Citations

Platelets have an emerging and incompletely understood role in a myriad of host immune responses, extending their role well beyond regulating thrombosis. Acute respiratory distress syndrome is a complex disease process characterized by a range of pathophysiologic processes including oxidative stress, lung deformation, inflammation, and intravascular coagulation. The objective of this review is to summarize existing knowledge on platelets and their putative role in the development and resolution of lung injury.

Background: The lateral tibial posterior slope (LTPS) has been reported in multiple studies to correlate with an increased risk for native anterior cruciate ligament (ACL) tearing. To date, no study has examined the effect of an increased LTPS as measured on magnetic resonance imaging (MRI) on the likelihood of ACL graft failure. Hypothesis: An increased LTPS as measured on MRI would correlate with an increased risk for ACL graft failure. Study Design: Case-control study; Level of evidence, 3. Methods: Fifty-eight patients were initially identified who experienced graft failure after primary ACL reconstruction and underwent revision between 1998 and 2009. Exclusion criteria were clinical follow-up of less than 4 years, graft failure occurring greater than 2 years after primary surgery, skeletal immaturity, deep infection, lack of available preoperative MRI, and history of trauma to the proximal tibia. This left 35 patients with early (within 2 years) failure of primary ACL reconstruction. These patients were matched to 35 control participants who had undergone ACL reconstruction with a minimum of 4 years of clinical follow-up and no evidence of graft failure. Patients were matched by age, sex, date of primary surgery, and graft type. The LTPS was then determined on MRI in a blinded fashion. Results: The mean time to failure in patients in the study group was 1 year (range, 0.6-1.4 years). The mean follow-up of those in the matched control group was 6.9 years (range, 4.0-13.9 years). The mean LTPS in the early ACL failure group was found to be 8.4°, which was significantly larger than that in the control group at 6.5° ( P = .012). The odds ratio for graft failure considering a 2° increase in the LTPS was 1.6 (95% CI, 1.1-2.2) and continued to increase to 2.4 (95% CI, 1.2-5.0) and 3.8 (95% CI, 1.3-11.3) with 4° and 6° increases in the LTPS, respectively. No significant association was identified between graft type and graft failure. Conclusion: An increased LTPS is associated with an increased risk for early ACL graft failure, regardless of graft type. Orthopaedic surgeons should consider measuring the LTPS as part of the preoperative assessment of ACL-injured patients.

Polycystic kidney disease (PKD) is a common cause of end-stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5 × 10 5 ) were intrarenally infused in 6-week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) versus controls (126.22 ± 2.74 vs. 116.45 ± 3.53 mmHg, p < 0.05) and decreased creatinine clearance (3.76 ± 0.31 vs. 6.10 ± 0.48 μl/min/g, p < 0.01), which were improved in PKD animals that received MSCs (SBP: 114.67 ± 1.34 mmHg, and creatinine clearance: 4.82 ± 0.24 μl/min/g, p = 0.001 and p = 0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using microcomputed tomography. PCK animals had increased urine osmolality (843.9 ± 54.95 vs. 605.6 ± 45.34 mOsm, p < 0.01 vs. control), which was improved after MSC infusion and not different from control (723.75 ± 56.6 mOsm, p = 0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of proangiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to 4 weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD.

Context The appropriate and timely performance of molecular testing in anatomic pathology is an indicator of quality. The National Comprehensive Cancer Network (NCCN) publishes a comprehensive treatment guideline that includes recommendations for ancillary testing. Objective To establish benchmarks for rates of adherence to NCCN testing recommendations through a multi-institutional study. Design Participants in a 2013 Q-Probes study of the College of American Pathologists reported data from molecular testing on anatomic pathology cases, excluding hematolymphoid neoplasms, breast primary carcinomas, and gynecologic cytology. Results Twenty-six institutions reported data from 2230 molecular testing events. In a retrospective study limited to colon, lung, and melanoma, there was strict adherence to guidelines in a median 71% (10th to 90th percentile range, 33%–90%) and there was at least loose adherence in a median 95% (10th to 90th percentile range, 57%–100%). There was adequate tissue to complete testing in a median 98% (10th to 90th percentile range, 86%–100%); in aggregate the adequacy rate for cell blocks was lower (84%, P &lt; .001). Median test turnaround time was 8 days (10th to 90th percentile range, 4–13 days). In a prospective collection of all organ sites, there was strict adherence to guidelines in a median 53% (10th to 90th percentile range, 20%–71%), and there was at least loose adherence in a median 94% (10th to 90th percentile range, 75%–100%). Adherence to guidelines was higher for lung specimens and in institutions with more multidisciplinary conferences. Conclusions This multi-institutional study provides benchmarking data on appropriateness and timeliness of molecular testing in anatomic pathology.

OBJECT Mild traumatic brain injury (TBI) has been proposed as a risk factor for the development of Alzheimer’s disease, Parkinson’s disease, depression, and other illnesses. This study’s objective was to determine the association of prior mild TBI with the subsequent diagnosis (that is, at least 1 year postinjury) of neurological or psychiatric disease. METHODS All studies from January 1995 to February 2012 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, study references, and review articles. Reviewers abstracted the data and assessed study designs and characteristics. RESULTS Fifty-seven studies met the inclusion criteria. A random effects meta-analysis revealed a significant association of prior TBI with subsequent neurological and psychiatric diagnoses. The pooled odds ratio (OR) for the development of any illness subsequent to prior TBI was 1.67 (95% CI 1.44–1.93, p < 0.0001). Prior TBI was independently associated with both neurological (OR 1.55, 95% CI 1.31–1.83, p < 0.0001) and psychiatric (OR 2.00, 95% CI 1.50–2.66, p < 0.0001) outcomes. Analyses of individual diagnoses revealed higher odds of Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment, depression, mixed affective disorders, and bipolar disorder in individuals with previous TBI as compared to those without TBI. This association was present when examining only studies of mild TBI and when considering the influence of study design and characteristics. Analysis of a subset of studies demonstrated no evidence that multiple TBIs were associated with higher odds of disease than a single TBI. CONCLUSIONS History of TBI, including mild TBI, is associated with the development of neurological and psychiatric illness. This finding indicates that either TBI is a risk factor for heterogeneous pathological processes or that TBI may contribute to a common pathological mechanism.

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA‐containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in‐person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.

ObjectiveTo evaluate the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Olmsted County, Minnesota in 1994–2013 and trends in juvenile rheumatoid arthritis (JRA) in 1960–2013.MethodsCases of arthritis in 1994–2013 were identified by diagnosis code with medical chart review to confirm diagnosis separately for JIA and JRA. Overall incidence rates with 95% confidence intervals (95% CIs) were age and sex adjusted to the 2010 US white population. Comparisons were made with an earlier (1960–1993) cohort from this same population.ResultsSeventy‐one incident cases of JIA in 1994–2013 were identified, with an overall age‐ and sex‐adjusted incidence rate of 10.3 per 100,000 (95% CI 7.9–12.7). Forty‐two (59%) were female, with an incidence of 12.4 per 100,000 (95% CI 8.6–16.2), as compared to 8.3 per 100,000 (95% CI 5.2–11.3) in males. The most common subtype was oligoarthritis (63%). The mean ± SD age at diagnosis was 8.2 ± 5.3 years. The prevalence of JIA on January 1, 2000 and January 1, 2010 was 51.0 per 100,000 (95% CI 25.2–76.8) and 57.6 per 100,000 (95% CI 31.0–94.5), respectively. When the annual incidence of JRA was compared over time from 1960 to 2013, there was no significant change in incidence overall; however, the incidence decreased among females (P = 0.003). A cyclic pattern of incidence was observed, with peaks approximately every 10 years. Similar to the findings with regard to incidence, prevalence did not change overall, but decreased among females (P = 0.048). There were 4 deaths in the cohort of JRA patients diagnosed in 1960–2013; the standardized mortality ratio was 1.50 (95% CI 0.41–3.83).ConclusionIncidence of juvenile arthritis overall in Olmsted County, Minnesota has not changed significantly in the past 53 years. A consistent cyclic pattern was noted.