Rationale: Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy. Objectives: To understand the relationship among central venous oxygen saturation (ScvO2), lactate, and base excess to better determine the origin of lactate. Methods: This was a post hoc analysis of baseline variables of 1,741 patients with sepsis enrolled in the multicenter trial ALBIOS (Albumin Italian Outcome Sepsis). Variables were analyzed as a function of sextiles of lactate concentration and sextiles of ScvO2. We defined the “alactic base excess,” as the sum of lactate and standard base excess. Measurements and Main Results: Organ dysfunction severity scores, physiologic variables of hepatic, metabolic, cardiac, and renal function, and 90-day mortality were measured. ScvO2 was lower than 70% only in 35% of patients. Mortality, organ dysfunction scores, and lactate were highest in the first and sixth sextiles of ScvO2. Although lactate level related strongly to mortality, it was associated with acidemia only when kidney function was impaired (creatinine >2 mg/dl), as rapidly detected by a negative alactic base excess. In contrast, positive values of alactic base excess were associated with a relative reduction of fluid balance. Conclusions: Hyperlactatemia is powerfully correlated with severity of sepsis and, in established sepsis, is caused more frequently by impaired tissue oxygen use, rather than by impaired oxygen transport. Concomitant acidemia was only observed in the presence of renal dysfunction, as rapidly detected by alactic base excess. The current strategy of fluid resuscitation could be modified according to the origin of excess lactate.

Mortality after hip fracture is a major problem in the Western world, but its mechanisms remain uncertain. This study assessed the 2-year mortality rate after hip fracture in elderly patients by including hospital factors (eg, intervention type, surgical delay), underlying health conditions, and, for a subset, lifestyle factors (eg, body mass index, smoking, alcohol). A total of 828 patients (183 men) 70 to 99 years old experiencing a hip fracture in 2009 in the province of Varese were included in the study. The risk factors for death were assessed through Kaplan-Meier analysis and Cox proportional hazards analysis. Hip fracture incidence per 1000 persons was higher in women (8.4 vs 3.7 in men) and in elderly patients (12.4 for 85–99 years vs 4.4 for 70–84 years). The mortality rate after 1, 6, 12, and 24 months was 4.7%, 16%, 20.7%, and 30.4%, respectively. For the province of Varese, sex (hazard ratio, 0.39 for women), age group (hazard ratio, 2.2 for 85–99 years), and Charlson Comorbidity Index score (hazard ratio, 2.06 for score greater than 1) were found to be statistically significant. The 2-year mortality rate in hip fractures is associated with sex, age, and comorbidities. Male sex, age older than 85 years, and Charlson Comorbidity Index score greater than 1 are associated with a higher risk. Surgical delay was significant in the Kaplan-Meier survival time analysis but not in the Cox hazard analysis, suggesting that early surgery reduces risk in patients with numerous comorbidities.

Background: Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression. Methods: Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40–80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory). Discussion: Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial. Trial registration: ClinicalTrails.gov, NCT03589014. Retrospectively registered on 17 July 2018.

Background: Higher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population. Methods: In an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m², 18.5–25.0 kg/m²; 25.0–30.0 kg/m²; 30.0 kg/m²). Primary endpoints included all-cause mortality and HF hospitalization-free survival. Results: Mean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity. Conclusions: The present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF. Graphic Categories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).

There are concerns about increased mortality in patients with metal-on-metal bearings in total hip arthroplasty (THA). To determine the mortality and the morbidity in patients with metal-on-metal articulations (MOM THA) compared to patients with non-metal-on-metal articulations (non-MOM THA) after primary total hip arthroplasty. Search of PubMed, MEDLINE, EMBASE, Web of Science, Cochrane, CINAHL, AcademicSearchPremier, ScienceDirect, Wiley and clinical trial registers through March 2015, augmented by a hand search of references from the included articles. No language restrictions were applied. Two reviewers screened and identified randomised controlled trials and observational studies of primary total hip arthroplasty comparing MOM THA with non-MOM THA. Two reviewers independently extracted study data and assessed risk of bias. Risk differences (RD) were calculated with random effect models. Meta-regression was used to explore modifying factors. Difference in mortality and difference in morbidity expressed as revisions and medical complications between patients with MOM THA and non-MOM THA. Forty-seven studies were included, comprising 4,000 THA in randomised trials and over 500,000 THA in observational studies. For mortality, random effects analysis revealed a higher pooled RD of 0.7%, 95%, confidence interval (CI) [0.0%, 2.3%], I-square 42%; the heterogeneity was explained by differences in follow-up. When restricted to studies with long term follow-up (i.e. 10 years or more), the RD for mortality was 8.5%, 95%, CI [5.8%, 11.2%]; number needed to treat was 12. Further subgroup analyses and meta-regression random effects models revealed no evidence for other moderator variables (study level covariates, e.g. resurfacing vs. non-resurfacing MOM) than follow-up duration. The quality of the evidence presented in this meta-analysis was characterized as moderate according to the CLEAR-NPT (for non-pharmacological trials) and Cochrane risk of bias Table. Meta-analysis suggests there may be an increased long-term risk of mortality and revision surgery for patients with MOM THA compared to patients with non-MOM THA. PROSPERO 2014:CRD42014007417