Non-steroid, non-antibiotic anti-biofilm therapy for the treatment of chronic rhinosinusitis: a systematic review.

OBJECTIVE: Chronic rhinosinusitis patients with biofilms cultured from their sinonasal cavity have greater symptom burden and risk of recalcitrant disease. A number of non-antibiotic, 'anti-biofilm' treatments exist which show anti-biofilm properties in preclinical studies. There is little evidence evaluating their impact on clinical symptom scores in chronic rhinosinusitis. METHOD: A systematic review was performed to assess the literature regarding the efficacy of non-steroid, non-antibiotic, anti-biofilm specific topical therapies in the treatment of chronic rhinosinusitis. The primary outcome assessed was change in validated patient reported outcome measures before and after anti-biofilm treatment. RESULTS: Thirteen studies assessing the effect of anti-biofilm therapies in chronic rhinosinusitis through validated patient-reported outcome measures were included. Seven different anti-biofilm specific therapies for chronic rhinosinusitis were identified. None of the seven anti-biofilm therapies was identified as being confidently efficacious beyond placebo. Only one therapy (intranasal xylitol) showed a statistically significant reduction in symptom scores compared with placebo in more than one trial. CONCLUSION: Robust evidence supporting the use of various anti-biofilm therapies in chronic rhinosinusitis is lacking. Further high quality, human, in vivo trials studying the effect of anti-biofilm therapies in chronic rhinosinusitis are needed to address the deficiencies of the current evidence base.

The association of hematological indices with the response to cardiac resynchronization therapy: a single-center study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established therapeutic option for patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≤35 % who meet specific criteria according to current guidelines. However, up to 40 % of patients have no response to CRT. Our study aimed to investigate the association between different hematological and biochemical indices and response to CRT. METHODS: Patients with HF due to ischemic or dilated cardiomyopathy referred to our hospital for CRT implantation from January 2013 to November 2017 were included in the study. Response to CRT was defined as an increase in LVEF ≥10 % or a decrease in left ventricular end-systolic volume (LVESV) ≥15 % at six months of follow-up. RESULTS: A total of 48 patients (mean age: 66.2 ± 9.5 years, 81.3 % males) were included in the study. Of these HF patients, 29 (60.4 %) had ischemic cardiomyopathy, and 19 (39.6 %) had dilated cardiomyopathy. At six months of follow-up, 37 patients (77.1 %) had responded to CRT. Ten patients (20.8 %) had ventricular tachycardia (VT), 24 (50 %) patients were hospitalized, and two patients (4.2 %) died during the follow-up period. Multivariate analysis demonstrated that age (p =0.03) and creatinine levels (p =0.02) were independent predictors of the response to CRT. No significant associations between hematological markers (white blood cells, neutrophils, lymphocytes, platelets, neutrophil to lymphocyte ratio, red blood cells distribution width) and CRT response were observed. CONCLUSIONS: A smaller increase in LVEF and a smaller decrease in LVESV were predictive for VT occurrence and hospitalizations in patients receiving CRT. No significant association between hematological markers and response to CRT was found. HIPPOKRATIA 2019, 23(3): 118-125.

Intermuscular implantation technique for subcutaneous cardioverter-defibrillators.

BACKGROUND: The conventional technique for subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation has been associated with pocket complications. The aim of this study was to evaluate the efficacy and safety of an alternative intermuscular technique for S­ICD implantation. METHODS: S-ICDs were implanted in ten consecutive patients (ten males, mean age: 46.8 ± 14.7 years). The pocket for the pulse generator was made above the serratus anterior muscular fascia and beneath the latissimus dorsi muscle by detaching the fibrous tissue between the muscles. Electrode implantation was performed using the three- (n = 4) or the two-incision technique (n = 6). RESULTS: All S­ICDs were successfully implanted in the absence of any procedure-related complications with a successful 65-J standard polarity defibrillation threshold testing, apart from one patient with Brugada syndrome who needed device repositioning more dorsally. During a mean follow-up of 16.5 ± 7.3 months, no major complications requiring surgical repair were encountered, while patients demonstrated high levels of comfort and satisfaction with the cosmetic result. One patient experienced an inappropriate shock due to noise detection, which was resolved after reprogramming to a different sensing vector. CONCLUSION: The intermuscular technique is a safe and efficacious approach for S­ICD implantation. This technique could lead to fewer pocket-related complications and better cosmetic results.

Impact of baseline renal function on all-cause mortality in patients who underwent cardiac resynchronization therapy: A systematic review and meta-analysis.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves both morbidity and mortality in selected patients with heart failure and increased QRS duration. However, chronic kidney disease (CKD) may have an adverse effect on patient outcome. The aim of this systematic review was to analyze the existing data regarding the impact of baseline renal function on all-cause mortality in patients who underwent CRT. METHODS: Medline database was searched systematically, and studies evaluating the effect of baseline renal function on all-cause mortality in patients who underwent CRT were retrieved. We performed three separate analyses according to the comparison groups included in each study. Data were analyzed using Review Manager software (RevMan version 5.3; Oxford, UK). RESULTS: We included 16 relevant studies in our analysis. Specifically, 13 studies showed a statistically significant higher risk of all-cause mortality in patients with impaired baseline renal function who underwent CRT. The remaining three studies did not show a statistically significant result. The quantitative synthesis of five studies showed a 19% decrease in all-cause mortality per 10-unit increment in estimated glomerular filtration rate (eGFR) [HR: 0.81, 95% CI (0.73-0.90), p<0.01, 86% I2]. Additionally, we demonstrated that patients with an eGFR<60 mL/min/1.73 m2 had an all-cause mortality rate of 66% [HR: 1.66, 95% CI (1.37-2.02), p<0.01, 0% I2], which was higher than in those with an eGFR≥60 mL/min/1.73 m2. CONCLUSION: Baseline renal dysfunction has an adverse effect on-all cause mortality in patients who underwent CRT.

Sample entropy predicts lifesaving interventions in trauma patients with normal vital signs.

INTRODUCTION: Heart rate complexity, commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice is not yet widely adopted. We previously demonstrated the ability of this noninvasive technology to predict lifesaving interventions (LSIs) in trauma patients. This study was conducted to prospectively evaluate the utility of real-time, automated, noninvasive, instantaneous sample entropy (SampEn) analysis to predict the need for an LSI in a trauma alert population presenting with normal vital signs. METHODS: Prospective enrollment of patients who met criteria for trauma team activation and presented with normal vital signs was conducted at a level I trauma center. High-fidelity electrocardiogram recording was used to calculate SampEn and SD of the normal-to-normal R-R interval (SDNN) continuously in real time for 2 hours with a portable, handheld device. Patients who received an LSI were compared to patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. Treating clinicians were blinded to results. RESULTS: Of 129 patients enrolled, 38 (29%) received 136 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. Lifesaving intervention patients had a lower Glasgow Coma Scale. The mean SampEn on presentation was 0.7 (0.4-1.2) in the LSI group compared to 1.5 (1.1-2.0) in the non-LSI group (P < .0001). The area under the curve with initial SampEn alone was 0.73 (95% confidence interval [CI], 0.64-0.81) and increased to 0.93 (95% CI, 0.89-0.98) after adding sedation to the model. Sample entropy of less than 0.8 yields sensitivity, specificity, negative predictive value, and positive predictive value of 58%, 86%, 82%, and 65%, respectively, with an overall accuracy of 76% for predicting an LSI. SD of the normal-to-normal R-R interval had no predictive value. CONCLUSIONS: In trauma patients with normal presenting vital signs, decreased SampEn is an independent predictor of the need for LSI. Real-time SampEn analysis may be a useful adjunct to standard vital signs monitoring. Adoption of real-time, instantaneous SampEn monitoring for trauma patients, especially in resource-constrained environments, should be considered.

5-HT(1A), 5-HT(2A), and 5-HT(2C) receptor mRNA modulation by antidepressant treatment in the chronic mild stress model of depression: sex differences exposed.

It is well established that women experience major depression at roughly twice the rate of men. Interestingly, accumulating clinical and experimental evidence shows that the responsiveness of males and females to antidepressant pharmacotherapy, and particularly to tricyclic antidepressants (TCAs), is sex-differentiated. Herein, we investigated whether exposure of male and female rats to the chronic mild stress (CMS) model of depression, as well as treatment with the TCA clomipramine may affect serotonergic receptors' (5-HTRs) mRNA expression in a sex-dependent manner. Male and female rats were subjected to CMS for 4 weeks and during the next 4 weeks they concurrently received clomipramine treatment (10 mg/ml/kg). CMS and clomipramine's effects on 5-HT(1A)R, 5-HT(2A)R, and 5-HT(2C)R mRNA expression were assessed by in situ hybridization histochemistry in selected subfields of the hippocampus and in the lateral orbitofrontal cortex (OFC), two regions implicated in the pathophysiology of major depression. CMS and clomipramine treatment induced sex-differentiated effects on rats' hedonic status and enhanced 5-HT(1A)R mRNA expression in the cornu ammonis 1 (CA1) hippocampal region of male rats. Additionally, CMS attenuated 5-HT(1A)R mRNA expression in the OFC of male rats and clomipramine reversed this effect. Moreover, 5-HT(2A)R mRNA levels in the OFC were enhanced in females but decreased in males, while clomipramine reversed this effect only in females. CMS increased 5-HT2CR mRNA expression in the CA4 region of both sexes and this effect was attenuated by clomipramine. Present data exposed that both CMS and clomipramine treatment may induce sex-differentiated and region-distinctive effects on 5-HTRs mRNA expression and further implicate the serotonergic system in the manifestation of sexually dimorphic neurobehavioral responses to stress.

Effect of atrial pressure increase on effective refractory period and vulnerability to atrial fibrillation in patients with lone atrial fibrillation.

BACKGROUND: There is evidence suggesting that atrial fibrillation (AF) may be induced by acute increase of atrial pressure. The aim of the present study was to investigate the effect of alterations in atrial pressure, induced by varying the atrioventricular (AV) interval, on atrial refractoriness, and on the frequency of induction of (AF), in patients with a history of lone atrial fibrillation (LAF). METHODS AND RESULTS: Twenty-five patients were included in this study. The patients were divided in two groups: the LAF group, and the control group. None of the patients in either group had organic heart disease. Effective refractory period (ERP) and duration of atrial extrastimulus electrogram (A(2)) were measured at two right atrial sites (high lateral wall, atrial appendage) during AV pacing (cycle length: 500 msec) with different AV intervals. Peak, minimal and mean atrial pressure increased from 8.57 +/- 2.37 to 18.14 +/- 4.74 mm Hg, 2 +/- 2.23 to 5.14 +/- 2.60 mm Hg (p = 0.0001) and from 4.28 +/- 1.6 mm Hg to 9.77 +/- 2.9 mm Hg (p = 0.001), respectively during AV interval modification. During lateral and atrial appendage pacing, with a progressive decrease of AV interval to 160, 100, 80, 40, 0 msec, the ERP, the dispersion of ERP, functional refractory period (FRP), A2 and latency period (LP) did not change significantly, in both groups. The frequency of induction of AF was not statistically different in both lateral atrial wall and appendage, during pacing in different AV intervals. CONCLUSIONS: This study demonstrates that alterations in the intraatrial pressure does not have important effects on atrial refractoriness and does not increase vulnerability to AF in patients with a history of LAF.

Combined dynamic cardiomyoplasty and transvenous implantable cardioverter defibrillator system.

A transvenous implantable cardioverter defibrillator (ICD) was implanted in a patient with drug refractory ventricular fibrillation who had undergone latissimus dorsi cardiomyoplasty. The skeletal muscle was stimulated by a pulse train generator (cardiostimulator) implanted at the time of cardiomyoplasty. With proper programming of the devices neither adverse ICD-cardiostimulator interactions nor device malfunction were observed. Thus, the combined implantation of a cardiostimulator and an ICD is a feasible and safe therapeutic option.

Excessive sinus pauses and their elimination in a patient with sleep apnea syndrome.

A 40-year-old man with severe sleep apnoea syndrome presented significant sinus pauses during a 48 h electrocardiogram Holter recording. Holter analysis showed one sinus pause of 6.4 s duration, and many pauses greater than 3 s. The 48 h Holter reevaluation, after a continuous positive air pressure device was applied, showed no pauses. The electrophysiological study was negative for sick sinus syndrome.

Carotid sinus hypersensitivity in patients undergoing coronary arteriography: relation with the severity of carotid atherosclerosis and the extent of coronary artery disease.

INTRODUCTION: The purpose of the present investigation was to study the precise relationship between carotid sinus hypersensitivity (CSH) and both the severity of carotid atherosclerosis and the extent of coronary artery disease in patients who were referred for evaluation for suspected ischemic heart disease. METHODS AND RESULTS: Duplex echocardiography and coronary angiography were used to assess carotid and coronary artery atherosclerosis in 130 consecutive patients. Carotid sinus stimulation was performed before coronary arteriography with simultaneous recordings of the ECG and aortic pressure. Coronary artery disease was present in 103 patients (79%). Thirty patients (23.08%) had one-vessel disease (1-VD), 31 (23.85%) had 2-VD, 29 (22.31%) had 3-VD, and 13 patients (10%) had left main coronary artery disease. Carotid artery atherosclerosis was present in 100 patients (76.92%) and carotid disease (diameter stenosis > 50%) was present in 24 patients (18.46%). CSH was found in 33 patients (25%). The incidence of CSH was 9% in patients with carotid stenosis 1%-15%, 17% in patients with stenosis 16%-49%, 85% in patients with stenosis 50%-79%, and 100% in patients with stenosis > or = 80%. The incidence of CSH was 11%, 17%, 23%, 34%, and 62% in patients with no VD, 1-VD, 2-VD, 3-VD, and left main coronary artery disease, respectively. Stepwise multiple logistic regression analysis revealed that carotid disease and left main coronary artery disease were the most significant determinants of CSH (P < 0.001 and P = 0.013, respectively). CONCLUSION: The incidence of CSH increased in proportion to the severity of carotid and coronary atherosclerosis. These data provide evidence that CSH is closely related to severe carotid atherosclerosis or left main coronary artery disease in patients being evaluated for suspected ischemic heart disease.

Stress echocardiography using adenosine combined with nitroglycerin-dobutamine in the detection of viable myocardium in patients with previous myocardial infarction.

The aim of this study was to assess the value of adenosine (A) and the combination of nitroglycerin (N) with dobutamine (D) stress echocardiography (SE) in the identification of viable myocardium. The clinical and electrocardiographic (ECG) effects of both tests were also evaluated. Fifty-two coronary artery disease patients, aged 56.4 +/- 8 years, with left ventricular dysfunction due to a previous myocardial infarction (mean ejection fraction: 49 +/- 8%) were included in the study. Cardiac catheterization was performed in all patients before A (140 micrograms/kg/minute for five minutes) and the combination of N with D (5-10 micrograms/kg/minute) stress echocardiography. On the echocardiogram, the left ventricle was divided into 16 segments and wall motion was graded semiquantitatively from 1 (normal) to 4 (dyskinesia). The echocardiographic index was also estimated. A segment was considered viable during A infusion when resting asynergy showed deterioration of one grade or more. In contrast, segmental viability was considered to be present during the combination of N with D infusion when resting asynergy showed improvement of one grade or more. A thallium 201 single photon emission computed tomography (SPECT) with reinjection was performed as reference standard for the identification of viable myocardium. Stress echocardiography during infusion of A was associated with short-duration angina attacks in 3 (5.8%) patients and transient complete atrioventricular (AV) block in 1 (1.9%), whereas during the combination of N with D infusion, 6 (11.5%) patients experienced ventricular bigeminy lasting for a short period. ST segment elevation greater than 1 mm was recorded in those leads having a Q wave, in 19 (36.5%) patients. In 10 of these 19 (52.6%), viable myocardium was present in SPECT, as it was in 33 patients (63.5%) having no ST segment elevation (P = NS). Of a total of 832 segments that were graded during A-SE, 276 exhibited resting asynergy and the remaining 556 had normal motion and thickening at rest. The echocardiographic index during A infusion increased from 1.52 +/- 0.22 to 1.71 +/- 0.24 (P < 0.001), whereas during D and N infusion it decreased from 1.53 +/- 0.31 to 1.30 +/- 0.42 (P < 0.001). With SPECT considered as the gold standard for the identification of viable myocardium, sensitivity, specificity, and positive and negative predictive values of A-SE in detecting viable myocardium were 54%, 86%, 65% and 80%, respectively. The respective values for the combination of nitroglycerin with D-SE were 91%, 89%, 78%, and 96%, respectively. Stress echocardiography during A, and the combination of N with D, constitute safe methods in the identification of viable myocardium. The detection of ST segment elevation in the ECG leads with a Q wave during the combined infusion of nitroglycerin and dobutamine is not related to the presence of viable myocardial tissue. The A-SE provide moderate diagnostic accuracy, while the combination of N with D during SE is much superior in detecting viable myocardium.

Stress echocardiography in elderly patients with coronary artery disease: applicability, safety and prognostic value of dobutamine and adenosine echocardiography in elderly patients.

OBJECTIVES: Our aim was to determine the applicability, safety and prognostic value of adenosine and dobutamine stress echocardiography in patients > or = 70 years old. BACKGROUND: These tests are sometimes mandatory because of difficulties and inaccuracies in interpreting traditional electrocardiographic stress tests. Furthermore, if these tests could be used to avoid coronary arteriography and cardiac catheterization, they would become essential in the care of the elderly, whose numbers are increasing. METHODS: We performed coronary arteriography and dobutamine and adenosine stress echocardiographic tests in 120 patients (72 men) > or = 70 years old who entered the hospital because of chest pain and had known or suspected coronary artery disease. The stress tests were performed on separate days, within 2 weeks of coronary arteriography. Both the arteriograms and the echocardiograms were analyzed by two experts who had no knowledge of the patients' other data or the other interpreter's report. Tests were judged to have positive or negative results, and the patients were followed up for the development of cardiac events. Univariate and multivariate analyses and other statistical modalities were applied for comparisons. RESULTS: Documented coronary artery disease was found in 89 patients. During the 14 +/- 7 of follow-up, cardiac events developed in 50 patients, including 3 (7.9%) of 38 patients with negative dobutamine and 12 (20.7%) of 58 patients with negative adenosine test results. Demonstration of any abnormality on stress echocardiography was an independent factor for cardiac events, both for dobutamine (relative risk 7.3) and for adenosine (relative risk 3.0). Both cessation of dobutamine or adenosine tests and diagnosis of disease in two or more coronary vessels were also independent predictors. ST segment depression > or = 1mm was related to future events only with the dobutamine test. CONCLUSIONS: These echocardiographic stress tests proved safe and well tolerated. They successfully stratified this cohort of elderly patients with coronary artery disease to low or high risk subgroups for subsequent cardiac events.

Effects of magnesium and potassium on Wolff-Parkinson-White syndrome.

To investigate the effects of electrolytes on anterograde conduction via accessory pathways, 12 patients with Wolff-Parkinson-White syndrome received, while in sinus rhythm, intravenous KCl (7 mEq in 200 mL of 0.9% NaCl), MgSO4 (10 mL 20% in 200 mL of 0.9% NaCl), NaCl (0.9%, 200 mL), and procainamide (maximal dose, 10 mg/kg of body weight over a 5-minute period) in a randomized fashion. NaCl had no effect on preexcitation. Procainamide abolished preexcitation in seven patients, of whom five had a similar response with MgSO4 and four with KCl. The finding that potassium and magnesium transiently abolish preexcitation in some Wolff-Parkinson-White patients deserves further study, especially during tachyarrhythmias in patients with accessory pathways.

Analysis of left atrioventricular plane movement during diastole in ischemic heart disease.

The aim of the present study was to investigate the properties of diastolic left atrioventricular plane displacement (AVPD) in coronary artery disease (CAD) patients. In 125 patients (mean age 58.7 +/- 13.7) with CAD and in 51 age-matched healthy subjects, a complete transthoracic echocardiographic study was performed. The AVPD was recorded by M-mode echocardiography, from apical four and two chamber views at four sites corresponding to the septal, lateral, anterior and inferior walls of the left ventricle. Mean AVPD in early diastole (E-AVPD), mean AVPD from atrial systole (A-AVPD) and the ratio A-AVPD/E-AVPD were determined. In normal subjects, such as in 35 patients without left ventricular segmental wall motion abnormalities (SWMA), stepwise multiple regression analysis showed none of these factors to be significantly related to E-AVPD or A-AVPD. Aging was correlated negatively to the E-AVPD/A-AVPD ratio (p < 0.05). In 90 patients with left ventricular SWMA, stepwise multiple regression analysis showed that indices of left ventricular systolic function correlated positively to E-AVPD (p < 0.001) and A-AVPD (p < 0.001). The E-AVPD/A-AVPD ratio was correlated to left ventricular ejection fraction and heart rate (p < 0.005). Mean E-AVPD was significantly lower in CAD patients than in normal subjects (p 0.001), while A-AVPD was higher in patients without left ventricular SWMA in comparison to normal subjects (p = 0.02). Also, mean A-AVPD/E-AVPD was higher in CAD patients than in the control group (p < 0.001). Mean E-AVPD/A-AVPD was correlated to the E/A ratio of transmitral flow in CAD patients with (r = 0.669) and without (r = 0.771) SWMA. The E-AVPD and A-AVPD in CAD patients with SWMA is reduced according to the deterioration of left ventricular systolic function. The atrial contribution to the longitudinal distension of the left ventricle is increased in CAD patients. In CAD patients, especially those without left ventricular SWMA, the E-AVPD/A-AVPD ratio has a good correlation to left ventricular filling behavior.

Retrograde nontransseptal balloon mitral valvuloplasty using a modified Inoue balloon catheter.

Retrograde nontransseptal balloon mitral valvuloplasty, a method developed in our institution for the treatment of symptomatic mitral stenosis, avoids transseptal catheterization. Until recently, the self-positioning Inoue balloon catheter, unlike all other commercially available balloon catheters, had not been employed in this nontransseptal technique due to the short length of its catheter shaft. To employ a self-positioning balloon in retrograde nontransseptal balloon mitral valvuloplasty, we modified the Inoue device by extension of the catheter shaft. After retrograde nontransseptal left atrial catheterization using a steerable cardiac catheter, the modified Inoue balloon catheter was inserted through the femoral artery and advanced to the mitral valve retrogradely. Valvuloplasty was performed in 20 patients, with a successful result achieved in all. The modified Inoue balloon catheter was easy to use in retrograde nontransseptal balloon mitral valvuloplasty and showed excellent stability during inflation. Mean mitral valve area increased from 1.0 +/- 0.29 to 2.23 +/- 0.64 cm2 (P < 0.001) and mean transmitral gradient decreased from 11.4 +/- 6 to 4.3 +/- 2.1 mm Hg (P < 0.001). No major or minor complications were observed. Retrograde nontransseptal balloon mitral valvuloplasty using a modified Inoue balloon catheter is a feasible and effective technique for the treatment of symptomatic mitral stenosis. It appears to combine the advantages of avoiding transseptal catheterization with the advantages of this balloon's special configuration.

Mitral regurgitation from papillary muscle rupture: role of transesophageal echocardiography.

A case of a 61 year old male with lateral myocardial infarction, congestive heart failure and fever of days is presented. The exact etiology of this patient's heart failure was established with the application of transesophageal echocardiography. The transthoracic two-dimensional and Doppler echo showed a mobile echogenic density attached to the tip of the anterior mitral leaflet accompanied by moderate mitral regurgitation. Transesophageal echocardiography attributed this echogenic density to a ruptured head of the anterolateral papillary muscle, resulting in severe mitral regurgitation. Cardiac catheterization confirmed the severe mitral regurgitation and uncovered significant stenotic lesions of the coronary arteries. The resultant surgical treatment for the replacement of the mitral valve and coronary artery by-pass confirmed the rupture of the head of the anterolateral papillary muscle. It is suggested that transesophageal echocardiography is particularly capable of providing a definitive and prompt diagnosis of papillary muscle rupture.

Learning convergence in the cerebellar model articulation controller.

A new way to look at the learning algorithm in the cerebellar model articulation controller (CMAC) proposed by J.S. Albus (1975) is presented. A proof that the CMAC learning always converges with arbitrary accuracy on any set of training data is obtained. An alternative way to implement CMAC based on the insights obtained in the process is proposed. The scheme is tested with a computer simulation for learning the inverse dynamics of a two-link robot arm.