Effect of rifampicin administration on CYP induction in a dermatomyositis patient with vasospastic angina attributable to nilmatrelvir/ritonavir-induced blood tacrolimus elevation: A case report.

Ritonavir (RTV), which is used in combination with nilmatrelvir (NMV) to treat coronavirus disease 2019 (COVID-19), inhibits cytochrome P450 (CYP) 3A, thereby increasing blood tacrolimus (TAC) levels through a drug-drug interaction (DDI). We experienced a case in which a DDI between the two drugs led to markedly increased blood TAC levels, resulting in vasospastic angina (VSA) and acute kidney injury (AKI). Rifampicin (RFP) was administered to induce CYP3A and promote TAC metabolism. A 60-year-old man with dermatomyositis who was taking 3 mg/day TAC contracted COVID-19. The patient started oral NMV/RTV therapy, and he was admitted to the hospital after 4 days because of chest pain and AKI. On day 5, his blood TAC level increased markedly to 119.8 ng/mL. RFP 600 mg was administered once daily for 3 days, and his blood TAC level decreased to the therapeutic range of 9.6 ng/mL on day 9, leading to AKI improvement. Transient complete atrioventricular block and nonsustained ventricular tachycardia were present during chest pain. In the coronary spasm provocation test, complete occlusion was observed in the right coronary artery, leading to a diagnosis of VSA. VSA and AKI are possible side effects of high blood TAC levels caused by DDI, and attention should be paid to cardiovascular side effects such as VSA and AKI associated with increased blood levels of TAC when it is used together with NMV/RTV. When blood levels of TAC increase, oral RFP can rapidly decrease TAC blood levels and potentially reduce its toxicity.

Computer-aided diagnosis with a convolutional neural network algorithm for automated detection of urinary tract stones on plain X-ray.

BACKGROUND: Recent increased use of medical images induces further burden of their interpretation for physicians. A plain X-ray is a low-cost examination that has low-dose radiation exposure and high availability, although diagnosing urolithiasis using this method is not always easy. Since the advent of a convolutional neural network via deep learning in the 2000s, computer-aided diagnosis (CAD) has had a great impact on automatic image analysis in the urological field. The objective of our study was to develop a CAD system with deep learning architecture to detect urinary tract stones on a plain X-ray and to evaluate the model's accuracy. METHODS: We collected plain X-ray images of 1017 patients with a radio-opaque upper urinary tract stone. X-ray images (n = 827 and 190) were used as the training and test data, respectively. We used a 17-layer Residual Network as a convolutional neural network architecture for patch-wise training. The training data were repeatedly used until the best model accuracy was achieved within 300 runs. The F score, which is a harmonic mean of the sensitivity and positive predictive value (PPV) and represents the balance of the accuracy, was measured to evaluate the model's accuracy. RESULTS: Using deep learning, we developed a CAD model that needed 110 ms to provide an answer for each X-ray image. The best F score was 0.752, and the sensitivity and PPV were 0.872 and 0.662, respectively. When limited to a proximal ureter stone, the sensitivity and PPV were 0.925 and 0.876, respectively, and they were the lowest at mid-ureter. CONCLUSION: CAD of a plain X-ray may be a promising method to detect radio-opaque urinary tract stones with satisfactory sensitivity although the PPV could still be improved. The CAD model detects urinary tract stones quickly and automatically and has the potential to become a helpful screening modality especially for primary care physicians for diagnosing urolithiasis. Further study using a higher volume of data would improve the diagnostic performance of CAD models to detect urinary tract stones on a plain X-ray.

Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation.

Mesenchymal stem cell (MSC)-mediated immunomodulation affects both innate and adaptive immune systems. These responses to environmental cues, such as pathogen-associated molecular patterns, damage-associated molecular patterns, or proinflammatory cytokines, are crucial for resolution of inflammation, as well as successful tissue healing and regeneration. We observed that intermittent, repeated exposure of MSCs to LPS induced stronger NF-κB activation than singular stimulation. A similar phenomenon, named innate immune memory or trained immunity, has been reported with macrophages. However, the potential regulation of "immune memory" in nonclassic immune cells, such as MSCs, has not been reported. In the current study, we chose IFN-γ plus TNF-α restimulation-induced iNOS expression as a model of MSC activation, because IFN-γ and TNF-α play crucial roles in MSC-mediated immunomodulation. The iNOS expression was enhanced in LPS-trained MSCs, 3 d after a washout period following primary stimulation. LPS-trained MSCs enhanced the anti-inflammatory (arginase 1 and CD206) marker expression, but decreased the proinflammatory marker (TNF-α, IL-1ß, iNOS, and IL-6) expression using an MSC-macrophage coculture model. In contrast, LPS-trained MSCs demonstrated a defective regulation on CD4 T-cell proliferation. Mechanistic studies suggested that histone methylation and the JNK pathway are involved in LPS-trained immunomodulation in MSCs. Our results demonstrate differential immunomodulatory effects of trained MSCs on macrophages and T cells. These immunomodulatory consequences are critical, because they will have a major impact on current MSC-based cell therapies.-Lin, T., Pajarinen, J., Kohno, Y., Huang, J.-F., Maruyama, M., Romero-Lopez, M., Nathan, K., Yao, Z., Goodman, S. B. Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation.

Acetabular retroversion in dysplastic hips is associated with decreased 3D femoral head coverage independently from lateral center-edge angle.

INTRODUCTION: The clinical significance of acetabular retroversion in non-dysplastic hips can be explained as pincer-type femoroacetabular impingement (FAI), whereas that in dysplastic hips is not clarified because FAI normally poses little problems for dysplastic hips. We aimed to evaluate three-dimensional (3D) femoral head coverage in dysplastic hips with and without acetabular retroversion and to elucidate the role of acetabular retroversion on the 3D femoral head coverage. MATERIALS AND METHODS: We retrospectively investigated 93 hips in 93 patients (9 males and 84 females) that underwent periacetabular osteotomy for hip dysplasia. Dysplastic hips were divided into anteversion and retroversion groups according to their cranial anteversion, which was measured on the axial section 5 mm caudal to the acetabular roof. The 3D femoral head coverage was provided as a percentage of the acetabulum-covered surface area of the upper femoral hemisphere using a 3D preoperative planning software for total hip arthroplasty. RESULTS: Of the 93 dysplastic hips, 15 hips (16%) were assigned to the retroversion group, which had significantly younger age at surgery (31.9 years versus 39.2 years; p = 0.033). The lateral center-edge angles were comparable between the groups (13.8° versus 12.9°; p = 0.68); however, the hips in the retroversion group had a trend of smaller 3D femoral head coverage than those in the anteversion group (59% versus 63%; p = 0.058). Multivariate analysis using two-way analysis of covariance showed that lateral center-edge angle (partial regression coefficient = 0.83; t value = 17.3; p < 0.001) and acetabular retroversion (partial regression coefficient = - 2.3; t value = - 4.9; p < 0.001) were independent factors that contributed to the 3D femoral head coverage. CONCLUSIONS: Acetabular retroversion in dysplastic hips was associated with decreased 3D femoral head coverage independently from lateral center-edge angle. The age at surgery in the retroversion group was significantly younger, suggesting a relationship between decreased 3D coverage and potentially earlier symptom onset.

Ghost imaging using a large-scale silicon photonic phased array chip.

We experimentally demonstrate the use of a large-scale silicon-photonic optical phased array (OPA) chip as a compact, low-cost, and potentially high-speed light illuminating device for ghost imaging (GI) applications. By driving 128 phase shifters of a newly developed silicon OPA chip using rapidly changing random electrical signals, we successfully retrieve a slit pattern with over 90 resolvable points in one dimension. We then demonstrate 2D imaging capability by sweeping the wavelength. With the potential of integrating high-speed phase modulators, tunable lasers, grating couplers, and CMOS driver circuit on the same silicon platform, this work paves the way towards realizing ultrahigh-speed and low-cost single-chip GI devices.

Transplanted interleukin-4--secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur.

BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation. METHODS: Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) activation. Cells were injected into the murine distal femoral bone marrow cavity. MSC viability and bone formation were examined in vivo. Cytokine secretion was determined in a femoral explant organ culture model. RESULTS: The reporter MSCs survived up to 4 weeks post-implantation. No difference in the number of viable cells was found between high (2.5 × 106) and low (0.5 × 106) cell-injected groups. Injection of 2.5 × 106 reporter MSCs increased local bone mineral density at 4 weeks post-implantation. Injection of 0.5 × 106 constitutive IL-4 or NFκB-sensing IL-4-secreting MSCs increased bone mineral density at 2 weeks post-implantation. In the femoral explant organ culture model, LPS treatment induced IL-4 secretion in the NFκB-sensing IL-4-secreting MSC group and IL-10 secretion in all the femur samples. No significant differences in tumor necrosis factor (TNF)α and IL-1ß secretion were observed between the MSC-transplanted and control groups in the explant culture. DISCUSSION: Transplanted GM MSCs demonstrated prolonged cell viability when transplanted to a compatible niche within the bone marrow cavity. GM IL-4-secreting MSCs may have great potential to enhance bone regeneration in disorders associated with chronic inflammation.

Clinical outcomes of conservative treatment with a non-weight-bearing abduction brace for Legg-Calvé-Perthes disease.

BACKGROUND: Treatment with a brace is the first choice as conservative treatment via the containment method for Legg-Calvé-Perthes disease (LCPD). The purpose of this study is to evaluate clinical outcomes and influential factors of conservative treatment with the non-weight-bearing abduction brace for LCPD. METHODS: One hundred thirty hips in 130 patients were examined in this study. The mean age at onset was 7.0 years (3.3-12.4 years) and the mean follow-up period was 8.4 years (4.1-17.6 years). The extent of necrosis and lateral collapse of the femoral head were evaluated using the Catterall classification and the lateral pillar classification, respectively. Radiological outcome was assessed as good (classes I and II), fair (III), and poor (IV), according to the modified Stulberg classification. RESULTS: Radiographic outcome at final follow-up was good in 82 hips (63%), fair in 40 hips (31%), and poor in 8 hips (6%). Multinomial logistic regression analysis showed that major influential factors for good outcomes were as follows: age at onset, lateral pillar classification, and Catterall classification. From the receiver operating characteristic curve, the cut-off value for age at onset was 8.4 years old to obtain good outcomes. Hips with Catterall group I and II and lateral pillar group A and B had significantly better results. CONCLUSION: Patients younger than 8.4 years old at onset with lateral pillar group A or B or Catterall group I or II showed good outcomes with a non-weight-bearing abduction brace for LCPD. These results show that alternative treatment, such as surgery, may be another option for patients who are not included in the above groups.

Lower Circulating Omega-3 Polyunsaturated Fatty Acids Are Associated with Coronary Microvascular Dysfunction Evaluated by Hyperemic Microvascular Resistance in Patients with Stable Coronary Artery Disease.

The consumption of omega-3 polyunsaturated fatty acids (PUFAs) reduces the incidence of cardiovascular events and sudden cardiac death. Coronary microvascular dysfunction (CMD) is a predictor of cardiac mortality, but little information is known on the relationship between CMD and omega-3 PUFAs. This study aimed to identify the relationship between the serum levels of omega-3 PUFAs and the CMD evaluated by the hyperemic microvascular resistance index (hMVRI) to assess coronary microvascular function in patients with stable coronary artery disease (CAD).Intracoronary physiological variables (fractional flow reserve (FFR), hMVRI, mean distal coronary pressure (Pd), and average peak velocity (APV)) were measured in 108 patients. These parameters were evaluated in 150 coronary arteries with stenosis of intermediate severity and without significant ischemia (FFR > 0.80). The PUFA levels and atherosclerotic risk factors were also measured. Univariate analysis shows that hMVRI was negatively correlated with eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (ß = -0.31, P = 0.001) and EPA (ß = -0.25, P = 0.009) and was positively correlated with dihomo-γ-linolenic acid (ß = 0.26, P = 0.006). Multivariate regression analysis shows that the EPA/AA ratio was the only independent determinant of hMVRI (ß = -0.234, SE = 0.231, P = 0.024). Furthermore, hMVRI decreased significantly from the lowest to highest tertiles of the EPA/AA ratio (P = 0.007). The EPA/AA ratio was positively correlated with APV at hyperemia (ß = 0.26, P = 0.008) but not with Pd at hyperemia.A lower serum EPA/AA ratio may cause CMD in patients with stable CAD.

Is the timing of surgery associated with avascular necrosis after unstable slipped capital femoral epiphysis? A multicenter study.

BACKGROUND: An unstable slipped capital femoral epiphysis (SCFE) is associated with a high rate of avascular necrosis (AVN). The etiology of AVN seems to be multifactorial, although it is not thoroughly known. The aims of our study were to determine the rate of AVN after an unstable SCFE and to investigate the risk factors for AVN, specifically evaluating the notion of an "unsafe window", during which medical interventions would increase the risk for AVN. METHODS: This retrospective multicenter study included 60 patients with an unstable SCFE diagnosed between 1985 and 2014. Timing of surgery was evaluated for three time periods, from acute onset of symptoms to surgery: period I, <24 h; period II, between 24 h and 7 days; and period III, >7 days. Multivariate logistic regression analysis was used to identify risk factors for AVN. RESULTS: Closed reduction and pinning was performed in 43 patients and in situ pinning in 17. Among these cases, 16 patients (27%) developed AVN. The rate of AVN was significantly higher in patients treated by closed reduction and pinning (15/43, 35%) than in those treated by in situ pinning (1/17, 5.9%) (p = 0.022). In patients treated by closed reduction and pinning, the incidence of AVN was 2/11 (18%) in period I, 10/13 (77%) in period II and 3/15 (20%) in period III, showing the significantly higher rate in period II (p = 0.002). The surgery provided in period II was identified as an independent risk factor for the development of AVN. CONCLUSIONS: Our rate of AVN was 27% using two classical treatment methods. Time-to-surgery, between 24 h and 7 days, was independently associated with AVN, supporting the possible existence of an "unsafe window" in patients with unstable SCFE treated by closed reduction and pinning.

The processus vaginalis transection method is superior to the simple prophylactic procedure for prevention of inguinal hernia after radical prostatectomy.

BACKGROUND: We compared retrospectively the efficacy of two methods for prevention of post-radical prostatectomy inguinal hernia: blunt dissection of the peritoneum at the internal inguinal ring, and isolation of the spermatic cord from the peritoneum (simple prophylactic procedure) and transection of the processus vaginalis. METHODS: Of the 367 patients who underwent open radical retropubic prostatectomy for clinically localized prostate cancer between February 2005 and March 2012 at Saitama Cancer Center Hospital, 344 patients whose follow-up period was more than 2 years were enrolled in this study. Of these patients, 178 patients received the simple prophylactic procedure and 57 underwent processus vaginalis transection. We evaluated the risk factors for inguinal hernia (age; anastomotic stricture post radical prostatectomy; prophylactic procedures for inguinal hernia; previous history of abdominal surgery; previous inguinal hernia surgery; body mass index) using univariate and multivariate analysis. The effects of the two prophylactic procedures on incidence of inguinal hernia were analyzed using Kaplan-Meier plots. RESULTS: The incidence of inguinal hernia was 24.8 % in those not undergoing the prophylactic procedure; 18.5 % in those undergoing the simple prophylactic procedure; and 0.00 % in those undergoing the processus vaginalis transection procedure (p < 0.001). In univariate and multivariate analysis, undergoing the processus vaginalis transection procedure and high body mass index were significant predictors for hernia-free survival after radical prostatectomy. CONCLUSION: Our data suggest that the processus vaginalis transection procedure is superior to the simple prophylactic procedure for the prevention of inguinal hernia after radical prostatectomy.

Does High Hip Center Decrease Range of Motion in Total Hip Arthroplasty? A Computer Simulation Study.

BACKGROUND: High placement of a cementless acetabular cup is often required to have sufficient bone coverage in hip dysplasia. We examined whether a high hip center decreases the postoperative range of motion (ROM) in total hip arthroplasty. METHODS: Using a computer software, ROM and bone coverage were examined in 32 patients with unilateral osteoarthritis of the hip with Crowe type II or III hip dysplasia. The cup was placed at the anatomic hip center and moved vertically in 5-mm increments. Vertical center of rotation (V-COR) was defined as the distance from the head center to the interteardrop line. The required ROM was defined as flexion ≥110°, internal rotation (IR) at 90° flexion ≥30°, extension ≥30°, and external rotation ≥30°. We determined the V-COR to satisfy the required ROM and cup center-edge angle (Cup-CE) ≥0°. RESULTS: Only 40.6% of the patients satisfied Cup-CE ≥0° at the anatomic hip center. Bone coverage increased with the peak at 30, 35 mm of V-COR (90.6% satisfied Cup-CE ≥0°) and decreased at ≥40 mm. Higher V-COR resulted in lower range of flexion and IR, but increased the range of extension and external rotation. The cutoff value from the receiver-operating characteristic curve for both flexion and IR was a V-COR of 35 mm. CONCLUSION: The higher hip center gained more bone coverage but decreased the range of hip flexion and IR. Acceptable V-COR in hip dysplasia was around 35 mm, about 20 mm above the true hip center, in terms of ROM.

Transtrochanteric rotational osteotomy for avascular necrosis of the femoral head after unstable slipped capital femoral epiphysis: 10-year clinical results.

BACKGROUND: Avascular necrosis of the femoral head (AVN) is the most serious complication after unstable slipped capital femoral epiphysis (SCFE), and is often unsalvageable. We report a minimum 10 years of clinical results for transtrochanteric rotational osteotomy of the femoral head (TRO) for AVN. METHODS: This study included 7 patients (7 hips) with a mean age at surgery of 13.3 years, and the follow-up period was 15.8 years. All patients had prior treatment via closed reduction and pinning of the unstable SCFE, and showed severely collapsed femoral heads. The direction of rotation was anterior in 3 hips and posterior in 4. The Merle d'Aubigné-Postel score (MDPS) was used for clinical assessment, and joint degeneration was assessed with the Kellgren and Lawrence classification (KL-grade). RESULTS: The spherical intact area of the femoral head was moved to the weight-bearing portion, and subluxation was corrected via rotation combined with intentional varus positioning. The mean MDPS improved from 10.3 points to 15.6 points at 5 years, and it was maintained at 15.0 points by 10 years; 3 hips were excellent, 1 was good, 2 were fair, and 1 showed poor outcomes. No patient experienced re-collapse after TRO or required conversion to hip replacement or arthrodesis. After 10 years, degenerative changes became evident over time, and 2 hips progressed to KL-4 with a decreased MDPS. CONCLUSIONS: Although some joint degeneration is inevitable in the long-term, TRO is an effective salvage procedure for treating AVN after unstable SCFE.

Cementless total hip arthroplasty for patients previously treated with femoral osteotomy for hip dysplasia: the incidence of periprosthetic fracture.

PURPOSE: Femur deformities can make stem fixation difficult in total hip arthroplasty (THA). We report the clinical results of cementless THA using a press-fit stem in patients who had previously undergone femoral osteotomy for hip dysplasia. METHODS: The subjects included 66 hips in 64 patients, with the mean follow-up period of 7.3 years. THA was performed at a mean period of 17.1 years after intertrochanteric femoral osteotomy. Valgus osteotomy was performed in 42 hips, and varus osteotomy in 24. Clinical results were evaluated by using the Merle d'Aubigne-Postel score. Implant survival was determined with revision as the end point, and any related complications were investigated. RESULTS: The Merle d'Aubigne-Postel score improved from 9.4 to 16.1 at the final follow-up, without any implant loosening. However, periprosthetic femoral fractures were observed in four hips (6.0 %), one intra-operatively and three within three weeks after THA. Among these cases, three hips previously had varus osteotomy (12.5 %) and one hip had valgus osteotomy (2.3 %). Two hips were revised with full porous stems and circumferential wiring. The five and ten year cumulative survivorship rates were 97 % (range, 88.8-99.3 %) and 97 % (88.8-99.3 %), respectively. CONCLUSIONS: Although the use of a press-fit cementless stem yielded acceptable results in most of the patients, perioperative femoral fracture was a major complication especially in the patients previously treated with intertrochanteric varus osteotomy. Careful planning and implant selection could be emphasized for these cases.

Does native combined anteversion influence pain onset in patients with dysplastic hips?

BACKGROUND: Combined anteversion is the sum of femoral and acetabular anteversion and represents their morphological relationship in the axial plane. Few studies have investigated the native combined anteversion in patients with symptomatic dysplastic hips. QUESTIONS/PURPOSES: We hypothesized the following: (1) dysplastic hips have two distinct populations, which differ from each other and from normal hips in their combined anteversion; and (2) these populations differ clinically in terms of correlation between age of onset of symptoms and amount of anteversion. METHODS: We measured radiographic parameters by CT of 100 dysplastic hips in 76 patients who were symptomatic enough to undergo periacetabular osteotomy and of 50 normal hips in 44 patients who had CT scans as part of preparation for computer-navigated TKAs; these patients had no visible hip arthritis or dysplasia and no hip symptoms. Dysplastic hips were divided into the anteversion (83 hips) and retroversion groups (17 hips) based on acetabular version. Age at pain onset was determined from their medical charts. RESULTS: Combined anteversion in the anteversion group was greater than that in the retroversion and control groups: 47° ± 12°, 30° ± 16°, and 36° ± 9°, respectively. In the anteversion group, combined anteversion (r = -0.49; 95% confidence interval [CI], -0.66 to -0.27; p < 0.001) and femoral anteversion (r = -0.41; 95% CI, -0.60 to -0.19; p < 0.001) were associated with an earlier age at pain onset; however, no such relationships were observed in the retroversion group. After controlling for relevant potential confounding variables, we found that combined anteversion (hazard ratio [HR], 1.04; 95% CI, 1.01-1.07; p = 0.006) and Sharp angle (HR, 1.10; 95% CI, 1.02-1.17; p = 0.008) were associated with an earlier age of pain onset in the anteversion group. CONCLUSIONS: These results suggest that not only lateral coverage of the femoral head, but also axial joint morphology is important for the development of pain in the anteversion group. Optimal combined anteversion should be considered during periacetabular osteotomy. LEVEL OF EVIDENCE: Level IV, prognostic study.

Optimal anterior femoral offset for functional range of motion in total hip arthroplasty--a computer simulation study.

PURPOSE: Compared to medial femoral offset (MFO), the role of anterior femoral offset (AFO) on range of motion (ROM) in total hip arthroplasty (THA) has not been fully examined. We therefore defined AFO as the anterior distance from the centre of the femoral head to the proximal femoral axis in the sagittal plane and determined the optimal AFO required for ROM needed for activities of daily living using a computer-simulated THA model. METHODS: Various AFOs were obtained by changing stem anteversion (stem-AV) and stem tilt in the sagittal plane (stem-tilt) using a CT-based simulation software. The required ROM was defined as: flexion ≥ 110°, internal rotation at 90° flexion (IR) ≥ 30°, external rotation (ER) ≥ 30°, and extension ≥ 30°, and we determined AFO and MFO to satisfy required ROM. RESULTS: AFO was positively correlated with stem-AV and anterior stem-tilt. MFO was negatively correlated with stem-AV and not influenced by stem-tilt. Flexion and IR increased with both increased AFO and MFO, whereas extension and ER decreased with increased AFO. A smoothing spline curve showed the optimal AFO and MFO for required ROM to be from 15 mm to 25 mm on average and more than 32.1 mm, respectively. CONCLUSIONS: This is the first study to show that AFO directly influenced ROM in THA. Optimal AFO as well as MFO should be reconstructed to achieve sufficient ROM.

Subclinical bilateral involvement of the hip in patients with slipped capital femoral epiphysis: a multicentre study.

PURPOSE: This study was conducted to assess the posterior inclination of the contralateral femoral epiphysis in patients with unilateral slipped capital femoral epiphysis (SCFE). METHODS: The posterior sloping angle (PSA) was measured using lateral radiographs in 67 patients with a unilateral SCFE and in 41 age-matched normal controls. A symptomatic epiphyseal slip was defined as the development of SCFE. RESULTS: The contralateral PSA in SCFE patients was more widely distributed and significantly larger compared to controls (15.0° vs. 9.0°, p < 0.0001). Forty-seven hips (70.1%) had a PSA of greater than 12.8°, which was +2SD of the control hips. Of the 65 hips excluding the two cases with prophylactic pinning, 11 hips (16.9%) eventually developed a contralateral SCFE during adolescence and their PSA at the initial visit was significantly larger compared to patients without a contralateral SCFE (18.0° vs. 14.3°, p < 0.005) with a cutoff value of 19°. CONCLUSIONS: These findings suggested the possibility of bilateral hip involvement in SCFE patients. Hips with greater degrees of PSA (> 19°) are likely to become symptomatic.

Life Course Epidemiology of Hip Osteoarthritis in Japan: A Multicenter, Cross-Sectional Study.

BACKGROUND: The incidence of developmental dysplasia of the hip (DDH) in Japanese newborns has reduced drastically following a primary prevention campaign initiated around 1972 to 1973; this perinatal education campaign promoted maintaining the hips of newborns in the naturally flexed-leg position. The purpose of the present study was to describe the life course epidemiology of hip osteoarthritis (OA) in adolescent and adult patients and to assess its association with exposure to the primary prevention campaign for DDH. METHODS: We included new patients with hip OA diagnosed from January 1, 2022, to December 31, 2022, at 12 core hospitals (8 special-function hospitals and 4 regional medical care support hospitals). The trend in the percentage of hips with a history of DDH treatment in childhood was estimated with use of a centered moving average using the birth year of the patient. We compared the prevalence of severe subluxation (Crowe type II, III, or IV) between patients with secondary hip OA due to hip dysplasia who were born in or before 1972 and those who were born in or after 1973. RESULTS: Overall, 1,095 patients (1,381 hips) were included. The mean age at the time of the survey was 63.5 years (range, 15 to 95 years). A total of 795 patients (1,019 hips; 73.8% of hips) were diagnosed with secondary OA due to hip dysplasia. Approximately 13% to 15% of hips among patients born from 1963 to 1972 had a history of DDH treatment in childhood; however, the percentage decreased among patients born in or after 1973. The prevalence of severe subluxation (Crowe type II, III, or IV) among patients born in or after 1973 was 2.4%, which was significantly less than that among patients born in or before 1972 (11.1%; odds ratio, 0.20; p < 0.001). CONCLUSIONS: As of 2022, secondary hip OA due to hip dysplasia is still responsible for most new cases of adolescent and adult hip OA seen in core hospitals in Japan. However, the perinatal education campaign initiated 50 years ago, which utilized a population approach and advocated for maintaining the hips of newborns in the naturally flexed-leg position, may have improved the environmental factors of DDH, as indicated by the apparently reduced need for treatment of DDH in childhood and the associated severe subluxation. This may result in a reduced need for challenging hip surgery later in life. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Treatment outcome of patients with extragonadal nonseminomatous germ cell tumors: the Saitama Cancer Center experience.

BACKGROUND: Survival of patients with extragonadal nonseminomatous germ cell tumors remains inferior to that of patients with advanced testicular cancer, although treatment is often the same for both conditions. In addition, the prognosis for nonseminomatous tumors has been shown to be worse than for seminoma. METHODS: Thirteen patients with extragonadal nonseminomatous germ cell tumors were treated between 1998 and 2011; the primary tumors were located in the mediastinum in six and in the retroperitoneum in seven. At initial diagnosis seven patients had distant metastases. According to the IGCCC, eleven patients had poor prognosis and two were intermediate. All 13 patients received cisplatin or carboplatin-based chemotherapy as initial treatment. The patients were further treated by use of a multi-modal strategy which included high-dose chemotherapy, aggressive surgery, and early introduction of salvage regimens. RESULTS: Complete response was obtained for eight patients. Among these complete responders, one patient remained relapse-free after post-chemotherapy surgical excision of viable cancer tissue. In the course of the chemotherapy, four patients died from cancer progression and one patient died as a result of post-chemotherapeutic sepsis. The other eight patients were alive at the end of the observation period. At the last observation all surviving patients were without evidence of disease. Five-year overall survival for all 13 patients was 62 %, and 5-year cancer-specific survival was 68 %. CONCLUSION: Our results indicate that even patients with far-advanced extragonadal nonseminomatous germ cell tumors can be cured by intensive chemotherapy plus surgery.

Remodelling of femoral head-neck junction in slipped capital femoral epiphysis: a multicentre study.

PURPOSE: We examined the remodelling of the femoral head-neck junction in patients with slipped capital femoral epiphysis (SCFE) and the frequency of residual cam deformities. METHODS: We reviewed 69 hips in 56 patients with stable SCFE who had undergone in situ pinning. Mean age at slip was 11.7 years and the follow-up period 63.4 months. Cam deformity was evaluated using the anterior offset alpha (α) angle and head-neck offset ratio (HNOR). RESULTS: The average α angle and HNOR significantly improved from 76.2° to 51.3° and 0.086 to 0.135, respectively; 25 hips (36.2%) still had an α angle greater than 50°, and 32 hips (46.4%) had an HNOR of under 0.145. A multivariate analysis selected age at onset and slip angle as risk factors for cam deformity, with cutoff values 11.1 years and 21.0°, respectively. CONCLUSIONS: Although most hips had remodelling of the head-neck junction, 29.4 % had residual cam deformities that may be susceptible to femoroacetabular impingement.