Michael J. Goldberg

The POSNA Pediatric musculoskeletal functional Health questionnaire : Report on reliability, validity, and sensitivity to change

The goal of orthopaedic interventions is to improve the functional health of patients, particularly physical function. The American Academy of Orthopaedic Surgeons and the Pediatric Orthopaedic Society of North America (POSNA) commissioned a work group to construct functional health outcomes scales for children and adolescents, focusing on musculoskeletal health. The work group developed scales assessing upper extremity function, transfers and mobility, physical function and sports, comfort (pain free), happiness and satisfaction, and expectations for treatment. Parent and adolescent self-report forms were developed and tested on 470 subjects aged 2-18 years. The POSNA scales demonstrated good reliability, construct validity, sensitivity to change over a 9-month period, and ability to outperform a standard instrument, the Child Health Questionnaire physical functioning scale. They were useful for a wide variety of ages and diagnoses. They appear to be ideally suited for orthopaedic surgeons to assess the functional health and efficacy of treatment of their patients at baseline and follow-up.

Production of cytokines around loosened cemented acetabular components. Analysis with immunohistochemical techniques and in situ hybridization.

The chronic inflammatory response to wear particles from orthopaedic joint implants is believed to cause osteolysis and to contribute to prosthetic loosening. Previous in vitro experiments have demonstrated that particulate debris from joint implants causes cells in culture to release products that have been implicated in this pathological bone resorption. The purpose of the current study was to investigate the in vivo features of this complex process in patients who had had a total hip replacement. Membraneous tissue was obtained from the cement-bone interface of ten polyethylene acetabular components that had been revised for aseptic loosening in ten patients. The immunoperoxidase technique, which involves the use of specific antibodies for each cell type, showed that macrophages were the predominant cellular constituents but also that fibroblasts, many of which were not identified on plain histological study, were present and were actively producing collagen. T lymphocytes were present variably, but they generally composed less than 10 percent of the cells. Particulate debris (polyethylene, methylmethacrylate, and metal) was present in all membrane specimens but was intracellular only in macrophages and multinucleated giant cells. 35S-labeled nucleic-acid probes, complementary to human interleukin-1-beta and to platelet-derived growth-factor-2 messenger RNA (mRNA), were hybridized with serial tissue sections. Hybridization demonstrated interleukin-1-beta mRNA predominantly in macrophages, and not in fibroblasts or in T lymphocytes to any major extent. In contrast, immunolocalization demonstrated interleukin-1-beta protein on both macrophages and fibroblasts, suggesting that macrophages release interleukin-1-beta, which then binds to both fibroblasts and macrophages. Platelet-derived growth-factor transcripts were found in both macrophages and fibroblasts.

Osteoporosis in Primary Biliary Cirrhosis: Effects of 25-Hydroxyvitamin D3 Treatment

Bone histology, bone mineral content, and calcium absorption were evaluated in 10 patients with primary biliary cirrhosis and osteopenia, before and after 1 yr of treatment with oral 25-hydroxycholecalciferol. Before treatment, quantitative histomorphometric analysis of full-thickness iliac crest bone biopsy specimens with double-tetracycline labeling demonstrated that 9 of 10 patients had osteoporosis. None had osteomalacia. Fasting intestinal calcium absorption correlated well with trabecular bone volume (r = 0.85). Bone mineral content measured by 125I-photon absorption was low in 6 of 10 patients, and it correlated poorly with iliac crest trabecular bone volume. After 1 yr of treatment with oral 25-hydroxyvitamin D3, bone mineral content fell in all 8 patients who were restudied. Iliac crest trabecular bone volume increased in 3 patients, 2 of whom had the greatest pretreatment impairment in calcium absorption, but fell in 5. Bone fractures continued to occur in 3 of 5 patients who were alive after 1 yr and developed for the first time in a sixth patient. We conclude that 25-hydroxyvitamin D3 is ineffective in reversing the bone thinning in the majority of primary biliary cirrhosis patients, but it may be helpful in a few selected patients.

Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer

We present a novel instrument to measure the spectral, angular, azimuthal, and polarization dependence of light backscattered by living biological tissues, thus providing the most comprehensive description of the light scattering to obtain unique quantitative information about the microarchitecture of living cells and tissues. We show the potential of this technique to characterize and diagnose early premalignant changes in the epithelia. In studies with a rodent model of colon carcinogenesis, we show that several parameters obtained using this technique, such as the number density of red blood cells in the capillary network immediately underlying the epithelium, the fractal dimension of the tissue, and the average roundness of subcellular structures, are significant for detection of precancerous changes at a very early stage of the carcinogenic process, at which no other histological or molecular markers have been identified.

Serum Biomarker Panels for the Detection of Pancreatic Cancer

Purpose: Serum–biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations. Experimental Design: Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n = 33), lung (n = 62), and breast (n = 108) cancers. Results: Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In the training set (n = 160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19–9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19–9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with an SN/SP of 76/90%. In an independent validation set (n = 173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19–9, ICAM-1 and OPG demonstrated an SN/SP of 78/94% while the panel of CA19–9, CEA, and TIMP-1 demonstrated an SN/SP of 71/89%. The CA19–9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP = 100%), lung (SP = 97%), or colon (SP = 97%) cancer. Conclusions: The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations. Clin Cancer Res; 17(4); 805–16. ©2010 AACR.

Treatment of distal radius fractures

The clinical practice guideline is based on a systematic review of published studies on the treatment of distal radius fractures in adults. None of the 29 recommendations made by the work group was graded as strong; most are graded as inconclusive or consensus; seven are graded as weak. The remaining five moderate-strength recommendations include surgical fixation, rather than cast fixation, for fractures with postreduction radial shortening >3 mm, dorsal tilt >10 degrees , or intra-articular displacement or step-off >2 mm; use of rigid immobilization rather than removable splints for nonsurgical treatment; making a postreduction true lateral radiograph of the carpus to assess dorsal radial ulnar joint alignment; beginning early wrist motion following stable fixation; and recommending adjuvant treatment with vitamin C to prevent disproportionate pain.

American Academy of Orthopaedic Surgeons clinical practice guideline on the treatment of osteoarthritis (OA) of the knee.

Summary of Recommendations The following is a summary of the recommendations in the AAOS’ clinical practice guideline, The Treatment of Osteoarthritis (OA) of the Knee. This guideline was explicitly developed to include only treatments less invasive than knee replacement (arthroplasty). This summary does not contain rationales that explain how and why these recommendations were developed nor does it contain the evidence supporting these recommendations. All readers of this summary are strongly urged to consult the full guideline and evidence report for this information. We are confident that those who read the full guideline and evidence report will also see that the recommendations were developed using systematic evidence-based processes designed to combat bias, enhance transparency, and promote reproducibility. This summary of recommendations is not intended to stand alone. Treatment decisions should be made in light of all circumstances presented by the patient. Treatments and procedures applicable to the individual patient rely on mutual communication between patient, physician and other healthcare practitioners. Patient Education and Lifestyle Modification

The American Academy of Orthopaedic Surgeons evidence-based guideline on: treatment of osteoarthritis of the knee, 2nd edition.

The AAOS Evidence-Based Guideline on Treatment of Osteoarthritis of the Knee, 2nd Edition, includes only less-invasive alternatives to knee replacement. This brief summary of the AAOS Clinical Practice Guideline contains a list of the recommendations and the rating of strength based on the quality of the supporting evidence. Discussion of how each recommendation was developed and the complete evidence report are contained in the full guideline at www.aaos.org/guidelines. ### Conservative Treatments: Recommendations 1-6 #### RECOMMENDATION 1 We recommend that patients with symptomatic osteoarthritis of the knee participate in self-management programs, strengthening, low-impact aerobic exercises, and neuromuscular education; and engage in physical activity consistent with national guidelines. Strength of Recommendation: Strong #### RECOMMENDATION 2 We suggest weight loss for patients with symptomatic osteoarthritis of the knee and a BMI ≥25. Strength of Recommendation: Moderate #### RECOMMENDATION 3A We cannot recommend using acupuncture in patients with symptomatic osteoarthritis of …

Cervical-spine instability in children with Down syndrome (trisomy 21).

Eighty-five children with Down syndrome, between sixteen months and eighteen years old, were evaluated for instability of the cervical spine at the atlanto-axial joint. The mean atlas-odontoid process interval was three millimeters in flexion and two millimeters in extension. Ten patients (12 per cent) exhibited abnormal intervals (4.5 millimeters or more) during either flexion or extension. The configuration of the odontoid process was considered normal in eighty patients and abnormal in another five patients (6 per cent). The correlation between the thickness of the interval and the degree of ligament laxity was statistically significant, as was the correlation between ligament laxity and age. Of the ten patients with an increased atlas-odontoid process interval, neurological deficit (hyperreflexia and clonus) developed in only one after a one-year follow-up.

Nanoscale Cellular Changes in Field Carcinogenesis Detected by Partial Wave Spectroscopy

Understanding alteration of cell morphology in disease has been hampered by the diffraction-limited resolution of optical microscopy (>200 nm). We recently developed an optical microscopy technique, partial wave spectroscopy (PWS), which is capable of quantifying statistical properties of cell structure at the nanoscale. Here we use PWS to show for the first time the increase in the disorder strength of the nanoscale architecture not only in tumor cells but also in the microscopically normal-appearing cells outside of the tumor. Although genetic and epigenetic alterations have been previously observed in the field of carcinogenesis, these cells were considered morphologically normal. Our data show organ-wide alteration in cell nanoarchitecture. This seems to be a general event in carcinogenesis, which is supported by our data in three types of cancer: colon, pancreatic, and lung. These results have important implications in that PWS can be used as a new method to identify patients harboring malignant or premalignant tumors by interrogating easily accessible tissue sites distant from the location of the lesion.