David W. Manning

Regulation of osteogenic differentiation during skeletal development.

Bone formation during skeletal development involves a complex coordination among multiple cell types and tissues. Bone is of crucial importance for the human body, providing skeletal support, and serving as a home for the formation of hematopoietic cells and as a reservoir for calcium and phosphate. Bone is also continuously remodeled in vertebrates throughout life. Osteoblasts and osteoclasts are specialized cells responsible for bone formation and resorption, respectively. Early development of the vertebrate skeleton depends on genes that control the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations, where cells differentiate to osteoblasts. Significant progress has been made over the past decade in our understanding of the molecular framework that controls osteogenic differentiation. A large number of morphogens, signaling molecules, and transcriptional regulators have been implicated in regulating bone development. A partial list of these factors includes the Wnt/beta-catenin, TGF-beta/BMP, FGF, Notch and Hedgehog signaling pathways, and Runx2, Osterix, ATF4, TAZ, and NFATc1 transcriptional factors. A better understanding of molecular mechanisms behind osteogenic differentiation would not only help us to identify pathogenic causes of bone and skeletal diseases but also lead to the development of targeted therapies for these diseases.

Multimodal Pain Management in Total Knee Arthroplasty: A Prospective Randomized Controlled Trial

We analyze the effects of a multimodal analgesic regimen on postoperative pain, function, adverse effects and satisfaction compared to patient-controlled analgesia (PCA). Thirty-six patients undergoing TKA were randomized to receive either (1) periarticular injection before wound closure (30cc 0.5% bupivacaine, 10mg MSO4, 15 mg ketorolac) and multimodal analgesics (oxycodone, tramadol, ketorolac; narcotics as needed) or (2) hydromorphone PCA. Preoperative and postoperative data were collected for VAS pain scores, time to physical therapy milestones, hospital stay length, patient satisfaction, narcotic consumption and medication-related adverse effects. The multimodal group had lower VAS scores, fewer adverse effects, lower narcotic usage, higher satisfaction scores and earlier times to physical therapy milestones. Multimodal pain management protocol decreases narcotic usage, improves pain scores, increases satisfaction and enhances early recovery.

A Prospective, Randomized, Double-Blind Study Evaluating the Efficacy of Postoperative Continuous Local Anesthetic Infusion at the Iliac Crest Bone Graft Site After Spinal Arthrodesis

Study Design. Parallel design, prospective, double-blind, randomized, controlled trial composed of two independent groups treated with a continuous infusion catheter (saline vs. Marcaine) placed into the iliac crest bone graft (ICBG) site. Objective. To determine the effects of postoperative continuous local anesthetic agent infusion at the ICBG harvest site in reducing pain, narcotic demand and usage, and improving early postoperative function after spinal fusion. Summary of Background Data. Harvesting iliac crest bone has been shown to be a source of pain and morbidity. Long-term patient complaints may be more closely associated with the procurement of the iliac crest graft rather than the primary surgical site. Methods. Thirty-seven patients were enrolled in a prospective, randomized, double-blind parallel-designed study after informed consent and IRB approval was obtained. Twenty-eight patients had ICBG harvested for lumbar arthrodesis and nine for cervical arthrodesis. During spinal arthrodesis surgery, patients were randomly assigned to receive 96 mL (2 mL/hr × 48 hours) of either normal saline (control group, n = 22) or 0.5% Marcaine (treatment group, n = 15) delivered via a continuous infusion catheter placed at the ICBG harvest site. All patients received Dilaudid PCA after surgery. Pain scores, narcotic use/frequency, activity level, and length of stay (LOS) were recorded. Physicians, patients, nursing staff, and statisticians were blinded to the treatment. Results. Mean patient age was 60 years and similar between groups. Narcotic dosage, demand frequency, and mean VAS pain score were significantly less in the treatment (Marcaine) group at 24 and 48 hours (P < 0.05). The average LOS was 4.1 days with no difference between Marcaine or control groups. No complications were attributed to the infusion-catheter system. Conclusions. Continuous infusion of 0.5% Marcaine at the ICBG harvest site reduced postoperative parenteral narcotic usage by 50% and decreased overall pain scores. No complications were attributed to the infusion-catheter system. The use of continuous local anesthetic infusion at the iliac crest may help in alleviating acute graft-related pain, hastening patient recovery and improving short-term satisfaction.

Factors Affecting Readmission Rates Following Primary Total Hip Arthroplasty

BACKGROUND Readmissions following total hip arthroplasty are a focus given the forthcoming financial penalties that hospitals in the United States may incur starting in 2015. The purpose of this study was to identify both preoperative comorbidities and postoperative conditions that increase the risk of readmission following total hip arthroplasty. METHODS Using the American College of Surgeons-National Surgical Quality Improvement Program data for 2011, a study population was identified using the Current Procedural Terminology code for primary total hip arthroplasty (27130). The sample was stratified into readmitted and non-readmitted cohorts. Demographic variables, preoperative comorbidities, laboratory values, operative characteristics, and surgical outcomes were compared between the groups using univariate and multivariate logistic regression models. RESULTS Of the 9441 patients, there were 345 readmissions (3.65%) within the first thirty days following surgery. Comorbidities that increased the risk for readmission were diabetes (p < 0.001), chronic obstructive pulmonary disease (p < 0.001), bleeding disorders (p < 0.001), preoperative blood transfusion (p = 0.035), corticosteroid use (p < 0.001), dyspnea (p = 0.001), previous cardiac surgery (p = 0.002), and hypertension (p < 0.001). A multivariate regression model was used to control for potential confounders. Having a body mass index of ≥40 kg/m2 (odds ratio, 1.941 [95% confidence interval, 1.019 to 3.696]; p = 0.044) and using corticosteroids preoperatively (odds ratio, 2.928 [95% confidence interval, 1.731 to 4.953]; p < 0.001) were independently associated with a higher likelihood of readmission, and a high preoperative serum albumin (odds ratio, 0.688 [95% confidence interval, 0.477 to 0.992]; p = 0.045) was independently associated with a lower risk for readmission. Postoperative surgical site infection, pulmonary embolism, deep venous thrombosis, and sepsis (p < 0.001) were also independent risk factors for readmission. CONCLUSIONS The risk of readmission following total hip arthroplasty increases with growing preoperative comorbidity burden, and is specifically increased in patients with a body mass index of ≥40 kg/m2, a history of corticosteroid use, and low preoperative serum albumin and in patients with postoperative surgical site infection, a thromboembolic event, and sepsis. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Can the American College of Surgeons Risk Calculator Predict 30-Day Complications After Knee and Hip Arthroplasty?

Accurate risk stratification of patients undergoing total hip (THA) and knee (TKA) arthroplasty is essential in the highly scrutinized world of pay-for-performance, value-driven healthcare. We assessed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculators ability to predict 30-day complications using 1066 publicly-reported Medicare patients undergoing primary THA or TKA. Risk estimates were significantly associated with complications in the categories of any complication (P = .005), cardiac complication (P < .001), pneumonia (P < .001) and discharge to skilled nursing facility (P < .001). However, predictability of complication occurrence was poor for all complications assessed. To facilitate the equitable provision and reimbursement of patient care, further research is needed to develop accurate risk stratification tools in TKA and THA surgery.

The Effect of BMI on 30 Day Outcomes Following Total Joint Arthroplasty

Hip and knee arthroplasty (THA, TKA) are safe, effective procedures with reliable, reproducible outcomes. We aim to investigate obesitys effect on complications following arthroplasty surgery. Using the American College of Surgeons-National Surgical Quality Improvement Program database, 13,250 subjects were stratified into 5 groups based on BMI and matched for gender, age, surgery type and ASA class. Matched, multivariable generalized linear models adjusting for demographics and comorbidities demonstrated an association between elevated BMI and overall (P<0.001), medical (P=0.005), surgical complications (P<0.001), including superficial (P=0.019) and deep wound infection (P=0.040), return to OR (P=0.016) and time from OR to discharge (P=0.003). Elevated BMI increases risk for post-operative complications following total joint arthroplasty.

Do Patients With Insulin-dependent and Noninsulin-dependent Diabetes Have Different Risks for Complications After Arthroplasty?

BackgroundPatients with diabetes are known to be at greater risk for complications after arthroplasty than are patients without diabetes. However, we do not know whether there are important differences in the risk of perioperative complications between patients with diabetes who are insulin-dependent (Type 1 or 2) and those who are not insulin-dependent. Questions/purposes The purpose of our study was to compare (1) medical complications (including death), (2) surgical complications, and (3) readmissions within 30 days between patients with insulin-dependent and noninsulin-dependent diabetes, and with patients who do not have diabetes.MethodsA total of 43,299 patients undergoing THA or TKA between 2005 and 2011 were selected from the American College of Surgeon’s National Surgical Quality Improvement Program’s (ACS-NSQIP®) database. Generalized linear models were used to assess the relationship between diabetes status and outcomes (no diabetes [n = 36,574], insulin dependent [n = 1552], and noninsulin dependent [n = 5173]). Multivariate models were established adjusting for confounders including age, sex, race, BMI, smoking, steroid use, hypertension, chronic obstructive pulmonary disease, and anesthesia type. Post hoc comparisons between patient groups were made using a Bonferroni correction.ResultsPatients who were insulin dependent had increased odds of experiencing a medical complication (OR, 1.6; 95% CI, 1.2–2.0; p < 0.001), as did patients who were noninsulin dependent (OR, 1.2; 95% CI, 1.1–1.4; p< 0.001). An increased likelihood of 30-day mortality was found only for patients who were insulin dependent (OR, 3.74; 95% CI, 1.6–8.5; p = 0.007). However, neither diabetic state was associated with surgical complications. Finally, readmission was found to be independently associated with insulin-dependent diabetes (OR, 1.6; 95% CI, 1.1–2.1; p = 0.023).ConclusionsPatients with insulin-dependent diabetes are most likely to have a medical complication or be readmitted within 30 days after total joint replacement. However, patients who are insulin dependent or noninsulin dependent are no more likely than patients without diabetes to have a surgical complication. Physicians and hospitals should keep these issues in mind when counseling patients and generating risk-adjusted outcome reports.Level of EvidenceLevel III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

A late vascular complication due to component migration after revision total hip arthroplasty.

Although vascular injuries associated with primary and revision total hip arthroplasty are infrequent, these complications can have devastating effects that can lead to morbidity and even mortality. No previous reports have described embolic distal limb ischemia secondary to a failed and migrated acetabular implant in discontinuity with the pelvis. We present a novel case in which a screw from a failed and migrated acetabular cage construct led to injury of the superficial femoral artery. While awaiting the construction of a custom prosthesis, the patient developed thromboembolism leading to distal extremity ischemia. The patient was treated with thrombolytic therapy, anticoagulation, removal of the offending hardware, forefoot amputation, and later hip reconstruction. Recognition of the risks associated with failed and migrated components may prevent this complication in the future.

Perioperative Outcomes Following Unilateral Versus Bilateral Total Knee Arthroplasty.

Simultaneous bilateral total knee arthroplasty (SB-TKA) is potentially a cost saving manner of caring for patients with bilateral symptomatic knee arthritis. We performed a retrospective analysis using the 2010-2012 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) to evaluate the risk of perioperative complication following SB-TKA. Demographic characteristics, comorbidities, and 30-day complication rates were studied using a propensity score-matched analysis comparing patients undergoing unilateral TKA and SB-TKA. A total of 4489 patients met the inclusion criteria, of which 973 were SB-TKA. SB-TKA was associated with increased overall complications (P = 0.023), medical complications (P = 0.002) and reoperation (OR 2.12, P = 0.020). Further, total length of hospital stay (4.0 vs 3.4 days, P < 0.001) was significantly longer following bilateral surgery.

Transfusion support for a patient with McLeod phenotype without chronic granulomatous disease and with antibodies to Kx and Km

Background and Objectives  Kell antigens are encoded by the KEL gene on the long arm of chromosome 7. Kx antigen is encoded by the XK gene on the short arm of the X chromosome. Kell and Kx proteins in the red cell membrane are covalently linked by a disulphide bond. The McLeod phenotype is characterized by weakened expression of antigens in the Kell blood group system, absence of Km and Kx antigens, and acanthocytosis. It has an X‐linked mode of inheritance with transmission through carrier females. Some males with the McLeod syndrome also have chronic granulomatous disease (CGD). It is generally believed that patients with non‐CGD McLeod may develop anti‐Km but not anti‐Kx, but that those with CGD McLeod can develop both anti‐Km and anti‐Kx.