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.

ImmuneApp for HLA-I epitope prediction and immunopeptidome analysis.

Advances in mass spectrometry accelerates the characterization of HLA ligandome, necessitating the development of efficient methods for immunopeptidomics analysis and (neo)antigen prediction. We develop ImmuneApp, an interpretable deep learning framework trained on extensive HLA ligand datasets, which improves the prediction of HLA-I epitopes, prioritizes neoepitopes, and enhances immunopeptidomics deconvolution. ImmuneApp extracts informative embeddings and identifies key residues for pHLA binding. We also present a more accurate model-based deconvolution approach and systematically analyzed 216 multi-allelic immunopeptidomics samples, identifying 835,551 ligands restricted to over 100 HLA-I alleles. Our investigation reveals the effectiveness of the composite model, denoted as ImmuneApp-MA, which integrates mono- and multi-allelic data to enhance predictive performance. Leveraging ImmuneApp-MA as a pre-trained model, we built ImmuneApp-Neo, an immunogenicity predictor that outperforms existing methods for prioritizing immunogenic neoepitope. ImmuneApp demonstrates its utility across various immunopeptidomics datasets, which will promote the discovery of novel neoantigens and the development of new immunotherapies.

Surgical intervention of a giant bronchogenic cyst in the right middle lobe with recurrent infections: a case report.

Bronchogenic cysts, a rare congenital pulmonary disorder, typically affect young adults and are often managed conservatively. However, large cysts with recurrent infections require surgical intervention. This case study highlights the successful management of a large bronchogenic cyst. A 53-year-old female presented with a decade-long history of recurrent respiratory infections manifesting as cough, yellow purulent sputum, and shortness of breath. Chest computed tomography revealed a large bronchogenic cyst in the right middle lobe, causing cardiac compression. Despite conservative management, the recurrent symptoms persisted. After multidisciplinary consultation, a thoracoscopic right middle lobectomy was planned. Severe pleural adhesions and bleeding complicated the procedure; therefore, thoracotomy was performed. Postoperatively, the patient developed transient fever and elevated white blood cell count, both of which resolved with appropriate antibiotic therapy. The patient was discharged in stable condition, with no recurrence of symptoms at follow-up. Large, symptomatic bronchogenic cysts that cause recurrent infections require surgical resection.

Real-World Outcomes with the KEYNOTE-522 Regimen in Early-Stage Triple-Negative Breast Cancer.

BACKGROUND: This study aimed to determine if the neoadjuvant (NAT) KEYNOTE-522 regimen was associated with higher rates of pathologic complete response (pCR), corresponding to higher rates of breast conservation therapy (BCT) in early-stage triple-negative breast cancer (TNBC) patients. PATIENTS AND METHODS: Stage II-III TNBC patients diagnosed between 2019 and 2022 who underwent NAT were analyzed retrospectively. NAT with KEYNOTE-522 versus control NAT were compared for rates of BCT, axillary node dissection (ALND), pCR, and survival outcomes. The prevalence of immune-related adverse events (irAE) from chemoimmunotherapy was recorded. RESULTS: Of 240 patients identified: 86 received KEYNOTE-522 and 154 received control. The frequency of pCR was significantly higher in KEYNOTE versus the control cohort, 59.3% and 33.1%, respectively (p = 0.001). There was no significant difference in the rate of BCT between the control (33.1%) and the KEYNOTE-522 (32.1%) groups (p = 0.47). Rates of ALND were significantly lower with KEYNOTE-522 (25.6%) as compared with control (39.6%); p = 0.03. The rate of development of grade 2 or higher irAEs was 34.9%. At a median follow-up of 2.4 years, there was no difference in survival outcomes. BRCA1 patients had high rates of pCR regardless of treatment group, KEYNOTE-522: 80.0% (4/5) and control: 75% (9/12), (p = 1). CONCLUSION: This real-world evidence supports the use of the KEYNOTE-522 regimen in patients with early-stage TNBC given the higher pCR rate and corresponding decrease in the rate of ALND. The majority of patients in both NAT cohorts became BCT eligible, but the rate of BCT did not differ between the two groups.

Racial disparities persist in mortality after firearm assault injuries: A national analysis of the Trauma Quality Improvement Program database.

OBJECTIVES: It is unclear whether improvements in the delivery of trauma care over the last decade have diminished racial disparities in mortality after firearm injuries. METHODS: The American College of Surgeons Trauma Quality Improvement Program was queried for patients (≥18 years old) who experienced penetrating firearm assault injuries between 2008 and 2018. Multivariable logistic regression was used to assess the association between mortality and race, controlling for demographics, comorbidities, shock index, injury severity score injury location, and hospital characteristics. RESULTS: This retrospective cohort study included 261,116 patients who experienced firearm injuries secondary to assault between 2008 and 2018. Patients most frequently identified as Black (64.1%, n = 167,494), followed by White (16.3%, n = 42,649), Hispanic/Latino (15.7%, n = 41,044), and other racial groups (3.8%, n = 9,929). On multivariable logistic regression, Black patients (odds ratio, 1.53; 95% confidence interval, 1.45-1.62), and Hispanic/Latino patients (odds ratio, 1.11; 95% confidence interval, 1.03-1.19) were more likely to die after a firearm assault injury than White patients. Black patients were more likely to die in the emergency department (62.2%, n = 13,438) compared with White patients (52.7%, n = 2,838), Hispanic/Latino patients (53.0%, n = 2,635), and patients of other races (54.8%, n = 681). Across all years of the study period, Black patients had a greater risk-adjusted mortality rate than White patients and Hispanic/Latino patients. CONCLUSION: Significant racial disparities in mortality after firearm assault continue to persist. Early death within the emergency department appears to be a significant driver of these persistent disparities.

Mitigation of Cisplatin-Induced Nephrotoxicity and Augmentation of Anticancer Potency via Tea Polyphenol Nanoparticles' Codelivery of siRNA from CRISPR/Cas9 Screened Targets.

Cisplatin, a frontline chemotherapeutic agent against cancer, faces challenges in clinical application due to significant toxicities and suboptimal efficacy. Renal toxicity, a dose-limiting factor of cisplatin, results from multifactorial processes including cisplatin-induced cellular pyroptosis, oxidative damage, and inflammatory responses. Our findings reveal that Tea Polyphenols Nanoparticles (TPNs) derived from Epigallocatechin gallate (EGCG) effectively could address these diverse mechanisms, comprehensively alleviating cisplatin-induced nephrotoxicity. Leveraging TPNs as carriers, chemical conjugation enables the encapsulation of tetravalent cisplatin prodrug, extending its systemic half-life, enhancing tumor tissue accumulation, while simultaneously mitigating renal toxicity. Concurrently, employing a CRISPR/Cas9 kinase library, we identified CSNK2A1 as a target sensitizing tumor cells to cisplatin, enabling specific siRNA sequences to augment cisplatin susceptibility, thereby minimizing the dosage requirement. Benefiting from the versatile carrier properties of TPNs to codeliver cisplatin prodrug and anti-CSNK2A1 siRNA, we developed a codelivery system, Pt-TPNs/siRNA. Pt-TPNs/siRNA not only enhances the anticancer effects but also mitigates cisplatin-induced renal toxicity, achieving efficacy while reducing toxicity. Mechanistic and safety assessments of these nanoparticles were conducted at both cellular and animal levels, opening new avenues for improved clinical utilization of cisplatin.

Human poisoning with glyphosate-surfactant herbicides: Retrospective analysis of mortality outcomes of patients treated in a poison center.

INTRODUCTION: The toxicity and carcinogenicity of glyphosate have long been debated. Nevertheless, the mortality rate in patients with acute glyphosate-surfactant poisoning varies across different groups. METHODS: Between 2002 and 2020, 109 patients with glyphosate-surfactant poisoning received treatment at Chang Gung Memorial Hospital. Patients were stratified into two subgroups according to their prognosis: good (n = 74) or poor (n = 35). Baseline demographics, psychiatric comorbidities, medical complications, and laboratory data were collected, and mortality data were analyzed. RESULTS: The patients were 54.1 ± 17.5 years of age and were mostly male (68.8%). Most patients (91.7%) ingested pesticides intentionally, and patients arrived at the hospital within 7.1 ± 12.7 h. Psychiatric comorbidities were prevalent, and the top three comorbidities were mental (71.6%), depressive (48.6%), and adjustment (14.7%) disorder. Patients with poor prognoses were older than those with good prognoses (p = .007). Moreover, patients with poor prognoses had lower Glasgow Coma Scale scores (p < .001) and diastolic blood pressure (p = .008), but higher incidences of upper gastrointestinal bleeding (p < .001), aspiration pneumonia (p < .001), hypotension (p < .001), hyperglycemia (p = .002), acute kidney injury (p < .001), and metabolic acidosis (p < .001) than patients with good prognoses. The mortality rate was 5.5%. A multivariate-logistic-regression model revealed that the Glasgow Coma Scale score was a significant risk factor for poor prognosis (odds ratio 0.653, confidence interval 0.427-0.998; p = .049). However, no risk factors for mortality were identified. CONCLUSIONS: A total of 32.1% of patients with glyphosate-surfactant poisoning had poor prognoses, and 5.5% of patients died despite treatment. The mortality outcome is comparable to that of published reports from other international poison centers.

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.

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.

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.

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.

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.

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.

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.

Impact of the ventral hernia working group's publication: a bibliometric analysis.

PURPOSE: The Ventral Hernia Working Group (VHWG) proposed a ventral hernia grading guideline, primarily supported by expert opinion, recommending biologic mesh placement in high-risk patients. We investigated the relationship between this industry-sponsored guideline and discourse around ventral hernia repair (VHR). METHODS: Medline platform from Web of Science's database identified publications "pre-VHWG"(1999-01-01 to 2009-12-31), and "post-VHWG"(2010-01-01 to 2020-12-31) describing VHR and complications or recurrence of VHR with the following comorbidities: COPD, smoking, diabetes, immunosuppression, or obesity. Poisson regression analyzed keyword frequency over time using logarithmically transformed data. RESULTS: Of 1291 VHR publications identified pre-VHWG and 3041 publications identified post-VHWG, 172 (13.3%) and 642 (21.1%) publications respectively included prespecified keywords. The keyword groups "biologic"(IRR 3.39,95%CI1.34-11.4,p = 0.022) and "comorbid"(IRR 1.95, 95%CI1.09-3.74,p = 0.033) significantly increased with frequency after publication of the VHWG. CONCLUSION: The VHWG publication likely contributed to a focus on comorbidities and biologic mesh in the ensuing literature within the field of VHR.

Does selective intraoperative music reduce pain following abdominal wall reconstruction? A double-blind randomized controlled trial.

PURPOSE: Although intraoperative music is purported to mitigate postoperative pain after some procedures, its application has never been explored in abdominal wall reconstruction (AWR). We sought to determine whether intraoperative music would decrease early postoperative pain following AWR. METHODS: We conducted a placebo-controlled, patient-, surgeon-, and assessor-blinded, randomized controlled trial at a single center between June 2022 and July 2023 including 321 adult patients undergoing open AWR with retromuscular mesh. Patients received noise-canceling headphones and were randomized 1:1 to patient-selected music or silence after induction, stratified by preoperative chronic opioid use. All patients received multimodal pain control. The primary outcome was pain (NRS-11) at 24 ± 3 h. The primary outcome was analyzed by linear regression with pre-specified covariates (chronic opioid use, hernia width, operative time, myofascial release, anxiety disorder diagnosis, and preoperative STAI-6 score). RESULTS: 178 patients were randomized to music, 164 of which were analyzed. 177 were randomized to silence, 157 of which were analyzed. At 24 ± 3 h postoperatively, there was no difference in the primary outcome of NRS-11 scores (5.18 ± 2.62 vs 5.27 ± 2.46, p = 0.75). After adjusting for prespecified covariates, the difference of NRS-11 scores at 24 ± 3 h between the music and silence groups remained insignificant (p = 0.83). There was no difference in NRS-11 or STAI-6 scores at 48 ± 3 and 72 ± 3 h, intraoperative sedation, or postoperative narcotic usage. CONCLUSION: For patients undergoing AWR, there was no benefit of intraoperative music over routine multimodal pain control for early postoperative pain reduction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05374096.

Open Retromuscular Sugarbaker vs Keyhole Mesh Placement for Parastomal Hernia Repair: A Randomized Clinical Trial.

Importance: Durable parastomal hernia repair remains elusive. There is limited evidence comparing the durability of the open retromuscular Sugarbaker and keyhole mesh configurations. Objective: To determine if the open retromuscular Sugarbaker mesh placement technique would lower parastomal hernia recurrence rates. Design, Setting, and Participants: In this single-center, randomized clinical trial, 150 patients with a permanent stoma and associated parastomal hernia who were candidates for open retromuscular parastomal hernia repair were enrolled and randomized from April 2019 to April 2022 and followed up for 2 years. Interventions: Following intraoperative assessment to determine the feasibility of either technique, enrolled patients were randomized to receive either retromuscular Sugarbaker or keyhole synthetic mesh placement. Main Outcomes and Measures: The primary outcome was parastomal hernia recurrence at 2 years. Secondary outcomes included mesh-related complications, wound complications, reoperations, as well as patient-reported pain, abdominal wall-specific quality of life, stoma-specific quality of life, and decision regret at 1 year and 2 years. Results: A total of 150 patients were randomized, and with 91% follow-up at 2 years, there were 13 (17%) parastomal hernia recurrences in the retromuscular Sugarbaker arm and 18 (24%) in the keyhole arm (adjusted risk difference, -0.029; 95% CI, -0.17 to 0.153, and adjusted risk ratio, 0.87; 95% CI, 0.42 to 1.69). There were no statistically significant differences between the Sugarbaker and keyhole groups regarding reoperations for recurrence (2 vs 7, respectively), nonhernia intra-abdominal pathology (4 vs 10, respectively), stoma necrosis (1 vs 0, respectively), mesh-related complications (4 vs 1, respectively), patient-reported pain, abdominal wall-specific quality of life, stoma-specific quality of life, and decision regret at any time point. Conclusions and Relevance: In the setting of open parastomal hernia repair, a retromuscular Sugarbaker mesh placement technique was not superior to a keyhole configuration 2 years after repair. Further innovation is necessary to improve parastomal hernia repair outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03972553.

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.

PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT.

Chemoresistance is one of the major causes of poor prognosis in osteosarcoma. Alternative therapeutic strategies for osteosarcoma are limited, indicating that increasing sensitivity to currently used chemotherapies could be an effective approach to improve patient outcomes. Using a kinome-wide CRISPR screen, we identified PRKDC as a critical determinant of doxorubicin (DOX) sensitivity in osteosarcoma. The analysis of clinical samples demonstrated that PRKDC was hyperactivated in osteosarcoma, and functional experiments showed that the loss of PRKDC significantly increased sensitivity of osteosarcoma to DOX. Mechanistically, PRKDC recruited and bound GDE2 to enhance the stability of protein GNAS. The elevated GNAS protein levels subsequently activated AKT phosphorylation and conferred resistance to DOX. The PRKDC inhibitor AZD7648 and DOX synergized and strongly suppressed the growth of osteosarcoma in mouse xenograft models and human organoids. In conclusion, the PRKDC-GDE2-GNAS-AKT regulatory axis suppresses DOX sensitivity and comprises targetable candidates for improving the efficacy of chemotherapy in osteosarcoma. Significance: Targeting PRKDC suppresses AKT activation and increases sensitivity to doxorubicin in osteosarcoma, which provides a therapeutic strategy for overcoming chemoresistance.