Cluster analysis and visualisation of electronic health records data to identify undiagnosed patients with rare genetic diseases.

Rare genetic diseases affect 5-8% of the population but are often undiagnosed or misdiagnosed. Electronic health records (EHR) contain large amounts of data, which provide opportunities for analysing and mining. Data mining, in the form of cluster analysis and visualisation, was performed on a database containing deidentified health records of 1.28 million patients across 3 major hospitals in Singapore, in a bid to improve the diagnostic process for patients who are living with an undiagnosed rare disease, specifically focusing on Fabry Disease and Familial Hypercholesterolaemia (FH). On a baseline of 4 patients, we identified 2 additional patients with potential diagnosis of Fabry disease, suggesting a potential 50% increase in diagnosis. Similarly, we identified > 12,000 individuals who fulfil the clinical and laboratory criteria for FH but had not been diagnosed previously. This proof-of-concept study showed that it is possible to perform mining on EHR data albeit with some challenges and limitations.

Evaluation of early osteochondral defect repair in a rabbit model utilizing fourier transform-infrared imaging spectroscopy, magnetic resonance imaging, and quantitative T2 mapping.

CONTEXT: Evaluation of the morphology and matrix composition of repair cartilage is a critical step toward understanding the natural history of cartilage repair and efficacy of potential therapeutics. In the current study, short-term articular cartilage repair (3 and 6 weeks) was evaluated in a rabbit osteochondral defect model treated with thrombin peptide (TP-508) using magnetic resonance imaging (MRI), quantitative T2 mapping, and Fourier transform-infrared imaging spectroscopy (FT-IRIS). METHODS: Three-mm-diameter osteochondral defects were made in the rabbit trochlear groove and filled with either TP-508 plus poly-lactoglycolidic acid microspheres or poly-lactoglycolidic acid microspheres alone (placebo). Repair tissue and adjacent normal cartilage were evaluated at 3 and 6 weeks postdefect creation. Intact knees were evaluated by magnetic resonance imaging for repair morphology, and with quantitative T2 mapping to assess collagen orientation. Histological sections were evaluated by FT-IRIS for parameters that reflect collagen quantity and quality, as well as proteoglycan (PG) content. RESULTS AND CONCLUSION: There was no significant difference in volume of repair tissue at either time point. At 6 weeks, placebo repair tissue demonstrated longer T2 values (p < 0.01) than TP-508 did. Although both placebo and TP-508 repair tissue demonstrated longer T2 values than adjacent normal cartilage did, the 6-week T2 values of the TP-508 specimens were closer to those of the adjacent normal cartilage than were the placebo values. FT-IRIS analysis demonstrated a significant increase in collagen content, integrity, and PG content of the TP-508 repair tissue from 3 to 6 weeks (p < or = 0.05). In addition, the collagen and PG content of the TP-508 samples were closer to normal cartilage at 3 weeks than were the placebo samples. Further, there was a significant inverse correlation between the T2 relaxation values and collagen orientation in the normal cartilage. However, there were no significant correlations between T2 relaxation values and any FT-IRIS parameter in the repair tissue. Together, the data demonstrate that MRI and FT-IRIS assessment of cartilage repair tissue provide molecular information that furthers understanding of the cartilage repair process.

The DMD knot: a new locking, flip knot.

To perform an arthroscopic rotator cuff or labral tear, surgeons need to know how to tie athroscopic knots. The ideal knot should be able to withstand large biomechanical loads while being easy to tie. With numerous knot configuration options available to surgeons, many recent studies have assessed the biomechanical characteristics of some of the more commonly used knots. Different studies have referred to the flip knot used by the senior author (DMD) as the "Dines knot," and in many of these studies, it has exhibited the best loop security, resistance to sliding, distance to failure, knot security, knot weight, and resistance to reverse slippage. To date, there is no published technique note on how to tie the Dines knot, which is referred to in this note as the "DMD knot."

Irreparable rotator cuff tears: what to do and when to do it; the surgeon's dilemma.

Irreparable rotator cuff tears have been defined as those tears that because of their size and retraction cannot be repaired primarily. Patients with an irreparable tear present with a variety of symptoms and physical findings, and their management depends on the clinical situation and the specific location of the tear. Most of these tears occur in the older, less active patient and many of these patients are best treated without surgery. For those in whom surgery is indicated, the best procedure should be tailored to the tear.