A dynamic Bayesian network model for predicting organ failure associations without predefining outcomes

Critical care medicine has been a field for Bayesian networks (BNs) application for investigating relationships among failing organs. Criticisms have been raised on using mortality as the only outcome to determine the treatment efficacy. We aimed to develop a dynamic BN model for detecting interrelationships among failing organs and their progression, not predefining outcomes and omitting hierarchization of organ interactions. We collected data from 850 critically ill patients from the national database used in many intensive care units. We considered as nodes the organ failure assessed by a score as recorded daily. We tested several possible DBNs and used the best bootstrapping results for calculating the strength of arcs and directions. The network structure was learned using a hill climbing method. The parameters of the local distributions were fitted with a maximum of the likelihood algorithm. The network that best satisfied the accuracy requirements included 15 nodes, corresponding to 5 variables measured at three times: ICU admission, second and seventh day of ICU stay. From our findings some organ associations had probabilities higher than 50% to arise at ICU admittance or in the following days persisting over time. Our study provided a network model predicting organ failure associations and their evolution over time. This approach has the potential advantage of detecting and comparing the effects of treatments on organ function

Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics. study protocol for a randomized controlled trial

Background: Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB. Methods/Design: The MagicBullet clinical trial is an investigator-driven clinical study, funded by the Seventh Framework Program of the European Commission. This is designed as a phase IV, randomized, controlled, open label, non-inferiority and international trial to assess the safety and efficacy of colistin versus meropenem in late onset VAP. The study is conducted in a total of 32 centers in three European countries (Spain, Italy and Greece) with specific high incidences of infections caused by MDR-GNB. Patients older than 18 years who develop VAP with both clinical and radiological signs, and are on mechanical ventilation for more than 96 hours, or less than 96 hours but with previous antibiotic treatment plus one week of hospitalization, are candidates for inclusion in the study. A total sample size of 496 patients will be randomized according to a severity clinical score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5 MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or meropenem 2 g every eight hours (control arm), both combined with levofloxacin. Mortality from any cause at 28 days will be considered as the main outcome. Clinical and microbiological cure will be evaluated at 72 hours, eight days, the finalization of antibiotic treatment, and 28 days of follow-up. The efficacy evaluation will be performed in every patient who receives at least one study treatment drug, and with etiologic diagnosis of VAP, intention-to-treat population and per protocol analysis will be performed

Microcirculatory changes and skeletal muscle oxygenation measured at rest by non-infrared spectroscopy in patients with and without diabetes undergoing haemodialysis

Introduction: Haemodialysis has direct and indirect effects on skin and muscle microcirculatory regulation that are severe enough to worsen tolerance to physical exercise and muscle asthenia in patients undergoing dialysis, thus compromising patients' quality of life and increasing the risk of mortality. In diabetes these circumstances are further complicated, leading to an approximately sixfold increase in the incidence of critical limb ischaemia and amputation. Our aim in this study was to investigate in vivo whether haemodialysis induces major changes in skeletal muscle oxygenation and blood flow, microvascular compliance and tissue metabolic rate in patients with and without diabetes. Methods: The study included 20 consecutive patients with and without diabetes undergoing haemodialysis at Sant Andrea University Hospital, Rome from March to April 2007. Near-infrared spectroscopy (NIRS) quantitative measurements of tissue haemoglobin concentrations in oxygenated [HbO(2)] and deoxygenated forms [HHb] were obtained in the calf once hourly for 4 hours during dialysis. Consecutive venous occlusions allowed one to obtain muscular blood flow (mBF), microvascular compliance and muscle oxygen consumption (mVO(2)). The tissue oxygen saturation (StO(2)) and content (CtO(2)) as well as the microvascular bed volume were derived from the haemoglobin concentration. Nonparametric tests were used to compare data within each group and among the groups and with a group of 22 matched healthy controls. Results: The total haemoglobin concentration and [HHb] increased significantly during dialysis in patients without and with diabetes. Only in patients with diabetes, dialysis involved a [HbO(2)], CtO(2) and mVO(2) increase but left StO(2) unchanged. Multiple regression analysis disclosed a significant direct correlation of StO(2) with HbO(2) and an inverse correlation with mVO(2). Dialysis increased mBF only in diabetic patients. Microvascular compliance decreased rapidly and significantly during the first hour of dialysis in both groups. Conclusions: Our NIRS findings suggest that haemodialysis in subjects at rest brings about major changes in skeletal muscle oxygenation, blood flow, microvascular compliance and tissue metabolic rate. These changes differ in patients with and without diabetes. In all patients haemodialysis induces changes in tissue haemoglobin concentrations and microvascular compliance, whereas in patients with diabetes it alters tissue blood flow, tissue oxygenation (CtO(2), [HbO(2)]) and the metabolic rate (mVO(2)). In these patients the mVO(2) is correlated to the blood supply. The effects of haemodialysis on cell damage remain to be clarified. The absence of StO(2) changes is probably linked to an opposite [HbO(2)] and mVO(2) pattern

Hypertension and Arrhythmias: A Clinical Overview of the Pathophysiology-Driven Management of Cardiac Arrhythmias in Hypertensive Patients

Because of demographic aging, the prevalence of arterial hypertension (HTN) and cardiac arrhythmias, namely atrial fibrillation (AF), is progressively increasing. Not only are these clinical entities strongly connected, but, acting with a synergistic effect, their association may cause a worse clinical outcome in patients already at risk of ischemic and/or haemorrhagic stroke and, consequently, disability and death. Despite the well-known association between HTN and AF, several pathogenetic mechanisms underlying the higher risk of AF in hypertensive patients are still incompletely known. Although several trials reported the overall clinical benefit of renin-angiotensin-aldosterone inhibitors in reducing incident AF in HTN, the role of this class of drugs is greatly reduced when AF diagnosis is already established, thus hinting at the urgent need for primary prevention measures to reduce AF occurrence in these patients. Through a thorough review of the available literature in the field, we investigated the basic mechanisms through which HTN is believed to promote AF, summarising the evidence supporting a pathophysiology-driven approach to prevent this arrhythmia in hypertensive patients, including those suffering from primary aldosteronism, a non-negligible and under-recognised cause of secondary HTN. Finally, in the hazy scenario of AF screening in hypertensive patients, we reviewed which patients should be screened, by which modality, and who should be offered oral anticoagulation for stroke prevention

The prognostic importance of chronic end-stage diseases in geriatric patients admitted to 163 Italian ICUs

BACKGROUND: The number of elderly patients undergoing major surgical interventions and then needing admission to intensive care unit (ICU) grows steadily. We investigated this issue in a cohort of 232,278 patients admitted in five years (2011-2015) to 163 Italian general ICUs. METHODS: Surgical patients older than 75 registered in the GiViTI MargheritaPROSAFE project were analyzed. The impact on hospital mortality of important chronic conditions (severe COPD, NYHA class IV, dementia, end-stage renal disease, cirrhosis with portal hypertension) was investigated with two prognostic models developed yearly on patients staying in the ICU less or more than 24 hours. RESULTS: 44,551 elderly patients (19.2%) underwent emergency (47.3%) or elective surgery (52.7%). At least one severe comorbidity was present in 14.6% of them, yielding a higher hospital mortality (32.4%, vs. 21.1% without severe comorbidity). In the models for patients staying in the ICU 24 hours or more, cirrhosis, NYHA class IV, and severe COPD were constant independent predictors of death (adjusted odds ratios [ORs] range 1.67-1.97, 1.54-1.91, and 1.34-1.50, respectively), while dementia was statistically significant in four out of five models (adjusted ORs 1.23-1.28). End-stage renal disease, instead, never resulted to be an independent prognostic factor. For patients staying in the ICU less than 24 hours, chronic comorbidities were only occasionally independent predictors of death. CONCLUSIONS: Our study confirms that elderly surgical patients represent a relevant part of all ICUs admissions. About one of seven bear at least one severe chronic comorbidity, that, excluding end-stage renal disease, are all strong independent predictors of hospital death

Successful treatment of cerebral arterial gas embolism following uneventful TBNA

Fibrobronchoscopy is commonly considered a safe procedure with a low major complication rate not including cerebral arterial gas embolism (CAGE) a severe life threatening iatrogenic complication. Several cases of transbronchial needle aspiration (TBNA) has been related with CAGE when patient happens to have the high airway pressure that exceeds the pressure of the pulmonary veins allowing the air to enter the systemic circulation through the left heart. HBOT is the only effective treatment available for CAGE that provides 100% oxygen at high pressure, which accelerates nitrogen reabsorption and improves oxygenation of ischemic tissue. We reported a case of successful treatment with full recovery after early Hyperbaric Oxygen therapy of CAGE induced by an uneventful transbronchial biopsy during fibrobronchoscopy

Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion: a double-blind, randomized, active-controlled trial

Abstract Background Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent μ-opioid agonist, reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia. Methods Sixty-four patients, undergoing remifentanil infusion during general anaesthesia and major lung surgery, were randomly assigned to receive either buprenorphine i.v. infusion (25 μg h −1 for 24 h) or morphine (equianalgesic dose) perioperatively. The presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative pain scores, opioid consumption and postoperative neuropathic pain assessed one and three months postoperatively. Results A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the buprenorphine-treated group than in the morphine-treated group: 18 vs 9 min ( P =0.002). At 30 min postoperatively, patients receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine ( P =0.009). At three months, no differences between groups were noted. Conclusions Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical incision but shows no long-term efficacy at three months follow-up

Long-Term Survival in Patients with Post-Operative Atrial Fibrillation after Cardiac Surgery: Analysis from a Prospective Cohort Study

9noopenBackground: Post-operative (POP) atrial fibrillation (AF) is frequent in patients who undergo cardiac surgery. However, its prognostic impact in the long term remains unclear. Methods: We followed 1386 patients who underwent cardiac surgery for an average of 10 ± 3 years. According to clinical history of AF before and after surgery, four subgroups were identified: (1) patients with no history of AF and without episodes of AF during the first 30 days after surgery (control or Group 1, n = 726), (2) patients with no history of AF before surgery in whom new-onset POP AF was detected during the first 30 days after surgery (new-onset POP AF or Group 2, n = 452), (3) patients with a history of paroxysmal/persistent AF before cardiac surgery (Group 3, n = 125, including 87 POP AF patients and 38 who did not develop POP AF), and (4) patients with permanent AF at the time of cardiac surgery (Group 4, n = 83). All-cause mortality was the primary outcome of the study. We tested the associations of potential determinants with all-cause mortality using univariable and multivariable statistical analyses. Results: Overall, 473 patients (34%) died during follow-up. After adjustment for multiple confounders, new-onset POP AF (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 0.90-1.89; p = 0.1609), history of paroxysmal/persistent AF before cardiac surgery (HR = 1.33, 95% CI: 0.71-2.49; p = 0.3736), and permanent AF (Group 4) (HR = 1.55, 95% CI 0.82-2.95; p = 0.1803) were not associated with a significantly increased risk of mortality when compared with Group 1 (patients with no history of AF and without episodes of AF during the first 30 days after surgery). In new-onset POP AF patients, oral anticoagulation was not associated with mortality (HR = 1.13, 95% CI: 0.83-1.54; p = 0.4299). Conclusions: In this cohort of patients who underwent different types of heart surgery, POP AF was not associated with an increased risk of mortality. In this setting, the role of long-term anticoagulation remains unclear.openMarazzato, Jacopo; Masnaghetti, Sergio; De Ponti, Roberto; Verdecchia, Paolo; Blasi, Federico; Ferrarese, Sandro; Trapasso, Monica; Spanevello, Antonio; Angeli, FabioMarazzato, Jacopo; Masnaghetti, Sergio; De Ponti, Roberto; Verdecchia, Paolo; Blasi, Federico; Ferrarese, Sandro; Trapasso, Monica; Spanevello, Antonio; Angeli, Fabi

Comparison between laser-induced nucleation of ZnS and CdS nanocrystals directly into polymer matrices

The nucleation of two kinds of crystalline nanoparticles, zinc sulfide (ZnS), and cadmium sulfide (CdS), is achieved directly into specific sites of polymer matrices after their irradiation with UV laser pulses. The starting samples consist of polymers doped with precursors of Zn or Cd thiolate that are proved to decompose after the absorption of UV light, resulting into the nanoparticles formation. The growth of the crystalline nanostructures is followed throughout the irradiation of the samples with successive incident pulses, by different methods, such as transmission electron microscopy, atomic force microscopy, confocal microscopy, and X-ray diffraction. Special attention is paid to the difference of the formation pathways of the two kinds of nanoparticles studied, because the Cd thiolate precursor exhibits much higher absorption efficiency than the Zn thiolate one, at the applied UV wavelength. Indeed, CdS nanoparticles become evident after the very first incident UV pulses, whereas the formation of ZnS nanocrystals requires rather prolonged irradiation, always through a macroscopically nondestructive procedure for the polymer matrix. POLYM. COMPOS., 2010. © 2009 Society of Plastics Engineer