The Combination of Auranofin and Celecoxib Suppresses Local Synovial Sarcoma Progression In Vivo.

BACKGROUND/AIM: Synovial sarcoma (SS) is a rare malignant tumor with a poor survival rate. We previously reported that a combination of auranofin (AUR), a thioredoxin reductase inhibitor, and celecoxib (CE), an anti-inflammatory drug, significantly impedes the local progression of osteosarcoma (OS). However, the role of redox regulation in SS remains to be elucidated. This study aimed to investigate the efficacy of combined treatment of AUR and CE on the local progression of SS in vivo. MATERIALS AND METHODS: Nu/nu mice were implanted with the human SS cell line, Aska-SS, and treated with vehicle control, AUR, or a combination of AUR and CE (AUR-CE). Primary tumor size and weight were evaluated for the study duration and upon resection, respectively. Hematoxylin and eosin (H&E) and Ki-67 staining were performed to assess the local progression of SS. RESULTS: A statistically significant reduction in tumor size and weight was observed in the AUR- and AUR-CE-treated groups upon excision compared to that in the vehicle-treated group. The AUR-CE-treated group showed synergistic inhibition of local tumor growth. H&E staining of local SS tumors revealed decreased cell density and nuclear deformation in the AUR- and AUR-CE-treated groups compared to those in the vehicle-treated group. Immunohistochemical staining revealed a statistically significant decrease in Ki-67-positive cells in the AUR-CE-treated group compared to the vehicle-treated group. CONCLUSION: The combination of AUR and CE showed significant potential for delaying the local progression of SS. These findings support the repurposing of AUR and CE as early treatment options for SS.

Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing.

Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast-like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton-type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26-year-old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography-computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31-positive atypical spindle cells proliferated in slit-like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide-resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected CD63::PRKCD fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.

The diagnostic utility of cytology specimen in a case of EWSR1::NFATC2 sarcoma.

EWSR1::NFATC2 sarcoma, a rare round cell sarcoma constituting the majority of EWSR1::non-ETS sarcomas, has recently been defined in the latest WHO classification. To date, the cytological findings of EWSR1::NFATC2 sarcoma remain undocumented. We present the case of a 25-year-old man with a history of polyostotic fibrous dysplasia in the right leg, referred to our hospital with left thigh pain. Cytological findings included metachromasia, minimally pleomorphic round cells, and eosinophilic infiltration. There was no precursor fibrous dysplasia and the initial diagnosis was undifferentiated pleomorphic sarcoma. Following histologic review, we successfully performed immunocytochemistry and fluorescence in situ hybridization (FISH) on archival cytology specimens. The tumor cells were positive for NKX2-2, NKX3-1, and PAX7 and showed amplified 5' single signals of EWSR1 gene. Reverse transcriptase-polymerase chain reaction revealed an in-frame fusion of EWSR1 and NFATC2. This report describes the cytological features of EWSR1::NFATC2 sarcoma and highlights the diagnostic utility of archival cytology specimens.

Effectiveness of Carbon Ion Radiotherapy for Bone and Soft Tissue Sarcoma in Older Patients.

BACKGROUND/AIM: The aging population is expected to increase the occurrences of bone sarcoma (BS) and soft tissue sarcoma (STS). Carbon ion radiotherapy (CIRT) is reported to be effective for BS and several STSs. However, the effect of CIRT on clinical outcomes, functional prognoses, and quality of life (QOL) in older patients who underwent CIRT has not been reported. Therefore, we aimed to evaluate the effect of CIRT on clinical outcomes, functional prognoses and QOL in older patients with BS or STS. PATIENTS AND METHODS: This retrospective cohort study included 235 patients aged >70 years with BS or STS who underwent CIRT. Overall survival (OS), cancer-specific survival (CSS), and local control (LC) were evaluated in chordoma and non-chordoma patients. Furthermore, factors associated with post-CIRT Toronto Extremity Salvage Score (TESS) and EuroQoL 5-dimension 5-level (EQ-5D-5L) index were assessed. RESULTS: The overall 5-year LC, OS, and CSS rates were 81%, 62%, and 76%, respectively. In the chordoma and non-chordoma groups, the 5-year LC, OS, and CSS rates were 84%, 72%, and 87%; and 77%, 47%, and 60%, respectively. The mean post-CIRT TESS and EQ-5D-5L index were 75% and 0.71, respectively. The TESSs and EQ-5D-5L indices tended to be better among males, younger patients (<76 years old), patients with small tumor volumes, and patients with chordoma. CONCLUSION: CIRT is effective for older patients with BS, especially with chordoma, and STS with good LC and survival rates. Furthermore, post-treatment limb function and QOL were comparable with those of the other treatments and age groups.

Combined Auranofin and Celecoxib Suppresses the Local Progression and Pulmonary Metastases of Osteosarcoma In Vivo.

BACKGROUND/AIM: Osteosarcoma (OS) is a rare malignant tumor with a poor survival rate. Our previous study reported that auranofin (AUR), a thioredoxin reductase inhibitor, suppresses OS pulmonary metastases; however, the local progression of OS is not affected, in vivo. Nonetheless, the development of augmentation therapy with AUR to inhibit OS local progression remains challenging. Celecoxib (CE), an anti-inflammatory drug, potently enhances the therapeutic activity of AUR against colon cancer. Consequently, this study investigated the combined effects of AUR and CE on OS local progression and pulmonary metastases, in vivo. MATERIALS AND METHODS: C3H/HeSlc mice were implanted with the murine OS cell line, LM8. The mice were treated either with a vehicle control, AUR, or combination of AUR and CE (AUR-CE). The primary tumor size and weight were evaluated for the study duration and at resection, respectively. Hematoxylin and eosin and Ki-67 staining were performed to evaluate OS local progression and pulmonary metastases. RESULTS: Mice in the AUR-CE group showed statistically significantly suppressed tumor sizes and weights at the time of excision compared with those in the vehicle. The mice in the AUR group did not show a statistically significant effect. Histopathological analysis of the primary tumor revealed a statistically significant decrease of the Ki-67-positive cells in the AUR-CE group compared with the vehicle group. Histopathological and quantitative analyses demonstrated that the AUR and AUR-CE groups had statistically significant reductions in the development of OS pulmonary metastases compared with the vehicle group. CONCLUSION: The combination of AUR and CE significantly inhibited OS local progression and pulmonary metastases.

Thioredoxin Reductase Inhibitor Suppresses the Local Progression of Rhabdomyosarcoma With PDX Models.

BACKGROUND/AIM: Chemoresistance in rhabdomyosarcoma (RMS) is associated with poor survival, necessitating the development of novel anticancer drugs. Auranofin (AUR), an anti-rheumatic drug, is a thioredoxin reductase (TXNRD) inhibitor with anticancer properties. Although patient-derived xenograft (PDX) models are essential for studying cancer biology, reports on sarcomas using the PDX model are scarce because of their rarity. This study aimed to investigate the effectiveness of AUR treatment in RMS using a PDX model to evaluate its impact on local progression. MATERIALS AND METHODS: A 20-year-old woman who was diagnosed with alveolar RMS was used to generate the PDX model. RMS PDX tumors were implanted in nude mice and divided into non-treated (vehicle) and treated (AUR) groups. Tumor volume and weight were evaluated, and immunohistochemical staining was performed to evaluate local progression of the sarcoma. The relationship between the TXNRD-1 expression and survival probability of patients with RMS was evaluated using publicly available expression cohorts. RESULTS: AUR significantly suppressed RMS tumor progression over time. It also significantly suppressed the tumor size and weight at the time of excision. Histological evaluation showed that AUR induced oxidative stress in the PDX mouse models and inhibited the local progression of RMS by inducing apoptosis. High TXNRD-1 expression was found to be a negative prognostic factor for overall survival in patients with RMS. CONCLUSION: AUR-induced inhibition of TXNRDs can significantly impede the local progression of RMS through the oxidative stress-apoptosis pathway as demonstrated in PDX models. Thus, targeting TXNRD inhibition may be a promising therapeutic strategy for the treatment of RMS.

18F-FDG PET/CT in left atrial undifferentiated pleomorphic sarcoma with osteosarcomatous differentiation.

Primary cardiac sarcomas are rare and sometimes difficult to discern from benign tumors and intracardiac thrombi. We describe the ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a case of left atrial undifferentiated pleomorphic sarcoma with osteosarcomatous differentiation, presenting with severe mitral regurgitation and pulmonary hypertension. The tumor presented as a broad-base mass protruding into the cardiac lumen, accompanied by punctate calcification-like high attenuation on CT. 18F-FDG PET/CT revealed high 18F-FDG uptake in the mass. Severe mitral regurgitation, a rare manifestation, was caused by tumor extension to the mitral valve leaflets and subvalvular tissue, which was best visualized on transesophageal echocardiography. This case illustrates the importance of multimodal diagnostic approaches including 18F-FDG PET/CT, which can facilitate accurate diagnosis and timely initiation of curative treatment, ultimately saving the patient's life. Learning objective: Firstly, cardiac sarcomas, particularly those with calcification/ossification, are rare and may mimic benign tumors and chronic intracardiac thrombi. Multimodal imaging approach, including 18F-FDG PET/CT, may be helpful in the accurate diagnosis of malignancies. Second, left atrial undifferentiated pleomorphic sarcoma has the potential to extensively spread along the endocardium and can extend to involve the valve leaflets, resulting in mitral regurgitation and pulmonary hypertension.

Objective Assessment of Sleep Disorders in Patients with Lumbar Spinal Stenosis Using Wearable Trackers.

Introduction: Low-back pain causes sleep disorders, which impairs the quality of life (QOL) of patients. Sleep disorders are associated with lumbar spinal stenosis (LSS); however, the postoperative effects of LSS surgery on sleep disorders are unknown. This study aimed to assess sleep disorders in patients with LSS using wearable activity trackers and determine whether surgery improves sleep quality. Methods: A total of 39 patients scheduled for LSS surgery (mean age 71.1±8.7 years; 22 men and 17 women) were studied. Sleep disorders in the participants were objectively evaluated using a wearable Motionlogger Micro system. Sleep efficiency (SEf), mean active count (MAC), and wake after sleep onset (WASO) were measured before and 6 months following surgery. Furthermore, the patient-based outcomes of pain and QOL-related scores were measured and compared with those of healthy participants. The group with improved SEf following surgery was designated as "nonpoor sleepers," whereas the group that did not exhibit improvements was designated as "poor sleepers." The two groups were compared based on patient factors, patient-based questionnaires, and sleep disorder measurements. Results: The SEf and WASO were significantly worse in patients with LSS compared with healthy participants (P<0.05). Furthermore, the SEf in patients with LSS was associated with the Oswestry Disability Index scores. No improvement was observed in the SEf, MAC, and WASO before and after surgery. Evaluation of each case revealed 21 and 12 cases of nonpoor and poor sleepers, respectively. Preoperative low-back pain was significantly associated with improvement in postoperative sleep quality. Conclusions: Sleep disorders in patients with LSS were evaluated, and improvement in sleep disorders following surgery was associated with the intensity of preoperative low-back pain. Sleep disorders are associated with QOL disorders, suggesting that focusing on the treatment of sleep disorders is important in the management of patients with LSS.

Postoperative Limb Function and QOL in Elderly Patients With Malignant Bone Tumor/Soft Tissue Sarcoma.

BACKGROUND/AIM: Malignant bone tumors (MBT) and soft tissue sarcomas (STS) require wide excision. Although the number of elderly patients is increasing, wide excision may decrease limb function and quality of life (QOL) for elderly patients. However, no detailed evaluation of the functional prognosis or QOL of elderly patients with sarcoma has been reported. This study evaluated postoperative limb function and QOL in elderly patients with MBT and STS. PATIENTS AND METHODS: This retrospective study included 67 patients aged >70 years with MBT or STS who underwent surgery at a single institution. The Toronto Extremity Salvage Score (TESS), EuroQoL 5-dimension 5-level (EQ-5D-5L) questionnaire, Musculoskeletal Tumor Society (MSTS) score, and psoas muscle index (PMI) were evaluated. We also assessed factors associated with the postoperative TESS and EQ-5D-5L index. RESULTS: Detailed examination of the MSTS items perioperatively revealed significant decline in manual dexterity/walking ability and support but significant improvement in pain and emotional acceptance. The mean PMI decreased significantly from 4.7 to 4.23 perioperatively. The postoperative mean TESS and EQ-5D-5L index was 76.9 and 0.74, respectively. Patients with good performance status and clinical frailty scale scores preoperatively had better postoperative TESS and EQ-5D-5L scores. CONCLUSION: The current study strongly suggests the possibility of maintaining postoperative limb function, satisfaction, and QOL in patients with MBT and STS by choosing patients in good condition and the appropriate procedure that the patient desires. However, perioperative progression of sarcopenia should be noted.

Does Multidisciplinary Therapy at a Sarcoma Center Improve the Prognosis of Patients With Soft Tissue Sarcoma? A Retrospective Case Study at a Single Institute.

BACKGROUND/AIM: The effect of multidisciplinary therapy conducted at the sarcoma center of our hospital was examined to determine whether therapy undertaken here improved the prognosis of patients with soft-tissue sarcoma. PATIENTS AND METHODS: The clinical findings and prognoses of patients treated before the establishment of the sarcoma center (72 patients from April 2016 to March 2018) and those treated after (155 patients from April 2018 to March 2021) were compared. RESULTS: The mean number of patients increased from 36.0 to 51.7 per year after the establishment of the sarcoma center. The proportion of patients with stage IV disease also increased from 8.3% to 12.9% after establishment of the sarcoma center. The 3-year survival rate of patients, considering all stages, decreased from 80.0% to 78.3% after establishment of the sarcoma center rather than showing an increase. The 3-year survival rate of patients with stage II and III disease increased from 78.6% to 84.7%, and that of stage III patients with retroperitoneal sarcoma increased from 70.0% to 86.7% after establishment of the sarcoma center. However, no statistically significant difference was observed in the survival curves. CONCLUSION: The establishment of a sarcoma center has contributed to centralizing treatment for soft-tissue sarcoma. Multidisciplinary therapy at sarcoma centers may improve the prognosis of patients with soft-tissue sarcomas.

Predictors of Postoperative Gain in Ambulatory Function After Decompressive Surgery for Metastatic Spinal Cord Compression.

BACKGROUND/AIM: Reports on the effects of timing of the surgery on the patient survival rate or the results of palliative laminectomy are limited. The aim of the study was to investigate the postoperative ambulatory status of neurologically impaired metastatic spinal cord compression (MSCC) patients who underwent laminectomy and evaluate predictors of postoperative ambulation recovery after laminectomy for MSCC. PATIENTS AND METHODS: We included 175 patients who underwent decompressive surgery for MSCC. Changes in the Frankel grade (FG) were evaluated perioperatively. Among all patients, 113 were unable to walk preoperatively and were divided into two groups: 70 and 43 patients in the ambulation-regained and ambulation-not regained postoperatively groups, respectively. The percentage of patients eligible for postoperative chemotherapy and overall survival rate in each group were investigated. Furthermore, predictors of postoperative ambulation recovery after laminectomy for MSCC were examined. RESULTS: The most common primary tumor sites were the lung, prostate, and breast. FG improved with surgery in 80 cases, remained unchanged in 94 cases, and worsened in one case. In the ambulation-regained group, 70% were eligible for postoperative chemotherapy, while only 26% of the not-regained group were eligible for postoperative chemotherapy. The postoperative survival rate of the ambulation-regained group was significantly better than that of the not-regained group. Univariate predictors for not regaining the ability to walk were Karnofsky Performance Status ≤40 prior to surgery, FG B prior to surgery, and time to surgery since the inability to walk >48 h. CONCLUSION: Decompressive surgery benefits motor function postoperatively. Both good neurological status prior to surgery and prompt surgery for non-ambulatory MSCC are important predictors of improved functional outcome.

Partial Sacral Resection for the Treatment of Isolated Testicular Tumor Metastasis.

We encountered an uncommon case of a non-seminomatous germ cell tumor with solitary bone metastasis at the initial presentation. A 30-year-old male patient with testicular cancer underwent an orchidectomy and was diagnosed with non-seminoma. Positron emission tomography-computed tomography detected an isolated metastatic lesion in the right sacral wing, which disappeared after a series of chemotherapy. En-bloc surgical resection was performed as curative local treatment, and the patient was able to perform his activities of daily living with no apparent recurrence. Therefore, this surgical method is considered safe and beneficial for the treatment of sacral wing lesions.

Efficacy, safety, and pharmacokinetics of inhaled treprostinil in Japanese patients with pulmonary arterial hypertension.

Treprostinil is a chemically stable analog of prostacyclin, and inhaled treprostinil was developed to deliver the effects directly to the pulmonary vasculature while minimizing systemic side effects. The objective of the study was to evaluate the efficacy on hemodynamics and exercise capacity, safety, and pharmacokinetics (PK) of inhaled treprostinil in Japanese patients with pulmonary arterial hypertension (PAH). Inhaled treprostinil was administered at three breaths (18 µg)/session four times daily, and the dose was gradually increased to a maximum of nine breaths (54 µg)/session. Endpoints included change in pulmonary vascular resistance index (PVRI) as primary, other efficacy parameters, safety, and PK. Seventeen PAH patients, the majority of whom (76.5%) had been receiving both an endothelin receptor antagonist (ERA) and a phosphodiesterase type-5 (PDE5) inhibitor/soluble guanylate cyclase (sGC) stimulator, received inhaled treprostinil. At Week 12, PVRI statistically decreased by -39.4 ± 25.5% (95% confidence interval: -52.6 to -26.3). The most frequently reported adverse events related to treprostinil were headache, cough, throat irritation, and hot flush. Regarding PK, there were no notable differences in the geometric mean C max and AUClast between Japanese and non-Japanese patients. Treatment with inhaled treprostinil using the dosing regimen approved in the United States resulted in significant improvement in hemodynamics, exercise capacity, and symptoms with a favorable tolerability and safety profile in Japanese patients. Inhaled treprostinil could be a valuable therapeutic option for Japanese patients with PAH, including those receiving a combination therapy with an ERA and a PDE5 inhibitor/sGC stimulator. Trial registration: JAPIC Clinical Trials Information [JapicCTI-194651].

Comparison of living-donor lobar lung transplantation and cadaveric lung transplantation for pulmonary hypertension.

OBJECTIVES: Living-donor lobar lung transplantation (LDLLT) is a life-saving procedure for critically ill patients with various lung diseases, including pulmonary hypertension (PH). However, there are concerns regarding the development of heart failure with pulmonary oedema after LDLLT in which only 1 or 2 lobes are implanted. This study aimed to compare the preoperative conditions and postoperative outcomes of LDLLT with those of cadaveric lung transplantation (CLT) in PH patients. METHODS: Between 2008 and 2021, 34 lung transplants for PH, including 12 LDLLTs (5 single and 7 bilateral) and 22 bilateral CLTs, were performed. Preoperative variables and postoperative outcomes were retrospectively compared between the 2 procedures. RESULTS: Based on the preoperative variables of less ambulatory ability (41.7% vs 100%, P < 0.001), a higher proportion of World Health Organization class 4 (83.3% vs 18.2%, P < 0.001) and higher mean pulmonary artery pressure (74.4 vs 57.3 mmHg, P = 0.040), LDLLT patients were more debilitated than CLT patients. Nevertheless, hospital death was similar between the 2 groups (8.3% vs 9.1%, P > 0.99, respectively). Furthermore, the 5-year overall survival rate was similar between the 2 groups (90.0% vs 76.3%, P = 0.489). CONCLUSIONS: Although LDLLT patients with PH had worse preoperative conditions and received smaller grafts than CLT patients, LDLLT patients demonstrated similar perioperative outcomes and prognoses as CLT patients. LDLLT is a viable treatment option for patients with PH.

Analysis of implants for metastatic bone tumors of the proximal femur: A retrospective study.

AIM: To investigate the relationship between surgical techniques used in our hospital to treat metastatic bone tumors of the proximal femur and activity level and prognosis of patients and whether the location of the tumor is considered when selecting surgical techniques. METHODS: We retrospectively reviewed 82 patients with metastatic bone tumors of the proximal femur who underwent intramedullary nail fixation (IMN), bipolar hip arthroplasty (BHP) or modular megaprosthesis (MMP) in our hospital from 2007 to 2020. We measured the distance from the center of femoral head to the proximal (x) and distal (y) end of the of tumor, using preoperative computed tomography images to determine the location of metastasis. We also measured revised Katagiri score at the time of fracture, postoperative ISOLS/MSTS (functional outcome) scores, and overall survival. RESULTS: The value of x was significantly different among the three groups. The value of y showed a significant difference between the IMN and BHP groups and the BHP and MMP groups. The functional outcome score was significantly lower in the IMN group. The survival rate of the patient tended to be higher in the BHP and MMP groups than in the IMN group 1 year postoperatively. CONCLUSION: IMN was favored when the distance from the center of femoral head to the proximal end of the tumor was ≥15 mm. In the case of prosthetic replacement, BHP was chosen if the distance from the center of femoral head to the distal end of the tumor was ≤70 mm. BHP and MMP were preferred over IMN functionally.

Prognostic Factors for Survival in Patients With High-grade Chondrosarcoma.

BACKGROUND/AIM: Chondrosarcoma (CS) is a rare primary malignant bone tumor, which is the second most common tumor after osteosarcoma. Since chemotherapy and radiotherapy have poor efficacy for CS, amputation or surgical wide resection is the main strategy for localized high-grade CS, making CS therapy difficult. As studies on high-grade CS are limited owing to its rare nature, there are many unknown prognostic factors for survival. PATIENTS AND METHODS: This retrospective cohort study included 44 patients with high-grade CS who underwent surgery at a single institution. Overall survival (OS), distant failure-free survival (DFFS), and local failure-free survival (LFFS) were evaluated using the Kaplan-Meier method. Furthermore, we evaluated prognostic factors for survival in patients with high-grade CS using univariate and multivariate analyses. RESULTS: The 5-year OS, LFFS, and DFFS rates of high-grade CS were 75.9%, 90.8%, and 66.5%, respectively. Univariate analysis revealed that tumor size, tumor grade, and surgical margin were significant prognostic factors for OS and DFFS, and distant metastasis was significantly associated with OS. Furthermore, the multivariate analysis indicated that the presence of local recurrence and distant metastasis was significantly associated with OS. CONCLUSION: Local recurrence and distant metastasis were significant prognostic factors for high-grade CS.

Clavicula Pro Humero Reconstruction for Malignant Tumor of the Proximal Humerus in Children and Adults.

BACKGROUND/AIM: The effectiveness of clavicula pro humero (CPH) reconstruction for pediatric proximal humerus sarcoma has been reported in a small number of cases. We aimed to investigate the effectiveness of biological CPH reconstruction for malignant bone tumors of the proximal humerus in children and adults. PATIENTS AND METHODS: This was a retrospective cohort study that included eight patients who underwent CPH reconstruction due to a malignant bone tumor around the proximal humerus. Postoperative parameters, including complications, postoperative upper limb function, and the period until bone fusion, were investigated. RESULTS: Three patients had non-union and fracture of the clavicular segment. Among them, one patient underwent revision surgery for internal fixation and bone grafting. Five patients achieved bone fusion, and the overall mean Musculoskeletal Tumor Society score was 70%, which is comparable to previous reports. CONCLUSION: CPH reconstruction is an effective technique for malignant bone tumors of the proximal humerus in all ages.

Association Between the Accumulation of Pentosidine at the Sciatic Nerve and Cutaneous Hindpaw Hypersensitivity in a Rat Ovariectomy Model.

Introduction Advanced glycation end-products (AGEs) have the potential to serve as biomarkers of aging and metabolic diseases; however, how their expression relates to clinical symptoms is not well defined. In this study, we sought to determine whether the accumulation of pentosidine, one type of AGE, at the peripheral nerve is associated with cutaneous pain or hypersensitivity caused by ovariectomy (OVX). Methods We assigned 12-week-old female Sprague Dawley rats into either the OVX group (n = 6) or the sham group (n = 6). Cutaneous hindpaw sensitivity to mechanical stimuli was measured with von Frey filaments, using Chaplan's adapted method, and the 50% withdrawal threshold was calculated. Then, the accumulation of pentosidine, which represents AGEs, was measured in sciatic nerve fibers after staining with an anti-pentosidine antibody. Results OVX rats showed significantly increased plantar hypersensitivity to mechanical stimuli compared to sham rats 8 weeks after OVX (P = 0.017). Pentosidine-positive sciatic nerves were detected at a higher rate in OVX rats than in sham rats (P = 0.035). The pentosidine positivity rate in sciatic nerve fibers showed a negative correlation with withdrawal threshold (P < 0.001). Conclusions This study showed that higher levels of pentosidine in sciatic nerve fibers are associated with higher plantar hypersensitivity. Accumulation of pentosidine at the sciatic nerve, caused by OVX, may result in cutaneous hindpaw hypersensitivity.

New strategy to resume and taper epoprostenol after lung transplant for pulmonary hypertension.

OBJECTIVE: The perioperative outcome of lung transplantation (LTx) for patients with severe pulmonary hypertension (PH) remains poor due to the occurrence of primary graft dysfunction (PGD) from left ventricular failure. We hypothesized that tapering pretransplant use of epoprostenol rather than abrupt discontinuation after transplantation might improve perioperative outcomes. METHODS: We performed 23 LTxs for patients with severe PH who received epoprostenol therapy from 2008 until 2021. In the discontinued group (n = 6), epoprostenol was discontinued after the establishment of extracorporeal circulation. In the tapered group (n = 17), epoprostenol was discontinued and resumed after reperfusion, and then gradually tapered over the following 2 weeks. We assessed survival, bleeding, blood transfusion, re-opening of the chest, oxygenation, PGD score, extracorporeal membrane oxygenation (ECMO) requirement for recovery after transplantation, and duration of mechanical ventilation. RESULTS: The PGD score was significantly lower in the tapered group than in the discontinued group at 0 h, 24 h, and 48 h after LTx. In addition, the discontinued group required longer mechanical ventilation than the tapered group. Delayed chest closure and post-transplant ECMO use for recovery occurred significantly more frequently in the discontinued group. CONCLUSIONS: To resume and taper epoprostenol administration after reperfusion in patients with severe PH may be a valuable new strategy associated with better perioperative outcomes.

Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody.

STUDY DESIGN: Prospective cohort study (open-label, single-arm, and non-blinded). PURPOSE: This study aims to determine the effects of systemic administration of tocilizumab, an anti-interleukin-6 (IL-6) receptor antibody on refractory low back pain and leg symptoms. OVERVIEW OF LITERATURE: IL-6 overexpression is associated with neuropathic pain pathogenesis, which is potentially followed by chronic low back pain, including leg pain and numbness. This finding suggest that inhibition of IL-6 at the site of pain or in the transmission pathway could provide novel therapeutic targets for chronic low back pain. METHODS: This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months' chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. RESULTS: Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. CONCLUSIONS: Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1-4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.