Femoral head translation in borderline and definite dysplastic hips during weight-bearing: 2D/3D image registration analysis.

PURPOSE: The aims of this study were to 1) assess femoral head translation during weight-bearing in symptomatic developmental dysplasia of the hip (DDH) and 2) compare it between borderline DDH and definite DDH. METHODS: The study included four individuals with borderline DDH and nine with definite DDH, scheduled for periacetabular osteotomy. Anteroposterior X-ray images of the hip joint were obtained in the standing position, and computed tomography images of the pelvis were obtained in the supine position. Femoral head translation from the supine to a standing position was measured using 2D/3D X-ray image registration. RESULTS: From a supine to a standing position, the femoral head translated 0.3 mm laterally, 0.5 mm anteriorly, and 0.5 mm superiorly on average. The mean femoral head translation in 3D between the supine and standing positions was 1.5 mm. The 3D femoral head translation in the borderline DDH group was significantly greater than that in the definite DDH group. In the definite DDH group, there was a significant correlation between the center edge (CE) angle and 3D femoral head translation (ρ = -0.78, P = 0.012). CONCLUSIONS: Symptomatic DDH showed femoral head translation in the anterior, lateral, and superior directions during weight-bearing. In definite DDH, the amount of femoral head translation was negatively correlated with the CE angle. The amount of 3D translation in patients with borderline DDH was larger than that in definite DDH. Dynamic joint instability during weight-bearing was observed in borderline DDH as well as definite DDH. Treatment to enhance joint stability during weight-bearing is important in both cases.

Imaging Features of Early Diffuse Idiopathic Skeletal Hyperostosis (pre-DISH): Analysis of Progression of Ligament Ossification over 5 Years by Computed Tomography.

Introduction: Some patients who have not been diagnosed with diffuse idiopathic skeletal hyperostosis (DISH) (patients in the preclinical stage of DISH [pre-DISH]) may develop DISH in the future. However, there are currently no clearly defined diagnostic criteria for pre-DISH. This study aims to define pre-DISH by analyzing the change in the ossification extent in each intervertebral space in the thoracic and lumbar spines over time using computed tomography (CT). Methods: Of the patients who underwent CT of the thoracic to pelvic region at least twice from 2009 to 2018, 188 who underwent CT at an interval of 5 years to 5 years and 2 months were enrolled. The prevalence of DISH during the first and second CT scans was investigated. The pre-DISH feature was defined, and the prevalence of pre-DISH on the first CT and the change after 5 years in patients with pre-DISH was investigated. Results: Of the 188 patients, 37 (19.7%) and 48 (25.5%) were diagnosed with DISH on the first and second CT scans, respectively. Pre-DISH was defined as the ossification characterized by the modified Mata score of three contiguous intervertebral spaces with a score of ≥2 points (222; 2 points, ligament ossification of half or more of the intervertebral disc height but incomplete fusion), and 52 patients were diagnosed with pre-DISH. Of the 52 patients with a score of ≥(222), 11 (21.2%) were diagnosed with DISH 5 years later. Conclusions: Patients who have three contiguous intervertebral spaces with a modified Mata score of 2 or 3 points should be considered pre-DISH.

Establishment of a uniform histological evaluation method for early stage osteophytes in the destabilization of the medial meniscus mouse model.

Background: Osteophyte formation is attracting attention as an early-stage pathology of knee osteoarthritis (OA). Although osteophyte formation is understood as a defense response to joint instability, its role and impact on OA remain largely unknown. Many studies have been conducted using the surgical destabilization of the medial meniscus (DMM) mouse model, but there are few standard evaluation methods, especially in the histological evaluation of early-stage osteophytes. The purpose of this study was to establish a reproducible and uniform method for histological evaluation of characteristics of early osteophyte formation in the DMM mouse model. Methods: Male mice were operated with DMM at 12 weeks old and histologically evaluated at 4 days and 1, 2 and 4 weeks after DMM. Osteophyte Width, Osteophyte Area, and Original and Modified Maturity Scores were used to evaluate osteophytes for all sections. Results: Osteophyte Width, Osteophyte Area and Maturity Scores were all greater anteriorly than posteriorly in the knee joint. The Modified Maturity Score was more strongly correlated with position than the Original Maturity Score, and could be used to evaluate early-stage osteophyte formation. Conclusion: The Modified Maturity Score as well as Osteophyte Width and Area at the section of the anterior cruciate ligament (ACL) attachment site can provide a reproducible evaluation method to histologically assess the early-stage osteophyte formation in the DMM mouse model.

Difference in implant design affects midflexion rotational laxity in cruciate-retaining total knee arthroplasty: a computer navigation study.

PURPOSE: This study aimed to compare midflexion rotational laxity between two different design concept models of cruciate-retaining total knee arthroplasty: symmetrical surface design of neutral joint line obliquity and asymmetrical surface design of varus joint line obliquity. METHODS: Sixty-three knees that underwent cruciate-retaining total knee arthroplasty were evaluated. Manual maximum passive rotational stress without acceleration was applied to the knees under navigation monitoring. Pre-operative and post-operative internal and external rotational angles were measured at 30°, 45°, 60°, and 90° knee flexion. RESULTS: The post-operative internal rotational laxity was significantly increased compared with pre-operative levels at 30°, 45°, 60°, and 90° flexion among all subjects (mean 9.7° vs 11.1°, 10.6° vs 11.6°, 11.2° vs 12.9°, and 13.2° vs 14.9°; p = 0.01, 0.04, 0.001, and 0.008, respectively). The post-operative external rotational laxity was significantly decreased compared to pre-operative levels at 30°, 45°, 60°, and 90° flexion among all subjects (mean 10.8° vs 6.8°, 12.5° vs 9.4°, 12.8° vs 10.0°, and 11.3° vs 9.5°; p < 0.0001, < 0.0001, < 0.0001, and 0.0008, respectively). The post-operative total rotational laxity significantly decreased, compared with pre-operative levels, at 30° and 45° flexion among all subjects (mean 20.4° vs 17.9°, and 23.1° vs 21.1°; p = 0.002 and 0.04, respectively). The post-operative total rotational laxity was significantly smaller in asymmetrically designed total knee arthroplasty than in symmetrically designed total knee arthroplasty at 30°, 45°, and 60° flexion (mean 19.3° vs 15.8°, 22.8° vs 18.7°, and 24.4° vs 20.8°; p = 0.03, 0.03, and 0.02, respectively), whereas no significant difference was observed at 90° flexion. CONCLUSION: Compared to symmetrical surface design, asymmetrical surface design resulted in lower rotational laxity at the midflexion range in cruciate-retaining total knee arthroplasty. LEVEL OF EVIDENCE: III.

Progression of varus deformity in osteoarthritic knees induces anterior paradoxical motion of the femur during early knee flexion.

PURPOSE: The purpose of this study was to investigate the position of the femur relative to the tibia throughout range of motion in the osteoarthritic knee to evaluate knee kinematics and assess its relationship with the degree of varus deformity. METHODS: In this study, 116 preoperative knees with varus deformity were evaluated using a navigation system. The internal-external, anteroposterior, and mediolateral positions of the femur relative to the tibia were measured at maximum extension, 15°, 30°, 45°, 60°, 90°, 105°, and 120°, and maximum flexion angles. From these parameters, two-dimensional translation of the surgical epicondylar axis was projected onto the tibial axial plane, and the femoral movement was evaluated relative to the tibia. In addition, the knees were retrospectively classified into three groups according to their degrees of preoperative hip-knee-ankle angle: mild (< 10°), moderate (10°-20°), and severe (> 20°). Then, the differences in each parameter between these groups were investigated. The Steel-Dwass test was performed to identify the difference among three groups. Statistical significance was set at p values < 0.05. RESULTS: There was a significant difference in the anteroposterior position of the femur relative to the tibia among the three groups, especially from extension to early flexion (p < 0.05). The anteroposterior position at knee extension deviated posteriorly according to the progression of varus deformity. Rotational and mediolateral translation were not significantly different among the groups. Normal knee kinematics were diminished in almost all cases in each group. In addition, anterior paradoxical motion of the femur during early knee flexion was observed in 45.6% (n = 26), 57.1% (n = 28), and 80.0% (n = 8) of cases in the mild, moderate, and severe groups, respectively. The anteroposterior position of the femur relative to the tibia at knee extension was significantly more posterior in patients with than in those without anterior paradoxical motion (p < 0.0001). CONCLUSION: The anteroposterior position of the femur relative to the tibia changed according to the progression of varus deformity in osteoarthritic knees, especially from knee extension to early flexion. Posterior deviation of the femur at knee extension induced its anteroposterior movement relative to the tibia, resulting in anterior paradoxical motion. LEVEL OF EVIDENCE: III.

Rotational Soft-Tissue Balance Is Highly Correlated with Rotational Kinematics in Total Knee Arthroplasty.

Recovery of normal knee kinematics is critical for improving functional outcomes and patient satisfaction after total knee arthroplasty (TKA). The kinematics pattern after TKA varies from case to case, and it remains unclear how to reproduce normal knee kinematics. The present study aimed to evaluate rotational knee kinematics and soft-tissue balance using a navigation system and to assess the influence of intraoperative soft-tissue balance on the rotational knee kinematics. We evaluated 81 osteoarthritic knees treated with TKA using a posterior stabilized (50 knees) or cruciate retaining (31 knees) prosthesis. Rotational kinematics were assessed at 0, 30, 45, 60, and 90 degrees flexion angles by using a computer-assisted navigation system. Correlation between femorotibial rotational position and measured soft tissue balance was assessed by using Spearman's rank correlation coefficient. Rotational soft-tissue balance (the median angle of rotational stress) was significantly correlated with rotational kinematics (rotational axis of the femur relative to the tibia throughout the range of motion) at all measured angles after TKA. The correlation coefficients between the median angle of rotational stress and rotational kinematics were 0.97, 0.80, 0.74, 0.71, and 0.70 at 0, 30, 45, 60, and 90 degrees of flexion, respectively (p-values <0.0001 in all measured angles). The correlation coefficient increased as the knee approached full extension. Our findings suggest that soft-tissue balance is a key factor for rotational kinematics, following both cruciate-retaining and posterior-stabilized TKA.

Feasibility and applicability of locomotive syndrome risk test in elderly patients who underwent total knee arthroplasty.

OBJECTIVES: The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS. METHODS: A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively. RESULTS: After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60-74 years) and older (≥75 years) age groups. CONCLUSIONS: We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms.

Examining the Association Between the Extent of Anterior Longitudinal Ligament Ossification Progression and Comorbidities in Diffuse Idiopathic Skeletal Hyperostosis.

BACKGROUND:  It has been documented that diffuse idiopathic skeletal hyperostosis (DISH) exhibits a higher prevalence among elderly, male, and obese individuals. Additionally, diabetes mellitus and other comorbidities are more frequently observed in this patient population. However, there is a lack of reports exploring the correlation between the extent of ossification and these demographic and clinical characteristics. OBJECTIVE: To examine the correlation between comorbidities and the severity of ossification of the anterior longitudinal ligament in patients with DISH. MATERIALS AND METHODS: The study included 468 patients who visited our hospital in 2018-2022. They were divided into DISH and non-DISH groups based on computed tomography image evaluation according to the Resnick criteria. The patients in the two groups were matched for age and sex. We compared comorbidity-related factors including body mass index (BMI), serum markers for metabolic syndrome and renal function, and hemoglobin A1c (HbA1c) levels between the matched groups. Moreover, we examined the correlation between the number of fused vertebral bodies and comorbidity-related factors, age, and sex within the DISH group. RESULTS: The DISH group included significantly more men and elderly patients than the non-DISH group. Furthermore, the average BMI and HbA1c levels were significantly higher in the matched-DISH group than in the matched-non-DISH group, whereas no differences were observed in other markers. In the DISH group, the number of fused vertebral bodies did not correlate with age, sex, BMI, or HbA1c levels. DISCUSSION: BMI and HbA1c levels were significantly higher in patients with DISH than those without; however, the number of fused vertebral bodies and the possibility of having coexisting obesity or diabetes mellitus showed no correlation with the age or sex of the patient. Therefore, each patient should be carefully assessed for ossification severity regardless of age, sex, and the comorbidities they possess.

Prognostic potential and pathological validation of a diagnostic application using Raman spectroscopy in the characterization of degenerative changes in the cartilage of the humeral head.

Significance: Raman spectroscopy is a well-established analytical method in the fields of chemistry, industry, biology, pharmaceutics, and medicine. Previous studies have investigated optical imaging and Raman spectroscopy for osteoarthritis (OA) diagnosis in weight-bearing joints such as hip and knee joints. However, to realize early diagnosis or a curable treatment, it is still challenging to understand the correlations with intrinsic factors or patients' background. Aim: To elucidate the correlation between the Raman spectral features and pathological variations of human shoulder joint cartilage. Approach: Osteoarthritic cartilage specimens excised from the humeral heads of 14 patients who underwent shoulder arthroplasty were assessed by a confocal Raman microscope and histological staining. The Raman spectroscopic dataset of degenerative cartilage was further analyzed by principal component analysis and hierarchical cluster analysis. Results: Multivariate association of the Raman spectral data generated three major clusters. The first cluster of patients shows a relatively high Raman intensity of collagen. The second cluster displays relatively low Raman intensities of proteoglycans (PGs) and glycosaminoglycans (GAGs), whereas the third cluster shows relatively high Raman intensities of PGs and GAGs. The reduced PGs and GAGs are typical changes in OA cartilage, which have been confirmed by safranin­O staining. In contrast, the increased Raman intensities of collagen, PGs, and GAGs may reflect the instability of the cartilage matrix structure in OA patients. Conclusions: The results obtained confirm the correlation between the Raman spectral features and pathological variations of human shoulder joint cartilage. Unsupervised machine learning methods successfully yielded a clinically meaningful classification between the shoulder OA patients. This approach not only has potential to confirm severity of cartilage defects but also to determine the origin of an individual's OA by evaluating the cartilage quality.

Efficacy of posterior capsular release for flexion contracture in posterior-stabilized total knee arthroplasty.

PURPOSE: Posterior capsular contracture causes stiffness during knee extension in knee osteoarthritis. Furthermore, in posterior-stabilized total knee arthroplasty (PS-TKA), a unique design such as the cam mechanism could conflict with the posterior capsule (PC) causing flexion contracture (FC). However, few studies have focused on the anatomical aspects of the PC. This study aimed to investigate the anatomical site and forms of posterior capsular attachment to the femoral cortex, and to evaluate the efficacy of posterior capsular release for FC by assessing changes in knee extension angles using a navigation system. METHODS: Attachment sites of the PC were investigated in 10 cadaveric knees using computed tomography. PS-TKA was performed in six cadaveric knees using a navigation system to evaluate the efficacy of posterior capsular release for FC. Posterior capsular release was performed stepwise at each part of the femoral condyle. RESULTS: The gastrocnemius tendon and PC were integrally attached to the femoral cortex at the medial and lateral condyles, whereas the PC at the intercondylar fossa was independently attached directly to the femoral cortex. Moreover, the PC at the intercondylar fossa was attached most distally among each femoral condyle. Posterior capsular release at the intercondylar fossa allowed 11.4° ± 2.8° improvement in knee extension. This angle was further improved by 5.5° ± 1.3°, after subsequent capsular release at the medial and lateral condyles. CONCLUSION: The forms and sites of posterior capsular attachment differed based on the part of the femoral condyle. Stepwise posterior capsular release was effective for FC in PS-TKA. LEVEL OF EVIDENCE: III.

Gender-specific difference in the recurrence of flexion contracture after total knee arthroplasty.

BACKGROUND: Range of motion after total knee arthroplasty (TKA) can impact patients' daily lives. Nevertheless, flexion contracture (FC) often recurs after TKA, even upon achieving full extension intraoperatively. This study aimed to evaluate the relationship among preoperative, intraoperative, and postoperative knee extension angles, and clarify the risk factor for postoperative FC. METHODS: One hundred forty-seven knees undergoing TKA using a navigation system were evaluated. We measured the pre- and postoperative (6 months after TKA) extension angles using a goniometer, and intraoperative (before and after TKA) extension angle using a navigation system; the correlation between these angles at each time point was evaluated. RESULTS: The mean preoperative, intraoperative (before and after TKA) and postoperative extension angles were -9.9°, -6.8°, -0.1°, and -2.0°. Regarding intraoperative extension angle after TKA, 58 knees showed ≤ 5° hyperextension and six knees showed > 5° hyperextension. At 6 months, no cases showed hyperextension and 105 knees showed full extension. The mean intraoperative extension angle after TKA in the postoperative full extension group was 0.4°. A significant correlation was found among extension angles at each point (p<0.01, respectively). However, the intraoperative extension angle after TKA correlated with the postoperative extension angle only in females. Contrarily, the recurrence rate of FC was significantly higher in males than in females (p<0.01). CONCLUSION: Intraoperative extension angles significantly correlated with pre- and postoperative extension angles in TKA. Moreover, intraoperative mild (≤ 5°) hyperextension is acceptable for postoperative full extension. There was a gender-specific difference in correlation between intra- and postoperative knee extension angles. LEVEL OF EVIDENCE: III.

In vivo anterior cruciate ligament length pattern assessment secondary to differences in the femoral attachment under loading condition using image-matching techniques.

BACKGROUND: The anterior cruciate ligament is composed of two functional bundles and is crucial for knee function. There is limited understanding of the role of each individual bundle and the influence on length pattern due to difference in bone tunnel position under loading conditions throughout the range of motion. We measured point to point length between the femoral and tibial footprints of the ligament throughout the range of motion in normal knees, under normal loading conditions, and investigated length pattern changes secondary to differences in the femoral footprint. We hypothesized that anteromedial and posterolateral bundles have complementary roles, and the ligament length pattern is influenced by the footprint position. METHODS: We studied the squat movements of six healthy knees and measured point to point footprint distance. The footprint distances were measured after changing them to be 10% lower, 10% shallower, and both 10% lower and shallower than the defined anatomical femoral footprint. RESULTS: Average length changes of 12.0 and 14.1 mm from maximum extension (10°) to deep flexion (150°) were observed when the anteromedial and posterolateral bundles were defined by the default anatomical position. Maximum and minimum length were reached during full extension and flexion for both the anteromedial and posterolateral bundles, respectively. At 10% lower, length increased 2.2 mm over the default value in both the anteromedial and posterolateral lengths. At 10% shallower, decreases of 4.1 mm and 3.9 mm were observed compared with the default anteromedial and posterolateral lengths, respectively. In the 10% lower and 10% shallower position, anteromedial and posterolateral lengths decreased 2.1 mm and 1.9 mm compared with the default value, respectively. CONCLUSIONS: The anteromedial and posterolateral bundles have a complementary role. Femoral footprint position defined in the lower direction leads to stronger tension during extension, while the higher and shallower direction leads to isometry during flexion, and the deeper direction leads to laxity during flexion. The target bone tunnel position is that the anteromedial bundle should not to be too low and too deep to maintain function of bundle with less change in length. In addition, the posterolateral bundle should be somewhat lower and/or deeper than the anteromedial, with the expectation that it will function to induce stronger tension at the extended position. However, we should avoid lower position when we cannot prepare a sufficient diameter of reconstructed bundle to avoid re-injury due to excessive tension.

Catalytic asymmetric 1,4-addition reactions using alpha,beta-unsaturated N-acylpyrroles as highly reactive monodentate alpha,beta-unsaturated ester surrogates.

Synthesis and application of alpha,beta-unsaturated N-acylpyrroles as highly reactive, monodentate ester surrogates in the catalytic asymmetric epoxidation and Michael reactions are described. alpha,beta-Unsaturated N-acylpyrroles with various functional groups were synthesized by the Wittig reaction using ylide 2. A Sm(O-i-Pr)(3)/H(8)-BINOL complex was the most effective catalyst for the epoxidation to afford pyrrolyl epoxides in up to 100% yield and >99% ee. Catalyst loading was successfully reduced to as little as 0.02 mol % (substrate/catalyst = 5000). The high turnover frequency and high volumetric productivity of the present reaction are also noteworthy. In addition, a sequential Wittig olefination-catalytic asymmetric epoxidation reaction was developed, providing efficient one-pot access to optically active epoxides from various aldehydes in high yield and ee (96-->99%). In a direct catalytic asymmetric Michael reaction of hydroxyketone promoted by the Et(2)Zn/linked-BINOL complex, Michael adducts were obtained in good yield (74-97%), dr (69/31-95/5), and ee (73-95%). This represents the first direct catalytic asymmetric Michael reaction of unmodified ketone to an alpha,beta-unsaturated carboxylic acid derivative. The properties of alpha,beta-unsaturated N-acylpyrrole are also discussed. Finally, the utility of the N-acylpyrrole unit for further transformations is demonstrated.

Direct catalytic asymmetric aldol reaction of hydroxyketones: asymmetric Zn catalysis with a Et(2)Zn/linked-BINOL complex.

Full details of our newly developed catalyses with asymmetric zinc complexes as mimics of class II zinc-containing aldolase are described. A Et(2)Zn/(S,S)-linked-BINOL complex was developed and successfully applied to direct catalytic asymmetric aldol reactions of hydroxyketones. A Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was initially developed, which efficiently promoted the direct aldol reaction of 2-hydroxy-2'-methoxyacetophenone (7d). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we obtained 1,2-dihydroxyketones syn-selectively in high yield (up to 95%), good diastereomeric ratio (up to 97/3), and excellent enantiomeric excess (up to 99%). Mechanistic investigation of Et(2)Zn/(S,S)-linked-BINOL 1, including X-ray analysis, NMR analysis, cold spray ionization mass spectrometry (CSI-MS) analysis, and kinetic studies, provided new insight into the active oligomeric Zn/(S,S)-linked-BINOL 1/ketone 7d active species. On the basis of mechanistic investigations, a modified second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with molecular sieves 3A (MS 3A) system was developed as a much more effective catalyst system for the direct aldol reaction. As little as 0.1 mol % of (S,S)-linked-BINOL 1 and 0.4 mol % of Et(2)Zn promoted the direct aldol reaction smoothly, using only 1.1 equiv of 7d as a donor (substrate/ligand = 1000). This is the most efficient, in terms of catalyst loading, asymmetric catalyst for the direct catalytic asymmetric aldol reaction. Moreover, the Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 system was effective in the direct catalytic asymmetric aldol reaction of 2-hydroxy-2'-methoxypropiophenone (12), which afforded a chiral tetrasubstituted carbon center (tert-alcohol) in good yield (up to 97%) and ee (up to 97%), albeit in modest syn-selectivity. Newly developed (S,S)-sulfur-linked-BINOL 2 was also effective in the direct aldol reaction of 12. The Et(2)Zn/(S,S)-sulfur-linked-BINOL 2 = 4/1 system gave aldol adducts anti-selectively in good ee (up to 93%). Transformations of the aldol adducts into synthetically versatile intermediates were also described.

Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex.

Full details of our direct Michael addition of unmodified ketones using new asymmetric zinc catalysis are described. Et(2)Zn/(S,S)-linked-BINOL complexes were successfully applied to direct 1,4-addition reactions of hydroxyketones. The first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was effective for 1,4-addition of 2-hydroxy-2'-methoxyacetophenone (3). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we found that a 1,4-addition reaction of beta-unsubstituted enone proceeded smoothly at 4 degrees C to afford products in high yield (up to 90%) and enantiomeric excess (up to 95%). In the case of beta-substituted enones, however, the first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was not at all effective. The second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with MS 3A system was developed and was effective for various beta-substituted enones to afford products in good dr, yield (up to 99%), and high enantiomeric excess (up to 99% ee). With the Et(2)Zn/1 = 4/1 systems, catalyst loading for beta-unsubstituted enone was reduced to as little as 0.01 mol % (substrate/chiral ligand = 10 000). The new system was also effective for 1,4-addition reactions of 2-hydroxy-2'-methoxypropiophenone (9) to afford chiral tert-alcohol in high enantiomeric excess (up to 96% ee). Mechanistic investigations as well as transformations of the Michael adducts into synthetically versatile intermediates are also described.