A goal of osteoporosis therapy is to restore lost bone with structurally sound tissue. Mice lacking the transcription factor nuclear matrix protein 4 (
,
,
,
) respond to several classes of ...osteoporosis drugs with enhanced bone formation compared with wild-type (WT) animals.
mesenchymal stem/progenitor cells (MSPCs) exhibit an accelerated and enhanced mineralization during osteoblast differentiation. To address the mechanisms underlying this hyperanabolic phenotype, we carried out RNA-sequencing and molecular and cellular analyses of WT and
MSPCs during osteogenesis to define pathways and mechanisms associated with elevated matrix production. We determined that
has a broad impact on the transcriptome during osteogenic differentiation, contributing to the expression of over 5,000 genes. Phenotypic anchoring of transcriptional data was performed for the hypothesis-testing arm through analysis of cell metabolism, protein synthesis and secretion, and bone material properties. Mechanistic studies confirmed that
MSPCs exhibited an enhanced capacity for glycolytic conversion: a key step in bone anabolism.
cells showed elevated collagen translation and secretion. The expression of matrix genes that contribute to bone material-level mechanical properties was elevated in
cells, an observation that was supported by biomechanical testing of bone samples from
and WT mice. We conclude that loss of
increases the magnitude of glycolysis upon the metabolic switch, which fuels the conversion of the osteoblast into a super-secretor of matrix resulting in more bone with improvements in intrinsic quality.
The opioid crisis has illuminated the risks of opioid use for pain management, with renewed interest in reducing opioid consumption after common orthopedic procedures. Anti-inflammatory medication is ...an important component of multimodal pain management for patients undergoing orthopedic surgery. The purpose of this study was to evaluate the effect of celecoxib on pain control and opioid use after shoulder surgery.
Patients scheduled for either total shoulder replacement (group 1) or rotator cuff repair (group 2) were candidates for the study. The exclusion criteria included allergy to celecoxib, coagulopathy, use of anticoagulants, baseline use of long-acting opioids, and a history of medical conditions such as myocardial infarction or stroke. Consenting patients were randomized by type of procedure using block randomization to receive either placebo or celecoxib 1 hour prior to the procedure and for 3 weeks postoperatively. The primary outcome measure assessed was opioid utilization as measured by morphine-equivalent dose (MED). Secondary outcome measures included pain scores at 3 and 6 weeks postoperatively. Data were analyzed using multiple linear regression.
Of 1081 patients scheduled for either total shoulder replacement or rotator cuff repair from February 2014 to February 2018, 78 were enrolled for arthroplasty (group 1, with 39 receiving celecoxib and 39 receiving placebo) and 79 were enrolled for rotator cuff repair (group 2, with 40 receiving celecoxib and 39 receiving placebo). Compared with the placebo arm, patients prescribed celecoxib took fewer MEDs by –168 (95% confidence interval CI, –272 to –64; P < .01) at 3 weeks in the total population and by –197.7 (95% CI, –358 to –38; P = .02) in the arthroplasty group. Similarly, at 6 weeks, total MEDs used was –199 (95% CI, –356 to –42; P < .01) in the total population and –270 (95% CI, –524 to –16; P = .04) in the arthroplasty group. No statistically significant differences in opioid consumption were found between study arms in the cuff repair group, at either 3 or 6 weeks. Of note, preoperative opioid use was statistically associated with higher levels of opioid use in the total population and group 1 at 3 and 6 weeks (P < .01 for all) but not in group 2 (P > .05 for both).
Use of morphine equivalents was statistically significantly less at 3 and 6 weeks in patients who took celecoxib in the total population and in the arthroplasty group. Patients prescribed celecoxib for 3 weeks after shoulder surgery took less opioid medication for pain at 3 and 6 weeks. Multimodal pain control using celecoxib is an effective way to reduce postoperative opioid use in shoulder arthroplasty patients. Preoperative opioid use is associated with higher levels of opioid use after shoulder arthroplasty.
To determine the cost-effectiveness of knotted (KT) versus knotless (KL) methods for rotator cuff surgical repair and to assess differences in patients’ outcomes.
We retrospectively identified all ...patients who underwent arthroscopic rotator cuff repair at 1 institution by 1 surgeon over 2 6-month periods of time (KT technique from August 1, 2013, through January 31, 2014; and KL technique from December 1, 2014, through May 31, 2015) to calculate the direct and indirect costs associated with arthroscopic KT or KL suture bridge rotator cuff repair. Patient demographics, number of anchors used, tendons repaired, procedure time, operative time, and clinical results were also evaluated. We used univariate generalized linear models with a Gaussian distribution for assessment scores and total and implant cost data.
We identified 87 patients for inclusion during the 2 time frames (35 KT, 54 KL). After excluding patients for tear size < 4 cm2 (n = 42), ≤ 3 anchors (n = 5), revision surgery (n = 1), and those in whom additional procedures were performed (n = 2), 37 eligible subjects remained (nKT = 15, nKL = 22). Median implant costs were statistically significantly higher in the KL group than in the KT group (MKL = $2,127, MKT = $1,520, β = 413.7, 95% CI: 242.8, 584.6, P < .01), and more anchors were used in the KL group, with KT requiring a median of 4 anchors (IQR: 4, 5) and KL requiring a median of 5 anchors (IQR: 5, 5, P = .02). Procedure time was cut in half with KL repair (estimated 43.5 minutes) versus KT repair (80 minutes) (β = 0.5, 95% CI: 0.4, 0.6, P < .001). Operating room time also was reduced by approximately 40% (79.5 minutes for KL; 121 minutes for KT β = 0.6, CI: 0.6, 0.7, P < .001). Once operating room costs were considered, median costs were found to be significantly lower in the KL group (MKL = $3788.40, MKT = $4262.90, β = –492.1, 95% CI: –840.0, –144.1, P < .01). No statistically significant differences were found between groups in mean preoperative, postoperative or postpreoperative differences in the visual analog scale, Simple Shoulder Test, American Shoulder and Elbow Surgeons, or University of California at Los Angeles scores (P > 0.05 for all).
Despite using more anchors and incurring higher implant costs, the KL technique for rotator cuff repair required less surgical procedure time and cost less overall than the KT technique and resulted in equivalent clinical results.
Level IV Economic and Decision Analyses.
Use of anti-inflammatory medications (NSAIDs) is an important component of multimodal pain control after orthopedic procedures to avoid opioid overutilization and abuse. However, the deleterious ...effects of NSAIDs on tendon healing are of particular concern in rotator cuff repair (RCR). The purpose of this study was to evaluate the effect of celecoxib or placebo on healing rates after RCR when administered in the perioperative and immediate postoperative period using MRI evaluation at one year postoperatively. A secondary aim was to determine whether clinical differences existed between patients with intact or non-intact repairs.
Patients aged ≤65 years with partial- or full-thickness rotator cuff tear (<25x25 mm) were randomized to receive celecoxib 400 mg or placebo 1 hour before the procedure and 200mg bid for 3 weeks postoperatively. All patients were treated as clinically indicated at the time of surgery and followed standard postoperative protocol. Repair integrity was evaluated with MRI using the Sugaya classification for repair integrity. Data were analyzed using multivariable logistic regression by intent to treat.
Seventy-nine patients were enrolled; 21 were lost to follow-up, 6 did not have cuff repair, 5 were revised, and 2 declined follow-up, leaving 45 patients with one-year follow-up. Five of these patients did not complete MRI, leaving 40 patients for review. Eighteen of 20 patients (90%) who received celecoxib completed all doses of study medication as did 15 of 20 patients (75%) who received placebo. The patient groups were similar for demographics, clinical results, and healing rate. After adjusting for tear size, no statistically significant difference in healing rate was found between groups, with 10 of 20 celecoxib patients (50%) having intact repair at 1 year compared with 14 of 20 placebo patients (70%) (OR = 0.53, 95% CI: 0.14, 2.08, P = 0.35).
Half of the patients who received celecoxib had an intact repair compared with 70% intact repair for patients receiving placebo. Although not statistically significant in this small study, larger studies are needed to clarify this important clinical concern. The authors do not recommend use of celecoxib for postoperative pain control after RCR.
Reported blood transfusion rates after total shoulder arthroplasty (TSA) range from 4.5% to 43%, and reported risk factors include race, female sex, prosthesis type (reverse), revision, age, anemia, ...low preoperative hemoglobin, and number of comorbidities. The purpose of this study was to develop a predictive model for transfusion in anatomic/hemi and reverse shoulder arthroplasty patients and to estimate the transfusion rate in a community hospital setting.
A retrospective cohort of 265 shoulder arthroplasties (79 anatomic, 182 reverse, and 4 hemiarthroplasties) performed consecutively by 1 surgeon at 1 institution from May 2013 to May 2016 was assembled. Two patients were excluded for insufficient data, leaving 263 patients for analysis. Sensitivity, specificity, area under the curve, and cut points using estimated blood loss (EBL), history of anemia, and preoperative hemoglobin level were calculated, based on a logistic regression model.
The overall transfusion rate was 2.3% (6/265). Higher EBL (P = .003), lower preoperative hemoglobin level (P = .030), and history of anemia (P = .088) were predictive of transfusion with a sensitivity of 80.0% and a specificity of 99.6%. In this cohort, patients with a history of anemia had transfusion risk when an EBL of ≥300 mL was combined with a preoperative hemoglobin level <10.9, resulting in a sensitivity of 1.0 and a specificity of 0.96. Factors associated with transfusion in univariate models included arthroplasty for fracture (P < .001), cemented stem (P < .001), length of stay (P < .001), EBL (P < .001), operative time (P < .001), and preoperative hemoglobin (P = .004) and hematocrit levels (P = .004).
Patients with a history of anemia, a preoperative hemoglobin level <10.9, and an intraoperative EBL ≥300 mL are at high risk for transfusion after TSA.
PURPOSEResults of a study comparing the performance of allometric versus consensus guideline–recommended vancomycin dosing in achieving initial trough concentrations within the desired range are ...reported.
METHODSA retrospective study was conducted to compare selected outcomes with 2 vancomycin dosing methods(1) dosing by total body weight, as recommended in current consensus guidelines, and (2) a new empirical vancomycin dosing strategy grounded in allometry (the study of the relationship between body size and physiology). The primary outcome was attainment of an initial vancomycin trough concentration within the target range (10–20 mg/L). Rates of nephrotoxicity associated with the 2 dosing methods were compared.
RESULTSAllometric dosing resulted in 77% of the evaluated patient sample (n = 81) achieving vancomycin trough concentration targets at the initial measurement, as compared with a target attainment rate of 57% (n = 81) with guideline-recommended dosing (p = 0.0121); the rate of target attainment in obese patients was also improved with allometric dosing (73% versus 46%, p = 0.0327). Nephrotoxicity rates did not differ significantly between the 2 groups, but a lower rate was observed with allometric versus guideline-based dosing (1.2% versus 7.4%, p = 0.0584).
CONCLUSIONIn hospitalized adults, allometric vancomycin dosing achieved a higher frequency of initial vancomycin trough concentrations within the target range of 10–20 mg/L, compared with dosing as recommended by consensus guidelines. The difference between methods in the percentage of troughs within the target range was most pronounced in obese patients.
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