Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial.

BACKGROUND: The long pentraxin PTX3 is a key component of the humoral arm of innate immunity related to sepsis severity and mortality. We evaluated the clinical and prognostic significance of circulating PTX3 in the largest cohort ever reported of patients with severe sepsis or septic shock. MATERIALS AND METHODS: Plasma PTX3 was measured on days 1, 2 and 7 after randomization of 958 patients to albumin or crystalloids for fluid resuscitation in the multicentre Albumin Italian Outcome Sepsis (ALBIOS) trial. We tested the association of PTX3 and its changes over time with clinical severity, prevalent and incident organ dysfunctions, 90-day mortality and treatment. RESULTS: PTX3 was high at baseline (72 [33-186] ng/mL) and rose with the severity and number of organ dysfunctions (P < 0·001) and the incidence of subsequent new failures. The PTX3 concentration dropped from day 1 to 7, but this decrease was less pronounced in patients with septic shock (P = 0·0004). Higher concentrations of PTX3 on day 1 predicted incident organ dysfunctions. Albumin supplementation was associated with lower levels of PTX3 in patients with septic shock (P = 0·005) but not in those without shock. In a fully adjusted multivariable model, PTX3 on day 7 predicted 90-day mortality. Smaller drops in PTX3 predicted higher 90-day mortality. CONCLUSIONS: In severe sepsis and septic shock, early high PTX3 predict subsequent new organ failures, while a smaller drop in circulating PTX3 over time predicts an increased risk of death. Patients with septic shock show lower levels of PTX3 when assigned to albumin than to crystalloids.

[Primary percutaneous coronary intervention and therapeutic hypothermia in comatose survivors after out-of-hospital cardiac arrest complicating acute myocardial infarction: a single-center experience]. / Angioplastica primaria ed ipotermia terapeutica in pazienti comatosi con infarto miocardico acuto sopravvissuti ad arresto cardiaco extraospedaliero: esperienza di un singolo centro.

BACKGROUND: Therapeutic hypothermia (TH) is associated with improved neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). There are currently limited data on the outcomes of patients presenting with resuscitated OHCA in the setting of acute myocardial infarction. The aim of this study was to assess the outcomes of comatose survivors of OHCA complicating acute myocardial infarction treated with primary percutaneous coronary intervention (PCI) and TH. METHODS: A retrospective cohort analysis was performed on all consecutive patients referred for primary PCI and TH between August 2008 and December 2013 in a single center. The primary endpoint was survival to hospital discharge with sufficient neurologic recovery (defined as Cerebral Performance Category score <2). RESULTS: Among 886 consecutive patients referred for primary PCI, 24 were comatose survivors of OHCA complicating acute myocardial infarction. All these patients underwent primary PCI followed by TH. Median patient age was 59 (IQR 35-87) years and 11 (45.8%) patients had anterior ST-elevation myocardial infarction. Median OHCA-to-balloon time was 120 min (IQR 75-340) while median OHCA-to-TH initiation time was 250 min (IQR 180-310). Survival with sufficient neurologic recovery to enable discharge home was reached in 16 (66.7%) patients. Time between initiation of cardiopulmonary resuscitation (CPR) to return of spontaneous circulation (ROSC) <20 min was associated with a lower occurrence of death and poor neurologic outcome compared to CPR-to-ROSC time ≥20 min (15.4 vs 54.5%, p=0.05). The occurrence of major bleeding was 8.3%, while no stent thrombosis was reported. CONCLUSIONS: TH in conjunction with primary PCI is feasible and associated with acceptable outcome in the majority of comatose survivors of OHCA complicating acute myocardial infarction, especially if CPR-to-ROSC time was <20 min. Randomized studies are needed to better assess the superiority of TH and primary PCI vs primary PCI alone in this complex subset of OHCA patients.

Rhodococcus equi infection in non-HIV-infected patients. Two case reports and review.

OBJECTIVE: To review two recent cases in HIV-negative subjects in the light of literature reports (52 patients without HIV infection till 1994). METHODS: Epidemiology (animal contacts, risk factors, year, country), clinical presentation, diagnostic methods (X-ray, tomography, microbiological techniques), therapeutic approach (antibiotics, surgery) and outcome were evaluated on the basis of clinical literature reports. RESULTS: Tumors constituted an important predisposing factor and less frequently hepatobiliary pathology, rheumatologic diseases, iatrogenic causes, psychiatric pathology and trauma. Exposure to animals was reported by 55% of the patients. Pneumonia and pleurisy, without preferential localization, were detected in 50% of the patients. Etiologic diagnosis was usually obtained after an invasive collection. Combined medical therapy and surgery were required by 27.8% of the patients, and 16.7% of the patients died. CONCLUSIONS: In recent years the number of Rhodococcus equi cases has been rising also in HIV-negative patients. The infection is ubiquitous. Accurate diagnosis and the prompt selection of the most appropriate therapy depend on close cooperation between clinicians and microbiologists.

Age-related heart rate response to exercise in heart transplant recipients. Functional significance.

The heart rate (HR) and O(2) uptake (VO(2)) responses to cycle ergometer exercise and the role of O(2) transport in limiting submaximal and maximal aerobic performance were assessed in 33 heart transplant recipients (HTR) [14 children (P-HTR), 11 young adults (YA-HTR) and 8 middle-age adults (A-HTR)] and in 28 age-matched control subjects (CTL). In 7 P-HTR ("responders") the HR response to the onset of exercise (on-response) was as fast as that of CTL, whereas in all other patients ("non-responders") the HR on-response was typical of the denervated heart. Compared with non-responder P-HTR, responder P-HTR were also characterized by a normal peak HR (177+/- 16 vs. 151+/- 25 beats/min), an equally slow time constant for the VO(2) on-response (tau: 54 +/- 11 vs. 62+/- 13 s) and a similar low (approximately 60% of that of CTL) peak VO(2) (28 +/- 7 vs. 26 +/- 10 ml/kg per min). On the other hand non-responder YA-HTR and A-HTR were characterized by a relatively low peak HR (151 +/- 21 and 144 +/- 29 beats/min, respectively), a slow tau for the on-response (63 +/- 12 and 70 +/- 11 s) and a low peak (28 +/- 7 and 19 +/- 6 ml/kg per min). In conclusion, a sizeable number of paediatric patients (responder P-HTR) may reacquire the normal HR response to exercise, both in terms of kinetics and maximal level. Despite the almost complete recovery of cardiovascular function, and, probably, oxygen delivery, both the kinetics of the VO(2) on-response and the maximal aerobic power of the responder P-HTR were similar to those of non-responder P-HTR. The latter finding is probably attributable to peripheral limitations, due to inborn and/or pharmacological muscle deterioration.

The heart rate response to exercise and circulating catecholamines in heart transplant recipients.

The plasma concentration of noradrenaline ([NA]) is higher than that of adrenaline ([A]) both in normal subjects and in heart transplant recipients (HTR). Since in both groups the myocardial density of beta1-adrenergenic receptors is much greater than that of beta2-adrenergenic receptors, the chronotropic response of a denervated heart to changes in plasma [NA] and [A] in the absence of reinnervation should be similar to that of agonist stimulation of beta1-receptors. To test this hypothesis, 17 HTR and 9 healthy subjects (CTL) performed incremental exercise on a cycle ergometer to voluntary exhaustion. Heart rate (HR) was recorded by electrocardiography. [NA] and [A] were measured by high-pressure liquid chromatography at rest and at increasing workloads (w). In both groups, HR and [NA+A] increased with w, and HR with [NA+A]. Normalized HR values, plotted against the logarithm of [NA+A], fitted significantly logistic curves. The affinity constants were different, i.e. 2599+/-350 and 487+/-37 ng.l(-1), for HTR and CTL, respectively. The chronotropic effect of changes in [NA+A] in HTR was similar to that of combined beta1- and beta2-adrenergic activation evoked by applying isoprenaline to isolated heart myocytes (Brodde OE, Pharmacol Ther 60:405-430, 1993). These findings suggest that over time sympathetic reinnervation and the modulation of beta-receptors may take place in HTR, ruling out the hypothesis of persistent heart denervation.