, accuracy, limit of quantitation, and matrix effect. The coefficient of variation was in the range of 1.2-13.6%.and the recovery 87.6-115.6%, respectively. Among the 29 applications of antibiotics thus far, including vancomycin, clindamycin, ciprofloxacin, oxacillin, cefepime, cefotaxime, cotrimoxazole, and gentamicin, total and free antibiotic concentrations in serum and exudate were correlated. CONCLUSION: This method can accurately quantify the total and free concentrations of 16 antibiotics. Comparison of concentration ratios between serum and exudates allows for monitoring individual antibiotics' penetration capacity in patients receiving NPWT.

Therapeutic monitoring of amiodarone and desethylamiodarone after surgical ablation of atrial fibrillation-evaluation of the relationship between clinical effect and the serum concentration.

BACKGROUND: Association between clinical effect and serum concentration of amiodarone (AMI) and its active metabolite desethylamidarone (DEA) in patients after surgical ablation (SA) of atrial fibrillation (AF) has not yet been studied. AIMS: We wanted to find a correlation between AMI and DEA serum concentration and maintaining sinus rhythm (SR) after SA of AF. METHODS: Sixty eight patients with AF who had undergone surgical ablation between 2014 and 2017 were included in a single-centre, prospective, observational study. Maintaining of SR was evaluated by standard 12-lead ECG and 24-hour Holter ECG monitoring at months 1, 3, 6 and 12 following surgery. Therapeutic monitoring of AMI and DEA concentrations was done to optimize therapy and adverse effects were followed up. RESULTS: We have noticed a high success rate in maintaining of SR (overall 83%). The median of serum concentration of AMI was 0.81 mg/L (range 0.16-2.35 mg/L) and DEA 0.70 mg/l (range 0.19-2.63 mg/L). No significant differences were found in the serum concentratration of AMI, DEA or DEA/AMI concentratration ratios between patients with SR and persistent supraventricular tachyarrhythmia except on the second outpatient visit. We observed significant correlation between serum concentration of DEA and thyroid-stimulating hormone elevation. CONCLUSION: We confirmed the efficacy of AMI and DEA at the measured serum concentrations. However, analysis of these concentrations alone cannot replace assessment of the clinical response for treatment. Establishment of individual AMI (and DEA) concentrations at which the optimal therapeutic response is achieved seems to be advantageous. Therapeutic monitoring of AMI and DEA is helpful in personalised pharmacotherapy after SA of AF.

Identifying Patient Access Barriers for Tumor Necrosis Factor Alpha Inhibitor Treatments in Rheumatoid Arthritis in Five Central Eastern European Countries.

INTRODUCTION: Although there is a significant utilization gap of biologic medicines in the EU, many studies estimate equity in patient access to biopharmaceuticals only based on their availability on the national list of reimbursed medicines. Hidden access barriers may facilitate financial sustainability of pharmaceuticals in less affluent EU countries; however, they have rarely been documented in scientific publications. Our objective was to explore these access barriers for tumor necrosis factor (TNF) alpha inhibitors in rheumatoid arthritis (RA) in five Central and Eastern European countries. METHODS: A detailed interview guide was developed based on multi-stakeholder workshops and a targeted literature review. In each participant country 3-3-3-3 interviews with payers, rheumatologists, patients/patient representatives, and industry representatives were conducted. Responses were aggregated at a country level and validated by primary investigators in each country. RESULTS: Limited number of RA centers and consequently significant travelling time and cost for patients in distant geographical areas, uneven budget allocation among centers, limited capacity of nurses, narrowed patient population in national financial protocols compared to international clinical guidelines in initiating or continuing biologics, high administrative burden in prescribing biologics and limited health literacy of patients were the most relevant barriers to timely patient access in at least three participant countries. CONCLUSION: Assessing only the availability of TNF alpha inhibitors on the national list of reimbursed medicines provides limited information about real-world patient access to these medicines. Revealing hidden access barriers may contribute to initiate policy actions which could reduce inequity in patient access.

Cardiac papillary fibroelastomas: A 10-year single-center surgical experience and long-term echocardiographic follow-up study.

AIMS: Limited contemporary data are available on the clinical and echocardiographic outcomes after surgery for cardiac papillary fibroelastoma (CPF). The aim of this study was to review the clinical manifestations, pathological characteristics, surgical management, and prognoses of patients with histologically verified CPF, who underwent surgery at our cardiac surgery center from 2008 to 2018. METHODS AND RESULTS: Twelve patients of median age 62 years (28 to 77 years) were treated. Embolic stroke or transient ischemic attack (five patients, 42%) were the only CPF clinical manifestations. Eleven (92%) tumors were localized on the valves, with the aortic valve being the most common tumor site (seven patients; 58%). Multiple factor analysis revealed no independent predictor of CPF-related embolization. Simple shave tumor excision was sufficient in most patients (10 patients, 83%). No operative or tumor-related late mortality during the median follow-up period of 4.7 years (1.1 to 10.2 years) was recorded. Asymptomatic metachronous valve tumor recurrence (in a location different from that of the original tumor) was revealed in two patients (17%) by transesophageal echocardiography (TEE), not detected by transthoracic echocardiography (TTE). One of these two patients underwent repeated surgery for CPF but later suffered a recurrent embolic stroke, due to another tumor recurrence. CONCLUSION: CPF can be safely and effectively treated surgically. TEE is superior to the TTE option in CPF post-operative recurrence detection. There is a clear need for a prospective study to determine criteria for embolization risk stratification and optimum management in patients with CPF.

The Power of Stoichiometry: Conditioning and Speciation of MgCl2/AlCl3 in Tetraethylene Glycol Dimethyl Ether-Based Electrolytes.

In many Mg-based battery systems, the reversibility of Mg deposition and dissolution is lowered by parasitic formation processes of the electrolyte. Therefore, high Coulombic efficiencies of Mg deposition and dissolution are only achieved after several "conditioning" cycles. As this phenomenon is especially reported for AlCl3-containing solutions, this study focuses on the "conditioning" mechanisms of MgCl2/AlCl3 and MgHMDS2/AlCl3 (HMDS = hexamethyldisilazide) in tetraethylene glycol dimethyl ether (TEGDME)-based electrolytes. Electrochemical (cyclic voltammetry) and spectroscopic investigations (27Al nuclear magnetic resonance spectroscopy, Raman spectroscopy, inductively coupled plasma optical emission spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy) reveal that cationic AlCl2+ species in TEGDME-based electrolytes with an AlCl3/MgCl2 ratio higher than 1:1 corrode the Mg metal. According to a cementation reaction mechanism, the corrosion of Mg is accompanied with Al deposition. In effect, the consumption of Mg results in low Coulombic efficiencies of Mg deposition and dissolution during the electrolyte "conditioning". After understanding the mechanism of this process, we demonstrate that a careful adjustment of the stoichiometry in MgCl2/AlCl3 and MgHMDS2/AlCl3 in TEGDME formulations prevents Mg corrosion and results in "conditioning"-free, highly efficient Mg deposition and dissolution.

Cost-effectiveness of denosumab versus zoledronic acid for preventing skeletal-related events in the Czech Republic.

AIMS: This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic. MATERIALS AND METHODS: A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses. RESULTS: Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively. LIMITATIONS: The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling. CONCLUSIONS: Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer, breast cancer, and OST in the Czech Republic.

Echocardiography-guided pericardiocentesis as the method of choice for treatment of significant pericardial effusion following cardiac surgery: a 12-year single-center experience.

BACKGROUND: There are limited contemporary data on the safety and efficacy of echo-guided pericardiocentesis following cardiac surgery in Europe. The aim of the study was to review tertiary cardiac surgery center experience with postoperative pericardial effusion (PE) diagnosis and treatment. METHODS: A total of 6830 patients underwent open-heart surgery at our center between December 2004 and November 2016. Of these patients, 208 (3%) required pericardiocentesis for significant PE. RESULTS: There was a significant reduction of the incidence of substantial PE requiring pericardiocentesis by use of alternative surgical pericardial cavity drainage system (the accessory Redon drain positioned along the diaphragmatic surface of the heart) compared to conventional retrosternal chest tube drainage (3.3% vs. 2.1%). The rate/relative risk of pericardiocentesis was significantly higher after valve surgery, aortic root and ascending aorta surgery, and surgical ablation of atrial fibrillation-i.e. among patients who had received postoperative anticoagulation therapy. Clinical manifestations of cardiac tamponade were observed in 36% of patients, while progressive large PE without tamponade was evacuated in 41% of patients. Initial echo-guided pericardiocentesis was therapeutically effective in 98.6% of cases, and the rate of major complications was 1%. There was no mortality related to pericardiocentesis. Eighteen patients (8.7%) required repeated pericardiocenteses due to recurrent effusion. Fifteen patients (7.2%) in the pericardiocentesis group required surgery due to recurrent effusion, persistent bleeding, or clotted hemopericardium. CONCLUSIONS: Echo-guided pericardiocentesis was very effective and safe method for primary treatment of postoperative PE. Most patients did not require further intervention after this treatment.

Effusive-constrictive pericarditis post surgical revision for iatrogenic hemopericardium.

AIM: A case report of subacute effusive-constrictive pericarditis in a patient with iatrogenic hemopericardium is presented. METHODS: A 69-year-old man was referred to our department for percutaneous coronary intervention complicated with hemopericardium with cardiac tamponade. Continuous bleeding after pericardiocentesis required an urgent surgical revision with evacuation of hemopericardium and local treatment of the sources of bleeding. A mild to moderate pericardial effusion persisted in the post-operative period, without any symptoms of cardiac tamponade. A global heart failure developed in the patient eleven months after complicated coronary intervention (surgical revision). A technically successful pericardiocentesis did not improve the clinical state of the patient. Echocardiography and magnetic resonance imaging confirmed the diagnosis of effusive-constrictive pericarditis. RESULTS: Subsequent pericardiectomy resulted in a prompt and complete relief of symptoms and signs of heart failure. CONCLUSION: Effusive-constrictive pericarditis is an uncommon disorder characterised by symptoms of refractory cardiac failure, thickening of the visceral pericardium and pericardial effusion, with no improvement after pericardiocentesis. In indicated cases, pericadiectomy leads to recovery in a large percentage of patients.

Cardiac rhythm and atrial transport function after surgical ablation of atrial fibrillation using cryoenergy: predictors and effectiveness of the procedure.

AIM: The aim of this prospective study was to assess the presence of sinus rhythm and atrial transport function after surgical ablation of atrial fibrillation using cryoenergy, and to evaluate predictors of the success of the procedure. METHODS: Between January 2005 and September 2006, 100 consecutive patients underwent left atrial cryoablation as a concomitant surgical procedure (46 patients with paroxysmal or persistent atrial fibrillation and 54 with permanent atrial fibrillation). Mitral valve surgery was performed in 74%. The mean and the median times of follow-up were 20 +/- 8.5, and 24 months respectively. Atrial mechanical function was assessed by echocardiography. RESULTS: Sinus rhythm was achieved during the postoperative follow-up in 71-81% of patients - significantly more often in the group with paroxysmal and persistent atrial fibrillation (90-98%), than patients with permanent atrial fibrillation prior to surgery (51-65%) (p<0.002). At 12 and 24 months after the surgery, a total of 68.2% and 51.2% of the patients were free from atrial fibrillation; 73.9% and 60.7% of the patients from the paroxysmal and persistent atrial fibrillation group, and 60.3% and 37.7% of patients with permanent atrial fibrillation (p=0.05). Five per cent of patients required postoperative permanent pacemaker implantation. An effective left and right atrial mechanical function was detected in 70-90%, and 96-98% of patients with sinus rhythm respectively. The following circumstances were identified as negative predictors of the presence of sinus rhythm after the ablation procedure: growing diameter of the left atrium, the duration of atrial fibrillation and the severity of mitral and tricuspid regurgitation before surgery (p<0.05). Restoration of the left atrial transport function was negatively predicted by the preoperative diameter of the left atrium, the presence of mitral valve stenosis and the severity of tricuspid regurgitation (p<0.05). A total of 95.4% of patients were free from stroke at one-year follow-up, and 94.1% at 2 years after surgery. CONCLUSION: Stable sinus rhythm and effective left atrial transport function are the main factors resulting in decreased morbidity after successful ablation of atrial fibrillation. A careful post-operative follow-up of the patients and individualised treatment are necessary.

[Aortic and mitral valve infective endocarditis caused by Tropheryma whipplei and with no gastrointestinal manifestations of Whipple's disease]. / Infekcní endokarditida aortálni a mitrální chlopne vyvolaná Tropheryma whipplei pri neprítomnosti gastrointestinálnich projevu Whippleovy choroby.

A case of blood culture-negative aortic and mitral valve infective endocarditis caused by the bacterium Tropheryma whipplei is reported. A 33-year-old man showed no clinical manifestations of Whipple's disease, with the exception of arthralgia as given in his history. The disease was complicated by recurrent cerebral and left upper limb embolization of vegetations. The causative agent was detected in a valve sample using broad-range polymerase chain reaction. The patient underwent successful surgery (aortic and mitral valve replacement) and his clinical condition during six-month antibiotic therapy was good.