General Method for the Amination of Aryl Halides with Primary and Secondary Alkyl Amines via Nickel Photocatalysis.

The Buchwald-Hartwig C-N coupling reaction has been ranked as one of the 20 most frequently used reactions in medicinal chemistry. Owing to its much lower cost and higher reactivity toward less reactive aryl chlorides than palladium, the C-N coupling reaction catalyzed by Ni-based catalysts has received a great deal of attention. However, there appear to be no universal, practical Ni catalytic systems so far that could enable the coupling of electron-rich and electron-poor aryl halides with both primary and secondary alkyl amines. In this study, it is reported that a Ni(II)-bipyridine complex catalyzes efficient C-N coupling of aryl chlorides and bromides with various primary and secondary alkyl amines under direct excitation with light. Intramolecular C-N coupling is also demonstrated. The feasibility and applicability of the protocol in organic synthesis is attested by more than 200 examples.

Establishing Quality and Safety in Hospital-based 3D Printing Programs: Patient-first Approach.

The adoption of three-dimensional (3D) printing is rapidly spreading across hospitals, and the complexity of 3D-printed models and devices is growing. While exciting, the rapid growth and increasing complexity also put patients at increased risk for potential errors and decreased quality of the final product. More than ever, a strong quality management system (QMS) must be in place to identify potential errors, mitigate those errors, and continually enhance the quality of the product that is delivered to patients. The continuous repetition of the traditional processes of care, without insight into the positive or negative impact, is ultimately detrimental to the delivery of patient care. Repetitive tasks within a process can be measured, refined, and improved and translate into high levels of quality, and the same is true within the 3D printing process. The authors share their own experiences and growing pains in building a QMS into their 3D printing processes. They highlight errors encountered along the way, how they were addressed, and how they have strived to improve consistency, facilitate communication, and replicate successes. They also describe the vital intersection of health care providers, regulatory groups, and traditional manufacturers, who contribute essential elements to a common goal of providing quality and safety to patients. ©RSNA, 2021.

Chiral Arylated Amines via C-N Coupling of Chiral Amines with Aryl Bromides Promoted by Light.

The Buchwald-Hartwig C-N coupling reaction has found widespread applications in organic synthesis. Over the past two decades or so, many improved catalysts have been introduced, allowing various amines and aryl electrophiles to be readily used nowadays. However, there lacks a protocol that could be used to couple a wide range of chiral amines and aryl halides, without erosion of the enantiomeric excess (ee). Reported in this article is a method based on molecular Ni catalysis driven by light, which enables stereoretentive C-N coupling of optically active amines, amino alcohols, and amino acid esters with aryl bromides, with no need for any external photosensitizer. The method is effective for a wide variety of coupling partners, including those bearing functional groups sensitive to bases and nucleophiles, thus providing a viable alternative to accessing synthetically important chiral N-aryl amines, amino alcohols, and amino acids esters. Its viability is demonstrated by 92 examples with up to 99 % ee.

Reoperation of decompression alone or decompression plus fusion surgeries for degenerative lumbar diseases: a systematic review.

PURPOSE: The objective of this paper was to compare the reoperation rates, timing and causes between decompression alone and decompression plus fusion surgeries for degenerative lumbar diseases through a systematic review of the published data. METHODS: A search of the literature was conducted on PubMed/MEDLINE, EMBASE and the Cochrane Collaboration Library. Reports that included reoperations after decompression alone and/or decompression plus fusion surgeries were selected using designed eligibility criteria. Comparative analysis of reoperation rates, timing and causes between the two surgeries was conducted. RESULTS: Thirty-two retrospective and three prospective studies were selected from 6401 papers of the literature search. The analysis of data reported in these studies revealed that both surgeries resulted in similar reoperation rates after the primary surgery. However, majority of reoperations following the fusion surgeries were due to adjacent-segment diseases, and following the decompression alone surgeries were due to the same-segment diseases. Reoperation rates were not found to decrease in patients operated more recently than those operated in early times. CONCLUSIONS: Reoperation rates were similar following decompression alone or plus fusion surgeries for degenerative lumbar diseases. However, different underlying major causes exist between the two surgeries. There is no evidence showing that the reoperation rate has a trend to decline with newer surgical techniques used. The exact mechanisms of reoperation after both surgeries are still unclear. Further researches are necessary to investigate the mechanisms of reoperation for improvement of surgical techniques that aim to delay or prevent reoperation after lumbar surgery. These slides can be retrieved under Electronic Supplementary Material.

An In Vivo Prediction of Anisometry and Strain in Anterior Cruciate Ligament Reconstruction - A Combined Magnetic Resonance and Dual Fluoroscopic Imaging Analysis.

PURPOSE: To evaluate the in vivo anisometry and strain of theoretical anterior cruciate ligament (ACL) grafts in the healthy knee using various socket locations on both the femur and tibia. METHODS: Eighteen healthy knees were imaged using magnetic resonance imaging and dual fluoroscopic imaging techniques during a step-up and sit-to-stand motion. The anisometry of the medial aspect of the lateral femoral condyle was mapped using 144 theoretical socket positions connected to an anteromedial, central, and posterolateral attachment site on the tibia. The 3-dimensional wrapping paths of each theoretical graft were measured. Comparisons were made between the anatomic, over the top (OTT), and most-isometric (isometric) femoral socket locations, as well as between tibial insertions. RESULTS: The area of least anisometry was found in the proximal-distal direction just posterior to the intercondylar notch. The most isometric attachment site was found midway on the Blumensaat line with approximately 2% and 6% strain during the step-up and sit-to-stand motion, respectively. Posterior femoral attachments resulted in decreased graft lengths with increasing flexion angles, whereas anterodistal attachments yielded increased lengths with increasing flexion angles. The anisometry of the anatomic, OTT and isometric grafts varied between tibial insertions (P < .001). The anatomic graft was significantly more anisometric than the OTT and isometric graft at deeper flexion angles (P < .001). CONCLUSIONS: An area of least anisometry was found in the proximal-distal direction just posterior to the intercondylar notch. ACL reconstruction at the isometric and OTT location resulted in nonanatomic graft behavior, which could overconstrain the knee at deeper flexion angles. Tibial location significantly affected graft strains for the anatomic, OTT, and isometric socket location. CLINICAL RELEVANCE: This study improves the knowledge on ACL anisometry and strain and helps surgeons to better understand the consequences of socket positioning during intra-articular ACL reconstruction.

Ranges of Cervical Intervertebral Disc Deformation During an In Vivo Dynamic Flexion-Extension of the Neck.

While abnormal loading is widely believed to cause cervical spine disc diseases, in vivo cervical disc deformation during dynamic neck motion has not been well delineated. This study investigated the range of cervical disc deformation during an in vivo functional flexion-extension of the neck. Ten asymptomatic human subjects were tested using a combined dual fluoroscopic imaging system (DFIS) and magnetic resonance imaging (MRI)-based three-dimensional (3D) modeling technique. Overall disc deformation was determined using the changes of the space geometry between upper and lower endplates of each intervertebral segment (C3/4, C4/5, C5/6, and C6/7). Five points (anterior, center, posterior, left, and right) of each disc were analyzed to examine the disc deformation distributions. The data indicated that between the functional maximum flexion and extension of the neck, the anterior points of the discs experienced large changes of distraction/compression deformation and shear deformation. The higher level discs experienced higher ranges of disc deformation. No significant difference was found in deformation ranges at posterior points of all the discs. The data indicated that the range of disc deformation is disc level dependent and the anterior region experienced larger changes of deformation than the center and posterior regions, except for the C6/7 disc. The data obtained from this study could serve as baseline knowledge for the understanding of the cervical spine disc biomechanics and for investigation of the biomechanical etiology of disc diseases. These data could also provide insights for development of motion preservation surgeries for cervical spine.

In Vivo Anterolateral Ligament Length Change in the Healthy Knee During Functional Activities-A Combined Magnetic Resonance and Dual Fluoroscopic Imaging Analysis.

PURPOSE: To measure the in vivo anterolateral ligament (ALL) length change in healthy knees during step-up and sit-to-stand motions. METHODS: Eighteen healthy knees were imaged using magnetic resonance and dual fluoroscopic imaging techniques during a step-up and sit-to-stand motion. The ALL length change was measured using the shortest three-dimensional wrapping path, with its femoral attachment located slightly anterior-distal (ALL-Claes) or posterior-proximal (ALL-Kennedy) to the fibular collateral ligament attachment. The ALL length measured from the extended knee position of the non-weight-bearing magnetic resonance scan was used as a reference to normalize the length change. RESULTS: During the step-up motion (approximately 55° flexion to full extension), both the ALL-Claes and ALL-Kennedy showed a significant decrease in length of 21.2% (95% confidence interval 18.0-24.4, P < .001) and 24.3% (20.6-28.1, P < .001), respectively. During the sit-to-stand motion (approximately 90° flexion to full extension), both the ALL-Claes and ALL-Kennedy showed a consistent, significant decrease in length of 35.2% (28.8-42.2, P < .001) and 39.2% (32.4-46.0, P < .001), respectively. From approximately 90° to 70° of flexion, a decrease in length of approximately 6% was seen; 70° of flexion to full extension resulted in an approximately 30% decrease in length. CONCLUSIONS: The ALL was found to be a nonisometric structure during the step-up and sit-to-stand motion. The length of the ALL was approximately 35% longer at approximately 90° of knee flexion when compared with full extension and showed decreasing length at lower flexion angles. Similar ALL length change patterns were found with its femoral attachment located slightly anterior-distal or posterior-proximal to the fibular collateral ligament attachment. CLINICAL RELEVANCE: These data suggest that, if performing anatomic ALL reconstruction, graft fixation may be performed beyond 70° flexion to reduce the chance of lateral compartment overconstraint. Anatomic ALL reconstruction may affect the knee kinematics more in high flexion than at low flexion angles.

Prediction of in vivo knee joint kinematics using a combined dual fluoroscopy imaging and statistical shape modeling technique.

Using computed tomography (CT) or magnetic resonance (MR) images to construct 3D knee models has been widely used in biomedical engineering research. Statistical shape modeling (SSM) method is an alternative way to provide a fast, cost-efficient, and subject-specific knee modeling technique. This study was aimed to evaluate the feasibility of using a combined dual-fluoroscopic imaging system (DFIS) and SSM method to investigate in vivo knee kinematics. Three subjects were studied during a treadmill walking. The data were compared with the kinematics obtained using a CT-based modeling technique. Geometric root-mean-square (RMS) errors between the knee models constructed using the SSM and CT-based modeling techniques were 1.16 mm and 1.40 mm for the femur and tibia, respectively. For the kinematics of the knee during the treadmill gait, the SSM model can predict the knee kinematics with RMS errors within 3.3 deg for rotation and within 2.4 mm for translation throughout the stance phase of the gait cycle compared with those obtained using the CT-based knee models. The data indicated that the combined DFIS and SSM technique could be used for quick evaluation of knee joint kinematics.

Quantitative computer tomography analysis of post-operative subdural fluid volume predicts recurrence of chronic subdural haematoma.

BACKGROUND: Post-operative volume of subdural fluid is considered to correlate with recurrence in chronic subdural haematoma (CSDH). Information on the applications of computer-assisted volumetric analysis in patients with CSDHs is lacking. OBJECTIVE: To investigate the relationship between haematoma recurrence and longitudinal changes in subdural fluid volume using CT volumetric analysis. METHODS: Fifty-four patients harbouring 64 CSDHs were studied prospectively. The association between recurrence rate and CT findings were investigated. RESULTS: Eleven patients (20.4%) experienced post-operative recurrence. Higher pre-operative (over 120 ml) and/or pre-discharge subdural fluid volumes (over 22 ml) were significantly associated with recurrence; the probability of non-recurrence for values below these thresholds were 92.7% and 95.2%, respectively. CSDHs with larger pre-operative (over 15.1 mm) and/or residual (over 11.7 mm) widths also had significantly increased recurrence rates. Bilateral CSDHs were not found to be more likely to recur in this series. On receiver-operating characteristic curve, the areas under curve for the magnitude of changes in subdural fluid volume were greater than a single time-point measure of either width or volume of the subdural fluid cavity. CONCLUSIONS: Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the 'self-resolution' period can be used as significantly radiological predictors of recurrence.

Morphological measurement of the knee: race and sex effects.

Three-dimensional knee models of 148 Chinese (61 males, 87 female) and of 127 Caucasian (79 male, 48 female) were constructed. The anteroposterior (fAP, tAP) and mediolateral (fML, tML) dimensions of cross-section of the femur and tibia after simulated TKA bony resection were measured. Females have smaller femoral aspect ratios (fML/fAP) than males (Chinese: 1.22 +/- 0.05 vs 1.29 +/- 0.04; Caucasians: 1.18 +/- 0.05 vs 1.25 +/- 0.05) (P < 0.05). The tibial aspect ratios (tML/tAP) of the Chinese males (1.56 +/- 0.07) and the Caucasian females (1.54 +/- 0.07) are smaller than that of the Caucasian males (1.61 +/- 0.08) (P < 0.05). In regression analysis, for the same fAP or tAP dimension, females have narrower femoral condyles or tibia platforms than males; the Caucasian males have narrower femoral condyle or wider tibial platform than the Chinese males. For the same fAP dimension, males have lager tibial platforms than females; the Chinese males have larger tibial platforms than the Caucasian males. Racial and sex differences of the resected femur and tibia surfaces were found between a Chinese population and a Caucasian population. The relationship between the femur and tibia also showed racial and sex differences. These results may provide guidelines for future development of sex-specific as well as race-specific total knee replacement surgeries.

[Application of dexmedetomidine for brain nuclei lesion of patients with Parkinson's disease].

OBJECTIVE: To observe the sedative and analgesic effects of dexmedetomidine (Dex) and its influence on respiration and blood pressure, evaluate electrophysiological monitoring and explore the optimal dose of Dex for brain nuclei lesion in Parkinson's disease (PD) patients. METHODS: Approved by hospital ethics committee, 60 PD patients undergoing brain nuclei lesion ablation were randomly allocated into 3 groups (n = 20 each). No sedative anesthetic was used in group A; In group B, Dex 0.3 µg/kg intravenously for initial bolus (duration 15 min) and then 0.3 µg·kg(-1)·h(-1) continuous infusion; In group C, Dex 0.5 µg/kg intravenously (duration 15 min) for initial load and then 0.3 µg·kg(-1)·h(-1) continuous infusion. The parameters of mean arterial pressure (MAP), heart rate (HR), pressure of end-tidal carbon dioxide (P ETCO2), respiratory rate, blood oxygen saturation (SpO2), observer's assessment of alertness/sedation (OAA/S) and verbal rating score (VRS) were recorded at 0 min (baseline), 5 min (T1), 10 min (T2), 15 min (T3), 20 min (T4), 30 min (T5) and 60 min (T6) after the dosing of Dex. RESULTS: HR and respiratory rate decreased in groups B and C compared with baseline. In group C, P ETCO2 was much higher, compared with baseline (P < 0.05). Blood pressures of three groups were well-controlled. The incidence of pain (VRS ≥ 1) in group A was significantly higher than those of groups B and C (P < 0.05). And the incidence of sedation (OAA/S > 1) in group C was much higher than those of groups A and B. The electrophysiological signal of two patients in group C was severely affected. CONCLUSION: At an initial intravenous dose of Dex 0.3 µg/kg and a maintenance dose of 0.3 µg ·kg(-1)·h(-1), electrophysiological monitoring for surgery is not affected in PD patients undergoing brain nuclei lesion ablation. With a minimal interference of breath, Dex has not only well-controlled effects on sedation, analgesia and blood pressure, but also makes patients comfortable.

Quantitative magnetic resonance imaging (MRI) morphological analysis of knee cartilage in healthy and anterior cruciate ligament-injured knees.

PURPOSE: To analyze the morphological change in the cartilage of the knee after anterior cruciate ligament (ACL) injury by comparing with that of the intact contralateral knee. METHODS: A total of 22 participants (12 male and 10 female patients) who had unilateral ACL injury underwent MRI scan of both the injured and intact contralateral knees. Sagittal plane images were segmented using a modeling software to determine cartilage volume and cartilage thickness in each part of the knee cartilage that were compared between the ACL-injured and the intact contralateral knees. Furthermore, the male and female patients' data were analyzed in subgroups. RESULTS: The ACL-injured knees had statistically significant lower total knee cartilage volume than the intact contralateral knees (P = 0.0020), but had similar mean thickness of total knee cartilage (not significant: n.s.). In the male subgroup, there was no significant difference in cartilage volume and thickness between normal and ACL-injured knees. In the female subgroup, the ACL-injured knees demonstrated statistically significant difference in total knee cartilage volume (P = 0.0004) and thickness (P = 0.0024) compared with the normal knees. The percentage change in the cartilage thickness in women was significantly greater than that in men. CONCLUSION: Cartilage volume was significantly smaller in the ACL-injured knees than in the contralateral intact knees in this cohort. Women tended to display greater cartilage volume and thickness change after ACL injury than men. These findings indicated that women might be more susceptible to cartilage alteration after ACL injuries. LEVEL OF EVIDENCE: III.

Cartilage contact characteristics of the knee during gait in individuals with obesity.

Obesity increases the risk of knee osteoarthritis (OA). Knee joint contact characteristics have been thought to provide insights into the pathogenesis of knee OA; however, the cartilage contact characteristics in individuals with obesity have not been fully described. We conducted cartilage-to-cartilage contact analyses through high-precision fluoroscopy imaging with subject-specific magnetic resonance cartilage models. Twenty-five individuals with obesity were recruited for this study, and previously published data consisted of eight nonobese individuals who were used as the comparator group. In both groups, knees were imaged by a dual fluoroscopic imaging system during treadmill walking, and the tibiofemoral cartilage contact locations were analyzed and described on the tibial plateau in the medial-lateral (ML) and anterior-posterior (AP) directions and on femoral condyle surfaces using contact angles in the sagittal plane and deviation angles in a plane perpendicular to the sagittal plane. On the medial tibial plateau, the ML contact locations in the individuals with obesity were located more medially than in the nonobese group throughout the stance phase. The medial plateau AP contact locations in individuals with obesity showed a different pattern compared with the nonobese group. The ML contact excursions on the medial plateau in the individuals with obesity were larger than in the nonobese group. These findings suggest that obesity affects the contact location mainly in the medial compartment, which explains, in part, the high prevalence of medial knee OA in the obese population.

Evaluation of novel plantar pressure-based 3-dimensional printed accommodative insoles - A feasibility study.

BACKGROUND: Custom insoles are commonly prescribed to patients with diabetes to redistribute plantar pressure and decrease the risk of ulceration. Advances in 3D printing have enabled the creation of 3D-printed personalized metamaterials whose properties are derived not only from the base material but also the lattice microstructures within the metamaterial. Insoles manufactured using personalized metamaterials have both patient-specific geometry and stiffnesses. However, the safety and biomechanical effect of the novel insoles have not yet been tested clinically. METHODS: Individuals without ulcer, neuropathy, or deformity were recruited for this study. In-shoe walking plantar pressure at baseline visit was taken and sensels with pressure over 200 kPa was used to define offloading region(s). Three pairs of custom insoles (two 3D printed insoles with personalized metamaterials (Hybrid and Full) designed based on foot shape and plantar pressure mapping and one standard-of-care diabetic insole as a comparator). In-shoe plantar pressure measurements during walking were recorded in a standardized research shoe and the three insoles and compared across all four conditions. FINDINGS: Twelve individuals were included in the final analysis. No adverse events occurred during testing. Maximum peak plantar pressure and the pressure time integral were reduced in the offloading regions in the Hybrid and Full but not in the standard-of-care compared to the research shoe. INTERPRETATION: This feasibility study confirms our ability to manufacture the 3D printed personalized metamaterials insoles and demonstrates their ability to reduce plantar pressure. We have demonstrated the ability to modify the 3D printed design to offload certain parts of the foot using plantar pressure data and a patient-specific metamaterials in the 3D printed insole design. The advance in 3D printed technology has shown its potential to improve current care.

A novel workflow to fabricate a patient-specific 3D printed accommodative foot orthosis with personalized latticed metamaterial.

Patients with diabetes mellitus are at elevated risk for secondary complications that result in lower extremity amputations. Standard of care to prevent these complications involves prescribing custom accommodative insoles that use inefficient and outdated fabrication processes including milling and hand carving. A new thrust of custom 3D printed insoles has shown promise in producing corrective insoles but has not explored accommodative diabetic insoles. Our novel contribution is a metamaterial design application that allows the insole stiffness to vary regionally following patient-specific plantar pressure measurements. We presented a novel workflow to fabricate custom 3D printed elastomeric insoles, a testing method to evaluate the durability, shear stiffness, and compressive stiffness of insole material samples, and a case study to demonstrate how the novel 3D printed insoles performed clinically. Our 3D printed insoles results showed a matched or improved durability, a reduced shear stiffness, and a reduction in plantar pressure in clinical case study compared to standard of care insoles.

[Clinical study of patients of arachnoid cyst associated with chronic subdural hematoma].

OBJECTIVE: To explore the clinical characteristics and treatment strategy of arachnoid cyst associated with chronic subdural hematoma. METHODS: A retrospective analysis was made for 11 cases of arachnoid cyst associated with chronic subdural hematoma at our hospital from December 1999 to December 2009. There were 9 males and 2 females with a mean age of 23.1 years old (range: 7 - 68). Their clinical characteristics were summarized. The symptoms included headache (n = 10) and facial muscle twitching & eye squinting (n = 1). History of previous head injury were found in 6 cases, strenuous exercise in 1 case and no history of injury in 4 cases. RESULTS: The clinical symptoms of 3 patients worsened after a conservative treatment and underwent a burred-hole procedure with drainage of hematoma. And 7/9 patients undergoing a burred-hole procedure with drainage of hematoma had a full recovery. But 2/9 had recurrent subdural hematoma at Days 20 and 40 post-operation respectively and underwent the same procedure. Another 2 cases underwent craniotomy to remove subdural hematoma and arachnoid cyst and had stayed free of any symptom since then. All patients were followed up for 10 - 154 months after discharge. And none had recurrent subdural hematoma. All could study, work or live normally with a KPS (Karnofsky performance scale) score of 80 or more. CONCLUSION: Arachnoid cysts is a possible risk factor for subdural hematoma, especially in young adults. Chronic subdural hematoma generally develops within 1 - 3 months after head injury. And a common clinical presentation is headache. A burred-hole procedure with drainage of hematoma is adequate as the first-line treatment for arachnoid cyst associated with chronic subdural hematoma.

Further purification of industrial quartz by much milder conditions and a harmless method.

A much "greener" and harmless leaching method for removing impurity aluminum further from industrial quartz sands by very dilute mixed acids has been presented. With the help of supersonic, the percentage of removal aluminum reached up to 52.5%/53%, that is, 17.4 ppm/17.7 ppm at 30 °C/80 °C, respectively. These results are 4.4/4.7 ppm lower than that supplied by a world famous quartz sands supplier, and the leaching conditions are much milder compared with other comparable methods: the concentration of hydrogen chloride in the mixed acid is only 10% of the others, the leaching temperature is much lower; at the same time, the operating time is only 13-20% of the others, thereby pollution of industrial strong acids and thermo-scattering is reduced substantially.

[The value of modified POSSUM scoring system in predicting mortality and morbidity for the intertrochanteric fracture in elder patients].

OBJECTIVE: To evaluate the value of modified physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) scoring system in predicting mortality and morbidity for the intertrochanteric fracture in elder patients. METHODS: A retrospective study was conducted over a period of nearly 2 years from January 2007 to December 2008. Complete data from 119 patients were analyzed to compare the mortality and morbidity predicted by the POSSUM and the observed mortality and morbidity. POSSUM risk was calculated using the original POSSUM equation. RESULTS: POSSUM predicted 11(9.2%) deaths, which had no statistical significance with the observed mortality 5 (4.2%) (chi² = 2.412, P = 0.120). The estimated incidence of postoperative complications was 42 (35.3%), which also has no statistical significance with the observed morbidity 39 (32.8%) (chi² = 0.168, P = 0.682). CONCLUSIONS: The modified POSSUM scoring system can predict accurately postoperative mortality and morbidity for the patients underwent intertrochanteric fracture and it predict more accurately in high risk band. The physiological score can be used to evaluate the physiological conditions preoperative and the pulmonary disease is the most important factor lead to death of the elder patients underwent intertrochanteric fracture.

Mediating Role of Bone Marrow Lesions, Synovitis, Pain Sensitization, and Depressive Symptoms on Knee Pain Improvement Following Substantial Weight Loss.

OBJECTIVE: Massive weight loss leads to marked knee pain reduction in individuals with knee pain, but the reason for the reduction in pain is unknown. This study was undertaken to quantify the contribution of magnetic resonance imaging (MRI)-evidenced changes in pain-sensitive structures, bone marrow lesions (BMLs), and synovitis, and changes in pain sensitization or depressive symptoms, to knee pain improvement after substantial weight loss. METHODS: Morbidly obese patients with knee pain on most days were evaluated before bariatric surgery or medical weight management and at 1-year follow-up for BMLs and synovitis seen on MRI, the pressure pain threshold (PPT) at the patella and the right wrist, depressive symptoms (using the Center for Epidemiologic Studies Depression scale [CES-D]), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain survey. Natural-effects models were used to quantify the extent that achieving a minimum clinically important difference (MCID) of ≥18% on the WOMAC pain scale could be mediated by weight loss-induced changes in BMLs, synovitis, PPT, and depressive symptoms. RESULTS: Of 75 participants, 53.3% lost ≥20% of weight by 1 year. Of these, 75% attained the MCID for pain improvement, compared with 34.3% in those who had <20% weight loss. Mediation analyses suggested that, in those with at least 20% weight loss, the odds of pain improvement increased by 62%, 15%, and 22% through changes in patella PPT, wrist PPT, and CES-D, respectively, but pain improvement was not mediated by MRI changes in BMLs or synovitis. CONCLUSION: Weight loss-induced knee pain improvement is partially mediated by changes in pain sensitization and depressive symptoms but is independent of MRI changes in BMLs and synovitis.

Correction: Six degree-of-freedom knee joint kinematics in obese individuals with knee pain during gait.

[This corrects the article DOI: 10.1371/journal.pone.0174663.].