Isolation of biofluids from tissues using a vacuum-assisted filtration biomedical device.

A biopsy is usually used to remove a piece of tissue from a patient for laboratory testing. The interstitial fluid is taken out at the same time as the tissue sample. Since interstitial fluid flows between cells and capillaries in tissues, similar to blood plasma, it is necessary to separate interstitial fluid from tissues in order to study them separately. Vacuum blood sampling has been used to draw blood into vacuum-sealed tubes, while interstitial fluid can be removed directly from the skin using microneedles with standard pumps. However, no methods are available to separate blood or interstitial fluid from the tissue itself for molecular characterization. In this study, we designed a biomedical device that can separate interstitial fluid from tissue using a vacuum-assisted filtration method. The device has a chamber that collects fluid extracted from the tissue that remains on top of the filter. We characterized the weight change and glycan profiles of tissues before and after vacuum-assisted filtration. The results demonstrate that the biomedical device can remove interstitial fluid and facilitate the analysis of tissue-specific molecules while minimizing information from the interstitial fluid.

Protein glycosylation in urine as a biomarker of diseases.

Human body fluids have become an indispensable resource for clinical research, diagnosis and prognosis. Urine is widely used to discover disease-specific glycoprotein biomarkers because of its recurrently non-invasive collection and disease-indicating properties. While urine is an unstable fluid in that its composition changes with ingested nutrients and further as it is excreted through micturition, urinary proteins are more stable and their abnormal glycosylation is associated with diseases. It is known that aberrant glycosylation can define tumor malignancy and indicate disease initiation and progression. However, a thorough and translational survey of urinary glycosylation in diseases has not been performed. In this article, we evaluate the clinical applications of urine, introduce methods for urine glycosylation analysis, and discuss urine glycoprotein biomarkers. We emphasize the importance of mining urinary glycoproteins and searching for disease-specific glycosylation in various diseases (including cancer, neurodegenerative diseases, diabetes, and viral infections). With advances in mass spectrometry-based glycomics/glycoproteomics/glycopeptidomics, characterization of disease-specific glycosylation will optimistically lead to the discovery of disease-related urinary biomarkers with better sensitivity and specificity in the near future.

Disparities in Total Hip Arthroplasty Versus Hemiarthroplasty in the Management of Geriatric Femoral Neck Fractures.

INTRODUCTION: Recent clinical evidence suggests that total hip arthroplasty (THA) provides improved clinical outcomes as compared to hemiarthroplasty (HA) for displaced femoral neck fractures in elderly individuals. However, THA is still utilized relatively infrequently. Few studies have evaluated the factors affecting utilization and the role socioeconomics plays in THA versus HA. METHODS: In the United States, the National Inpatient Sample (NIS) database was used to identify patients treated surgically for femoral neck fracture, between 2009 and 2010. Patients were identified using International Classification of Diseases, Ninth Revision, codes for closed, transcervical femoral neck fractures and closed fractures at unspecified parts of the femoral neck. All candidate predictors of THA versus HA were entered into a multilevel mixed-effect regression model. RESULTS: Older patient age, being Asian or Pacific Islander, and having Medicaid payer status were all associated with lower odds of receiving THA. Patients with private insurance including Health Maintenance organization (HMO) had higher odds of THA as did patients with other insurance. Odds of THA were significantly lower among patients in teaching hospitals and higher at hospitals with greater THA volume. DISCUSSION: Ethnicity, payer status, hospital size, and institutional THA volume were all associated with the utilization of THA versus HA in the treatment of geriatric femoral neck fractures. LEVEL OF EVIDENCE: Level III Retrospective Cohort study.

Evaluation of Contemporary Trends in Femoral Neck Fracture Management Reveals Discrepancies in Treatment.

BACKGROUND: Recent evidence supports total hip arthroplasty (THA) as compared to hemiarthroplasty (HA) for the management of displaced femoral neck fractures in a significant subset of elderly patients. The purpose of this study was to examine trends in femoral neck fracture management over the last 12 years. METHODS: Using the National Inpatient Sample database, we identified patients treated for femoral neck fractures between 1998 and 2010 with THA, HA, or internal fixation (IF). We examined treatment trends and demographic variables including patient age, gender, socioeconomic status, and payer and hospital characteristics. RESULTS: We identified 362 127 femoral neck fracture patients treated between 1998 and 2010. Overall, there were statistically significant increases in rates of THA and HA, whereas rates of IF decreased. Total hip arthroplasty varied based on patient age, with significant increases occurring in age-groups 0 to 49 years, 50 to 59 years, 60 to 69 years, and 70 to 79 years. Utilization of THA varied significantly based on socioeconomic status and race. Patient sex, urban versus rural hospital location, and teaching versus nonteaching hospital status were not related to rates of THA. CONCLUSION: Rates of THA for femoral neck fractures increased between 1998 and 2010 in patients younger than 80 years, suggesting that surgeons are responding to clinical evidence supporting THA for the treatment of elderly femoral neck fractures. This is the first study to demonstrate this change and expose disparities in practice patterns over time in response to this evidence in the United States. Further research is indicated to explore the effect of socioeconomic status and race on femoral neck fracture management.

The Effects of Limb Elevation on Muscle Oxygen Saturation: A Near-Infrared Spectroscopy Study in Humans.

BACKGROUND: Orthopaedic and rehabilitation physicians often instruct patients to elevate a traumatized or postoperative lower extremity. Elevation is thought to improve patient comfort, as well as decrease swelling, wound complications, and the risk of compartment syndrome. Elevating a limb with increased compartment pressures, however, has been shown to reduce perfusion pressure and contribute to tissue ischemia. This investigation aims to advance our understanding of the tissue effects of limb elevation using a healthy patient model. OBJECTIVE: To quantify the effects of elevation, experimentally induced ischemia, and immobilization on muscle oxygen saturation in the human leg using near-infrared spectroscopy (NIRS). DESIGN: Experimental crossover study. SETTING: Orthopaedic Surgery research laboratory, Stanford Hospitals & Clinics. PATIENTS FOR PARTICIPATION: Twenty-six healthy volunteers. METHODS: Using transcutaneous sensors, we measured muscle oxygen saturation of the anterior compartment of the left (control) leg at 0, 15, and 30 cm of elevation relative to the heart using NIRS. A standardized short leg splint and a thigh tourniquet inflated to 50 mmHg were then applied to the right (experimental) leg to simulate a traumatized state. NIRS measurements were then repeated, again at 0, 15, and 30 cm of elevation. Muscle oxygen saturation values at various degrees of elevation of the control and experimental limb were then compared and analyzed by the use of a crossover study design and mixed-effects regression. MAIN OUTCOME MEASUREMENTS: Muscle oxygen saturation at varying levels of elevation in both the (1) control leg and (2) experimental leg in a simulated traumatic state. RESULTS: Male (18) males and female (8) patients between 22 and 62 years of age (mean 29.8 years) were enrolled. Mean regional muscle oxygen saturation (rSO2) of the control limbs at 0, 15 and, 30 cm of elevation were 74.2%, 72.5%, and 70.6%, respectively, whereas mean rSO2 of the experimental limbs were 66.3%, 65.0%, and 63.3%. A statistically significant decrease of rSO2 was observed (mean 7.65%) in the experimental limbs compared with the control limbs. As elevation increased, there was a statistically significant decrease in rSO2 of 0.12% per centimeter of elevation. Elevation did not decrease the rSO2 in the experimental limb to a greater degree than in the control limb. CONCLUSION: Increasing levels of elevation in a human limb results in progressively compromised muscle oxygen saturation as measured by NIR.

The Orthopaedic Foot and Ankle Outcomes Research (OFAR) network: feasibility of a multicenter network for patient outcomes assessment in foot and ankle.

INTRODUCTION: There is an increasing need for orthopaedic practitioners to measure and collect patient-reported outcomes data. In an effort to better understand outcomes from operative treatment, the American Orthopaedic Foot & Ankle Society (AOFAS) established the Orthopaedic Foot and Ankle Outcomes Research (OFAR) Network, a national consortium of foot and ankle orthopaedic surgeons. We hypothesized that the OFAR Network could successfully collect, aggregate, and report patient-reported outcome (PRO) data using the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS). METHODS: Ten sites enrolled consecutive patients undergoing elective surgery for 1 of 6 foot/ankle disorders. Outcome instruments were collected preoperatively and at 6 months postoperatively using the PROMIS online system: Foot and Ankle Ability Measure (FAAM), Foot Function Index (FFI), and PROMIS physical function (PF) and pain computerized adaptive tests (CAT). During the 3-month period, 328 patients were enrolled; 249 (76%) had completed preoperative patient-reported outcomes data and procedure-specific data. Of these, 140 (56%) also completed 6-month postoperative patient- reported outcomes data. RESULTS: Ankle arthritis and flatfoot demonstrated consistently worse preoperative scores. Five of 6 disorders showed significant improvement at 6 months on PF CAT and FAAM, 4 of 6 showed improvement on pain interference CAT, and no disorders showed improvement on FFI. Ankle arthritis and flatfoot demonstrated the greatest magnitude of change on most patient-reported outcomes scales. CONCLUSION: We were able to enroll large numbers of patients in a short enrollment period for this preliminary study. Data were easily aggregated and analyzed. Substantial loss of follow-up data indicates a critical area requiring further effort. The AOFAS OFAR Network is undergoing expansion with goals to ultimately facilitate large, prospective multicenter studies and optimize the quality and interpretation of available outcome instruments for the foot and ankle population. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Black sentinel lymph node and 'scary stickers'.

An unusual case is presented of a young adult patient with two black-stained, radio-nucleotide tracer-active sentinel lymph nodes biopsied following her primary cutaneous melanoma treatment. This was subsequently confirmed to be secondary to cutaneous tattoos, averting the need of an elective regional node dissection. History of tattooing and tattoo removal should therefore be obtained as a routine in all melanoma patients considered for sentinel node biopsy (SLN). SLN biopsy and any subsequent completion node dissection should be strictly staged so that proper histologic diagnosis of the sentinel node is available for correct decision making and treatment.

Surgical management of craniofacial and skull base rhabdomyosarcomas.

INTRODUCTION: Craniofacial and skull base rhabdomyosarcomas (RMSs) are rare. Surgeons are involved both in the resection and the reconstruction of these tumors and in the management of late sequelae of earlier treatment. These tumors are highly heterogeneous, and the initial presentation may be insidious. We wished to determine how diagnostic difficulties could be overcome and how management outcomes could be optimized. MATERIALS AND METHODS: All cases of RMS in patients who presented to our craniofacial program between 2004 and 2008 were retrospectively reviewed. RESULTS: Eight consecutive patients with RMS were treated. Six patients are Maori. Four patients had surgical resections of their primary tumors including 3 with curative intent. One had a recurrent tumor, and 3 had functional reconstruction after an earlier treatment. Inaccuracies in histologic diagnosis occurred in 2 patients. Two patients developed postoperative cerebrospinal fluid leakage. Two patients had leptomeningeal involvement and died within 10 months. All patients treated with curative intent achieved complete macroscopic margins. Two remained disease-free at 10 and 22 months. DISCUSSION: Treatment must be in the context of a multidisciplinary team with the appropriate craniofacial, neurosurgical, and reconstructive skills. Expedient and accurate histologic diagnoses by experienced pathologists are critical in optimizing the outcomes. Oncologists must be well resourced to administer chemoradiation in a timely manner. Leptomeningeal invasion is a dire prognostic feature. Cerebrospinal fluid leak after resection must be identified early and repaired. Late consequences of early childhood craniofacial cancer treatment may be ameliorated by tailored reconstructions. The predominance of Maori in our series has not been reported previously.

Evolution of surgery for sagittal synostosis: the role of new technologies.

BACKGROUND: Techniques for sagittal synostosis correction continue to evolve to improve outcomes and minimize morbidity. The techniques now used by our craniofacial service are spring-assisted cranioplasty for younger children (generally up to 9 months of age) and biparietal barrel staving with cross-struts using bioabsorbable plates for older children. We evaluate the evolution of, and rationale for, our current methods of treatment. METHOD: All patients who underwent surgery for craniosynostosis over the period 1982 to 2007 were retrospectively reviewed. Patients with sagittal synostosis were analyzed according to the type of operative procedure performed. Blood loss, operative time, and hospital stay were compared between techniques using analysis of variance. RESULTS: Seventy-one patients had a cranial vault remodeling procedure for craniosynostosis. Thirty-four patients had sagittal synostosis with scaphocephaly. During the period 1982 to 2000, 13 patients had a strip craniectomy, and 5 patients had a barrel stave and morcellation procedure. Since 2001, the cross-strut technique using bioabsorbable plates has been used in 7 patients. In 2005, the spring cranioplasty technique was introduced and has been used in 9 patients. There were no deaths and no serious complications. One patient treated with springs had a second spring procedure performed to further increase biparietal width. Spring-assisted cranioplasty had a significantly shorter operating time than other techniques (P < 0.01). CONCLUSION: The availability of both absorbable plates and expansile cranial springs has revolutionized the techniques our unit uses for scaphocephaly correction. Our early experience with these techniques has shown that the techniques are reliable and give good cranial shape and form with minimal treatment morbidity.