Severe midfoot Charcot neuroarthropathy (CN) presents a significant surgical challenge because of extensive bone loss and poor bone quality. This report presents the outcome of a case treated with realignment arthrodesis using a superconstruct technique, supplemented by the postoperative use of denosumab. A patient with Eichenholtz Stage III CN (Brodsky Type 1 and 2) underwent a single-stage surgical reconstruction. Postoperatively, denosumab was administered to enhance bone stability. The 1-year and 1-month follow-up showed that the severe deformity had been successfully corrected to a stable, plantigrade foot, confirmed by radiographic and clinical evaluation.This case suggests that a combined surgical approach using a superconstruct with adjuvant denosumab can be an effective treatment for severe midfoot CN.

Minimally invasive surgery (MIS) for hallux valgus correction has become increasingly popular over the past decade as an alternative to traditional open osteotomy techniques. Following the limitations of first- and second-generation percutaneous techniques, third-generation MIS, characterized by percutaneous osteotomy with a Shannon burr and stable screw fixation, has shown improved reproducibility and clinical outcomes. This review summarizes the current concepts of third-generation and later MIS techniques for hallux valgus correction, focusing on the surgical principles, technical considerations, fixation strategies, and postoperative management. In addition, the clinical and radiographic outcomes of MIS are compared with conventional open osteotomies. The available evidence consistently shows that MIS provides comparable deformity correction, functional improvement, complication rates, and recurrence rates to those of open procedures, while offering advantages such as reduced early postoperative pain, smaller incisions, and faster recovery. Recent studies support expanding MIS indications to include severe hallux valgus deformities that can provide satisfactory correction and acceptable complication profiles when appropriate techniques and fixation methods are used. Despite the ongoing debates regarding the optimal osteotomy type, fixation strategy, and proximal correction in severe deformities, MIS has emerged as a safe and effective surgical option across a broad spectrum of hallux valgus severity. Continued refinement of the surgical techniques, broader application across a wide range of hallux valgus etiologies, and long-term outcome data will further define the role of MIS in hallux valgus surgery.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Background: Tibiotalocalcaneal (TTC) arthrodesis is a viable salvage option for failed total ankle arthroplasty (TAA), but it is typically a complex procedure associated with a high complication rate. This study analyzed outcomes of salvage TTC arthrodesis using a retrograde intramedullary (IM) nail without subtalar joint preparation after failed TAA. Methods: This study included 18 patients (18 ankles) who underwent TTC arthrodesis without subtalar joint preparation for failed TAA from July 2008 to March 2023 and were followed up for at least 2 years. Visual analog scale pain scores and Ankle Osteoarthritis Scale pain and disability scores were used to assess functional outcomes. Radiographic union, time to union, complications, and clinical success—defined as pain improvement without the need for revision surgery or amputation—were also evaluated. Results: The mean follow-up duration after TTC arthrodesis was 79.8 months (range, 26–199 months). Tibiotalar joint union was achieved in 13 ankles (72.2%) at a mean of 7.5 months after TTC arthrodesis. Subtalar joint union was achieved in 7 ankles (38.9%). All functional scores improved significantly from preoperatively to the last follow-up. The overall clinical success rate was 83.3% (15 ankles). Conclusions TTC arthrodesis using a retrograde IM nail without subtalar joint preparation produced favorable outcomes in patients with failed TAA. No complications associated with the subtalar joint were observed in any patient during follow-up. Therefore, TTC arthrodesis using a retrograde IM nail without subtalar joint preparation may be a considerable salvage option for failed TAA.

Purpose: Total ankle arthroplasty (TAA) is a surgical option for end-stage ankle arthritis, including that caused by rheumatoid arthritis (RA). However, concerns persist regarding postoperative complications associated with inflammatory responses and immunosuppression in patients with RA. This study evaluated clinical outcomes and prosthesis survivorship in RA patients who underwent TAA for painful ankle arthritis. Materials and Methods: Thirty-four consecutive TAAs performed in RA patients with a minimum follow-up of 2 years were included and reviewed retrospectively. The visual analog scale for pain, ankle osteoarthritis scale pain and disability subscores, and ankle range of motion were used to assess clinical outcomes. Prosthesis survivorship, reoperations, complications, and risk factors were also analyzed. Results: The mean follow-up duration was 95.5 months (range, 26–221 months). All clinical scores significantly improved from preoperative values to the final follow-up. Revision surgery was performed on 6 ankles (17.6%), and 1 ankle (2.9%) failed due to deep infection. No minor wound complications were observed. Kaplan–Meier survival analysis demonstrated prosthesis survivorship rates of 97.4% at both 5 and 10 years postoperatively, and revision-free survivorship rates of 81.5% at 5 years and 74.7% at 10 years.No individual factor was significantly associated with revision. Conclusion Mobile-bearing TAA resulted in favorable clinical outcomes and high prosthesis survivorship in RA patients. No disease-specific factor was associated with revision surgery. These findings support TAA as a viable surgical option for RA patients with painful end-stage ankle arthritis.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Purpose: To evaluate the compatibility and usability of test results obtained from the IDRA and Keratograph 5M in clinical settings by comparing their performance in patients with dry eye disease. Methods: From December 27 to 30, 2022, a study was conducted on 30 patients diagnosed with dry eye utilizing both the Keratograph 5M and IDRA devices. The parameters compared and analyzed included lipid layer thickness, tear meniscus height, tear film break-up time, and meibography. A paired t-test was used for statistical comparison. The lipid layer thickness in the Keratograph 5M was graded on a scale from 0 to 4 based on thickness. Results: No significant differences were found between the two devices in tear film break-up time, tear meniscus height, and meibography (p = 0.148, 0.072, 0.124, respectively). However, the tear lipid layer thickness measured by IDRA showed a proportional relationship with the grade assigned by the Keratograph 5M (Kendall R = 0.217, p = 0.037; Spearman R = 0.260, p = 0.045). Conclusions The IDRA device offers the advantage of performing multiple dry eye tests; simultaneously, thereby saving time compared to the Keratograph 5M. Both devices can be used compatibly with IDRA particularly advantageous for providing a numerical value for tear lipid layer thickness which enhances the convenience of dry eye diagnosis and treatment.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Purpose: To evaluate the compatibility and usability of test results obtained from the IDRA and Keratograph 5M in clinical settings by comparing their performance in patients with dry eye disease. Methods: From December 27 to 30, 2022, a study was conducted on 30 patients diagnosed with dry eye utilizing both the Keratograph 5M and IDRA devices. The parameters compared and analyzed included lipid layer thickness, tear meniscus height, tear film break-up time, and meibography. A paired t-test was used for statistical comparison. The lipid layer thickness in the Keratograph 5M was graded on a scale from 0 to 4 based on thickness. Results: No significant differences were found between the two devices in tear film break-up time, tear meniscus height, and meibography (p = 0.148, 0.072, 0.124, respectively). However, the tear lipid layer thickness measured by IDRA showed a proportional relationship with the grade assigned by the Keratograph 5M (Kendall R = 0.217, p = 0.037; Spearman R = 0.260, p = 0.045). Conclusions The IDRA device offers the advantage of performing multiple dry eye tests; simultaneously, thereby saving time compared to the Keratograph 5M. Both devices can be used compatibly with IDRA particularly advantageous for providing a numerical value for tear lipid layer thickness which enhances the convenience of dry eye diagnosis and treatment.