Daily bathing with 4% chlorhexidine gluconate in intensive care settings: a randomized controlled trial.

OBJECTIVES: To investigate whether daily bathing with a soap-like solution of 4% chlorhexidine (CHG) followed by water rinsing (CHGwr) would decrease the incidence of hospital-acquired infections (HAI) in intensive care settings. METHODS: Randomized, controlled trial; infectious diseases specialists were blinded to the intervention status. All patients admitted to the Intensive Care Unit (ICU) and to the Post-operative Cardiosurgical Intensive Care Unit (PC-ICU) of the University Hospital of Perugia were enrolled and randomized to the intervention arm (daily bathing with 4% CHGwr) or to the control arm (daily bathing with standard soap). The incidence rate of acquisition of HAI was compared between the two arms as primary outcome. We also evaluated the incidence of bloodstream infections (BSI), central-line-associated BSI (CLABSI), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTI), and 4% CHGwr safety. RESULTS: In all, 449 individuals were enrolled, 226 in treatment arm and 223 in control arm. Thirty-four individuals of the 226 (15%) and 57 (25.6%) suffered from at least an HAI in the intervention and control arms, respectively (p 0.008); 23.2 and 40.9 infections/1000 patient-days were detected in the intervention arm and control arm, respectively (p 0.037). The incidence of all bloodstream infections (BSI plus CABSI) was significantly reduced in the intervention arm (9.2 versus 22.6 infections/1000 patient-days, p 0.027); no differences were observed in the mortality between the two arms. CONCLUSIONS: Daily bathing with 4% CHGwr significantly reduced HAI incidence in intensive care settings. CLINICALTRIAL. GOV REGISTRATION: NCT03639363.

The incidence of cardiovascular events is largely reduced in patients with maximally tolerated drug therapy and lipoprotein apheresis. A single-center experience.

AIM: Lipoprotein apheresis (LA) is the elective therapy for homozygous and other forms of familial hypercholesterolemia (FH) and familial combined hypercholesterolemia (FCH), resistant/intolerant to lipid lowering drugs, and hyperlipoproteinemia(a) for which drugs are not available. To assess the effect of LA on the incidence of adverse cardiac or vascular events (ACVE) at the time period of pre-initiation of apheresis and during the LA treatment. METHODS: We collected data of 30 patients (mean age 62 ± 8 years, males 73%), with FH, or FCH and cardiovascular disease on maximally tolerated lipid lowering therapy and LA treatment (median 5 years, interquartile range 3-8 years). Associated hyperlipoproteinemia(a) was present in 16/30 subjects. The LA treatment was performed biweekly as clinically indicated by dextran-sulfate or heparin-induced LDL precipitation apheresis. The ACVE incidence, before and after treatment, was evaluated by statistical analyses. RESULTS: The ACVE incidence occurred before and after the LA treatment inception, were 86 and 15 events respectively. Notably, 6/15 of ACVE were secondary to stent restenosis and 7/15 follow-up events occurred during the first 5 years. The AVCE rates/year were 0.58 and 0.13 respectively (p < 0.001). CONCLUSIONS: Our data confirm long-term efficacy and positive impact of LA on morbidity in patients with FH and FCH and atherosclerotic disease at maximally tolerated lipid lowering therapy.

KPC-producing Klebsiella pneumoniae rectal colonization is a risk factor for mortality in patients with diabetic foot infections.

To evaluate the relationship between carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) gut colonization and mortality in diabetic patients with a foot infection (DFI) we performed a single-centre, retrospective, matched case-control study. In the study period, we identified 21 patients with DFI who had KPC-Kp gut colonization and 21 controls. The 90-day mortality rate was significantly higher in patients with colonized guts (47%) than the controls (4%) (p 0.013). A multivariate analysis demonstrated that gut colonization with KPC-Kp was the only independent predictor of mortality: odds ratio 13.33, 95% CI 1.90-272.80, p 0.024. In patients with DFI, KPC-Kp gut colonization appears to be an important risk factor for mortality.

Serotonergic antidepressant drugs and L-dopa-induced dyskinesias in Parkinson's disease.

BACKGROUND: Serotonergic system is believed to play a role in levodopa-induced-dyskinesias pathogenesis, and serotonin transporter has been evaluated as potential target. AIM OF THE STUDY: To retrospectively investigate the potential effect of selective serotonin reuptake inhibitors (SSRIs) during dopaminergic treatment, in the development of dyskinesias in patients with Parkinson's disease (PD). METHODS: One hundred and thirty-five consecutive patients with PD, with 10-year follow-up since diagnosis. Age at PD onset, duration of levodopa treatment, maximum daily dose, and SSRIs exposure were collected. Risk, latency, and severity of dyskinesias were evaluated comparing patients with and without SSRIs exposure. RESULTS: Forty-nine patients received SSRIs for a variable period, 86 were never treated; no significant difference between the groups was observed (P = 0.897) in the prevalence of dyskinesias. Considering latency between PD diagnosis and dyskinesias onset, patients exposed to SSRIs developed dyskinesias later (6.48 ± 1.99 vs 5.70 ± 1.89 years, P = 0.020). The median dyskinesia severity score was 0 in the exposed group vs 1 in non-exposed patients (P = 0.025). Multivariate analysis demonstrated SSRIs exposure as the only independent predictor, protecting from severe dyskinesia. CONCLUSIONS: Use of SSRIs in patients with PD did not protect from dyskinesias; however, exposure may delay the onset and reduce the severity, confirming modulation of the serotonergic system as possible antidyskinetic strategy.

A prospective study to evaluate the efficacy of Cistiquer in improving lower urinary tract symptoms in females with urethral syndrome.

AIM: The aim of the study was to compare Cistiquer, a new phytotherapeutic product developed for chronic bladder inflammatory diseases, and intra-vesical administration of gentamicin plus betametasone, in females with urethral syndrome. METHODS: Between september 2013 and may 2014, 60 women with urethral syndrome and trigonitis were incuded in this study. Patients were randomly assigned to treatment with intra-vesical administration of betametasone 8 mg plus gentamicin 80 mg (group A), and oral administration of Cistiquer (group B) for 7 weeks. Before and after the therapeutic protocol, symptoms were assessed by three days voiding diary, the overactive bladder questionnaire short form and a ten points visual analogic scale adopted to assess the micturition discomfort. Histologic findings were assessed by the examination of specimens obtained by cold bladder biopsies of the bladder trigone at baseline in all the subjects. RESULTS: The two groups had significant and comparable symptoms improvement. However, the score obtained from the visual analogic scale decreased significantly only in the group submitted to oral therapy. Furthermore, in the group treated with endovesical approach, higher drop out rate and higher incidence of urinary infection were observed. CONCLUSION: Patients with urethral syndrome and trigonitis improved symptoms either with oral therapy with Cistiquer and with intra-vesical administration of gentamicin plus betametasone. However, treatment adherence resulted higher for patients treated by oral therapy and rate of adverse events resulted higher for those submitted to endovesical treatment.

Severe obstructive sleep apnoea syndrome and erectile dysfunction: a prospective randomised study to compare sildenafil vs. nasal continuous positive airway pressure.

BACKGROUND: A high incidence of erectile dysfunction (ED) among patients with obstructive sleep apnoea syndrome (OSAS) has been reported, with a strong correlation between obstructive sleep apnoea, ED, and quality of life (QOL), and it has been estimated that 10-60% of patients with OSAS suffer from ED. In this prospective randomised controlled trial, we investigated 82 men with ED consecutively who were referred to the outpatient clinic for sleep disorders and had severe OSAS (AHI> 30 events/h) without any other comorbidities as a possible cause of ED. The aim of this study was to evaluate and compare the efficacy of sildenafil vs. continuous positive airway pressure (CPAP) in men with ED and severe OSAS. METHODS: Eighty-two patients were randomised to two main treatment groups: group 1 patients (n = 41) were treated with 100-mg sildenafil 1 h before sexual intercourse without CPAP, and group 2 patients (n = 41 men) were treated with only nasal CPAP during night time sleep. Both groups were evaluated with the same questionnaires (International Index of Erectile Function-EF domain; Sex Encounter Profile; Erectile Dysfunction Inventory Treatment Satisfaction) 12 weeks after treatment. RESULTS: In patients receiving sildenafil treatment, 58.2% of those who attempted sexual intercourses were successful compared to 30.4% in the CPAP group. The mean number of successful attempts per week was significantly higher in the sildenafil group compared with the CPAP group (2.9 vs. 1.7, respectively; p < 0.0001). The mean IIEF-EF domain scores were significantly higher in the sildenafil group compared with the CPAP group (p < 0.0001). The overall satisfaction rate was 68% with sildenafil treatment and 29% with CPAP treatment. CONCLUSIONS: This study confirms that severe OSAS is strongly associated with erectile dysfunction. CPAP and sildenafil (100 mg) are safe and effective therapies for OSAS-related ED patients. In the present study sildenafil was more effective than CPAP in treating ED associated with OSAS, as indicated by a significantly higher rate of successful attempts at intercourse and higher IIEF-EF domain scores. Our study, to date, is the only that has investigated sildenafil in patients with severe OSAS.

LH, progesterone, and TSH can stimulate aldosterone in vitro: a study on normal adrenal cortex and aldosterone producing adenoma.

Endocrine factors different from ACTH or angiotensin II can stimulate aldosterone secretion and have a role in the pathophysiology of hyperaldosteronism. Aldosterone may increase in luteotropic/progestogenic and in hypothyroid states; LH and, occasionally, TSH receptors have been detected in normal adrenal cortex and aldosterone-producing adenoma. The aim of the study was to compare adrenal contents of LH and TSH receptors between normal cortex and aldosterone-producing adenoma and to evaluate the ability of LH, its product progesterone, and TSH to stimulate aldosterone secretion in vitro from primary adrenocortical cells. Surgical aldosterone-producing adenoma fragments from 19 patients and adrenal cortex fragments from 10 kidney donors were used for Western blotting and cell cultures. LH (n=26), TSH (n=19) and progesterone (n=8) receptor proteins were investigated; LH receptor-mRNA was also tested in 8 samples. Aldosterone responses in vitro to LH, progesterone, and TSH stimulation were assayed. LH and TSH receptors were more expressed in adenoma than normal cortex (p<0.01, p<0.05, respectively); progesterone receptor was observed in 6/8 samples. Aldosterone increased after in vitro stimulation with LH (5/12 adenoma, 1/7 normal cells), progesterone (4/5 adenoma, 5/6 normal cells), and TSH (3/5 adenoma and 3/5 normal cells). LH and TSH receptors were more expressed in aldosterone producing adenoma than normal adrenal cortex. LH, progesterone, and TSH can stimulate aldosterone in vitro. Similar mechanisms could participate in vivo in the aldosterone increase in lutheotropic, progestogenic, or hypothyroid states and may exist in both normal adrenal cortex and adenoma in responsive individuals.

The biological effects of diagnostic cardiac imaging.

In this paper the authors deal with the main imaging techniques available to clinical cardiologists, with a brief overview of biophysical and biological aspects which are of relevance for the assessment of health effects related to the exposure of patients to both ionizing and non ionizing radiation. A main contribute is the reviewing published evidence on biological effects of radiation, trying to compose a balanced issue in order to increase awareness and knowledge about radiation exposure from cardiac imaging and implications for health risk.

The ovarian cycle as a factor of variability in the laboratory screening for primary aldosteronism in women.

Primary aldosteronism is increasingly investigated in hypertension being associated with an elevated cardiovascular risk. Aldosterone has been reported to increase in the luteal phase in normal women but to our knowledge the influence of the ovarian cycle on the first screening for primary aldosteronism (that is, on the levels of plasma aldosterone and its relationship to PRA levels) was never investigated. We measured hormonal levels during one cycle in 26 low-renin mild hypertensive outpatients. LH, FSH, 17 beta-estradiol, progesterone, aldosterone and PRA were assayed at the seventh, fourteenth, twenty-first and twenty-eighth days of the cycle after 30 min of recumbency. Aldosterone and PRA increased from the seventh (follicular phase) to twenty-first day (luteal phase) from 11.2 to 17.8 ng 100 ml(-1) and from 0.23 to 0.35 ng ml(-1) h(-1), respectively (both P=0.004) The proportion of patients with aldosterone >15 ng 100 ml(-1) significantly increased from the follicular to the luteal phase, (8/26 vs 19/25, P=0.018); a similar increase was found for Aldosterone-PRA Ratio >30 combined with either a minimum PRA value of 0.5 ng ml(-1) h(-1) or aldosterone >15 ng 100 ml(-1) (7/26 vs 16/25 and 7/26 vs 17/25 respectively, P<0.05). Aldosterone was positively related to PRA and progesterone. Higher aldosterone levels may be frequently encountered in the second part of the ovarian cycle in low-renin hypertensive women. This variability appears to be an important factor to be taken into account in the first-step laboratory screening for primary aldosteronism and should be considered in the process of standardization of the diagnostic work-up for this disease.

microRNA(interference) networks are embedded in the gene regulatory networks.

microRNAs (miRNAs) are a class of endogenous 22-25 nt single-stranded RNA molecules that regulate gene expression post-transcriptionally. They are highly conserved among species with distinct temporal and spatial patterns of expression, each of them potentially interacting with hundreds of messenger RNAs. Since miRNAs, like transcription factors (TFs), are trans-acting factors that interact with cis-regulatory elements, they potentially generate a complex combinatorial code. Moreover, as TFs and genes containing binding sites for TFs have a high probability of being targeted by miRNAs, the basic interplay miRNA/TF renders miRNAs key components of gene regulatory networks. Several biological processes, including diseases such as cancer, have been causatively associated to disturbances of miRNAs/TF interplay both in vitro and in vivo. These aspects, cumulatively, indicate that miRNAs and transcription factors have a crucial role in determining cellular behaviour, highlighting the role of small RNA molecules in regulatory mechanisms and indicating other routes in the evolutionary path of gene expression.

Is the low tri-iodothyronine state a crucial factor in determining the outcome of coronary artery bypass patients? Evidence from a clinical pilot study.

The cardiovascular system is an important target for thyroid hormones. The present study evaluates the changes affecting thyroid hormone metabolism during and 6 days after coronary artery bypass and their relationship with the post-operative outcome of the patients. Thirty-three patients were enrolled in the study; their thyroid hormone profiles were determined at 13 sampling points during surgery and for 6 days afterwards. Serum total tri-iodothyronine (T3) and free T3 (FT3) concentrations decreased significantly after surgery (P<0.001) and they remained significantly low until the end of the study. Free thyroxine (FT4) and T4 declined significantly immediately after surgery (P<0.05 for FT4, P<0.001 for T4) but they returned to baseline values (24 h and 96 h post-surgery respectively). Serum reverse T3 increased remarkably 36 h after surgery (P<0.001) and remained significantly higher than the baseline value throughout the study. A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. Our data suggest a prolonged reduction of T4 to T3 conversion in patients undergoing cardiac surgery and indicate that the recovery period is the most critical in the evaluation of a possibly successful approach for T3 substitutive therapy.

The prognostic value of myocardial viability recognized by low dose dipyridamole echocardiography in patients with chronic ischaemic left ventricular dysfunction.

AIMS: The aim of this study was to assess the prognostic value of myocardial viability recognized as a contractile response to vasodilator stimulation in patients with left ventricular dysfunction in a large scale, prospective, multicentre, observational study. METHODS AND RESULTS: Three hundred and seven patients (mean age 60 +/- 10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction and severe left ventricular dysfunction (ejection fraction <35%; mean ejection fraction: 28 +/- 7%) were enrolled in the study. Each patient underwent low dose dipyridamole echo (0.28 mg x kg(-1) in 4 min). Myocardial viability was identified as an improvement of >0.20 in the wall motion score index. By selection, all patients were followed up for a median of 36 months. One-hundred and twenty-four were revascularized either by coronary artery bypass grafting (n=83) or coronary angioplasty (n=41). The only end-point analysed was cardiac death. In the revascularized group, cardiac death occurred in one of the 41 patients with and in 16 of the 83 patients without a viable myocardium (2.4% vs 19.3%, P<0.01). Outcome, as estimated by Kaplan-Meier survival, was better for patients with, compared to patients without, a viable myocardium, who underwent coronary revascularization (97.6 vs 77.4%, P=0.01). Using a Cox proportional hazards model, the presence of myocardial viability was shown to exert a protective effect on survival (chi-square 4.6, hazard ratio 0.1, 95% CI 0.01-0.8, P<0.03). The survival rate in medically treated patients was lower than in revascularized patients irrespective of the presence of a viable myocardium (79.7% vs 86.2, P=ns). CONCLUSION: In severe left ventricular ischaemic dysfunction, myocardial viability, as assessed by low dose dipyridamole echo, is associated with improved survival in revascularized patients.

Perioperative prognostic value of dipyridamole echocardiography in vascular surgery: A large-scale multicenter study in 509 patients. EPIC (Echo Persantine International Cooperative) Study Group.

BACKGROUND: Patients undergoing major vascular surgery are at a relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for perioperative risk stratification. The aim of the current study was to evaluate the value of dipyridamole echocardiography test (up to 0.84 mg/kg over 10 minutes) in predicting cardiac events in a large-scale, multicenter, prospective, observational study design. METHODS AND RESULTS: Five hundred nine patients (mean age 66+/-10 years) were studied before vascular surgery by dipyridamole stress echocardiography in 11 different centers. All patients underwent preoperative clinical risk assessment according to the American Heart Association guidelines. No major complications occurred during dipyridamole stress echocardiography. Technically adequate images were obtained in all patients; however, in 4 patients only the low dipyridamole dose (0.56 mg/kg over 4 minutes) was given for limiting side effects. Eighty-eight (17.3%) had a positive test. Perioperative events occurred in 31 (6.1%) patients: 6 deaths, 11 myocardial infarctions, and 14 episodes of unstable angina. Sensitivity and specificity of dipyridamole stress echocardiography for predicting spontaneous cardiac events were 81% and 87%, respectively, with a positive predictive value of 28% and negative predictive value of 99%. By multivariate analysis, the difference between wall motion score index at rest and peak stress (Deltawall motion score index), test positivity, and ST-segment depression during dipyridamole infusion were independent predictors of any perioperative cardiac event. CONCLUSIONS: Dipyridamole stress echocardiography is safe and well tolerated in patients undergoing major vascular surgery and provides an effective preoperative screening test for the risk stratification of these patients, mainly because of the extremely high negative predictive value, which is a potent predictor of complication-free procedure.

An effective algorithm for quick fractal analysis of movement biosignals.

The problem of numerically classifying patterns, of crucial importance in the biomedical field, is here faced by means of their fractal dimension. A new simple algorithm was developed to characterize biomedical mono-dimensional signals avoiding computationally expensive methods, generally required by the classical approach of the fractal theory. The algorithm produces a number related to the geometric behaviour of the pattern providing information on the studied phenomenon. The results are independent of the signal amplitude and exhibit a fractal measure ranging from 1 to 2 for monotonically going-forwards monodimensional curves, in accordance with theory. Accurate calibration and qualification were accomplished by analysing basic waveforms. Further studies concerned the biomedical field with special reference to gait analysis: so far, well controlled movements such as walking, going up and downstairs and running, have been investigated. Controlled conditions of the test environment guaranteed the necessary repeatability and the accuracy of the practical experiments in setting up the methodology. The algorithm showed good performance in classifying the considered simple movements in the selected sample of normal subjects. The results obtained encourage us to use this technique for an effective on-line movement correlation with other long-term monitored variables such as blood pressure, ECG, etc.

On the contribution of biomedical engineering and technology to the understanding and the management of arterial hypertension.

There are several reasons why arterial blood pressure, i.e. the pressure within the large arterial vessels, is out of the physical parameters of the human body, one of the most frequently measured. Firstly, arterial blood pressure is a physiologically meaningful parameter, since it represents the driving pressure generated by the heart which maintains blood perfusion in the periphery. Secondly, it is a clinically important parameter: a decline of arterial blood pressure (e.g. in shock) may represent a life-threatening emergency which requires prompt recognition and correction; elevated blood pressure (hypertension) on the other hand is a very common condition, which bears a high risk of cardiovascular mortality and morbidity and can be controlled with appropriate pharmacological means. Thirdly, but not lastly, arterial blood pressure is easily measurable with a fair degree of accuracy by the standard manual sphygmomanometric method and, more recently, by non-invasive automatic techniques. This paper discusses some of the aspects related to arterial blood pressure measurement, in which, in the author's opinion, medical engineering and technology are expected to provide useful advancements. Two major areas will be considered. The first regards the methodologies for arterial blood pressure assessment; the second the identification and acquisition of information additional to blood pressure which would be helpful for a better understanding of blood pressure measurements and/or of risk profiling. For the purpose of this brief paper, we shall mainly use examples and reasonings from our own experience.