Sagittal tibial tuberosity to trochlear groove distance measurements may reflect patellofemoral contact pressures.

Tibial tubercle to trochlear groove (TTTG) distance is a commonly utilized measurement in the assessment of knees with patellar instability, representing malalignment in the form of tuberosity lateralization relative to the trochlear groove. More recently, the concept of the anteroposterior TTTG (AP-TTTG), renamed as the sagittal TTTG (sTTTG), has been studied as a measurement to assess the relationship between the two structures in a different direction, potentially representing patellofemoral contact pressures through its assessment in the sagittal plane. As we incorporate this measurement to capture how our surgical procedures can offload the joint and 'correct' the sTTTG distance, the utility of this measurement as a proxy for patellofemoral contact pressures will continue to grow, allowing us to better consider joint preservation in addition to stability in the management of patellar instability.

Patellofemoral instability part 1 (When to operate and soft tissue procedures): State of the art.

Patellofemoral instability is usually initially treated non-operatively. Surgery is considered in patients with recurrent patellar dislocation and after a first-time patellar dislocation in the presence of either an associated osteochondral fracture or high risk of recurrence. Stratifying the risk of recurrence includes evaluating risk factors such as age, trochlear dysplasia, contralateral dislocation, and patellar height. Surgery with soft tissue procedures includes restoring the medial patellar restraints and balancing the lateral side of the joint. Reconstruction of the medial patellofemoral ligament is the most frequent way of addressing the medial soft tissues in patients with patellofemoral instability. Meanwhile, lateral tightness can be achieved by lateral retinaculum lengthening or release. Approaching patellofemoral instability in a patient-specific approach, combined with a shared decision-making process with the patient/family, will guide surgeons to the deliver optimal care for the patellar instability patient.

Editorial Commentary: Diverse Factors Affect Measurement of Patella Alta: Trochlear Morphology and Sagittal Knee Balance Represent Defining Factors of Patellofemoral Stability.

Patella alta is a known risk factor for patellar instability, contributing to increased length changes of the medial patellofemoral complex, and associated with high rates of failure after medial patellofemoral complex reconstruction. Distalization through tibial tuberosity osteotomy (TTO) is a surgical option to address patella alta during patellar stabilization surgery. However, distalization has been shown to have greater complication rates than other types of TTO, and therefore precise indications through proper assessments of patellar height are needed. The Caton-Deschamps index is a commonly used measurement and is independent of patellar tendon length, allowing for assessment of patellar height before and after distalizing TTO. Additional options that may offer this ability are femoral-based measurements such as the patellotrochlear index and sagittal patellar engagement, which also do not rely on the position of the tubercle and may better represent the functional engagement of the patellofemoral joint. However, femoral-based measurements depend on trochlear morphology; theoretically, an advantage of femoral-based measurements is that they may reflect the functional engagement of the patella within the trochlea. However, in knowing the common relation between patella alta and trochlear dysplasia, the question becomes whether an overlap between the patella and a dysplastic proximal trochlea on a sagittal measurement truly represents functional engagement and stability of the patellofemoral joint. Measurement of patella alta and determining indications for distalization can be influenced by measurement techniques including magnetic resonance imaging versus radiography, tibial- versus femoral-based measurements, and positional and morphologic considerations. Increased understanding of trochlear morphology and sagittal knee balance as they relate to patella alta will be important for defining the factors that affect patellofemoral stability.

Evaluation of Differences in Patellar Height After Patellar Stabilization Procedures Not Intended to Address Patella Alta: A Multicenter Study.

Background: Recent studies have reported conflicting results as to whether isolated medial patellofemoral ligament reconstruction (MPFLr) leads to decreased patellar height. Purpose: To investigate if patellar stabilization surgery not intended to address patella alta influences patellar height. Study Design: Cohort study; Level of evidence, 3. Methods: A multicenter retrospective chart review was conducted, and patients who underwent MPFLr, medializing tibial tuberosity osteotomy (TTO), and/or trochleoplasty between 2016 and 2020 were included. The Caton-Deschamps index (CDI) was calculated from radiographs obtained preoperatively, 2 weeks postoperatively, and 3 months postoperatively. The preoperative CDI value was compared with the 2-week postoperative and 3-month postoperative values according to stabilization procedure (isolated MPFLr, isolated TTO, MPFLr + TTO, MPFLr + trochleoplasty, and MPFLr + trochleoplasty + TTO) using the paired t test. Analyses of the 1-bundle versus 2-bundle MPFLr technique and the presence of lateral retinacular release or lateral retinacular lengthening were conducted on the isolated MPFLr and combined MPFLr + TTO cohorts. Results: A total of 356 knees were included. Statistically significant pre- to postoperative decreases in CDI were seen in all stabilization procedures analyzed (P≤ .017 for all). Within the isolated MPFLr cohort, this significant decrease was seen at 2 weeks postoperatively with the 2-bundle technique (ΔCDI = -0.09; P < .001) but not with the 1-bundle technique (ΔCDI = -0.01; P = .621). Conclusion: The different surgical techniques analyzed in the current study affected patellar height, even when a distalizing TTO was not performed. The decrease was dependent on surgical technique, with a 2-bundle MPFLr leading to a statistically significant decrease and a 1-bundle MPFLr effecting no change.

Clinical features, future cardiac events, and prognostic factors following percutaneous coronary intervention in young female patients.

BACKGROUND: The proportion of young females among the patients who undergo percutaneous coronary intervention (PCI) is relatively small, and information on their clinical characteristics is limited. This study investigated the clinical characteristics and prognostic factors for future cardiac events in young females who underwent PCI. METHODS: This multicenter observational study included 187 consecutive female patients aged < 60 years who underwent PCI in seven hospitals. The primary composite endpoint was the incidence of cardiac death, nonfatal myocardial infarction, and target vessel revascularization. RESULTS: The mean patient age was 52.1 ± 6.1 years and 89 (47.6%) had diabetes, and renal dysfunction (an estimated glomerular filtration rate < 60 mL/min/1.73 m2) was observed in 38 (20.3%). During a median follow-up of 3.3 years, the primary endpoint occurred in 28 patients. The Cox proportional hazards models showed that renal dysfunction was an independent predictor for the primary endpoint (hazard ratio 3.04, 95% confidence interval 1.25-7.40, p = 0.01), as well as multivessel disease (hazard ratio 2.79, 95% confidence interval 1.12-6.93, p = 0.03). Patients with renal dysfunction had a significantly higher risk for the primary endpoint than those without renal dysfunction. CONCLUSIONS: Renal dysfunction was strongly associated with future cardiac events in young females who underwent PCI.

Endoscopic healing is associated with a reduced risk of biologic treatment failure in patients with ulcerative colitis.

Increasing number of patients with ulcerative colitis (UC) have received biologic treatment during the last decade. The association between endoscopic healing (EH) and biologic treatment failure remains understudied. Medical information of UC patients who started biologic treatment was retrospectively collected. EH was defined as Mayo endoscopic subscore of 0 or 1. Loss of response (LOR)-free drug continuation rate was compared between patients who achieved EH and those who did not using Kaplan-Meier estimator. Fifty-two patients received 53 biologic treatments and underwent follow-up colonoscopies within 2 years. Thirty-three patients achieved EH, all of which remained on the same treatment without LOR during the observational period. Twenty patients did not achieve EH, 8 of which ultimately discontinued the treatment due to LOR to biologic agents. Kaplan-Meier estimator found a significantly lower drug continuation rate in patients without EH (p < 0.001; log-rank test). A Cox regression analysis identified EH as an independent factor associated with a reduced risk of LOR-related biologic treatment failure irrespective of the types of biologic agents (Hazard Ratio = 0.0324, p < 0.001). EH within 2 years is associated with a reduced risk of LOR-related biologic treatment failure in patients with UC.

Predictive factors and scoring system for intravascular large B-cell lymphoma among suspected cases: a single-center retrospective analysis.

BACKGROUND: Although the utility of random skin biopsies in the diagnosis of intravascular large B-cell lymphoma (IVLBCL) has been confirmed, the patients who should undergo random skin biopsies remain unclear. OBJECTIVES: To assess predictive factors for IVLBCL and establish a scoring system for the applicability of random skin biopsies. METHODS: We conducted a retrospective case-control study of IVLBCL-suspected patients who underwent random skin biopsies between April 2010 and March 2022. We compared the general symptoms, imaging findings, and laboratory findings between IVLBCL and non-IVLBCL cases. RESULTS: Fifty-three patients were enrolled in this study. Eight patients were diagnosed with IVLBCL, and 35 patients were diagnosed with other diseases. The final diagnosis was unclear in 10 patients. There were no significant differences in the frequency of general symptoms and imaging findings between IVLBCL and non-IVLBCL cases. Among laboratory findings, IVLBCL cases showed significantly higher serum lactate dehydrogenase (LDH) and soluble IL-2 receptor (sIL-2R) levels and lower platelet counts than non-IVLBCL cases. We established a scoring system to predict IVLBCL by using these three parameters. The cut-off values were as follows: serum LDH level, 256 IU/l; serum sIL-2R level, 2011 U/ml; and platelet count, 107 × 109 /l. IVLBCL was not included in patients with scores of <2. The probabilities of IVLBCL in patients with scores 2 and 3 were 18% and 86%, respectively. CONCLUSIONS: Our simple scoring system can help clinicians determine the applicability of random skin biopsies in IVLBCL-suspected cases.

Radiographic Landmark Measurements for the Femoral Footprint of the Medial Patellofemoral Complex May Be Affected by Visible Femoral Shaft Length on Lateral Knee Radiographs.

PURPOSE: To assess the effect of visible femoral shaft length on the accuracy of radiographic landmarks of the medial patellofemoral complex (MPFC). METHODS: In 9 cadaveric knees, the MPFC footprint was exposed on the medial femur, and its proximal and distal boundaries were marked. Lateral fluoroscopic images of the knee were assessed in 1-cm length increments, beginning 1 cm proximal to the medial condyle and continuing proximally to 8 cm. The MPFC midpoint was described on each image relative to the posterior cortical line of the femur and a line perpendicular to this line through the proximal margin of the medial condyle. In addition, the MPFC midpoint was assessed relative to a line from the proximal posterior cortex to the midpoint of Blumensaat line. RESULTS: Using the posterior cortical line as a reference, the MPFC radiographic landmark moved anteriorly with decreasing visible femoral shaft on radiographs, particularly at 4 cm and less. However, no proximal-distal change was noted. Linear regression analysis demonstrated a relationship between visible femoral shaft and MPFC position on radiographs (R = 0.461, R2 = 0.212, B = -0.636, P < .001). For every centimeter decrease in the visible femoral shaft, the radiographic MPFC footprint moved anteriorly by 0.636 mm. Receiver operating characteristic curve analysis revealed that a minimum of 4 cm of femoral shaft on lateral radiographs is required for accurate MPFC footprint localization (area under the curve = 0.80; sensitivity = 76.7%; specificity = 69.0%; P < .001). In contrast, no anterior-posterior change was seen when referencing a line from the proximal posterior cortex to the midpoint of Blumensaat line. CONCLUSIONS: When using the posterior cortical line to identify the midpoint of the MPFC, at least 4 cm of femoral shaft should be visible for accurate assessment. If less than 4 cm of shaft is visible, a line through the midpoint of Blumensaat line and the proximal posterior cortex can be used as an alternative method to estimate the position of the femoral footprint. CLINICAL RELEVANCE: As fluoroscopy is frequently used intraoperatively for MPFC reconstruction, our findings may serve as a guide when assessing femoral tunnel placement on fluoroscopy.

Location and Progression of Chondral Injuries at the Time of Revision ACL Surgery Varies by Sex.

PURPOSE: To quantify progression of chondral and meniscal injuries between primary and revision anterior cruciate ligament (ACL) surgery. METHODS: Patients who underwent both index and revision ACL reconstruction between 2000 and 2020 at our institution were identified, and dates of injury and surgery, demographics, and clinical data were obtained from operative reports. Outerbridge grade was recorded in each compartment, along with presence and location of meniscal injury. The frequency of each injury between first and second cases was calculated. Differences in injury and progression were compared over time as well as between patient sex and age. RESULTS: The study included 189 patients (96 female, 93 male). Age at first surgery was 31.7 ± 13.2 years. Mean time to second injury was 3.3 ± 3.0 years. In total, 116 patients had a new or previous chondral injury (odds ratio, 1.6; 95% CI, 1.2-2.1). The medial femoral condyle (31%) and the patella (21%) accounted for the highest proportion of new injury to articular surfaces, whereas new injury to menisci was comparable between the medial (25%) and lateral (23%) meniscus. At the time of revision ACL reconstruction, females had a high prevalence of chondral injuries to the lateral compartment, whereas males had a high prevalence of chondral injury to the medial femoral condyle. The prevalence of new chondral injuries was comparable between sexes, with males having a slightly higher proportion. While time between surgeries, sex, and age had graphical evidence of moderating risk, the effects were small and imprecise. CONCLUSIONS: Revision ACL reconstruction carried a 1.6 increase in the odds for new or progressive chondral lesions in our cohort. At the time of revision, females had a relatively higher proportion of lateral-sided chondral injuries, whereas males had a relatively higher proportion of medial femoral condyle injuries. The greatest increase in the prevalence of new and progressive lesions was observed in the medial femoral condyle and trochlea. This progression appeared to be moderated by time between surgeries, patient sex, and age; however, the differences were small and imprecise. STUDY DESIGN: Level IV, therapeutic case series.

Increased Interleukin-36ß Expression Promotes Angiogenesis in Japanese Atopic Dermatitis.

While atopic dermatitis (AD) is considered as a T helper 2 (Th2)-centered disease, an increase in other types of inflammatory cytokines is also noted in AD and they may also contribute to the development of the disease. Recently, the efficacy of an anti-IL-36 receptor antibody in AD was demonstrated in a clinical trial. Although there have been several reports on IL-36α and IL-36γ expression and function in AD, IL-36ß has been barely studied. In this report, we examined IL-36ß expression and function using clinical samples of AD and the epidermal keratinocyte cell line, HaCaT cells. We demonstrated that IL-36ß expression in epidermal keratinocytes was increased in AD lesional skin compared to healthy skin. IL-36ß promoted vascular endothelial growth factor A production in HaCaT keratinocytes through phosphorylation of extracellular signal-regulated kinases 1 and 2. In addition, IL-36ß up-regulated placental growth factor mRNA expression in HaCaT keratinocytes. IL-36ß expression levels in epidermal keratinocytes were correlated with the number of dermal vessels in AD skin. These results suggest that IL-36ß may play an important role for angiogenesis in lesional skin of AD and that IL-36ß can be a therapeutic target in AD.

Association of Trochlear Length on Sagittal MRI to Trochlear Dysplasia in Knees With Patellar Instability.

Background: Trochlear dysplasia is a primary risk factor for patellar instability and leads to loss of the osteochondral constraint of the patella. Trochleoplasty techniques include the Peterson grooveplasty, which alters the length of the trochlea; however, a radiographic measurement of trochlear length to support this has not been described. Purpose: To describe measurements to quantify trochlear length on sagittal magnetic resonance imaging in patients with and without patellar instability and to correlate trochlear length with measurements of trochlear dysplasia. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 66 age- and sex-matched knees (36 female and 30 male; mean age, 20.8 ± 4.8 years) were included in this study, of which 33 had patellar instability. Trochlear extension length (TEL) and trochlear alpha angle (TAA) were measured on 3 sagittal magnetic resonance imaging scans (center of the knee, center of the medial condyle, and center of the lateral condyle), and measurements were compared between symptomatic and control knees. Receiver operating characteristic curve analysis was performed, and the area under the curve (AUC) was calculated to describe the accuracy of each measurement to distinguish between knees with and without patellar instability. Linear and multivariate regression analyses were performed to assess the relationship between sagittal measurements and axial measurements of trochlear dysplasia, including lateral trochlear inclination, sulcus angle, and trochlear depth, as well as patient size reflected by the epicondylar distance. Results: In symptomatic knees, the central trochlea extended more proximally than in control knees, as determined by the TEL (14.0 ± 3.0 vs 11.5 ± 2.3 mm, respectively; P < .001) and TAA (68.4° ± 3.8° vs 70.5° ± 3.4°, respectively; P = .017). AUC calculations showed that a TEL ≥11 mm at the central trochlea was predictive of patellar instability in both male and female knees (AUC = 0.83 and 0.77, respectively), as was a TAA ≤67° in female knees (AUC = 0.72). An independent association between the central TEL and sulcus angle was found. The central TEL showed a weak correlation with patient size, as measured by the epicondylar distance, while the TAA did not. Conclusion: In knees with symptomatic patellar instability, the central trochlea was found to extend 2.5 mm more proximally than in control knees, and this increase in length correlated with severity of trochlear dysplasia. As radiographic examinations of the trochlea and grooveplasty procedures are often based on the proximal extent of the cartilaginous trochlea, further studies are needed to identify the role of trochlear length in the assessment and treatment of trochlear dysplasia in the setting of patellar instability.

Tumor cell heterogeneity drives spatial organization of the intratumoral immune response in squamous cell skin carcinoma.

Intratumoral heterogeneity (ITH)-defined as genetic and cellular diversity within a tumor-is linked to failure of immunotherapy and an inferior anti-tumor immune response. The underlying mechanism of this association is unknown. To address this question, we modeled heterogeneous tumors comprised of a pro-inflammatory ("hot") and an immunosuppressive ("cold") tumor population, labeled with YFP and RFP tags respectively to enable precise spatial tracking. The resulting mixed-population tumors exhibited distinct regions comprised of YFP+ (hot) cells, RFP+ (cold) cells, or a mixture. We found that tumor regions occupied by hot tumor cells (YFP+) harbored more total T cells and a higher frequency of Th1 cells and IFNγ+ CD8 T cells compared to regions occupied by cold tumor cells (RFP+), whereas immunosuppressive macrophages showed the opposite spatial pattern. We identified the chemokine CX3CL1, produced at higher levels by our cold tumors, as a mediator of intratumoral macrophage accumulation, particularly immunosuppressive CD206Hi macrophages. Furthermore, we examined the response of heterogeneous tumors to a therapeutic combination of PD-1 blockade and CD40 agonist on a region-by-region basis. While the combination successfully increases Th1 abundance in "cold" tumor regions, it fails to bring overall T cell activity to the same level as seen in "hot" regions. The presence of the "cold" cells thus ultimately leads to a failure of the therapy to induce tumor rejection. Collectively, our results demonstrate that the organization of heterogeneous tumor cells has a profound impact on directing the spatial organization and function of tumor-infiltrating immune cells as well as on responses to immunotherapy.

Medial Patellofemoral Reconstruction Techniques for Patellar Instability.

The medial patellofemoral complex (MPFC) is the term used to describe the primary soft tissue stabilizer of the patella, which consists of fibers that attach to the patella (medial patellofemoral ligament, or MPFL), and the quadriceps tendon (medial quadriceps tendon femoral ligament, or MQTFL). Despite the variability of its attachment on the extensor mechanism, the midpoint of this complex is consistently at the junction of the medial quadriceps tendon with the articular surface of the patella, indicating that either patellar or quadriceps tendon fixation can be used for anatomic reconstruction. Multiple techniques exist to reconstruct the MPFC, including graft fixation on the patella, quadriceps tendon, or both structures. Various techniques using several graft types and fixation devices have all reported good outcomes. Regardless of the location of fixation on the extensor mechanism, elements critical to the success of the procedure include anatomic femoral tunnel placement, avoiding placing undue tension on the graft, and addressing concurrent morphological risk factors when present. This infographic reviews the anatomy and techniques for the reconstruction of the MPFC, including graft configuration, type, and fixation, while addressing common pearls and pitfalls in the surgical treatment of patellar instability.

In Vivo Length Changes Between the Attachments of the Medial Patellofemoral Complex Fibers in Knees With Anatomic Risk Factors for Patellar Instability.

BACKGROUND: Medial patellofemoral complex (MPFC) reconstruction plays an important role in the surgical treatment of patellar instability. Anatomic reconstruction is critical in re-creating the native function of the ligament, which includes minimizing length changes that occur in early flexion. Anatomic risk factors for patellar instability such as trochlear dysplasia, patella alta, and increased tibial tuberosity to trochlear groove (TT-TG) distance have been shown to influence the function of the MPFC graft in cadaveric studies, but the native length change patterns of the MPFC fibers in knees with anatomic risk factors have not been described. PURPOSE: To describe the in vivo length changes of the MPFC fibers in knees with anatomic risk factors for patellar instability and identify the optimal attachment sites for MPFC reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Dynamic computed tomography imaging was performed on the asymptomatic knee in patients with contralateral patellar instability. Three-dimensional digital knee models were created to assess knees between 0° and 50° of flexion in 10° increments. MPFC fiber lengths were calculated at each flexion angle between known anatomic attachment points on the extensor mechanism (quadriceps tendon, MPFC midpoint [M], and patella) and femur (1, 2, and 3, representing the proximal to distal femoral footprint). Changes in MPFC fiber length were compared for each condition and assessed for their relationships to morphologic risk factors (trochlear depth, Caton Deschamps Index [CDI], and TT-TG distance). RESULTS: In 22 knees, native MPFC fibers were found to be longer at 0° than at 20° to 50° of flexion. Length changes observed between 0° and 50° increased with the number of risk factors present. In the central fibers of the MPFC (M-2), 1.7% ± 3.1% length change was noted in knees with no anatomic risk factors, which increased to 5.6% ± 4.6%, 17.0% ± 6.4%, and 26.7% ± 6.8% in the setting of 1, 2, and 3 risk factors, respectively. Nonanatomic patella-based attachments were more likely to demonstrate unfavorable length change patterns, in which length was greater at 50° than 0°. In patellar attachments, an independent relationship was found between increasing length changes and TT-TG distance, while in quadriceps tendon attachments, a trend toward a negative relationship between length changes and CDI was noted. All configurations demonstrated a strong relationship between percentage change in length and number of morphologic risk factors present, with the greatest influence found in patella-based attachments. CONCLUSION: The MPFC fibers demonstrated increased length changes in knees when a greater number of morphological risk factors for patellar instability were present, which worsened in the setting of nonanatomic configurations. This suggests that the function of the intact MPFC in patients with anatomic risk factors may not reflect previously described findings in anatomically normal knees. Further studies are needed to understand the pathoanatomy related to these changes, as well as the implications for graft placement and assessment of length changes during MPFC reconstruction techniques. CLINICAL RELEVANCE: MPFC length change patterns vary based on the number of morphologic risk factors for patellar instability present and should be considered during reconstructive procedures.

Effects of a smartphone app-based diet and physical activity program for men living with HIV who have dyslipidemia: A pilot randomized controlled trial.

AIMS: People living with HIV are at a high risk for cardiovascular disease owing to antiretroviral therapy use and chronic inflammation. There is limited evidence on the evaluation of serum lipid levels through lifestyle modification. This study aims to evaluate the effect of a smartphone application-based diet and exercise improvement program on men living with HIV and dyslipidemia. METHODS: This was a randomized controlled trial recruiting Japanese men living with HIV who have dyslipidemia: intervention group (n = 19) and control group (n = 19). The intervention group received a third individual guidance session during the 6-month intervention and was encouraged to record their diet on a smartphone application. An intention-to-treat analysis of the results was conducted. RESULTS: The intervention group showed significantly reduced change in low-density lipoprotein levels compared to the control group (-4.00 ± 20.2 mg/dL vs. 10.11 ± 21.1 mg/dL) (p = .042) from baseline to 6 months post-intervention. No significant differences were found in other serum lipid levels. Abdominal circumference decreased significantly in the intervention group (p = .048) from baseline to 6 months post-intervention. Total energy, protein, carbohydrate, fat, and salt intake, dietary and physical activity behavior change stages and social support, dietary self-efficacy, and loneliness significantly improved in the intervention group (p < .05) from baseline to 6 months post-intervention. CONCLUSIONS: A diet and physical activity improvement program using a smartphone application based on Japanese-specific health guidance may reduce low-density lipoprotein cholesterol levels in this population. Further sample expansion and examination of long-term effects are needed.

Redefining Trochlear Dysplasia: Normal Thresholds Vary by Measurement Technique, Landmarks, and Sex.

BACKGROUND: Trochlear dysplasia is a known risk factor for patellar instability. Multiple radiographic measurements exist to assess trochlear morphology, but the optimal measurement technique and threshold for instability are unknown. PURPOSE: To describe the optimal measurements and thresholds for trochlear dysplasia on magnetic resonance imaging (MRI) that can identify knees with patellar instability in male and female patients. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Knee MRI scans of patients with patellar instability were compared with those of age- and sex-matched controls. Measurements of the sulcus angle, lateral trochlear inclination (LTI), and trochlear depth were performed on axial images using bony and cartilaginous landmarks. Receiver operating characteristic curve analysis was performed, with the area under the curve (AUC) describing the accuracy of each diagnostic test. Optimal cutoff values were calculated to distinguish between knees with and without patellar instability. AUC and cutoff values were reported for each measurement as well as for male and female subgroups. RESULTS: A total of 238 knee MRI scans were included in this study (138 female, 100 male; age range, 18-39 years). Trochlear depth measurements had the greatest diagnostic value, with AUCs of 0.79 and 0.82 on bone and cartilage, respectively. All measurements (sulcus angle, LTI, trochlear depth) on bone and cartilage had an AUC ≥0.7 (range, 0.70-0.86), with optimal cutoff values of 145° (bone) and 154° (cartilage) for the sulcus angle, 17° (bone) and 13° (cartilage) for LTI, and 4 mm (bone) and 3 mm (cartilage) for trochlear depth. Optimal cutoff values in female patients varied from those in male patients for all measurements except for cartilaginous trochlear depth. CONCLUSION: Normal thresholds for trochlear dysplasia varied based on the use of bony versus cartilaginous landmarks. Cartilaginous trochlear depth measurements had the greatest ability to identify knees with patellar instability. Furthermore, optimal cutoff values for all measurements except for cartilaginous trochlear depth differed between female and male patients. These findings suggest that sex-specific parameters of normal values may be needed in the assessment of risk factors for patellofemoral instability.

d-amino acid auxotrophic Escherichia coli strain for in vivo functional cloning of novel d-amino acid synthetic enzyme.

Various d-amino acids have been found in a wide range of organisms, including mammals. Although the physiological functions of various d-amino acids have been reported or suggested, the molecular basis of these biological functions has been elucidated in only a few cases. The identification of a d-amino acid biosynthetic enzyme is a critical step in understanding the mechanism of the physiological functions of d-amino acids. While in vivo functional screening can be a powerful tool for identifying novel metabolic enzymes, none of the existing organisms exhibit growth dependent on d-amino acid other than d-Ala and d-Glu. Here, we report the first organism that exhibits non-canonical d-amino acid auxotrophy. We found that an Escherichia coli strain lacking the major d-Ala and d-Glu biosynthetic enzymes, alr, dadX, and murI, and expressing the mutated d-amino acid transaminase (DAAT) gene from Bacillus sp. YM-1 (MB3000/mdaat+ ) grew well when supplemented with certain d-amino acid. A multicopy suppression study with plasmids encoding one of the 51 PLP-dependent enzymes of E. coli showed that MB3000/mdaat+ could detect weak and moonlighting racemase activity, such from cystathionine ß-lyase (MetC) and a negative regulator of MalT activity/cystathionine ß-lyase (MalY)-these exhibit only a few tenths to a few thousandths of the racemization activity of canonical amino acid racemases. We believe that this unique platform will contribute to further research in this field by identifying novel d-amino acid-metabolizing enzymes.

Clinical characteristics and outcomes of Mott cell lymphoma in nine miniature dachshunds.

BACKGROUND: Lymphoma with Mott cell change, or Mott cell lymphoma (MCL), is an uncommon variant of canine lymphoma. Because of its rare occurrence, there has been no comprehensive study describing the disease so far. Miniature dachshunds, a popular breed in Japan, sometimes experience MCL. OBJECTIVES: To investigate the clinical characteristics and outcomes of MCL in miniature dachshunds. METHODS: Medical records were retrospectively reviewed to identify miniature dachshunds diagnosed with MCL and other types of lymphoma. Data on clinical and laboratory findings, treatments and outcomes were collected. Survival times were compared between miniature dachshunds with MCL and other types of lymphoma. RESULTS: Of the 87 miniature dachshunds diagnosed with lymphoma, 9 (10%) had cytological characteristics of MCL. All 9 miniature dachshunds with MCL were categorised as having alimentary lymphoma (small and/or large intestine, 6 dogs; mesenteric lymph node, 3 dogs). The median age was 3.1 years (range, 2.0-9.4 years). All nine dogs were treated with chemotherapeutic protocols used for large cell lymphoma or alkylating agents such as melphalan or chlorambucil. The overall response rate to initial chemotherapy was 78%, and the median progression-free survival was 105 days. Overall survival in these nine dogs ranged from 6 to >1513 days (median, 240 days), which was significantly longer than in 29 miniature dachshunds with alimentary large cell lymphoma other than MCL (median, 57 days; p = 0.0491). CONCLUSIONS: MCL in miniature dachshunds can be recognised as a peculiar type of B-cell lymphoma occurring in relatively young dogs as an alimentary form and has a longer survival compared with typical alimentary large cell lymphoma.