Human protein C concentrates in adult septic patients

Some case reports and case series suggest that protein C concentrates may improve the outcome in patients with congenital or acquired protein C deficiency (not only in those with sepsis induced purpura fulminans). We reviewed the published literature on the use of protein C concentrates in adult septic patients and found that it is limited to less than 70 patients reported in observational studies with a 70% survival, and added our personal experience (two adult patients with sepsis and contraindications to recombinant activated protein C)

Administration of protein C concentrates in patients without congenital deficit: a systematic review of the literature

Endogenous protein C levels are frequently decreased in septic patients, probably due to increased conversion to activated protein C. Protein C levels inversely correlate with morbidity and mortality of septic patients regardless of age, infecting microorganisms, presence of shock, disseminated intravascular coagulation, degree of hypercoagulation, or severity of illness. Taken together, these considerations suggest a strong correlation between protein C pathways and survival from severe sepsis/septic shock, and reinforce the rationale for the attempts to normalize plasma activity of protein C to improve survival, hamper coagulopathy, and modulate inflammation. We therefore conducted a systematic review of all manuscripts describing protein C concentrates administration in adult and pediatric populations. We identified 28 studies, for a total of 340 patients, 70 of whom died (20.6%). Septic patients were the most represented in this review of case reports and case series. In the majority of these patients sepsis was associated with meningitis, purpura fulminans or disseminated intravascular coagulation. No bleeding complications related to the study drug were reported and most studies underlined normalization of inflammatory markers and of coagulation abnormalities. We conclude that protein C concentrate is an attractive option in septic patients (especially those with meningitis, purpura fulminans, or disseminated intravascular coagulation) and that its cost-benefit ratio must be studied with a large multicenter randomized control trial, possibly including also high risk patients with septic shock and multiple organ failure

Familial breast cancer: characteristics and outcome of BRCA 1–2 positive and negative cases

BACKGROUND: The clinical and pathological characteristics and the clinical course of patients with breast cancer and BRCA 1–2 mutation are poorly known. METHODS: From 1997, patients with breast cancer and a family history of breast or ovarian cancer were offered BRCA testing. The clinical and pathological features of patients with known BRCA status were retrospectively assessed and comparisons were made between cancers arising in BRCA positive and BRCA wild type (WT) patients respectively. Type of treatment, pattern of relapse, event (local relapse, contralateral breast cancer, metastases) free and overall survival were also compared in the two groups. Out of the 210 patients tested, 125 had been treated and followed-up at our Institution and were evaluated in this study. RESULTS: BRCA positive patients tended to be more often premenopausal (79% vs 65%) and to have positive lymphnodes (63% vs 49%), poorly differentiated tumours (76% vs 40% – p = 0.002 at univariate analysis, not significant at multivariate analysis) and negative estrogen receptors (43% vs 29%). Treatment was not different in the two groups. In the 86 BRCA-WT patients, the first event was a local relapse in 3 (3%), metachronous contralateral breast cancer in 7 (8%) and distant metastases in 16 (19%). In the 39 BRCA positive patients, the corresponding figures were 3 (8%), 8 (21%) and 3 (8%). There was no difference in event free survival, with a median of 180 months in both groups of patients. At 20 years, projected survival was 85% for BRCA positive patients and 55% for BRCA-WT, but this difference was not statistically significant. CONCLUSION: Although BRCA positive patients have more frequently negative prognostic factors, their prognosis appears to be equal to or better than in patients with BRCA-WT

Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial

Background Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. Methods This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive ‘standard cancer care plus on-demand EPC’ (n = 100) or ‘standard cancer care plus systematic EPC’ (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. Findings The mean changes in TOI score and HCS score between T0 and T1 were −4.47 and −0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10–7.57) (p = 0.041), and −2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40–4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Interpretations Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis

Importance: Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, setting, and participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main outcomes and measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial registration: ClinicalTrials.gov Identifier: NCT03452839

Inherently safer choices in early design of offshore oil & gas installations: A multi-target KPI approach

As offshore oil & gas activities are currently evolving towards more productive yet complex situations, the availability of efficient safety metrics has become essential in the early stages of offshore oil & gas projects to underline potential major accidents hazards and clearly communicate safety criticalities. Inherent safety has demonstrated to be a widespread concept in offshore risk management strategies, but there are few preliminary studies in the existing literature about systemic indexing to orient the conceptual and basic design stages of the project lifecycle. In the present work, a methodology for the selection of inherently safer solutions was developed as a support tool for decision-making in early design activities of offshore oil & gas installations. The expected inherent safety performance of alternative design options is assessed by means of a comprehensive set of key performance indicators (KPIs) based on the simulation of consequences of offshore accident scenarios and credit factors of the possible loss of containment events from offshore equipment. The proposed KPIs aim to capture the hazard level of single units and to address selectively multiple targets of the potential threats than personnel and process equipment on the installation, such as marine organisms on the sea environment. Moreover, overall aggregated KPIs were introduced as a sound synthetic measure of the inherent safety performance of the offshore system. The method was applied to the assessment of alternative designs of an offshore production facility, particularly characterized by environmental and safety concerns. The results from the case study evidenced the capability of the proposed method in ranking the potential and credible critical units of each alternative configuration and identifying the relative magnitude of targets contributions to the global safety profile of the installation

Human protein C concentrate in a patient with meningitis and bleeding as a complication of treatment with recombinant activated protein C

Some case reports suggest that protein C zymogen supplementation may improve the outcome of patients with congenital or acquired protein C deficiency, such as sepsis-induced purpura fulminans. We describe the case report of a patient suffering from meningitis who developed a bleeding complication after recombinant human activated protein C administration and was successfully treated without any further bleeding complication with protein C concentrate. Protein C concentrate can be considered in adult patients with meningitis, even if at risk or in the presence of bleeding

Miniaturized cardiopulmonary bypass improves short-term outcome in cardiac surgery: A meta-analysis of randomized controlled studies

Objective: To investigate whether the use of miniaturized cardiopulmonary bypass translates into decreased morbidity and mortality in patients having cardiac surgery. Methods: We independently conducted a systematic review and meta-analysis of data pooled from existing trials listed in PubMed and conference proceedings. Sixteen studies were identified, including 1619 patients having cardiac surgery. Inclusion criteria were random allocation to treatment and comparison of a miniaturized cardiopulmonary bypass system versus conventional cardiac surgery. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The end points were the rate of neurologic and myocardial damage and the number of patients transfused. Results: Miniaturized cardiopulmonary bypass was associated with significant reductions of neurologic damage (4/548 [0.7%] vs 19/555 [3.4%], odds ratio = 0.30 [0.12-0.73], P = .008), reduction in peak cardiac troponin (weighted mean difference = -0.15 ng/dL [-0.18, -0.11], P < .001), and in the number of transfused patients (55/552 [9.9%] vs 101/563 [17.9%], odds ratio = 0.42 [0.28-0.63], P < .001). No difference in mortality was noted (8/758 [1.0%] vs 14/771 [1.8%], odds ratio = 0.60 [0.26-1.39]). Conclusions: Miniaturized cardiopulmonary bypass has beneficial effects resulting in decreased transfusion rate and cardiac and neurologic damage. © 2010 The American Association for Thoracic Surgery