Clinical Orthopaedics and Related Research

Clinical Orthopaedics and Related Research

Editorial: Thanking CORR’s Peer Reviewers

01-12-2019 – Leopold, Seth S.

Journal Article

No abstract available

Editor’s Spotlight/Take 5: Is Insurance Status Associated with the Likelihood of Operative Treatment of Clavicle Fractures?

01-12-2019 – Leopold, Seth S.

Journal Article

No abstract available

Is Insurance Status Associated with the Likelihood of Operative Treatment of Clavicle Fractures?

01-12-2019 – Congiusta, Dominick V.; Amer, Kamil M.; Merchant, Aziz M.; Vosbikian, Michael M.; Ahmed, Irfan H.

Journal Article

Background Most closed clavicle fractures are treated nonoperatively. Research during the past decade has reported differences in the treatment of clavicle fractures based on insurance status in the US and may highlight unmet needs in a vulnerable population, particularly because new data show that surgery may lead to improved outcomes in select populations. Large-scale, national data are needed to better inform this debate.
Questions/purposes (1) Does the likelihood of operative fixation of closed clavicle fractures vary among patients with different types of insurance? (2) What demographic and socioeconomic factors are associated with the likelihood of clavicle fracture surgery? (3) Has the proportion of operative fixation of clavicle fractures changed over time?Methods A retrospective analysis of the Nationwide Inpatient Sample 2001-2013 database was performed. This database is the largest publicly available all-payer inpatient database in the US that provides pertinent socioeconomic data on a nationwide scale. Data were queried for patients with closed clavicle fractures using International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes, and surgery was determined using ICD-9 procedural codes. A total of 252,109 patients were included in the final analysis after 158,619 patients were excluded because of missing demographic or insurance data, ambiguous fracture location, or age younger than 19 years. Of the 252,109 included patients, 21,638 (9%) underwent surgical fixation of clavicle fractures. A chi-square analysis was performed to determine variables to be included in a multivariable analysis. A binary logistic regression analysis was used to examine demographic and other important variables, with a significance level of p < 0.01. Poisson’s regression and a t-test were used to analyze trends over time. Results were recorded as odds ratios (OR) and incidence rate ratios.
Results After controlling for demographic and potentially relevant variables, such as the median income and fracture location, we found that patients with Medicare, Medicaid, and no insurance had a lower likelihood of undergoing operative fixation of clavicle fractures than did those with private insurance. Patients without insurance were the least likely to undergo surgery (OR, 0.63; 95% CI, 0.60-0.66; p < 0.001), followed by those with Medicare (OR, 0.73; 95% CI, 0.70-0.78; p < 0.001) and those with Medicaid (OR, 0.74; 95% CI, 0.69-0.78; p < 0.001). Women, black, and Hispanic patients were also less likely to undergo surgery than men and white patients (OR, 0.95; p = 0.003; OR = 0.67; p < 0.001; and OR = 0.82; p < 0.001, respectively) There was an increase in the overall proportion of patients undergoing surgery, from 5% in 2001 to 11% in 2013 (incidence rate ratio, 2.99; p < 0.001).
Conclusions We believe that the greater use of surgery among adult patients with clavicle fractures who have private insurance than among those with nonprivate or no insurance—as well as among men and white patients compared with women and patients of color—may be a manifestation of important health care disparities in the inpatient population. This may be owing to variable access to care or a difference in the likelihood that a surgeon will offer surgery based on a patient’s insurance status. Because operative fixation of closed clavicle fractures increases in the adult population, future research should elucidate conscious and subconscious motivations of patients and surgeons to better inform the discussion of health care disparities in orthopaedics.
Level of Evidence Level III, therapeutic study.

Clinical Faceoff: Should Orthopaedic Surgeons Have Strict BMI Cutoffs for Performing Primary TKA and THA?

01-12-2019 – Ricciardi, Benjamin F.; Giori, Nicholas J.; Fehring, Thomas K.

Journal Article

No abstract available

Not the Last Word: Roll Them Bones—Selecting Orthopaedic Surgery Residents by Lottery

01-12-2019 – Bernstein, Joseph

Journal Article

No abstract available

Virtue Ethics in a Value-driven World: Ethical Telemedicine

01-12-2019 – Humbyrd, Casey Jo

Journal Article

No abstract available

From Bench to Bedside: Synthesizing Better Replacements and Reconstructions

01-12-2019 – Potter, Benjamin K.

Journal Article

No abstract available

Your Best Life: Unlock More Time in Your Day for Rest and Relaxation—That’s an Order

01-12-2019 – Kelly, John D. IV

Journal Article

No abstract available

Giants of Orthopaedic Surgery: Henry J. Mankin MD

01-12-2019 – Hornicek, Francis J.

Journal Article

No abstract available

ArtiFacts: Fighting Wartime Wound Infections with the Carrel-Dakin Method

01-12-2019 – Hawk, Alan J.

Journal Article

No abstract available

Depression and Non-modifiable Patient Factors Associated with Patient Satisfaction in an Academic Orthopaedic Outpatient Clinic: Is it More Than a Provider Issue?

01-12-2019 – Tisano, Breann K.; Nakonezny, Paul A.; Gross, Bruno S.; Martinez, J. Riley; Wells, Joel E.

Journal Article

Background Patient satisfaction surveys play an increasingly important role in United States healthcare policy and serve as a marker of provided physician services. In attempts to improve the patient’s clinical experience, focus is often placed on components of the healthcare system such as provider interaction and other experiential factors. Patient factors are often written off as “non-modifiable”; however, by identifying and understanding these risk factors for dissatisfaction, another area for improvement and intervention becomes available.
Questions/purposes (1) Do patients in the orthopaedic clinic with a preexisting diagnosis of depression report lower satisfaction scores than those without a preexisting diagnosis of depression? (2) What other non-modifiable patient factors influence patient-reported satisfaction?Methods We reviewed Press Ganey Survey scores, which assess patient experiential satisfaction with a single clinical encounter, from 3044 clinic visits (2527 patients) in adult reconstructive, sports, and general orthopaedic clinics at a single academic medical center between November 2010 and May 2017, during which time approximately 19,000 encounters occurred. Multiple patient factors including patient age, gender, race, health insurance status, number of previous clinic visits with their physician, BMI, and a diagnosis of depression were recorded. Patient satisfaction was operationalized as a binary outcome as satisfied or less satisfied, and a multiple logistic regression analysis was used to estimate the odds of being satisfied.
Results After adjusting for all other covariates in the model, we found that patients with a diagnosis of depression were less likely to be satisfied than patients without this diagnosis (odds ratio 0.749 95% confidence interval, 0.600-0.940; p = 0.01). Medicare-insured patients were more likely to be satisfied than non-Medicare patients (OR 1.257 95% CI, 1.020-1.549; p = 0.03), patients in the sports medicine clinic were more likely to be satisfied than those seen in the general orthopaedic clinic (OR 1.397 95% CI, 1.096-1.775; p = 0.007), and established patients were more likely to be satisfied than new patients (OR 0.763 95% CI, 0.646-0.902; p = 0.002).
Conclusions Given the association of depression with lower satisfaction with a single visit at the orthopaedic clinic, providers should screen for depression and address the issue during the outpatient encounter. The impact of such comprehensive care or subsequent treatment of depression on improving patient-reported satisfaction offers areas of future study.
Level of Evidence Level III, therapeutic study.

CORR Insights®: Depression and Non-modifiable Patient Factors Associated with Patient Satisfaction in an Academic Orthopaedic Outpatient Clinic: Is it More Than a Provider Issue?

01-12-2019 – Novicoff, Wendy M.

Journal Article

No abstract available

What are the Implications of Excessive Internet Searches for Medical Information by Orthopaedic Patients?

01-12-2019 – Blackburn, Julia; Fischerauer, Stefan F.; Talaei-Khoei, Mojtaba; Chen, Neal C.; Oh, Luke S.; Vranceanu, Ana-Maria

Journal Article

Background Cyberchondria may be defined as heightened distress evoked through excessive searches of the internet for medical information. In healthy people, cyberchondria is associated with a greater intolerance of uncertainty and greater health anxiety. These relationships are likely bidirectional. People who have a greater intolerance of uncertainty may be more likely to search the internet for medical information and have greater health anxiety. This greater health anxiety may lead to an increased likelihood of engaging in further internet searches and greater intolerance of uncertainty. These three constructs are important for patients because they impact patient function and health care costs. We were specifically interested in understanding the role of cyberchondria in the association between intolerance of uncertainty and health anxiety among orthopaedic patients because it has not been explored before and because knowledge about these interactions could inform treatment recommendations.
Questions/purposes Does cyberchondria mediate (that is, explain) the association between intolerance of uncertainty and health anxiety in orthopaedic patients searching for medical information on the internet, after controlling for potentially confounding variables?Methods This was a cross-sectional study of 104 patients who had searched the internet for any medical information about their current condition. A research assistant approached 155 patients attending two orthopaedic outpatient clinics, one hand and upper extremity service and one sports medicine clinic, during a 3-month period. Ten patients declined to participate and 41 patients were excluded, predominantly because they had never searched for medical information online. The patients completed the Cyberchondria Severity Scale, Intolerance of Uncertainty Scale-short version, Short Health Anxiety Inventory, and a numerical rating scale for pain intensity at baseline, as well as demographic and clinical questionnaires. We performed a series of linear regression analyses to determine whether a greater intolerance of uncertainty predicts greater cyberchondria (mediator) and whether cyberchondria predicts greater health anxiety. Although it is more appropriate to use the language of association (such as “whether cyberchondria is associated with health anxiety”) in many observational studies, here, we opted to use the language of causation because this is the conventional language for studies testing statistical mediation.
Results After controlling for potentially confounding variables including pain intensity, multiple pain conditions, and education, cyberchondria explained 33% of the variance of the effect of intolerance of uncertainty on health anxiety (95% CI, 6.98 to 114.72%; p < 0.001).
Conclusions Among orthopaedic patients who search the internet for medical information, a greater intolerance of uncertainty is associated with greater cyberchondria, which is associated with greater anxiety about health. Identifying patients with an intolerance of uncertainty and educating them about the negative role of compulsive searches for medical information may improve the success of orthopaedic treatment. Orthopaedic surgeons should also consider making referrals for cognitive behavioral therapy in these instances to increase the patient’s tolerance of uncertainty, decrease internet searching habits, and reduce anxiety about health.
Level of Evidence Level III, prognostic study.

CORR Insights®: What are the Implications of Excessive Internet Searches for Medical Information by Orthopaedic Patients?

01-12-2019 – Crijns, Tom J.

Journal Article

No abstract available

Prediction of Autograft Hamstring Size for Anterior Cruciate Ligament Reconstruction Using MRI

01-12-2019 – Hollnagel, Katharine; Johnson, Brent M.; Whitmer, Kelley K.; Hanna, Andrew; Miller, Thomas K.

Journal Article

Background Hamstring autografts with a diameter of less than 8 mm for ACL reconstruction have an increased risk of failure, but there is no consensus regarding the best method to predict autograft size in ACL reconstruction.
Questions/purposes (1) What is the relationship between hamstring cross-section on preoperative MRI and intraoperative autograft size? (2) What is the minimum hamstring tendon cross-sectional area on MRI needed to produce an autograft of at least 8 mm at its thickest point?Methods This was a retrospective cohort study of 68 patients. We collectively reviewed patients who underwent ACL reconstruction by three separate fellowship-trained surgeons at the Carilion Clinic between April 2010 and July 2013. We searched the patient records database of each surgeon using the keyword “ACL”. A total of 293 ACL reconstructions were performed during that time period. Of those, 23% (68 patients) had their preoperative MRI (1.5 T or 3 T magnet) performed at the Carilion Clinic with MRI confirmation of acute total ACL rupture. Exclusion criteria included previous ACL reconstructions, multiligamentous injuries, and history of acute hamstring injuries.
After applying the exclusion criteria, there were 29 patients in the 1.5 T magnet group and 39 in the 3 T group. Median age (range) was 29 years (12 to 50) for the 1.5 T group and 19 years (9 to 43) for the 3 T group. The patients were 41% female in the 1.5 T group and 23% female in the 3 T group. Use of 1.5 T or 3 T magnets was based on clinical availability and scheduling. The graft’s preoperative cross-sectional area was compared with the intraoperative graft’s diameter. The MRI measurements were performed by a single musculoskeletal radiologist at the widest point of the medial femoral condyle and at the joint line. Intraoperative measurements were performed by recording the smallest hole the graft could fit through at its widest point. Pearson’s correlation coefficients were calculated to determine the relationship between graft size and tendon cross-sectional area. A simple logistic regression analysis was used to calculate the cutoff cross-sectional areas needed for a graft measuring at least 8 mm at its thickest point. Intrarater reliability was evaluated based on re-measurement of 19 tendons, which produced an overall intraclass correlation coefficient (ICC) of 0.96 95% (CI 0.93 to 0.98). A p value < 0.05 was considered significant.
Results In general, the correlation between MRI-measured hamstring thickness and hamstring graft thickness as measured in the operating room were good but not excellent. The three measurements that demonstrated the strongest correlation with graft size in the 1.5 T group were the semitendinosus at the medial femoral condyle (r = 0.69; p < 0.001), the semitendinosus and gracilis at the medial femoral condyle (r = 0.70; p < 0.001), and the mean semitendinosus and gracilis (r = 0.64; p < 0.001). These three measurements had correlation values of 0.53, 0.56, and 0.56, respectively, in the 3 T MRI group (all p values < 0.001). To create an 8-mm hamstring autograft, the mean semitendinosus plus gracilis cutoff values areas were 18.8 mm2 and 17.5 mm2 for the 1.5 T and 3.0 T MRI groups, respectively.
Conclusions Imaging performed according to routine knee injury protocol can be used to preoperatively predict the size of hamstring autografts for ACL reconstructions. In clinical practice, this can assist orthopaedic surgeons in graft selection and surgical planning.
Level of Evidence Level II, diagnostic study.

CORR Insights®: Prediction of Autograft Hamstring Size for Anterior Cruciate Ligament Reconstruction Using MRI

01-12-2019 – Nuber, Gordon W.

Journal Article

No abstract available

The “Cough Trick” Reduces Pain During Removal of Closed-suction Drains after Total Knee Arthroplasty: A Randomized Trial

01-12-2019 – Yuenyongviwat, Varah; Iamthanaporn, Khanin; Tuntarattanapong, Pakjai; Hongnaparak, Theerawit

Journal Article

Background Drain removal after TKA can be painful. Prior research suggests that the “cough trick,” in which a patient coughs at the same time she or he receives an injection, effectively decreases pain. To our knowledge, this intervention has not been evaluated as a way to reduce pain during other brief but painful interventions, such as removal of closed-suction drains after orthopaedic surgery.
Question/purpose Does the cough trick reduce pain while a surgeon is removing a closed-suction drain after TKA?Methods Fifty-six patients with primary osteoarthritis who underwent primary TKA were randomized into two groups: drain removal as the patient coughed (n = 28 patients; three men, 25 women) or drain removal using the usual process, without the cough trick (n = 28 patients; three men, 25 women). The study groups were not different in terms of gender, BMI, surgical time, or other baseline variables, and other than the addition of the cough trick, there were no differences in surgical treatment or other elements of aftercare. Likewise, at baseline, the verbal numeric rating scale (VNRS) score for pain before the drain was removed was not different between the groups (3.1 ± 1.7 versus 3.3 ± 1.3; p = 0.72). The level of pain before and during drain removal was recorded using a VNRS by an orthopaedic surgeon who was not involved in the care of the study patients. We considered the minimum clinically important difference on the 10-point scale to be 2 points, based on prior evidence.
Results The mean ± SD VNRS for the pain level during drain removal was lower in the cough trick group than that in the control group (1.6 ± 1.0 versus 3.7 ± 1.9, mean difference 2.1; 95% CI, 1.3-2.9; p < 0.001).
Conclusions The cough trick during removal of a closed-suction drain tube in patients undergoing TKA reduced the level of pain in this small randomized trial. We suggest that surgeons consider this technique when removing drains after TKA because it is a noninvasive technique and it is easy to perform. Because the cough trick has been shown by others to be effective at reducing pain during venipuncture and parenteral injections, and we found it was effective for that purpose during drain removal after TKA, we believe this finding probably generalizes well to most minor procedures that cause transient, sharp pain. We suggest that it could be used to make such procedures more comfortable for patients, as well as for drain removal in other types of surgery where drains still are commonly used (including spine surgery and tumor surgery).
Level of Evidence Level I, therapeutic study.

Are Skin Fiducials Comparable to Bone Fiducials for Registration When Planning Navigation-assisted Musculoskeletal Tumor Resections in a Cadaveric Simulated Tumor Model?

01-12-2019 – Zamora, Rodolfo; Punt, Stephanie E.; Christman-Skieller, Claudia; Yildirim, Cengiz; Shapton, John C.; Conrad, Ernest U. 3rd,

Journal Article

Background To improve and achieve adequate bony surgical margins, surgeons may consider computer-aided navigation a promising intraoperative tool, currently applied to a relatively few number of patients in whom freehand resections might be challenging. Placing fiducials (markers) in the bone, identifying specific anatomical landmarks, and registering patients for navigated resections are time consuming. To reduce the time both preoperatively and intraoperatively, skin fiducials may offer an efficient and alternative method of navigation registration.
Questions/purposes (1) Does preoperative navigation using skin fiducials for registration allow the surgeon to achieve margins similar to those from bone fiducial registration in a simulated lower extremity tumor resection model in cadavers? (2) Does the use of preoperative navigation using skin fiducials for registration allow the surgeon to achieve similar bony margins in pelvic resections of simulated tumors as those achieved in long-bone resections using only skin fiducials for navigation in a cadaver model?Methods Simulated bone tumor resections were performed in three fresh-frozen cadavers with intact pelvic and lower-extremity anatomy using navigation guidance. We placed 5-cm intraosseous cement simulated bone tumors in the proximal/distal femur (n = 12), and proximal/distal tibia (n = 12) and pelvis (supraacetabular; n = 6). After bone tumor implantation, CT images of the pelvis and lower extremities were obtained. Each planned osseous resection margin was set at 10 mm. Navigation registration was performed for each simulated tumor using bone and skin markers that act as a point of reference (fiducials). The simulated bone tumor was resected based on a resection line that was established with navigation, and the corresponding osseous margins were calculated after resection. These margins were determined by an orthopaedic surgeon who was blinded to resection planning by the removal of cancellous bone around the cement simulated tumor. The shortest distance was measured from the cement to the resection line. Smaller mean differences between planned and postoperative margins were considered accurate. Independent t-tests were conducted to assess measurement differences between planned and postoperative margins at the 95% CI. Bland-Altman analyses were conducted to compare the deviation in margin difference between planned and postoperative margins in skin and bone fiducial registration, respectively.
Results In all, 84 total resection margins were measured with 48 long bone and 20 pelvic obtained with skin fiducials and 16 long bone obtained with bone fiducials. The planned mean margin was 10 mm for all long bone and pelvic resections. We found that skin fiducial and bone fiducial postoperative margins had comparable accuracy when resecting long bones (10 ± 2 mm versus 9 ± 2 mm, mean difference 1 95% CI 0 to 2; p = 0.16). Additionally, skin fiducial long bone postoperative margins were comparable in accuracy to pelvic supraacetabular postoperative margins obtained with skin fiducials (10 ± 2 mm versus 11 ± 3 mm, mean difference -1 mm 95% CI -3 to 1; p = 0.22). When comparing the deviation in margin difference between planned and postoperative margins in skin and bone fiducial registration, 90% (61 of 68) of skin fiducial and 100% (16 of 16) bone fiducial postoperative margins fell within 2 SDs.
Conclusions In this pilot study, skin fiducial markers were easy to identify on the skin surface of the cadaver model and on CT images used to plan margins. This technique appears to be an accurate way to plan margins in this model, but it needs to be tested thoroughly in patients to determine if it may be a better clinical approach than with bone fiducials.
Clinical Relevance The margins obtained using skin fiducials and bone fiducials for registration were similar and comparable in this pilot study with a very small effect size. Boundaries of the simulated tumors were not violated in any resections. Skin fiducials are easier to identify than bone fiducials (anatomic landmarks). If future clinical studies demonstrate that margins obtained using skin fiducials for registration are similar to margins obtained with anatomical landmarks, the use of navigation with skin fiducials instead of bone fiducials may be advantageous. This technique may decrease the surgeon’s time used to plan for and localize registration points and offer an alternative registration technique, providing the surgeon with other registration approaches.

CORR Insights®: Are Skin Fiducials Comparable to Bone Fiducials for Registration When Planning Navigation-assisted Musculoskeletal Tumor Resections in a Cadaveric Simulated Tumor Model?

01-12-2019 – Temple, H. Thomas

Journal Article

No abstract available

What is the Likelihood That Tumor Endoprostheses Will Experience a Second Complication After First Revision in Patients With Primary Malignant Bone Tumors And What Are Potential Risk Factors?

01-12-2019 – Theil, C.; Röder, J.; Gosheger, G.; Deventer, N.; Dieckmann, R.; Schorn, D.; Hardes, J.; Andreou, D.

Journal Article

Background Endoprosthetic reconstruction of massive bone defects has become the reconstruction method of choice after limb-sparing resection of primary malignant tumors of the long bones. Given the improved survival rates of patients with extremity bone sarcomas, an increasing number of patients survive but have prosthetic complications over time. Several studies have reported on the outcome of first endoprosthetic complications. However, no comprehensive data, to our knowledge, are available on the likelihood of an additional complication and the associated risk factors, despite the impact of this issue on the affected patients.
Questions/purposes (1) What are the types and timing of complications and the implant survivorship free from revision after the first complication? (2) Does survivorship free from repeat revision for a second complication differ by anatomic sites? (3) Is the type of first complication associated with the risk or the type of a second complication? (4) Are patient-, tumor-, and treatment-related factors associated with a higher likelihood of repeat revision?Methods Between 1993 and 2015, 817 patients underwent megaprosthetic reconstruction after resection of a tumor in the long bones with a single design of a megaprosthetic system. No other prosthetic system was used during the study period. Of those, 75% (616 of 817) had a bone sarcoma. Seventeen patients (3%) had a follow-up of less than 6 months, 4.5% (27 of 599) died with the implant intact before 6 months and 43% (260 of 599 patients) underwent revision. Forty-three percent of patients (260 of 599) experienced a first prosthetic complication during the follow-up period. Ten percent of patients (26 of 260) underwent amputation after the first complication and were excluded from further analysis. Second complications were classified using the classification of Henderson et al. to categorize surgical results. Briefly, this system categorizes complications as wound dehiscence (Type 1); aseptic loosening (Type 2); implant fractures or breakage and periprosthetic fracture (Type 3); infection (Type 4); and tumor progression (Type 5). Implant survival curves were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HR) were estimated with their respective 95% CIs in multivariate Cox regression models.
Results A second complication occurred in 49% of patients (115 of 234) after a median of 17 months (interquartile range IQR 5 to 48) after the surgery for the first complication. The time to complication did not differ between the first (median 16 months; IQR 5 to 57) and second complication (median 17 months; IQR 5 to 48; p = 0.976). The implant survivorship free from revision surgery for a second complication was 69% (95% CI 63 to 76) at 2 years and 46% (95% CI 38 to 53) at 5 years. The most common mode of second complication was infection 39% (45 of 115), followed by structural complications with 35% (40 of 115). Total bone and total knee reconstructions had a reduced survivorship free from revision surgery for a second complication at 5 years (HR 2.072 95% CI 1.066 to 3.856; p = 0.031) compared with single joint replacements. With the numbers we had, we could not show a difference between the survivorship free of revision for a second complication based on the type of the first complication (HR 0.74 95% CI 0.215 to 2.546; p = 0.535). We did not detect an association between total reconstruction length, patient BMI, and patient age and survivorship free from revision for a second complication. Patients had a higher risk of second complications after postoperative radiotherapy (HR 1.849 95% CI 1.092 to 3.132; p = 0.022) but not after preoperative radiotherapy (HR 1.174 95% CI 0.505 to 2.728; p = 0.709). Patients with diabetes at the time of initial surgery had a reduced survivorship free from revision for a second complication (HR 4.868 95% CI 1.497 to 15.823; p = 0.009).
Conclusions Patients who undergo revision to treat a first megaprosthetic complication must be counseled regarding the high risk of future complications. With second complications occurring relatively soon after the first revision, regular orthopaedic follow-up visits are advised. Preoperative rather than postoperative radiotherapy should be performed when possible. Future studies should evaluate the effectiveness of different approaches in treating complications considering implant survivorship free of revision for a second complication.
Level of Evidence Level III, therapeutic study.

CORR Insights®: What is the Likelihood That Tumor Endoprostheses Will Experience a Second Complication After First Revision in Patients With Primary Malignant Bone Tumors And What Are Potential Risk Factors?

01-12-2019 – Gilg, Magdalena M.

Journal Article

No abstract available

Early Mechanical Failure of a Tumoral Endoprosthesic Rotating Hinge in the Knee: Does Bumper Wear Contribute to Hyperextension Failure?

01-12-2019 – Barrientos-Ruiz, Irene; Ortiz-Cruz, Eduardo José; Peleteiro-Pensado, Manuel; Merino-Rueda, Rodrigo

Journal Article

Background Tumor surgeons use a variety of endoprosthetic designs for reconstruction after bone tumor resection. However, functional results and implant survival have not been evaluated for each design. Because the outcomes and failure modes (for example, implant breakage, loosening) may differ between prosthetic design types, it is important to examine the problems associated with different designs. Because of experiences in our practice, we became concerned about a surprisingly high frequency of device breakage with one particular design, and we wished to report on that experience.
Question/purposes (1) In a small series of patients, what proportion of a particular design (Zimmer® Segmental Zimmer Inc, Warsaw, IN, USA) of rotating-hinge endoprosthesis experienced implant breakage at short-term follow-up? (2) What patient symptoms were associated with this finding? (3) What is the function as assessed by Musculoskeletal Tumor Society (MSTS) score with the use of this implant before and after revision?Methods We treated 87 patients in our tertiary center from 1987 to 2014 who had sarcomas around the knee with wide resection and reconstruction with tumoral endoprosthesis; five patients were lost to follow-up. In all, 33 of the remanining 82 prostheses, treated from 1987 to 2006, were reconstructed with fixed-hinge designs. From 2006 to 2014, 49 patients were reconstructed with a knee endoprosthesis, and 48 of them had a rotating-hinge prosthesis. In our center, we mostly used four designs: 16 of 49 patients were reconstructed with GMRS™ (Stryker Howmedica, Kalamazoo, MI, USA), seven received the LPS™ (De
Puy Synthes, Warsaw, IN, USA), 20 of 49 had the METS (Stanmore, Hertfordshire, UK), and six of 49 received the Zimmer Segmental. The focus of this report is on the six patients with the Segmental. We retrospectively gathered clinical and radiologic data from these six patients’ records and we assessed radiographic images. We evaluated function with the MSTS score of the 49 patients. The median follow-up duration of the Segmental prosthesis reconstruction was 65 months (range 24 to 85).
Results Three of the six patients had posterior instability and recurrent joint effusion on physical examination. Three patients who did not have hyperextension presented with restricted knee ROM. Six revision procedures were performed in three patients. The median MSTS score at 6 months for the Segmental® prosthesis was 15 of 30 (range 6 to 24). The score in the three patients who had posterior instability was 9 of 30 (range 6 to 15) and it improved to median 25 of 30 (range 19 to 30) 6 months after revision. The patients with the Segmental® prosthesis who did not undergo revision had a median MSTS score of 20 (range 16 to 24).
Conclusions The Zimmer Segmental rotating-hinge tumoral prosthesis underwent revision for implant breakage at short term in three of six patients after tumor resection and reconstruction of the knee. Bumper breakage was associated with posterior instability that was related to wear of the bushing blocking system. We are unaware of reports of these issues by other observers or in other prosthetic designs, but we feel larger registries should be created to see if this failure mechanism has been observed by others. If so, this design needs to be improved or the blocking system should be avoided.
Level of Evidence Level IV, therapeutic study.

What Regions of the Distal Clavicle Have the Greatest Bone Mineral Density and Cortical Thickness? A Cadaveric Study

01-12-2019 – Chen, Raymond E.; Soin, Sandeep P.; El-Shaar, Rami; Nicandri, Gregg T.; Awad, Hani A.; Maloney, Michael D.; Voloshin, Ilya

Journal Article

Background Osteosynthesis of distal clavicle fractures can be challenging because of comminution, poor bone quality, and deforming forces at the fracture site. A better understanding of regional differences in the bone structure of the distal clavicle is critical to refine fracture fixation strategies, but the variations in BMD and cortical thickness throughout the distal clavicle have not been previously described.
Purpose /questions (1) Which distal clavicular regions have the greatest BMD? (2) Which distal clavicular regions have the greatest cortical thickness values?Methods Ten distal clavicle specimens were dissected from cadaveric shoulders. Eight specimens were female and two were male, with a mean (range) age of 63 years (59 to 67). The specimens were selected to match known epidemiology, as distal clavicular fractures occur more commonly in older patients with osteoporotic bone, and clavicular fractures in older patients are more common in females than males. The clavicles were then imaged using quantitative micro-CT to create 3-D images. The BMD and cortical thickness were calculated for 10 regions of interest in each specimen. These regions were selected to represent locations where distal clavicular fractures commonly occur and locations of likely bony comminution. Findings were compared between different regions using repeated measures ANOVA with Geiser-Greenhouse correction, followed by Bonferroni method multiple comparison testing. Effect size was also calculated to estimate the magnitude of difference between regions.
Results The four most medial regions of the distal clavicle contained the greatest BMD (anterior intertubercle space 887 ± 31 mg
HA/cc, posterior intertubercle space 879 ± 26 mg
HA/cc, anterior conoid tubercle 900 ± 21 mg
HA/cc, posterior conoid tubercle 896 ± 27 mg
HA/cc), while the four most lateral regions contained the least BMD (anterior lateral distal clavicle 804 ± 32 mg
HA/cc, posterior lateral distal clavicle 800 ± 38 mg
HA/cc, anterior medial distal clavicle 815 ± 27 mg
HA/cc, posterior medial distal clavicle 795 ± 26 mg
HA/cc). All four most medial regions had greater BMD than the four most lateral regions, with p < 0.001 for all comparisons. For the BMD ANOVA, η2 was determined to be 0.81, representing a large effect size. The four most medial regions of the distal clavicle also had the greatest cortical thickness (anterior intertubercle space 0.7 ± 0.2 mm, posterior intertubercle space 0.7 ± 0.3 mm, anterior conoid tubercle 0.9 ± 0.2 mm, posterior conoid tubercle 0.7 ± 0.2 mm), while the four most lateral regions had the smallest cortical thickness (anterior lateral distal clavicle 0.2 ± 0.1 mm, posterior lateral distal clavicle 0.2 ± 0.1 mm, anterior medial distal clavicle 0.3 ± 0.1 mm, posterior medial distal clavicle 0.2 ± 0.1 mm). All four most medial regions had greater cortical thickness than the four most lateral regions, with p < 0.001 for all comparisons. For the cortical thickness ANOVA, η2 was determined to be 0.80, representing a large effect size. No differences in BMDs and cortical thicknesses were found between anterior and posterior regions of interest in any given area.
Conclusions In the distal clavicle, BMD and cortical thickness are greatest in the conoid tubercle and intertubercle space. When compared with clavicular regions lateral to the trapezoid tubercle, the BMD and cortical thickness of the conoid tubercle and intertubercle space were increased, with a large magnitude of difference.
Clinical Relevance Distal clavicular fractures are prone to comminution and modern treatment strategies have centered on the use of locking plate technology and/or suspensory fixation between the coracoid and the clavicle. However, screw pullout or cortical button pull through are known complications of locking plate and suspensory fixation, respectively. Therefore, it seems intuitive that implant placement during internal fixation of distal clavicle fractures should take advantage of the best-available bone. Although osteosynthesis was not directly studied, our study suggests that the best screw purchase in the distal clavicle is available in the areas of the conoid tubercle and intertubercle space, as these areas had the best bone quality. Targeting these areas during implant fixation would likely reduce implant failure and strengthen fixation. Future studies should build on our findings to determine if osteosynthesis of distal clavicular fractures with targeted screw purchase or cortical button placement in the conoid tubercle and intertubercle space increase fixation strength and decreases construct failure. Furthermore, our findings provide consideration for novel distal clavicular locking plate designs with modified screw trajectories or refined surgical techniques with suspensory fixation implants to reliably capture these areas of greatest bone quality.

CORR Insights®: What Regions of the Distal Clavicle Have the Greatest Bone Mineral Density and Cortical Thickness? A Cadaveric Study

01-12-2019 – Gutiérrez, Sergio

Journal Article

No abstract available

Patients With Thumb-base Osteoarthritis Scheduled for Surgery Have More Symptoms, Worse Psychological Profile, and Higher Expectations Than Nonsurgical Counterparts: A Large Cohort Analysis

01-12-2019 – Wouters, Robbert M.; Vranceanu, Ana-Maria; Slijper, Harm P.; Vermeulen, Guus M.; van der Oest, Mark J.W.; Selles, Ruud W.; Porsius, Jarry T.; The Hand-Wrist Study Group

Journal Article

Background Psychological characteristics, such as depression, anxiety or negative illness perception are highly prevalent in patients with several types of OA. It is unclear whether there are differences in the clinical and psychological characteristics of patients with thumb carpometacarpal (CMC-1) osteoarthritis (OA) scheduled for nonsurgical treatment and those with surgical treatment.
Questions/purposes (1) What are the differences in baseline sociodemographic characteristics and clinical characteristics (including pain, hand function, and health-related quality of life) between patients with thumb CMC-1 OA scheduled for surgery and those treated nonoperatively? (2) What are the differences in psychological characteristics between patients scheduled for surgery and those treated nonsurgically, for treatment credibility, expectations, illness perception, pain catastrophizing, and anxiety and depression? (3) What is the relative contribution of baseline sociodemographic, clinical, and psychological characteristics to the probability of being scheduled for surgery?Methods This was a cross-sectional study using observational data. Patients with CMC-1 OA completed outcome measures before undergoing either nonsurgical or surgical treatment. Between September 2017 and June 2018, 1273 patients were screened for eligibility. In total, 584 participants were included: 208 in the surgery group and 376 in the nonsurgery group. Baseline sociodemographic, clinical, and psychological characteristics were compared between groups, and a hierarchical logistic regression analysis was used to investigate the relative contribution of psychological characteristics to being scheduled for surgery, over and above clinical and sociodemographic variables. Baseline measures included pain, hand function, satisfaction with the patient’s hand, health-related quality of life, treatment credibility and expectations, illness perception, pain catastrophizing, and anxiety and depression.
Results Patients in the surgery group had longer symptom duration, more often a second opinion, higher pain, treatment credibility and expectations and worse hand function, satisfaction, HRQoL, illness perception and pain catastrophizing compared with the non-surgery group (effect sizes ranged from 0.20 to 1.20; p values ranged from < 0.001 to 0.044). After adjusting for sociodemographic, clinical, and psychological factors, we found that the following increased the probability of being scheduled for surgery: longer symptom duration (standardized odds ratio SOR, 1.86; p = 0.004), second-opinion visit (SOR, 3.81; p = 0.027), lower satisfaction with the hand (SOR, 0.65; p = 0.004), higher treatment expectations (SOR, 5.04; p < 0.001), shorter perceived timeline (SOR, 0.70; p = 0.011), worse personal control (SOR, 0.57; p < 0.001) and emotional response (SOR, 1.40; p = 0.040). The hierarchical logistic regression analysis including sociodemographic, clinical, and psychological factors provided the highest area under the curve (sociodemographics alone: 0.663 95% confidence interval 0.618 to 0.709; sociodemographics and clinical: 0.750 95% CI 0.708 to 0.791; sociodemographics, clinical and psychological: 0.900 95% CI 0.875 to 0.925).
Conclusions Patients scheduled to undergo surgery for CMC-1 OA have a worse psychological profile than those scheduled for nonsurgical treatment. Our findings suggest that psychological characteristics should be considered during shared decision-making, and they might indicate if psychological interventions, training in coping strategies, and patient education are needed. Future studies should prospectively investigate the influence of psychological characteristics on the outcomes of patients with CMC-1 OA.
Level of Evidence Level III, therapeutic study.

CORR Insights®: Patients With Thumb-base Osteoarthritis Scheduled for Surgery Have More Symptoms, Worse Psychological Profile, and Higher Expectations Than Nonsurgical Counterparts: A Large Cohort Analysis

01-12-2019 – McKee, Desirae

Journal Article

No abstract available

Which Psychological Variables Are Associated With Pain and Function Before Surgery for de Quervain’s Tenosynovitis? A Cross-sectional Study

01-12-2019 – Blackburn, Julia; van der Oest, Mark J. W.; Selles, Ruud W.; Chen, Neal C.; Feitz, Reinier; Vranceanu, Ana-Maria; Porsius, Jarry T.

Journal Article

Background Depression, anxiety, and pain catastrophizing have been associated with worse pain and function in studies of patients with de Quervain’s tenosynovitis. Illness perceptions are the patient’s thoughts and feelings about their illness. More negative perceptions of the illness such as the illness having a long duration or serious consequences are associated with worse physical function in patients with hand osteoarthritis. It is currently unknown whether these psychological factors play a similar role in de Quervain’s. We chose to study patients who have tried nonoperative management and have chosen surgical decompression due to persistent symptoms. Psychological factors may be associated with their ongoing pain and impaired function, so it is particularly important to investigate the role of psychosocial factors that may be targeted with non-invasive interventions.
Questions/purposes Which psychological variables are independently associated with baseline pain and function in patients undergoing surgical treatment for de Quervain’s tenosynovitis, after controlling for clinical and demographic variables?Methods This cross-sectional study included data from a longitudinally maintained database on 229 patients who had surgery for de Quervain’s tenosynovitis between September 2017 and October 2018. All management options were discussed with patients, but many had already tried nonoperative management and chose surgery once referred to our institution. Our database included 958 patients with de Quervain’s, with 69% (659) managed nonoperatively and 34% (326 of 958) who underwent surgical decompression. A total of 70% (229 of 958) completed all questionnaires and could be included in the study. With the numbers available, we found no differences between those included and those not analyzed in terms of age, gender, duration of symptoms, BMI, smoking status, and workload.
Patients completed the Patient-Rated Wrist/Hand Evaluation (PRWHE), Patient Health Questionnaire for emotional distress, Pain Catastrophizing Scale (PCS), and the Brief Illness Perception Questionnaire. We investigated the relative contribution of patient demographics and individual psychosocial factors using a hierarchical multivariable linear regression model. In the first step we considered how demographic factors were associated with the baseline PRWHE score. In the second step we investigated the effect of pain catastrophizing and emotional distress on the baseline PRWHE score after accounting for confounding demographic factors. In the final step, the effect of illness perceptions on baseline PRWHE were considered after accounting for the confounding effects of demographic factors as well as pain catastrophizing and emotional distress.
Results After controlling for confounding variables including workload and emotional distress, a more negative patient perception of the consequences of their condition and worse pain catastrophizing were associated with worse pain and function (consequences, β = 0.31; p < 0.01, pain catastrophizing β = 0.17; p = 0.03). A hierarchical multivariable regression analysis found that 11% of variance in baseline pain and function was explained by pain catastrophizing and emotional distress. Illness perceptions brought the total explained variance of the final model to 34%.
Conclusions More negative perceptions of the consequences of de Quervain’s tenosynovitis and worse pain catastrophizing are associated with worse pain and reduced function at baseline in patients awaiting surgical decompression of de Quervain’s tenosynovitis. In light of these findings, future studies might explore interventions to reduce pain catastrophizing and lower the perceived consequences of the condition. This may reduce the number of patients choosing surgical decompression or may also improve surgical outcomes. Further work should consider if these psychological factors are also associated with postoperative patient-reported outcomes.
Level of Evidence Level III, therapeutic study.

CORR Insights®: Which Psychological Variables Are Associated With Pain and Function Before Surgery for de Quervain’s Tenosynovitis? A Cross-sectional Study

01-12-2019 – Ring, David

Journal Article

No abstract available

Patient Position Is Related to the Risk of Neurovascular Injury in Clavicular Plating: A Cadaveric Study

01-12-2019 – Chuaychoosakoon, Chaiwat; Suwanno, Porames; Boonriong, Tanarat; Suwannaphisit, Sitthiphong; Klabklay, Prapakorn; Parinyakhup, Wachirapan; Maliwankul, Korakot; Duangnumsawang, Yada; Tangtrakulwanich, Boonsin

Journal Article

Background Fixation of clavicle shaft fractures with a plate and screws can endanger the neurovascular structures if proper care is not taken. Although prior studies have looked at the risk of clavicular plates and screws (for example, length and positions) to vulnerable neurovascular structures (such as the subclavian vein, subclavian artery, and brachial plexus) in the supine position, no studies to our knowledge have compared these distances in the beach chair position.
Questions/purposes (1) In superior and anteroinferior plating of midclavicle fractures, which screw tips in a typical clavicular plating approach place the neurovascular structures at risk of injury? (2) How does patient positioning (supine or beach chair) affect the distance between the screws and the neurovascular structures?Methods The clavicles of 15 fresh-frozen cadavers were dissected. A hypothetical fracture line was marked at the midpoint of each clavicle. A precontoured six-hole 3.5-mm reconstruction locking compression plate was applied to the superior surface of the clavicle by using the fracture line to position the center of the plate. The direction of the drill bits and screws through screw holes that offer the greater risk of injury to the neurovascular structures were identified, and were defined as the risky screw holes, and the distances from the screw tips to the neurovascular structures were measured according to a standard protocol with a Vernier caliper in both supine and beach chair positions. Anteroinferior plating was also assessed following the same steps. The different distances from the screw tips to the neurovascular structures in the supine position were compared with the distances in the beach chair position using an unpaired t-test.
Results The risky screw holes were the first medial and second medial screw holes. The relative distance ratios compared with the entire clavicular length for the distances from the sternoclavicular joint to the first medial and second medial screw holes were 0.46 and 0.36 in superior plating and 0.47 and 0.37 in anteroinferior plating, respectively. The riskiest screw hole for both superior and anteroinferior plates was the second medial screw hole in both the supine and beach chair positions (supine superior plating: 8.2 mm ± 3.1 mm minimum: 1.1 mm; beach chair anteroinferior plating: 7.6 mm ± 4.2 mm minimum: 1.1 mm). Patient positioning affected the distances between the riskiest screw tip and the nearest neurovascular structures, whereas in superior plating, changing from the supine position to the beach chair position increased this distance by 1.4 mm (95% CI -2.8 to -0.1; supine 8.2 ± 3.1 mm, beach chair 9.6 ± 2.1 mm; p = 0.037); by contrast, in anteroinferior plating, changing from the beach chair position to the supine position increased this distance by 5.4 mm (95% CI 3.6 to 7.4; beach chair 7.6 ± 4.2 mm, supine 13.0 ± 3.2 mm; p < 0.001).
Conclusions The second medial screw hole places the neurovascular structures at the most risk, particularly with superior plating in the supine position and anteroinferior plating in the beach chair position.
Clinical Relevance The surgeon should be careful while making the first medial and second medial screw holes. Superior plating is safer to perform in the beach chair position, while anteroinferior plating is more safely performed in the supine position.

CORR Insights®: Patient Position Is Related to the Risk of Neurovascular Injury in Clavicular Plating: A Cadaveric Study

01-12-2019 – Hawi, Nael

Journal Article

No abstract available

Partially Melted Ti6Al4V Particles Increase Bacterial Adhesion and Inhibit Osteogenic Activity on 3D-printed Implants: An In Vitro Study

01-12-2019 – Xie, Kai; Guo, Yu; Zhao, Shuang; Wang, Lei; Wu, Junxiang; Tan, Jia; Yang, Yangzi; Wu, Wen; Jiang, Wenbo; Hao, Yongqiang

Journal Article

Background A porous Ti6Al4V implant that is manufactured using selective laser melting (SLM) has broad potential applications in the field of orthopaedic implants. The pore structure of the SLM porous Ti6Al4V implant allows for cell migration and osteogenic differentiation, which is favorable for bone ingrowth and osseointegration. However, it is unclear whether the pore structure and partially melted Ti6Al4V particles on a SLM porous Ti6Al4V implant will increase bacterial adhesion and, perhaps, the risk of implant-related infection.
Questions/purposes (1) Is there more bacterial adhesion and colonization on SLM porous Ti6Al4V implants than on polished orthopaedic implants? (2) Do partially melted Ti6Al4V particles on SLM porous Ti6Al4V implants reduce human bone mesenchymal stem cells (h
BMSCs) adhesion, viability, and activity?Methods To determine bacterial adhesion and biofilm formation, we incubated five different Ti6Al4V discs (polished, grit-blasted, plasma-sprayed, particle SLM porous, and nonparticle SLM porous discs) with methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Bacterial coverage on the surface of the five different Ti6Al4V discs were evaluated based on scanning electron microscopy (SEM) images quantitatively. In addition, a spread-plate method was used to quantitatively evaluate the bacterial adhesion on those implants. The biofilm formation was stained with crystal violet and semi-quantitatively determined with a microplate reader. The morphology and adhesion of h
BMSCs on the five Ti6Al4V discs were observed with SEM. The cell viability was quantitatively evaluated with a Cell Counting Kit-8 assay. In addition, the osteogenic activity was determined in vitro with a quantitatively alkaline phosphatase activity assay and alizarin-red staining. For semiquantitative analysis, the alizarin-red stained mineralized nodules were dissolved and determined with a microplate reader.
Results The polished discs had the lowest MRSA adhesion (8.3% ± 2.6%) compared with grit-blasted (19.1% ± 3.9%; p = 0.006), plasma-sprayed (38.5% ± 5.3%; p < 0.001), particle (23.1% ± 2.8%; p < 0.001), and nonparticle discs (15.7% ± 2.5%; p = 0.003). Additionally, when comparing the two SLM discs, we found that particle discs had higher bacterial coverage than nonparticle discs (23.1% ± 2.8% versus 15.7% ± 2.5%; p = 0.020). An E. coli analysis showed similar results, with the higher adhesion to particle SLM discs than to nonparticle discs (20.7% ± 4.2% versus 14.4% ± 3.6%; p = 0.011). In addition, on particle SLM porous discs, bacterial colonies were localized around the partially melted Ti6Al4V particles, based on SEM images. After a 7-day incubation period, the cell viability in the particle group (optical density value 0.72 ± 0.05) was lower than that in the nonparticle groups (optical density value: 0.87 ± 0.08; p = 0.003). Alkaline phosphatase activity, as a marker of osteogenic differentiation, was lower in the particle group than in the nonparticle group (1.32 ± 0.12 U/m
L versus 1.58 ± 0.09 U/m
L; p = 0.012).
Conclusion Higher bacterial adhesion was observed on SLM porous discs than on polished discs. The partially melted Ti6Al4V particles on SLM porous discs not only enhanced bacterial adhesion but also inhibited the osteogenic activity of h
BMSCs. Postprocessing treatment is necessary to remove partially melted Ti6Al4V particles on an SLM implant before further use. Additional studies are needed to determine whether an SLM porous Ti6Al4V implant increases the risk of implant-related infection in vivo.
Clinical Relevance As implants with porous Ti6Al4V made using SLM are being designed, our preliminary findings suggest that postprocessing treatment is needed to remove partially melted Ti6Al4V particles before further use. In addition, the depth of the porous structure of the SLM implant should not exceed the maximum depth of bone ingrowth because the host immune defense cannot prevent bacterial adhesion without integration.

CORR Insights®: Partially Melted Ti6Al4V Particles Increase Bacterial Adhesion and Inhibit Osteogenic Activity on 3D-printed Implants: An In Vitro Study

01-12-2019 – Garino, Jonathan P.

Journal Article

No abstract available

Intra-articular Injection of Chloramphenicol Reduces Articular Cartilage Degeneration in a Rabbit Model of Osteoarthritis

01-12-2019 – Wu, Xiaoqing; Cai, Yongsong; Lu, Shemin; Xu, Ke; Shi, Xuanren; Yang, Le; Huang, Zhenjian; Xu, Peng

Journal Article

Background Osteoarthritis (OA) is characterized by degeneration of articular cartilage. Studies have found that enhancement of autophagy, an intracellular catabolic process, may limit the pathologic progression of OA. Chloramphenicol is a potent activator of autophagy; however, the effects of chloramphenicol on articular cartilage are unknown.
Questions/purposes Using human OA knee chondrocytes in vitro, we asked, does chloramphenicol (1) activate autophagy in chondrocytes; (2) protect chondrocytes from IL-1β-induced apoptosis; and (3) reduce the expression of matrix metallopeptidase (MMP)-13 and IL-6 (markers associated with articular cartilage degradation and joint inflammation). Using an in vivo rabbit model of OA, we asked, does an intra-articular injection of chloramphenicol in the knee (4) induce autophagy; (5) reduce OA severity; and (6) reduce MMP-13 expression?Methods Human chondrocytes were extracted from 10 men with OA undergoing TKA. After treatment with 25 μg/m
L, 50 μg/m
L, or 100μg/m
L chloramphenicol, the autophagy of chondrocytes was detected with Western blotting, transmission electron microscopy, or an autophagy detection kit. There were four groups in our study: one group was untreated, one was treated with 100 μg/m
L chloramphenicol, another was treated with 10 ng/m
L of IL-1β, and the final group was treated with 10 ng/m
L of IL-1β and 100 μg/m
L of chloramphenicol. All groups were treated for 48 hours; cell apoptosis was detected with Western blotting and flow cytometry. Inflammation marker IL-6 in the cell culture supernatant was detected with an ELISA. Articular cartilage degradation-related enzyme MMP-13 was analyzed with Western blotting. A rabbit model of OA was induced by intra-articular injection of type II collagenase in 20 male 3-month-old New Zealand White rabbits right hind leg knees; the left hind leg knees served as controls. Rabbits were treated by intra-articular injection of saline or chloramphenicol once a week for 8 weeks. Autophagy of the articular cartilage was detected with Western blotting and transmission electron microscopy. Degeneration of articular cartilage was analyzed with Safranin O-fast green staining and the semi-quantitative index Osteoarthritis Research Society International (OARSI) grading system. Degeneration of articular cartilage was evaluated using the OARSI grading system. The expression of MMP-13 in articular cartilage was detected with immunohistochemistry.
Results Chloramphenicol activated autophagy in vitro in the chondrocytes of humans with OA and in an in vivo rabbit model of OA. Chloramphenicol inhibited IL-1-induced apoptosis (flow cytometry results with chloramphenicol, 25.33 ± 3.51%, and without chloramphenicol, 44.00 ± 3.61%, mean difference, 18.67% 95% CI 10.60 to 26.73; p = 0.003) and the production of proinflammatory cytokine IL-6 (ELISA results, with chloramphenicol, 720.00 ± 96.44 pg/m
L, without chloramphenicol, 966.67 ± 85.05 pg/m
L; mean difference 74.24 pg/m
L 95% CI 39.28 to 454.06; p = 0.029) in chondrocytes. After chloramphenicol treatment, the severity of cartilage degradation was reduced in the treatment group (OARSI 6.80 ± 2.71) compared with the control group (12.30 ± 2.77), (mean difference 5.50 95% CI 1.50 to 9.50; p = 0.013). Furthermore, chloramphenicol treatment also decreased the production of MMP-13 in vitro and in vivo.
Conclusions Chloramphenicol reduced the severity of cartilage degradation in a type II collagen-induced rabbit model of OA, which may be related to induction of autophagy and inhibition of MMP-13 and IL-6.
Clinical Relevance Our study suggests that an intra-articular injection of chloramphenicol may reduce degeneration of articular cartilage and that induction of autophagy may be a method for treating OA. The animal model we used was type II collagen-induced OA, which was different from idiopathic OA and post-traumatic OA. Therefore, we need to use other types of OA models (idiopathic OA or a surgically induced OA model) to further verify its effect, and the side effects of chloramphenicol also need to be considered, such as myelosuppression.

Classifications in Brief: The Spinal Instability Neoplastic Score

01-12-2019 – Murtaza, Hamza; Sullivan, Connor W.

Journal Article

No abstract available

Letter to the Editor: Not the Last Word: Prizes for Cures

01-12-2019 – O’Keefe, Regis J.

Journal Article

No abstract available

Reply to the Letter to the Editor: Not the Last Word: Prizes for Cures

01-12-2019 – Bernstein, Joseph

Journal Article

No abstract available

Letter to the Editor: Editorial: Beware of Studies Claiming that Social Factors are “Independently Associated” with Biological Complications of Surgery

01-12-2019 – Simkin, Jennifer; Bronstone, Amy; Chapple, Andrew; Clement, R. Carter; Cohen-Rosenblum, Anna; Czarny-Ratajczak, Malwina; Dasa, Vinod; Hilliard, Colette; King, Andrew; Krause, Peter; Marrero, Luis; Maupin, Robert; Mix, Kimberlee; Ronis, Martin J.; Sammarco, Mimi C.; Trapido, Edward J.; Zura, Robert; Steen, R. Grant

Journal Article

No abstract available

Reply to the Letter to the Editor: Editorial: Beware of Studies Claiming that Social Factors are “Independently Associated” with Biological Complications of Surgery

01-12-2019 – Leopold, Seth S.

Journal Article

No abstract available

Letter to the Editor: Editorial: What Do You Say When a Patient Says Thank You?

01-12-2019 – Pitto, Rocco P.

Journal Article

No abstract available

Thank You to Our Peer Reviewers

01-12-2019 –

No abstract available