PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study.

BACKGROUND: Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. METHODS: Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman's coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality. RESULTS: Median plasma PCSK9 levels were 278 [182-452] ng mL-1 on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles. CONCLUSION: In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.

Enhanced recovery pathways in colorectal surgery: a consensus paper by the Associazione Chirurghi Ospedalieri Italiani (ACOI) and the PeriOperative Italian Society (POIS).

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

Kaposi' s sarcoma in HIV-positive patients: the state of art in the HAART-era.

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunodeficiency, i.e. coinfection with Human Immonodeficiency Virus (HIV) or transplantation. The incidence of KS has dramatically decreased in both US and Europe in the Highly Active Antiretroviral Therapy (HAART) era. However, KS remains the second most frequent tumor in HIV-infected patients worldwide and it has become the most common cancer in Sub-Saharan Africa. In 1994, Yuan Chang et al discovered a novel γ-herpesvirus in biopsy specimens of human KS. Epidemiologic studies showed that KS-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) was the etiological agent associated with all subtypes of KS. KS has a variable clinical course ranging from very indolent forms to a rapidly progressive disease. HAART represents the first treatment step for slowly progressive disease. Chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease. The current understanding of KS as a convergence of immune evasion, oncogenesis, inflammation and angiogenesis has prompted investigators to develop target therapy, based on anti-angiogenic agents as well as metalloproteinase and cytokine signaling pathway inhibitors. These drugs may represent effective strategies for patients with AIDS-associated KS, which progress despite chemotherapy and/or HAART. In this review, we focus on the current state of knowledge on KSHV epidemiology, pathogenesis and therapeutic options.

End-of-life care is still a challenge for Italy.

The aim of this paper was to review current end of life (EOL) practice in Italy. The authors have made an appraisal of the existing literature in order to understand current end of life care practice in Italy. This manuscript focuses on analyzing the dying process, the transoceanic similarities and differences in the end of life decision-making practice, and the family involvement. The authors acknowledge the importance of the recent Englaro court case verdict on current practice in Italy. Dying has changed as a process over the last century in term of causes of death, costs, communication of the prognosis, and needs of the patient's family. Regardless of national and international guidelines, there is no agreement among Italian doctors regarding the gold standards of daily clinical practice at the EOL.

Effectiveness and efficiency of intensive care medicine: variable costs in different diagnosis groups.

BACKGROUND: To establish the effectiveness of ICU treatment and the efficiency in the use of resources in patients stratified according to 10 diagnosis and two levels-of-care. To propose strategies aimed at reducing costs and improving efficiency in each patient group. METHODS: Multicentre prospective observational study. ICUs enrolled two cohorts of up to 10 consecutive patients with ICU stay >/= 48 h. Each with one of these diagnoses: trauma, brain-trauma, brain-hemorrhage, stroke, acute-on-chronic-obstructive-pulmonary disease, lung-injury/acute respiratory distress syndrome, heart failure, and scheduled/unscheduled abdominal surgery. The presence of active-life support divides high from low level-of-care treatments. Variable ICU costs were collected daily (bottom-up) for 21 days. We evaluated effectiveness (hospital survival) and efficiency (hospital-survivors variable-cost as a ratio of overall cost). RESULTS: Forty-two Italian general ICUs recruited 529 patients in 5 months. Mean ICU variable-costs significantly differed with diagnosis and level-of-care. Costs were positively affected by ICU length-of-stay, by duration of active-treatment. Outcome variably influenced costs. Medians of variable-costs per patient (1715 Euro) and patient-groups efficiencies (60.7%) identified four possible combinations between (low and high) cost and (low and high) efficiency groups. Moreover, efficiency was better than effectiveness in stroke, brain-hemorrhage and trauma, while it was worse in heart failure, acute-on-COPD or acute-lung injury. Overall ICU cost attributed only to survivors ranged from 699 (scheduled surgical) to 5906 (unscheduled surgical) Euro. Cost of non-survivors distributed to all patient was between 95 (scheduled-surgical) to 1633 (unscheduled-surgical) Euro. CONCLUSIONS: Analysis of variable patient-specific cost was used as a tool to assess intensive care performance in patient subgroups with different diagnosis and levels-of-care.

Nutrition given to critically ill patients during high level/complex care (on Italian ICUs).

BACKGROUND & AIMS: Within a prospective study on costs in 45 Italian intensive units we reviewed nutrition support practice given during critical illness. METHODS: From June to October 1999, patients with an ICU stay longer than 47 h were studied. Nutrition (i.e. fasting, parenteral, enteral and mixed) and calorie supply by the enteral route were monitored during the first consecutive days (up to seven) of invasive support of organ failure (high-care). RESULTS: 388 patients received high-care for at least 1 day, 200 patients had seven consecutive high-care-days. Some form of nutrition was given in 90.7% of patients, 9.3% were never fed (25.8% of the cardiac patients). Parenteral nutrition was given in 13.9% of patients (78.9% of the abdominal surgery patients), 39.7% received only enteral nutrition, and 36.4% received mixed nutrition. Finally, 77.1% of the patients received nutrient by gut. Nutrition was given in 78.5% of 2115 collected days, 44.1% of the first high-care-days and 93.5% of the 7th days were positive for nutrition. Enteral calorie load on the first day was similar for enteral and mixed nutrition (range 8-14 kcal/kg), it was higher for exclusive enteral nutrition between the 4th and the 7th day (15-19 vs. 11-14 kcal/kg). It differed according to diagnosis group. CONCLUSIONS: In Italian ICUs, in complex critically ill patients, nutrition is consistently given in critical illness, gut is widely used except in abdominal surgery patients.

Description of trends in the course of illness of critically ill patients. Markers of intensive care organization and performance.

OBJECTIVE: To identify objective trends of the course of illness that might be used as benchmarks in the auditing of the organization/performance of Intensive Care Units (ICU). DESIGN: Retrospective analysis. PATIENTS AND SETTING: A group of 12,615 patients and 55,464 patient-days prospectively collected in 89 ICUs of 12 European countries. METHODS: The complexity of daily care in the ICU was classified as high (HT) or low (LT), according to six activities registered in NEMS,a daily therapeutic index for ICUs. RESULTS: Six trends of clinical course were identified: LT during the whole ICU stay (5,424 patients, mortality 1.8%); HT (3,480 patients, mortality 30.4%); HT followed by LT (2,781 patients, mortality 2.8%); LT followed by HT (197 patients, mortality 39.1%); finally, LT/HT/LT in 298 patients (mortality 10.5%); and HT/LT/HT (mortality 20.1%) in 438 patients. A group of 930 patients had the complexity of treatment increased (mortality 21.1%) and 3,711 patients received both treatments. Low-care before high-care periods had a mean duration of 2.2 +/- 3.5 days, low-care after high-care 2.7 +/- 3.1 days, and between two high-care periods 2.1 +/- 2.2 days. A group of 1,538 'surgical scheduled' patients only received LT, whereas 2,231 received HT (whether or not exclusively). Overall ICU mortality rate was low (3%) and the length of stay short, regardless of diagnosis and complexity of care received. CONCLUSIONS: The use of therapeutic indexes help to classify the daily complexity of ICU care. The classification can be used as an indicator of clinical performance and resource utilization.

Daily classification of the level of care. A method to describe clinical course of illness, use of resources and quality of intensive care assistance.

OBJECTIVE: To develop a simple and comparable clinical method able to distinguish between higher and lower complexities of care in the ICU. DESIGN: Retrospective analysis. SETTING: Database of European ICUs Study I (Euricus-I: including 12,615 patients and 55,464 patient/days), prospectively collected in 89 ICUs of 12 European countries. METHODS AND RESULTS: A panel of experts developed the classification of the complexity of care. Six (in addition to monitoring, two levels of respiratory support--R and r--two levels of circulatory support--C and c--and dialysis) out of the nine items of Nine Equivalents of Nursing Manpower use Score (NEMS), a therapeutic index, were utilised. Two levels of care (LOCs) were defined according to a more (HT) and a less complex (LT) combination of common activities of care. The two LOCs were significantly related to mortality: higher in HT and they rose with increasing cumulative number of HT days. HT accounted for 31,976 NEMS days (57.7%) while 23,488 (42.3 %) were LT. Major respiratory and cardiovascular support accounted for about 80 % of the HT days. Respiratory assistance and monitoring were responsible for an equivalent percentage of LT days. The distribution of the clinical classification of LOCs coincided with that of the managerial scores of LOCs in the literature. CONCLUSIONS: The managerial instrument described uses simple and reliable clinical data. It is able to distinguish between patients with different severity and outcome, and shows that every additional consecutive day spent in ICU as HT increases the probability of death. Moreover, (1) it suggests the possibility of describing the clinical course of illness by relating the complexity/level of medical care to the available technology and staff; (2) using relevant markers of clinical activity, it might be useful to include in quality control programmes.

[Pharmacologic treatment of migraine. Critical review of the literature]. / Il trattamento farmacologico dell'emicrania. Revisione critica della letteratura.

The current aim of migraine treatment is to control attacks and reduce their frequency and intensity. Numerous drugs have been experimented in the pharmacological treatment of migraine, often with positive results. Almost always, only the main action mechanism can be hypothesised and sometimes drugs seem to act with very different mechanisms. Here mention is made of the principles, symptomatic and preventive, on which the pharmacological treatment of migraine is based. The drugs used in the two types of treatment are examined in terms of their action mechanism and their pharmacological group. Particular attention is paid to indications, contraindications and limitations of each treatment and the results reported in the literature are reviewed. For optimal treatment, prevention is considered indispensable for controlling symptomatology and preventing the pain becoming chronic. Correct preventive action also serves to avoid constant resort to symptomatic drugs, particularly analgesics, for which the risk of developing dependence or headache upon suspension of treatment is described.