Citations

Accumulating pre-clinical data suggests that matrix metalloproteinase (MMP) expression plays a critical role in the pathophysiology of secondary brain injury. We conducted a prospective multimodal monitoring study in order to characterize the temporal MMP response after severe traumatic brain injury (TBI) in eight critically ill humans and its relationship with outcomes. High-cutoff, cerebral microdialysis ( n =8); external ventricular drainage ( n =3); and arterial and jugular venous bulb catheters were used to collect microdialysate, cerebrospinal fluid, and arterial and jugular bulb blood over 6 days. Levels of MMP-8 and -9 were initially high in microdialysate and then gradually declined over time. After these MMPs decreased, a spike in the microdialysate levels of MMP-2 and -3 occurred, followed by a gradual rise in the microdialysate concentration of MMP-7. Use of generalized estimating equations suggested that MMP-8 concentration in microdialysate was associated with mortality ( p =0.019) and neurological outcome at hospital discharge ( p =0.013). Moreover, the mean microdialysate concentration of MMP-8 was 2.4-fold higher among those who died after severe TBI than in those who survived. Mean microdialysate levels of MMP-8 also rose with increasing intracranial pressure (ICP), whereas those of MMP-7 decreased with increasing cerebral perfusion pressure (CPP). Significant changes in the mean microdialysate concentrations of MMP-1, -2, -3, and -9 and MMP-1, -2, -3, -7, and -9 also occurred with increases in microdialysate glucose and the lactate/pyruvate ratio, respectively. These results imply that monitoring of MMPs following severe TBI in humans is feasible, and that their expression may be associated with clinical outcomes, ICP, CPP, and cerebral metabolism.

Genetic College Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467 , published online 30 May; see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.

Background— Implantable cardioverter-defibrillator (ICD) therapy in children and congenital heart disease patients is hampered by poor long-term lead survival. Lead extraction is technically difficult and carries substantial morbidity. We sought to determine the outcomes of ICD leads in pediatric and congenital heart disease patients. Methods and Results— The Pediatric Lead Extractability and Survival Evaluation (PLEASE) is a 24-center international registry. Pediatric and congenital heart disease patients with ICD lead implantations from 2005 to 2010 were eligible. Study subjects comprised 878 ICD patients (44% congenital heart disease). Mean±SD age at implantation was 18.6±9.8 years. Of the 965 total leads, 54% were thin (≤7F), of which 57% were Fidelis, and 23% were coated with expanded polytetrafluoroethylene. There were 139 ICD lead failures (14%) in 132 patients (15%) at a mean lead age of 2.0±1.4 years, causing shocks in 53 patients (40%). Independent predictors of lead failure included younger implantation age and Fidelis leads. Actuarial analysis showed an incremental risk of lead failure with younger age at implantation: <8 years compared with >18 years ( P =0.015). The actuarial yearly failure rate was 2.3% for non-Fidelis and 9.1% for Fidelis leads. Extraction was performed on 143 leads (80% thin, 7% expanded polytetrafluoroethylene coated), with lead age as the only independent predictor for advanced extraction techniques. There were 6 major extraction complications (4%) but no procedural mortality. Conclusions— This study demonstrates that ICD leads in children and congenital heart disease patients have an age-related suboptimal performance, further compounded by a high failure rate of Fidelis leads. Advanced extraction techniques were common and correlated with older lead age. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00335036.

AimThe minimally‐invasive Nuss procedure has become the preferred technique for pectus excavatum repair. This procedure is still associated with significant postoperative pain, and an optimal pain‐management strategy is yet to be determined. The purpose of this study was to compare the efficacy of patient‐controlled analgesia (PCA) to thoracic epidural analgesia (TEA).Patients and MethodsWe retrospectively reviewed 112 charts from a single paediatric centre. Patients were grouped according to pain‐management strategy: 90 patients received a PCA, and 22 patients received TEA. Outcomes included length of hospitalization and daily pain scores, operating room time and duration of Foley catheterization.ResultsDemographic data were similar between the two groups. The daily pain scores were not statistically different between the groups. Length of hospitalization was similar (PCA: 4.6 days, epidural: 4.3 days, P = 0.33). The PCA group required less operating room time (2:44 vs 2:58, P = 0.04) and shorter Foley catheter duration (2.1 days vs 2.5 days, P = 0.04).ConclusionIn our patient population, TEA for the Nuss procedure does not offer an advantage over PCA‐centred analgesia in terms of subjective daily pain scores or length of hospital stay. The potential risks of TEA need to be carefully considered in this patient population.

Background: Symptomatic femoroacetabular impingement (FAI) is associated with hip pain, functional limitations, and secondary osteoarthritis. There is limited information from large patient cohorts defining the specific population affected by FAI. Establishing a large cohort will facilitate the identification of “at-risk” patients and will provide a population for ongoing clinical research initiatives. The authors have therefore established a multicenter, prospective, longitudinal cohort of patients undergoing surgery for symptomatic FAI. Purpose: To report the clinical epidemiology, disease characteristics, and contemporary surgical treatment trends in North America for patients with symptomatic FAI. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Upon approval of the institutional review boards at 8 institutions, 12 surgeons enrolled consecutive patients undergoing surgical intervention for symptomatic FAI. Patient demographics, physical examination data, radiographic data, diagnoses, operative data, and standardized patient-reported outcome measures were collected. The first 1130 cases are summarized in this study. Results: A total of 1076 consecutive patients (1130 hips) were enrolled; 55% (n = 622) were female, and 45% (n = 508) were male, with an average age of 28.4 years and average body mass index (BMI) of 25.1. Demographics revealed that 88% of patients who were predominantly treated for FAI were white, 19% reported a family history of hip surgery, 47.6% of hips had a diagnosis of cam FAI, 44.5% had combined cam/pincer FAI, and 7.9% had pincer FAI. Preoperative clinical scores (pain, function, activity level, and overall health) indicated a major dysfunction related to the hip. Surgical interventions were arthroscopic surgery (50.4%), surgical dislocation (34.4%), reverse periacetabular osteotomy (9.4%), limited open osteochondroplasty with arthroscopic surgery (5.8%), and limited open by itself (1.5%). More than 90% of the hips were noted to have labral and articular cartilage abnormalities at surgery; femoral head-neck osteochondroplasty was performed in 91.6% of the surgical procedures, acetabular rim osteoplasty in 36.7%, labral repair in 47.8%, labral debridement in 16.3%, and acetabular chondroplasty in 40.1%. Conclusion: This multicenter, prospective, longitudinal cohort is one of the largest FAI cohorts to date. In this cohort, FAI occurred predominantly in young, white patients with a normal BMI, and there were more female than male patients. The disease pattern of cam FAI was most common. Contemporary treatment was predominantly arthroscopic followed by surgical hip dislocation.

AbstractWe previously reported an increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first‐degree relatives of MGUS and multiple myeloma patients. Here, we examine whether primary cytogenetic categories of myeloma differ between patients with and without a family history of MGUS or myeloma. We studied 201 myeloma patients with available data on family history and molecular cytogenetic classification. Myeloma with trisomies was more common in probands who had an affected first‐degree relative with MGUS or myeloma compared with those without a family history (46.9% vs. 33.5%, P = 0.125); however, the difference was not statistically significant. Additional studies on the cytogenetic types of myeloma associated with familial tendency are needed.

This study is a retrospective analysis of the influence of previous cardiac surgery on the outcome of heart transplantation in 118 consecutive recipients from January 1988 to December 1996. Group 1 consisted of 67 patients who had no previous sternotomy, group 2 was 33 patients who had one previous sternotomy, and group 3 was 18 patients who had two or more previous sternotomies. The three groups were demographically similar apart from the indication for transplantation and the sex distribution. Preoperative hemodynamic data, except systolic pulmonary artery pressure, were similar among the three groups. There was no significant difference in hospital mortality, 1-year and 5-year actuarial survival rates, incidence of renal dysfunction requiring dialysis, prolonged respiratory support, elevated total bilirubin, re-exploration for bleeding, incidence of mediastinitis, or postoperative hospital stay between the groups. The rejection-free and infection-free survival rates were similar in the three groups. However, previous sternotomy resulted in significantly longer cardiopulmonary bypass times and increased requirement for blood and blood products. The use of a cell saver limited the need for stored red blood cells. This study demonstrated no survival disadvantage of previous sternotomy in patients undergoing heart transplantation.

OBJECTIVE We hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODS We genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTS Genotype frequencies of rs5068 are AA, 93.5%; AG, 6.4%; and GG, 0.1%. All subsequent analyses are AA versus AG+GG. After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]: −1.7 kg/m2 [0.8], P = 0.04). In the AG+GG group, males with HDL cholesterol levels &lt;40 mg/dL are less frequent (P = 0.05) and obesity tends to be less prevalent (P = 0.07). Importantly, the G allele is associated with a lower prevalence of metabolic syndrome (P = 0.02). After adjusting for BMI, the above associations were attenuated. Independently of age, sex, and BMI, the minor allele is also associated with lower systolic blood pressure (−6.0 mmHg [2.5], P = 0.02) and lower prevalence of hypertension (odds ratio 0.41 [95% CI 0.20–0.83], P = 0.01). CONCLUSIONS The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype that we previously reported in a U.S. population is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure, BMI, and prevalence of hypertension and metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and lay the foundation for the future development of an ANP or ANP-like therapy for metabolic syndrome.