Clinical outcomes of bariatric surgery in patients with obesity and idiopathic intracranial hypertension.

INTRODUCTION: Obesity is a major risk factor for idiopathic intracranial hypertension (IIH). Effective therapeutics for preventing disease progression and alleviating symptoms are limited. This study aims to examine the effects of bariatric surgery on clinical outcomes of IIH. METHODS: We retrospectively collected data from the medical record of 97 patients with obesity and an existing diagnosis of IIH who underwent primary bariatric surgery at the Cleveland Clinic health system in the USA between 2005 and 2023. Pre- and postoperative data on presence of symptoms and clinical markers of IIH (headaches, visual field defects, papilledema, visual symptoms), intracranial pressure, and usage of IIH medications were compared. RESULTS: A total of 97 patients (98% female, median age 46.7 years, median BMI 48.3 kg/m2) with IIH who underwent bariatric surgery including Roux-en-Y gastric bypass (n = 66, 68%), sleeve gastrectomy (n = 27, 27.8%), and gastric banding (n = 4, 4.1%) were analyzed. In a median follow-up time of 3.0 years, the median total weight loss was 24% (interquartile range, 13-33%). There was a significant improvement in headache, papilledema, visual field deficits, and visual symptoms after bariatric surgery. The mean lumbar opening pressure before and after bariatric surgery was 34.8 ± 8.2 cm CSF and 24.2 ± 7.6 cm CSF, respectively, with a mean reduction of 10.7 cm CSF (95% confidence interval, 4.7 to 16.6), p = 0.003. The dosage of acetazolamide and topiramate, as well as the number of medications taken for IIH, decreased significantly after bariatric surgery (p < 0.001). CONCLUSION: For patients who have obesity, bariatric surgery is a viable treatment modality for alleviation or improvement of symptoms of IIH.

Downregulation of B4GALNT1 inhibits proliferation and metastasis of osteosarcoma cells. / B4GALNT1表达下调抑制骨肉瘤细胞增殖和转移.

OBJECTIVES: Osteosarcoma is the most common malignant bone tumor in children and adolescents, characterized by a high potential for proliferation and metastasis. Patients with osteosarcoma who have distant metastases generally have a poor prognosis. Challenges in treatment include incomplete resection of tumor and chemotherapy resistance, with no effective cure currently available. Recent studies suggest that ß-1,4-N-acetyl-galactosaminyltransferase 1 (B4GALNT1) plays a role in the progression of various malignant tumors. However, the function of B4GALNT1 in osteosarcoma cells has not been reported. This study aims to investigate the expression of B4GALNT1 in osteosarcoma tissues compared to normal tissues and to explore its effects on the proliferation, migration, and invasion of osteosarcoma cells, thereby providing new theoretical foundations and directions for the treatment of osteosarcoma patients. METHODS: Tumor tissues and corresponding normal tissue samples were collected from 16 osteosarcoma patients who underwent tumor resection at the Second Xiangya Hospital of Central South University. The patients' ages ranged from 8 to 17 years (median age 12 years). The expression of B4GALNT1 mRNA in osteosarcoma tissues, corresponding normal tissues, 3 osteosarcoma cell lines (MG63, Saos-2, and U2OS), and human fetal osteoblastic cells (hFOB) was detected using real-time reverse transcription PCR (real-time RT-PCR). The effects of B4GALNT1 knockdown on the proliferation of osteosarcoma cells Saos-2 and U2OS were analyzed using cell counting kit-8 (CCK-8) assays and colony formation assays. The effects of B4GALNT1 knockdown on the migration and invasion abilities of Saos-2 and U2OS cells were evaluated using Transwell migration and invasion assays. Western blotting analysis was performed to assess the impact of B4GALNT1 knockdown on the expression of epithelial-mesenchymal transition (EMT) and invasion-related proteins in Saos-2 and U2OS cells. RESULTS: Real-time RT-PCR results showed that B4GALNT1 mRNA expression levels were significantly higher in osteosarcoma tissues and the 3 osteosarcoma cell lines compared to normal tissues and hFOB cells (all P<0.01). CCK-8 and colony formation assays indicated that B4GALNT1 knockdown significantly reduced the proliferation rate of osteosarcoma cells compared to the control group (all P<0.05). Transwell migration and invasion assays demonstrated that B4GALNT1 knockdown significantly decreased the number of migrating and invading osteosarcoma cells (all P<0.01). Western blotting analysis revealed that B4GALNT1 knockdown inhibited the expression of N-cadherin, Snail, Vimentin, and matrix metalloproteinase 9 (MMP9) compared to the control group (all P<0.01). CONCLUSIONS: B4GALNT1 is upregulated in osteosarcoma tissues and cell lines, and its knockdown suppresses the malignant phenotype of osteosarcoma cells. B4GALNT1 may function as an oncogene in the proliferation and metastasis of osteosarcoma cells.

Association between admission inflammatory indicators and 3-year mortality risk in geriatric patients after hip fracture surgery: a retrospective cohort study.

Background: Recent research indicates that the monocyte lymphocyte ratio (MLR), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), C-reactive protein (CRP), and systemic immune-inflammation index (SII) may serve as valuable predictors of early postoperative mortality in elderly individuals with hip fractures. The primary objective of the study was to examine the association between preoperative MLR, NLR, PLR, CRP, and SII levels and 3-year mortality risk in geriatric patients after hip fracture surgery. Patients and methods: The study included patients aged 65 years or older who underwent hip fracture surgery between November 2018 and November 2019. Admission levels of MLR, NLR, PLR, CRP, and SII were measured. The median follow-up period was 3.1 years. Cox proportional hazards models were used to calculate the hazard ratio (HR) for mortality with adjusting for potential covariates. Time-dependent receiver operating characteristic (ROC) curves were employed to assess the predictive capability of inflammatory indicators for mortality. Results: A total of 760 patients completed the follow-up (79.4 ± 7.8 years, 71.1% female). A higher preoperative MLR was found to be significantly associated with an increased 3-year postoperative mortality risk (HR 1.811, 95% CI 1.047-3.132, P = 0.034). However, no significant correlations were observed between preoperative NLR, PLR, CRP, SII and 3-year mortality. The areas under the ROC curve (AUCs) of MLR for predicting 30-day, 120-day, 1-year, and 3-year mortality were 0.74 (95% CI 0.53-0.95), 0.70 (95% CI 0.57-0.83), 0.67 (95% CI 0.60-0.74), and 0.61 (95% CI 0.56-0.66), respectively. Conclusion: Preoperative MLR is a useful inflammatory marker for predicting 3-year mortality in elderly hip fracture patients, but its predictive ability diminishes over time.

Preoperative Thyroid-Stimulating Hormone Levels and Three-Year Mortality in Elderly Hip Fracture Patients: Insights from a Prospective Cohort Study.

BACKGROUND It is unclear whether preoperative thyroid-stimulating hormone (TSH) level is correlated with long-term mortality in the elderly after hip fracture surgery. We aimed to assess the association between TSH levels and 3-year mortality in these patients. MATERIAL AND METHODS We enrolled patients aged 65 and above who had hip fracture surgery and thyroid function tests upon admission from 2018 to 2019. Patients were categorized based on TSH median value, quartiles, or thyroid function status. The median follow-up time was 3.1 years. Cox proportional hazards models were used to examine the correlation between TSH levels and mortality, adjusting for covariates. RESULTS Out of 799 eligible patients, 92.7% (741/799) completed the follow-up, with 20.6% (153/741) of those having died by the end of the follow-up. No statistically significant differences in mortality risks were found when stratified by TSH median value (HR 0.88, 95% CI 0.64-1.22, P=0.448) or quartiles (HR ranging from 0.90 to 1.13, P>0.05). Similarly, when categorized based on admission thyroid function status, patients who presented with hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism upon admission did not demonstrate a statistically significant difference in mortality risk compared to those who were considered euthyroid (HR 1.34, 95% CI 0.72-2.49, P=0.359; HR 0.77, 95% CI 0.38-1.60, P=0.489; HR 1.15, 95% CI 0.16-8.30, P=0.890; HR 1.07, 95% CI 0.34-3.38, P=0.913, respectively). CONCLUSIONS Admission TSH is not significantly associated with 3-year mortality in geriatric patients after hip fracture surgery.

Prognostic Nutritional Index (PNI) as an Independent Predictor of 3-Year Postoperative Mortality in Elderly Patients with Hip Fracture: A Post hoc Analysis of a Prospective Cohort Study.

OBJECTIVE: The prognostic nutritional index (PNI) has been reported as a significant predictor in various diseases. However, the prognostic value of the PNI in geriatric hip fracture patients has not been thoroughly evaluated. This study aimed to investigate the association between admission PNI and 3-year mortality in those patients. METHODS: In this post hoc analysis, we included patients aged ≥65 years who underwent surgery for hip fracture between 2018 and 2019. The admission PNI was calculated as serum albumin (g/L) +5 × total lymphocyte count (×109/L). Patients were categorized into four groups based on PNI quartiles (≤ 43.55, 43.55-46.55, 46.55-49.20, and >49.20, respectively). The median follow-up duration was 3.1 years. Cox proportional hazards models were used to calculate the hazard ratio (HR). Receiver operating characteristic curve (ROC) was conducted for using PNI to predict mortality. RESULTS: Of the 942 eligible patients, 190 (20.2%) patients died during the follow-up. Compared to patients in the first quartile (Q1), those in the second (Q2), third (Q3), and fourth (Q4) quartiles had significantly lower mortality risks (HRs 0.50, 95% CI 0.35-0.74; 0.41, 95% CI 0.26-0.64; and 0.26, 95% CI 0.15-0.45, respectively). The optimal cutoff of PNI for predicting mortality was set as 45.275 (sensitivity, 0.674; specificity, 0.692; area under the curve (AUC), 0.727). Patients with higher PNI (>45.275) had a significant lower mortality risk (HR 0.39, 95% CI 0.28-0.55) compared to those with lower PNI (≤ 45.275). CONCLUSION: PNI is a reliable and independent predictor of 3-year mortality after hip fracture surgery in the elderly.

Curcumin inhibits the proliferation and migration of osteosarcoma by regulating the expression of super-enhancer-associated genes. / å§œé»„ç´ é€šè¿‡è°ƒæŽ§è¶ çº§å¢žå¼ºå­ç›¸å ³åŸºå› æŠ‘åˆ¶éª¨è‚‰ç˜¤çš„å¢žæ®–å’Œè¿ç§».

OBJECTIVES: Super-enhancer-associated genes may be closely related to the progression of osteosarcoma, curcumin exhibits a certain inhibitory effect on tumors such as osteosarcoma. This study aims to investigate the effects of curcumin on osteosarcoma in vitro and in vivo, and to determine whether curcumin can inhibit the progression of osteosarcoma by suppressing the expression of super-enhancer-associated genes LIM and senescent cell antigen-like-containing domain 1 (LIMS1), secreted protein acidic and rich in cysteine (SPARC), and sterile alpha motif domain containing 4A (SAMD4A). METHODS: Human osteosarcoma cell lines (MG63 cells or U2OS cells) were treated with 5 to 50 µmol/L curcumin for 24, 48, and 72 hours, followed by the methyl thiazolyl tetrazolium (MTT) assay to detect cell viability. Cells were incubated with dimethyl sulfoxide (DMSO) or curcumin (2.5, 5.0 µmol/L) for 7 days, and a colony formation assay was used to measure in vitro cell proliferation. After treatment with DMSO or curcumin (10, 15 µmol/L), a scratch healing assay and a transwell migration assay were performed to evaluate cell migration ability. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and Western blotting were used to detect mRNA and protein expression levels of LIMS1, SPARC, and SAMD4A in the cells. An osteosarcoma-bearing nude mouse model was established, and curcumin was administered via gavage for 14 days to assess the impact of curcumin on tumor volume and weight in vivo. Real-time RT-PCR was used to measure mRNA expression levels of LIMS1, SPARC, and SAMD4A in the cancer and adjacent tissues from 12 osteosarcoma patients. RESULTS: After treating cells with different concentrations of curcumin for 24, 48, and 72 hours, cell viability were all significantly decreased. Compared with the DMSO group, the colony formation rates in the 2.5 µmol/L and 5.0 µmol/L curcumin groups significantly declined (both P<0.01). The scratch healing assay showed that, compared with the DMSO group, the migration rates of cells in the 10 µmol/L and 15 µmol/L curcumin groups were significantly reduced. The exception was the 10 µmol/L curcumin group at 24 h, where the migration rate of U2OS cells did not show a statistically significant difference (P>0.05), while all other differences were statistically significant (P<0.01 or P<0.001). The transwell migration assay results showed that the number of migrating cells in the 10 µmol/L and 15 µmol/L curcumin groups was significantly lower than that in the DMSO group (both P<0.001). In the in vivo tumor-bearing mouse experiment, the curcumin group showed a reduction in tumor mass (P<0.01) and a significant reduction in tumor volume (P<0.001) compared with the control group. Compared with the DMSO group, the mRNA expression levels of LIMS1, SPARC, and SAMD4A in the 10 µmol/L and 15 µmol/L curcumin groups were significantly down-regulated (all P<0.05). Additionally, the protein expression level of LIMS1 in U2OS cells in the 10 µmol/L curcumin group was significantly lower than that in the DMSO group (P<0.05). Compared with adjacent tissues, the mRNA expression level of SPARC in osteosarcoma tissues was significantly increased (P<0.001), while the mRNA expression levels of LIMS1 and SAMD4A did not show statistically significant differences (both P>0.05). CONCLUSIONS: Curcumin inhibits the proliferation and migration of osteosarcoma both in vitro and in vivo, which may be associated with the inactivation of super-enhancer-associated gene LIMS1.

Nanomaterials for bone metastasis.

Bone metastasis, a prevalent occurrence in primary malignant tumors, is often associated with a grim prognosis. The bone microenvironment comprises various coexisting cell types, working together in a coordinated manner. This dynamic microenvironment plays a pivotal role in the initiation and progression of bone metastases. While cancer therapies have made advancements, the available options for addressing bone metastases remain insufficient. The advent of nanotechnology has ushered in a new era for managing and preventing bone metastases because of the physicochemical and adaptable advantages of nanoplatforms. In this review, we make an introduction of the underlying mechanisms and the current clinical therapies of bone metastases, highlighting the advances of intelligent nanosystems that can stimulate vascular regeneration, promote bone regeneration, eliminate tumor cells, minimize bone damage, and expedite bone healing. The innovation surrounding bone-targeting nanoplatforms presents a fresh approach to the theranostics of bone metastases.

Malignant myopericytoma originating from the colon: A case report.

BACKGROUND: Myopericytoma is a benign tumor that typically occurs within subcutaneous tissue and most often involves the distal extremities, followed by the proximal extremities, neck, thoracic vertebrae and oral cavity. Complete resection is often curative. Malignant myopericytoma is extremely rare and has a poor prognosis. Here, we report for the first time a case of malignant myopericytoma originating from the colon. CASE SUMMARY: A 69-year-old male was admitted to our hospital with right upper quadrant pain for five days. Imaging suggested a liver mass with hemorrhage. A malignant hepatic tumor was the initial diagnosis. Surgical resection was performed after a complete preoperative work up. Initial postoperative pathology suggested that the mass was a malignant myoblastoma unrelated to the liver. Four months after the first surgery, an enhanced computed tomography (CT) scan revealed a recurrence of the tumor. The diagnosis of malignant myopericytoma derived from the colon was confirmed on histopathological examination of the specimen from the second surgery. The patient did not return to the hospital regularly for surveillance. The first postoperative abdominal CT examination six months after the second surgery demonstrated multiple liver metastases. Survival time between the diagnosis of the tumor to death was approximately one year. CONCLUSION: Malignant myopericytoma is a rare cancer. Preoperative diagnosis may be difficult. Due to a lack of treatment options, prognosis is poor.

3D Models of Sarcomas: The Next-generation Tool for Personalized Medicine.

Sarcoma is a complex and heterogeneous cancer that has been difficult to study in vitro. While two-dimensional (2D) cell cultures and mouse models have been the dominant research tools, three-dimensional (3D) culture systems such as organoids have emerged as promising alternatives. In this review, we discuss recent developments in sarcoma organoid culture, with a focus on their potential as tools for drug screening and biobanking. We also highlight the ways in which sarcoma organoids have been used to investigate the mechanisms of gene regulation, drug resistance, metastasis, and immune interactions. Sarcoma organoids have shown to retain characteristics of in vivo biology within an in vitro system, making them a more representative model for sarcoma research. Our review suggests that sarcoma organoids offer a potential path forward for translational research in this field and may provide a platform for developing personalized therapies for sarcoma patients.