Immunopathological Analysis of a Mouse Model of Arthritis-Associated Scleritis and Implications for Molecular Targeted Therapy for Severe Scleritis.

Scleritis involves inflammation of the sclera, which constitutes 75% of the wall of the eye. This pathology is often seen as an ocular lesion associated with systemic inflammatory diseases. Severe types of scleritis such as posterior scleritis require urgent immunosuppressive treatments, including molecularly targeted therapies to avoid permanent visual impairment. Which molecules should be selected as targets has remained unclear. To clarify the pathogenesis of scleritis and propose appropriate target molecules for therapy, we have established novel animal model of scleritis by modifying the Collagen-II Induced Arthritis (CIA) model. Immunization twice with collagen II emulsified with complete Freund's adjuvant (CFA) caused arthritis and scleritis. The clinical appearance resembled human diffuse scleritis. Histopathological analysis suggested that macrophages, plasma cells, deposition of immune complexes, and growth of blood and lymphatic vessels are involved in the pathogenesis of CIA-associated scleritis. In addition, we analysed the background diseases of posterior scleritis and responses to molecularly targeted therapies as a case series study. We inferred from both the animal model and case series study that targets should not be T cells, but factors inhibiting macrophage activity such as tumor necrosis factor (TNF) and interleukin (IL)-6, and molecules suppressing antibody-producing cells such as CD20 on B cells should be targeted by molecularly targeted therapies.

Correlation between knee kinematics and patellofemoral contact pressure in total knee arthroplasty.

The aim of this study is to evaluate the relationship between patellofemoral contact stress and intraoperative knee kinematic patterns after mobile bearing total knee arthroplasty (TKA). Medial osteoarthritic knees of forty-six posterior-stabilized total knee prostheses were evaluated using a computed tomography-guided navigation system. Subjects were divided into two groups based on intraoperative knee kinematic patterns: the medial pivot group (n=19) and the non-medial pivot group (n=27). Mean intraoperative patello-femoral contact stress was significantly lower in the medial pivot group than in the non-medial pivot group (1.7MPa vs. 3.2MPa, P<0.05). An intraoperative medial pivot pattern results in reduced patello-femoral contact stress.

Intraoperative medial pivot affects deep knee flexion angle and patient-reported outcomes after total knee arthroplasty.

The aim of this study was to evaluate the relationship between clinical results including patient-reported outcomes and intraoperative knee kinematic patterns after total knee arthroplasty (TKA). A cross-sectional survey of forty consecutive medial osteoarthritis patients who had a primary TKA using a CT-based navigation system was conducted. Subjects were divided into two groups based on intraoperative kinematic patterns: a medial pivot group (n = 20) and a non-medial pivot group (n = 20). Subjective outcomes with the new Knee Society Score and clinical outcomes were evaluated. The functional activities, patient satisfaction and the knee flexion angle of the medial pivot group were significantly better than those of the non-medial pivot group. An intraoperative medial pivot pattern positively influences deep knee flexion and patient-reported outcomes.

24-Hour Intraocular Pressure Fluctuation Suppressed by Microhook Trabeculotomy in Ocular Hypertension: A Case Report.

A 76-year-old woman was referred to our hospital for evaluation of markedly high intraocular pressures (IOPs): ≥40 mmHg in both eyes. No intraocular inflammation, pseudoexfoliation, or glaucomatous optic neuropathy was observed on ophthalmological examination. The 24-hour IOP fluctuations, measured with a Goldmann tonometer in the sitting position at 8, 12, 16, 20, and 24 o' clock, were 22/17, 33/28, 41/33, 30/22, and 30/24 mmHg, respectively, and showed a peak in the afternoon. The patient was diagnosed with ocular hypertension, and microhook trabeculotomy (µLOT) (right eye with lens reconstruction, left eye initially pseudophakic) was performed. After µLOT surgery in both eyes (4 days postoperatively in the right eye and 1 day postoperatively in the left eye), IOP decreased in both eyes to 12/15, 11/14, 12/15, 10/11, and 10/10 mmHg, and the fluctuation range was suppressed. At 3 months postoperatively (measured at 8, 12, 16, 20, 24, and 4 o' clock), the effect was maintained at 14/15, 15/19, 14/19, 11/12, 13/14, and 13/13 mmHg, respectively, but was slightly attenuated. In a patient with marked 24-hour IOP fluctuation, µLOT was effective in reducing IOP values and fluctuation.

Statistical Analysis of Factors Affecting Surgically Induced Astigmatism Following Trabeculectomy.

Purpose: To objectively evaluate surgically induced astigmatism (SIA) after trabeculectomy with mitomycin C and investigate the relationships between SIA and various factors. Patients and Methods: This retrospective study included the right eyes of 66 consecutive patients who underwent standard trabeculectomy performed in the superior temporal quadrant for the first time by a single surgeon. Keratometry recordings made before surgery and 3 months after surgery were collected to calculate the SIA in each patient. The arithmetic mean of SIA (M-SIA) and the centroid of SIA (C-SIA) were determined using vector analysis. The relationships between the magnitude of SIA and the following possible related factors were assessed: age, sex, pre-operative corneal astigmatism, pre-operative intraocular pressure (IOP), 3-month postoperative IOP, pre-operative best-corrected visual acuity (BCVA), 3-month postoperative BCVA, the number of total scleral flap sutures (T-SFS), the number of leftover scleral flap sutures without laser suture lysis at 3 months postoperatively (L-SFS), shape of the scleral flap (triangle or trapezoid), and incision type of the conjunctival flap (fornix- or limbal-based). Results: The mean (± standard deviation) M-SIA was 1.00 ± 0.85 D, and the mean C-SIA was 0.34 ± 1.28 D at 104°. The direction of C-SIA showed a trend of corneal steepening to the superior temporal location, in the direction of the scleral flap location. There were significant correlations of the magnitudes of SIA with the number of T-SFS (P = 0.001) and the number of L-SFS (P < 0.001). Conclusion: Trabeculectomy induced SIA in the direction of the scleral flap location, and scleral sutures are significantly associated with the SIA. The scleral suture may play a key role in steepening the cornea toward the scleral flap direction in post-trabeculectomy patients.

Calcium/calmodulin-dependent regulation of Rac GTPases and Akt in histamine-induced chemotaxis of mast cells.

Histamine induces chemotaxis of mast cells through the histamine H4 receptor. This involves the activation of small GTPases, Rac1 and Rac2, downstream of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Activation of the H4 receptor also results in phospholipase C (PLC)-mediated calcium mobilization; however, it is unclear whether the PLC­calcium pathway interacts with the PI3K-Rac pathway. Here, we demonstrated that calcium mobilization regulates the PI3K-dependent activation of Rac GTPases through calmodulin. A PLC inhibitor (U73122) and an intracellular calcium chelator (BAPTA-AM) suppressed the histamine-induced activation of Rac, whereas the calcium ionophore ionomycin increased the active Rac GTPases, suggesting that intracellular calcium regulates the activation of Rac. The calmodulin antagonist (W-7) inhibited the histamine-induced activation of Rac and migration of mast cells, indicating that calmodulin mediates the effect of calcium. Inhibition of calcium/calmodulin signaling suppressed histamine-induced phosphorylation of Akt. The Akt inhibitor MK-2206 attenuated histamine-induced migration of mast cells. However, it did not suppress the activation of Rac GTPases. These results suggest that Rac GTPases and Akt play independent roles in the histamine-induced chemotaxis of mast cells. Our findings enable further elucidation of the molecular mechanism of histamine-induced chemotaxis of mast cells and help identify therapeutic targets for allergic and inflammatory conditions involving mast cell accumulation.

A Patient with Primary Open-Angle Glaucoma with Re-Elevated Nocturnal Sitting Intraocular Pressure after Restarting Medical Therapy due to a Bleb Failure.

We describe the case of a primary open-angle glaucoma patient with re-elevated nocturnal sitting intraocular pressure (IOP) after restarting medical therapy due to a failing bleb. IOP was markedly higher than diurnal IOP during multiple-drug therapy in both eyes, but it did not increase in the left eye with a functional bleb without medical therapy after trabeculectomy with adjuvant mitomycin. However, nocturnal sitting IOP was re-elevated after restarting multiple-drug therapy due to a failing bleb, while diurnal IOP was maintained at a low level.

Twenty-Four-Hour Intraocular Pressure Control with Omidenepag Isopropyl 0.002% in Patients with Glaucoma and Ocular Hypertension.

PURPOSE: To clarify the intraocular pressure (IOP)-lowering effect of a selective prostanoid EP2 receptor agonist, omidenepag isopropyl (OMDI) during a 24-hour period. PATIENTS AND METHODS: Subjects aged ≥20 years and with diagnosed, untreated primary open-angle glaucoma or ocular hypertension were enrolled. IOP measurements were performed every 4 hours over a 24-hour period using a Goldmann applanation tonometer (GAT) and Icare PRO tonometer (PRO). The baseline 24-hour IOP was measured in untreated subjects. After the baseline measurements, participants were given OMDI 1 drop once daily at night for 4 weeks. At week 4, the IOP measurement was repeated under the same conditions. Diurnal (9 am, 1 pm, 5 pm) and nocturnal (9 pm, 1 am, 5 am) IOP measurements were compared between baseline and treatment with OMDI. Safety measures included adverse events, slit-lamp biomicroscopy, visual acuity, heart rate and blood pressure. RESULTS: Of 27 participants enrolled, 25 patients (20 males and 5 females, average age 52.2 ± 8.5 years) completed the study. In the sitting position, the baseline diurnal and nocturnal mean IOPs (GAT) were 19.1 ± 2.1 mmHg and 18.2 ± 2.6 mmHg, respectively, the diurnal and nocturnal mean IOP reduction from baseline were -2.8 ± 2.6 mmHg (p < 0.0001) and -3.3 ± 2.9 mmHg (p < 0.0001), respectively, mean 24-hour IOP (GAT) was significantly lower with the OMDI treatment (-3.1 ± 2.5 mmHg, p < 0.0001). In the supine position, the baseline nocturnal mean IOP (PRO) was 17.99 ± 2.22 mmHg, and the nocturnal mean IOP reduction from baseline was -1.78 ± 2.37 mmHg (p = 0.0009) after 4 weeks of the treatment. Nine adverse events were observed in 8 patients including mild conjunctival hyperemia (n = 8) and mild iritis (n=1). There were no significant effects on systemic safety. CONCLUSION: Once daily OMDI treatment was able to produce stable 24-hour IOP reduction.

Cystoid Macular Edema Associated with Omidenepag Isopropyl in Phakic Eyes after Laser Iridotomy: A Case Report.

Decreased vision and cystoid macular edema (CME) developed in phakic eyes of a patient who underwent laser iridotomy after changing the glaucoma eye drops from carteolol 2% long-acting ophthalmic solution to omidenepag isopropyl 0.002%. CME completely disappeared at approximately 2 months after discontinuation of omidenepag isopropyl in conjunction with the use of bromfenac sodium 0.1%.

A variant of acute promyelocytic leukemia with t(4;17)(q12;q21) showed two different clinical symptoms.

A 63-year-old man was diagnosed with a rare variant of acute promyelocytic leukemia (APL) with t(4;17)(q12; q21) that showed atypical morphological features and two different clinical symptoms. He was started on standard induction chemotherapy for acute myeloid leukemia, which decreased myeloblast numbers; however, APL-like blasts remained. He then received a salvage therapy that added all-trans retinoic acid (ATRA). After ATRA commenced, APL-like blasts disappeared and cytogenetic analysis became normal. However, myeloblasts subsequently increased, and he became resistant. In summary, this patient exhibited two different clinical courses of acute myeloid leukemia and APL.

Double-Bundle Anterior Cruciate Ligament Reconstruction Using Hamstring Tendon Hybrid Grafts in Patients Over 40 Years of Age: Comparisons Between Different Age Groups.

BACKGROUND: Several recent studies have reported that favorable clinical results and a high level of patient satisfaction can generally be obtained with no increased risk of complications after single-bundle anterior cruciate ligament (ACL) reconstruction performed in patients >40 years of age. However, no studies have yet clarified the age-based differences in clinical outcomes after double-bundle reconstruction. PURPOSE: To compare clinical outcomes after double-bundle ACL reconstruction using hamstring tendon hybrid grafts between patients in 2 different age groups: ≥40 years and <40 years. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective study was conducted using 96 patients (48 men, 48 women ; mean age, 37 years) who underwent unilateral ACL reconstruction between 2008 and 2011. These patients were divided into 2 groups: group M included patients ≥40 years of age (n = 40 patients), and group Y included patients <40 years of age (n = 56 patients). All patients underwent the same anatomic double-bundle ACL reconstruction procedure. Clinical outcomes were evaluated at 2 years after surgery. Tunnel enlargement was also evaluated by computed digital radiography at 1 week and 2 years after surgery. RESULTS: Mean postoperative side-to-side differences in anterior laxity were 0.5 ± 1.9 mm and 1.2 ± 1.5 mm in groups M and Y, respectively; there was a significant difference between the 2 groups (P = .039). There were no significant differences between the groups in Lysholm knee scores, International Knee Documentation Committee (IKDC) scores, or peak muscle torque of the hamstring. On the other hand, peak muscle torque of the quadriceps was significantly lower in group M (81%) than in group Y (89%) (P = .025). With respect to femoral tunnel enlargement, the posterolateral tunnel in group M was significantly larger than that in group Y on anteroposterior and lateral radiographs (P = .015 and P = .002, respectively). CONCLUSION: Equivalent clinical outcomes were seen between the 2 age groups after double-bundle ACL reconstruction. Postoperative anterior laxity was significantly less in older patients than in younger patients, however, older patients had significantly less quadriceps muscle strength than younger patients. Surgeons should be aware of residual muscle weakness and tunnel enlargement when performing double-bundle ACL reconstruction in older patients.