Clinical outcomes among patients with concurrent blunt cerebrovascular injury and traumatic intracranial hemorrhage.

BACKGROUND: Blunt cerebrovascular injury (BCVI) accounts for 1-3 % of patients with blunt trauma, which should be promptly diagnosed and managed due to risk of cerebral infarction and death. Antithrombotic therapy had been proven to reduce risk of stroke and mortality. However, due to concern of hematoma progression, treatment suggestion is still inconclusive for patients with concurrent traumatic intracranial hemorrhage. MATERIALS AND METHODS: We performed a retrospective, observational study from 2002 to 2020 at a Level I trauma center, all patients with BCVI and concurrent traumatic intracranial hemorrhage were recruited. Patients' demographics, initial CT findings, severity of BCVI, treatment and outcomes were documented and analyzed to define possible risk factors of death and stroke. RESULTS: Among all 57 patients, 49 (86.0 %) patients had injury at ICA, 6 (10.5 %) had VA injury, and 2 (3.5 %) suffered from both. Targeted treatments for BCVI were provided to 33 (57.9 %) patient, mostly endovascular intervention (78.8 %), antithrombotic treatment was given to 11 (19.3 %) patients. At 3-month follow-up, 17 (29.8 %) patients expired, and 18 (31.6 %) patients had cerebral infarction due to BCVI. We identified more severe initial CT findings (p = 0.016), higher head Abbreviated Injury Scale (p = 0.049) and initial life-threatening events (p = 0.047) as risk factors of death, and traumatic basal cistern subarachnoid hemorrhage(SAH) (p = 0.040) as single risk factor of cerebral infarction. CONCLUSIONS: Around one-thirds of patients with concurrent BCVI and traumatic intracranial hemorrhage were death or suffered from cerebral infarction within 3 months, with severity of initial head injury and SAH at basal cistern as risk factors, respectively.

Metastasis of WHO Grade II and Grade III Meningiomas: Long-term Survival and Associated Factor Analysis.

OBJECTIVE: Metastasis of WHO grade II or grade II meningiomas are rare. The aim of this study was to investigate their incidence, associated risk factors and treatment course. METHODS: Patients with surgically resected WHO grade II or grade III meningiomas were reviewed based on histopathology with the 2016 WHO criteria. Metastasis was diagnosed through whole body image scan followed by surgical resection or biopsy. Clinical factors were analyzed for their association with metastasis. RESULTS: Among the 131 enrolled patients, metastasis was diagnosed after tumor relapse in 7 (incidence rate 3.6%) at a mean 30.9 months after the initial surgery. The metastasis after tumor relapse group had the worst overall survival, followed by tumor relapse without metastasis and non-relapse groups (p<0.001). The independent factors associated with metastasis were major vessel compromise by primary tumors (hazard ratio [HR]=9.9, p=0.035), tumor relapse time less than 24 months (HR=7.0, p=0.036), and subtotal resection without adjuvant radiotherapy to the primary tumor (HR=3.5, p=0.047). Neither grading nor histochemical staining was significantly associated with metastasis, whereas higher vascularity seemed to be more common in metastatic lesions than primary tumors. CONCLUSIONS: The presence of metastasis contributed to poor outcomes and was related to earlier tumor relapse and major vessel compromise. Subtotal resection should be followed by adjuvant radiotherapy to reduce the risk of metastasis. Further research is warranted to identify circulating or pathologic biomarkers for the early detection of metastasis.

One-Stage Bilateral Severe Trismus Reconstruction: Simultaneous Utilization of Free Anterolateral Thigh and Tensor Fascia Latae Flaps From a Single Donor Thigh: Report of Three Cases.

Bilateral trismus associated with oral cancer was commonly occurred in those who had received surgical intervention and radiotherapy. Complete release of bilateral fibrotic tissues followed by free flaps reconstruction was the main current surgical intervention. However, reconstructions of both defects mostly needed to harvest two flaps from different donor sites were time-consuming and increasing morbidities. Herein, we presented three cases who undergone modified reconstructive method by harvesting the anterolateral thigh (ALT) flap and tensor fascia latae (TFL) flap simultaneously from the same donor site. Trismus release was performed including resection of the buccal part and fibrotic tissue, myotomy of the masticatory and medial pterygoid muscles, and bilateral coronoidectomy. Case 1, a 52 years-old man, with severe trismus as the interincisal distance (IID) was about 0 mm. He undergone a combined 12 × 7.5 cm ALT and 11 × 6 cm TFL flap reconstruction from a single-donor thigh. The IID apparently increased to 37 mm after 1-year follow-up. Case 2, a 64 years-old man, went through a combination of 6 × 7 cm ALT and 6 × 6 cm TFL flap reconstruction from unilateral thigh for severe trismus. The IID significantly improved from 10 mm to 30 mm after one and a half-year follow-up. Case 3, a 53 years-old woman, with IID was around 0 mm before the surgery. A combined 9 × 3 cm ALT and 9 × 3 cm TFL flap reconstruction was performed as the IID enhanced to 20 mm after 6 months follow-up. This reconstruction method using ALT and TFL flaps harvested from a single-donor thigh simultaneously could be suitable for patients with bilateral severe trismus.

One-stage burr hole surgery and middle meningeal arterial embolization for treating chronic subdural hematoma in a hybrid operative angiography suite.

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition that is known to recur and that leads to unfavorable clinical outcomes. Middle meningeal artery embolization (MMAE) has emerged as an alternative treatment to prevent recurrence. This study investigated the efficacy of combined two therapies in a hybrid operative suite for high-risk patients. METHODS: This retrospective review provides evidence for the indications and benefits of one-stage combined therapy in a hybrid neurovascular operative suite. The procedures include burr hole craniostomy, irrigation, and drainage followed by adjuvant MMAE at the lesion site. Subsequently, routine cone beam computed tomography is conducted after the whole process. RESULTS: Five patients with symptomatic CSDH and mass effect were enrolled in this study. Among them, three patients had undergone burr hole surgery previously but experienced hematoma recurrence. Two patients presented with a history of recent cardiac stent placement due to coronary artery disease, precluding the cessation of antiplatelet or anticoagulant therapy. All patients experienced symptom resolution and demonstrated no evidence of CSDH recurrence during the follow-up period. CONCLUSION: In our initial case experiences, one-stage burr hole surgery and adjuvant MMAE for treating chronic subdural hematoma in a hybrid operative angiography suite could be a feasible and effective treatment modality.

Elevated cerebrospinal fluid galectin-3 and associated cytokines after severe traumatic brain injury in patients.

This study aimed to investigate the galectin-3 and associated cytokines levels in the cerebrospinal fluid (CSF) of severe traumatic brain injury (sTBI) patients. Temporal CSF expression of galectin-3 and associated cytokines levels in sTBI patients within 1-week post-injury were studied using the multiplex bead array. STBI patient group was stratified using the Modified Rankin Score (mRS) into 3 groups: mRS 6 (died), mRS 5 (severely disabled) and mRS 1-4 (mild-to-moderately disabled) group. Analysis for bead array data using Kruskal-Wallis test with post hoc Dunn's multiple comparisons test, and temporal changes and correlation analysis using Spearman's correlation were carried out. At day 1 post-injury, CSF galectin-3 and interleukin-6 (IL-6), interleukin-10 (IL-10), cysteine-cysteine motif chemokine ligand-2 (CCL-2), and cysteine-cysteine motif chemokine ligand-20 (CCL-20), but not interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF-α) levels were significantly elevated in mRS 5 group compared to non-TBI controls. Temporal correlation analysis at 1-7 days showed decreased IL-10 level in the mRS 6 group, decreased IL-10 and CCL-2 levels in mRS 5 group, and decreased IL-6, CCL-2, and CCL-20 levels in the mRS 1-4 group. Receiver operating characteristic curve analyses revealed a significant area under the curve for comparison between mRS 6 and mRS 5 groups for galectin-3 and IL-6. No significant differences in sex, age, Glasgow Coma Scale score, C-reactive protein levels and types of TBI-induced hemorrhages were observed between the groups. CSF galectin-3 and associated cytokines, especially IL-6, CCL-2 and CCL-20 levels were different within sub-groups of sTBI patients, suggesting their potential use in sTBI prognostics.

Effectiveness of high-intensity focused ultrasound combined with gonadotropin-releasing hormone agonist or combined with levonorgestrel-releasing intrauterine system for adenomyosis: A systematic review and meta-analysis.

Gonadotropin-Releasing Hormone Agonist (GnRH-a) and levonorgestrel releasing intrauterine system (LNG-IUS) are conventional conservative treatments for adenomyosis, and high-intensity focused ultrasound (HIFU) is a novel ablation technique. This study aimed to investigate the effectiveness of HIFU combined with GnRH-a or LNG-IUS for adenomyosis patients. In this systematic review and meta-analysis, Pubmed, Embase, Cochrane Library and Scopus databases were searched up to December 2021. Published studies comparing HIFU plus GnRH-a with HIFU plus LNG-IUS in adenomyosis patients were assessed for eligibility by two independent authors. Risk of bias tool was utilized for risk evaluation. We selected treatment effective rate of dysmenorrhea (pain during menstruation) as the primary outcome; effective rate of menorrhagia severity and reduction rate of adenomyotic lesion as the secondary outcomes. Adverse effects were assessed. Four studies with a total 729 patients were enrolled in the meta-analysis. HIFU plus LNG-IUS showed lower dysmenorrhea [within 6 months: risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83-0.93, p < 0.00001; over 1 year: RR 0.73, 95% CI 0.65-0.82, p < 0.00001] and less menorrhagia severity (RR 0.63, 95% CI 0.60-0.66, p < 0.00001) than HIFU plus GnRH-a. Both groups demonstrated equal efficacy in adenomyotic lesion reduction rate (RR 1.03, 95% CI 0.97-1.09, p = 0.30). Adverse effects happened equally in both groups. Combination therapy of HIFU and LNG-IUS revealed better effectiveness in treating dysmenorrhea and menorrhagia than that of HIFU and GnRH-a. However, interpreting the conclusion should be approached with caution as a result of significant heterogeneity.

Simplified Fabrication of a Lingual Splint for Management of Mandibular Fractures.

Lingual splints have been used to treat mandibular fractures, particularly in cases of complicated mandibular fractures, and serve as a noninvasive adjunctive procedure for reduction and fixation. Furthermore, when used in conjunction with open reduction and internal fixation, the lingual splint provides feasible external fixation against displacing forces exerted by the robust musculature of the mandible. However, the conventional method for lingual splint fabrication is performed preoperatively, and the procedure is time-consuming. This technical note describes a simplified and efficient technique for the intraoperative manufacture of a lingual splint for mandibular fractures using a thermoplastic material, polycaprolactone. Our results demonstrated satisfactory fixation outcomes, reduced lingual splint fabrication time, and superior cost-effectiveness, offering an alternative option for adjunctive external fixation of mandibular fractures.

Deep learning to assess microsatellite instability directly from histopathological whole slide images in endometrial cancer.

Molecular classification, particularly microsatellite instability-high (MSI-H), has gained attention for immunotherapy in endometrial cancer (EC). MSI-H is associated with DNA mismatch repair defects and is a crucial treatment predictor. The NCCN guidelines recommend pembrolizumab and nivolumab for advanced or recurrent MSI-H/mismatch repair deficient (dMMR) EC. However, evaluating MSI in all cases is impractical due to time and cost constraints. To overcome this challenge, we present an effective and efficient deep learning-based model designed to accurately and rapidly assess MSI status of EC using H&E-stained whole slide images. Our framework was evaluated on a comprehensive dataset of gigapixel histopathology images of 529 patients from the Cancer Genome Atlas (TCGA). The experimental results have shown that the proposed method achieved excellent performances in assessing MSI status, obtaining remarkably high results with 96%, 94%, 93% and 100% for endometrioid carcinoma G1G2, respectively, and 87%, 84%, 81% and 94% for endometrioid carcinoma G3, in terms of F-measure, accuracy, precision and sensitivity, respectively. Furthermore, the proposed deep learning framework outperforms four state-of-the-art benchmarked methods by a significant margin (p < 0.001) in terms of accuracy, precision, sensitivity and F-measure, respectively. Additionally, a run time analysis demonstrates that the proposed method achieves excellent quantitative results with high efficiency in AI inference time (1.03 seconds per slide), making the proposed framework viable for practical clinical usage. These results highlight the efficacy and efficiency of the proposed model to assess MSI status of EC directly from histopathological slides.

Adipose-derived stem cell modulate tolerogenic dendritic cell-induced T cell regulation is correlated with activation of Notch-NFκB signaling.

BACKGROUND: Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs. METHODS: Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs. RESULTS: Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway). CONCLUSIONS: ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application.

Hyaluronic acid-based injectable formulation developed to mitigate metastasis and radiation-induced skin fibrosis in breast cancer treatment.

The standard treatment for early-stage breast cancer involves breast-conserving surgery followed by adjuvant radiotherapy. However, approximately 20 % of patients experience distant metastasis, and adjuvant radiotherapy often leads to radiation-induced skin fibrosis (RISF). In this study, we develop an on-site injectable formulation composed of selenocystamine (SeCA) and hyaluronic acid (HyA), referred to as SeCA cross-linked HyA (SCH) agent, and investigate its potential to mitigate metastasis and prevent RISF associated with breast cancer therapy. SCH agents are synthesized using the nanoprecipitation method to modulate cell-cell tight junctions and tissue inflammation. The toxicity assessments reveal that SCH agents with a higher Se content (Se payload 17.4 µg/mL) are well tolerated by L929 cells compared to SeCA (Se payload 3.2 µg/mL). In vitro, SCH agents significantly enhance cell-cell tight junctions and effectively mitigate migration and invasion of breast cancer cells (4T1). In vivo, SCH agents mitigate distant lung metastasis. Furthermore, in animal models, SCH agents reduce RISF and promote wound repair. These findings highlight the potential of SCH agents as a novel therapeutic formulation for effectively mitigating metastasis and reducing RISF. This holds great promise for improving clinical outcomes in breast cancer patients undergoing adjuvant radiotherapy.

Novel mutation of COG5 in a Taiwanese girl with congenital disorders of glycosylation manifesting as developmental delay.

We are documenting the case of An 11-year-old girl who has been followed up at our out-patient clinic since birth with clinical presentations including intrauterine growth restriction, recurrent periodic fever in infancy, hypotonia, global developmental delay, liver function impairment with cirrhotic changes, and clinodactyly. Congenital abnormalities were suspected but a series of examinations including brain MRI, liver biopsy and muscle biopsy yielded insignificant findings. Whole genome sequencing (WGS) was conducted and revealed three novel mutations (c2T > G, c1826T > C, c.556-560delAGTAAinsCT) of the COG5 gene. A diagnosis of COG5-congenital disorders of glycosylation (COG5-CDG, or CDG IIi), with neurologic presentation was established. Sanger sequencing in the patient and her parents confirmed the compound heterozygous mutation. Upon literature review, we identified the patient as the first case of COG5-CDG in Taiwan. Our study enhances the clarity of the correlation between the mutative genes and the presentation of COG5-CDG.

Rapid identification of mushroom toxins by direct electrospray probe mass spectrometry for emergency care.

Mushroom poisoning occurs frequently after the ingestion of toxic wild mushrooms misidentified as edible species. The goal of this study is to develop a mass spectrometric platform to bypass the need for morphological recognition of poisonous mushrooms by experts and rapidly identify the toxins in the mushrooms for emergency care. Trace mushroom toxins were collected by penetrating and removing the mushrooms surface for 3 mm with a direct electrospray probe (DEP). The analytes on the DEP were then dissolved in the solution (70% isopropanol containing 0.1% acetic acid) flowing out of a solvent reservoir on the DEP. Electrospray ionization was induced from the sample solution as a high electric field was generated between the DEP and MS inlet. The obtaining mass spectrometric results were further analyzed with principal component analysis (PCA) to classify mushroom toxins. The mass spectrometric platform for detecting mushroom toxins was assessed for its sensitivity, precision, and efficiency by determining its limit-of-detection (LOD), repeatability, and turnaround time, respectively. As a result, the LODs of the mushroom toxins in pure methanol and spiked in human vomitus by DEP/MS were within 0.001-0.5 ng/µL and 0.01-1 ng/µL, respectively. Linear responses of the mushroom toxins in pure methanol with concentrations between 0.01 and 5 ng/µL (R2 between 0.9922 and 0.998) were obtained. The repeatability of the approach (n = 10) was shown in the low relative standard deviation value (<15%) from ten repeat analysis of mushroom toxins standard solution. The corresponding toxic compounds were identified through matching of the obtained mass spectrometric data with those provided by its companion database library of mushroom toxins. Since no time-consuming pretreatment of the samples is required, identification of mushroom toxins with DEP/MS was complete within 1 min. This will be helpful for the emergency physicians to make correct clinical judgment and prescribe appropriate medical treatment in a timely manner.

Psychological Distress and Suicidality Among Transgender Young Adults in the United States.

PURPOSE: Transgender young adults (TYA) are burdened by adverse mental health outcomes. Guided by intersectionality and minority stress frameworks, we compared prevalence of psychological distress and suicidality among TYA of different social identities to inform future interventions. METHODS: In this secondary data analysis of 12,738 TYA, ages 18-25 years, from the 2015 United States Transgender Survey, we developed multivariable regression models examining associations between social identities and psychological distress and suicidality, adjusting for relevant covariates. Self-reported identities were used as proxies for minority stress resulting from structural oppressions related to gender binarism, transmisogyny, heterosexism, and racism. RESULTS: Overall, 53% met criteria for serious psychological distress, and 66% reported suicidal ideation. Statistically higher odds of serious psychological distress and suicidal ideation and plan were found for TYA assigned male compared to assigned female at birth (adjusted odds ratios [aORs] = 1.14-1.50). Nonbinary TYA assigned male at birth also had lower odds of all outcomes compared to all other TYA (aORs = 0.6-0.7). Compared to White TYA, Latiné/x TYA were more likely to experience serious psychological distress (aOR = 1.19, 95% confidence interval: 1.02, 1.39) and multiracial TYA were more likely to report suicide plan(s) and attempt(s) (aORs = 1.25-1.30). Finally, compared to heterosexual TYA, bisexual/pansexual TYA were more likely to report suicide plan(s) (aOR = 1.28, 95% confidence intervals: 1.04, 1.52), and all sexual minority TYA were more likely to report serious psychological distress and suicidal ideation (aORs = 1.31-2.00). DISCUSSION: Results highlight complex associations between intersectional minority stress and mental health outcomes among TYA. Associations between identities and mental health morbidity highlight an urgent need for targeted mental health interventions.

Turbocharging as a strategy to boost extended perforator flap vascularity in head and neck reconstruction-A report of two cases.

Perforator flap has been applied as the most common flap for soft tissue defect reconstruction. Here, we presented two cases using turbocharging procedure of perforator to perforator as a salvage strategy. The first case was a 54-year-old male with recurrent squamous cell carcinoma (SCC) in the left buccal area and mouth floor. A 6 × 22 cm posteromedial thigh (PMT) flap was designed for reconstruction. The two eccentric perforators of the PMT flap could not conjoin together during dissection nearby the main pedicle of profunda femoral artery (PFA) resulting in inadequate perfusion. Side branched stump before clipped the branch of distal perforator was preserved, then the proximal perforator was divided and end-to-end anastomosis of side branch of distal perforator was done successfully. The second case was a 52-year-old male underwent wide composite excision of right tongue SCC. After excision, anterolateral thigh (ALT) flap around 7 × 15 cm was harvested from left thigh and two perforators were included which one tiny perforator supplied by the descending branch (DB) and the other major perforator originated from oblique branch (OB) of lateral circumflex femoral artery (LCFA). However, the OB main perforator injury showed inadequate perfusion of flap. We trimmed the injury zone of OB perforator, and shift to re-anastomosis of OB perforators to side branch of DB of LCFA directly. The flap demonstrated excellent perfusion immediately after the operation, and it exhibited complete survival 2 weeks postoperatively. These results indicated that the turbocharging procedure, from perforator to perforator, could serve as a strategy for salvaging perfusion-compromised flaps, especially in cases of eccentric perforators or perforator injury resulting in inadequate perfusion.

Minimally invasive endoscopic evacuation with the novel, portable Axonpen neuroendoscopic system for spontaneous intracerebral hemorrhage.

Minimally invasive surgeries have shown potential to improve mortality and clinical outcomes of spontaneous intracerebral hemorrhage (ICH). The present study assessed the first-in-human outcomes of a novel, portable neuroendoscopic system for ICH evacuation at our single center. This neuroendoscopic system integrates real-time visualization into a handpiece which has controllable suction, irrigation, and coagulation to allow a neurosurgeon to conduct minimally invasive ICH evacuation independently with bimanual dexterity. Pre- and postoperative data of ten patients who had spontaneous basal ganglia hemorrhage (mean: 46.5 ± 12.2 mL) and underwent evacuation with the specified neuroendoscopic system were collected prospectively. The mean time to receive surgery was 12.1 ± 7.6 h. Mean operative time was 3.4 ± 0.9 h. The mean hematoma volume decreased to 6.0 ± 3.9 mL at postoperative 6 h, resulting in a mean volume reduction of 86.0 ± 11.2% (P = 0.005). The median length of intensive care unit stay was 3 days (IQR, 3-4 days). At discharge, the median Glasgow Coma Scale (GCS) score significantly improved to 11.5 (IQR, 11-15; P = 0.016), and the median modified Rankin Scale (mRS) score was 4 (IQR, 4-5). Six patients (60%) showed a favorable mRS score of ≤ 3 on their last return visit. Neither death nor rebleeding occurred during the follow-up periods. Integrated design of the innovative device is valuable to optimize minimally invasive endoscopic ICH evacuation procedure. Further studies are needed to clarify long-term benefits from such type of the innovative device to early intervention of ICH.

Synergistically Enhancing Immunotherapy Efficacy in Glioblastoma with Gold-Core Silica-Shell Nanoparticles and Radiation.

Purpose: Glioblastoma is a highly aggressive brain tumor with universally poor outcomes. Recent progress in immune checkpoint inhibitors has led to increased interest in their application in glioblastoma. Nonetheless, the unique immune milieu in the brain has posed remarkable challenges to the efficacy of immunotherapy. We aimed to leverage the radiation-induced immunogenic cell death to overcome the immunosuppressive network in glioblastoma. Methods: We developed a novel approach using the gold-core silica-shell nanoparticles (Au@SiO2 NPs) in combination with low-dose radiation to enhance the therapeutic efficacy of the immune checkpoint inhibitor (atezolizumab) in brain tumors. The biocompatibility, immune cell recruitment, and antitumor ability of the combinatorial strategy were determined using in vitro assays and in vivo models. Results: Our approach successfully induced the migration of macrophages towards brain tumors and promoted cancer cell apoptosis. Subcutaneous tumor models demonstrated favorable safety profiles and significantly enhanced anticancer effects. In orthotopic brain tumor models, the multimodal therapy yielded substantial prognostic benefits over any individual modalities, achieving an impressive 40% survival rate. Conclusion: In summary, the combination of Au@SiO2 NPs and low-dose radiation holds the potential to improve the clinical efficacy of immune checkpoint inhibitors. The synergetic strategy modulates tumor microenvironments and enhances systemic antitumor immunity, paving a novel way for glioblastoma treatment.

Potential of thermoresponsive hydrogel as an alternative therapy for rat knee osteoarthritis.

Osteoarthritis is a degenerative condition that is highly prevalent and primarily affects the joints. The knee is the most commonly affected site, impacting the lives of over 300 million individuals worldwide. This study presents a potential solution to address the unmet need for a minimally invasive technique in the treatment of osteoarthritis: a biocompatible, injectable, and thermoresponsive hydrogel. In comparison to commercially available products such as lyophilized platelets, dextrose, and triamcinolone, the thermoresponsive hydrogel exhibits significantly superior performance in dynamic behaviors, including print area, stability, and step cycle, when tested on rats with knee osteoarthritis. However, it demonstrates similar treatment efficacy to these products in static behaviors, as observed through histopathological and immunohistochemical analysis. Therefore, the thermoresponsive hydrogel holds promise as an effective alternative therapy for osteoarthritis. Moreover, by blending the hydrogel with drugs, controlled and sustained release can be achieved, thereby facilitating the long-term management of osteoarthritis symptoms.

Extended frontalis orbicularis oculi muscle flap shortening for treating refractory apraxia of eyelid opening associated with blepharospasm.

BACKGROUND: Refractory apraxia of eyelid opening (AEO) is mostly unresponsive to botulinum toxin (BTx) and inevitably leads to functional blindness. To treat this challenging condition, an innovative surgical technique was proposed. METHODS: The extended frontalis orbicularis oculi muscle (FOOM) flap shortening consisting of frontalis suspension, partial myectomy, and myotomy in situ of eyelid protractors was applied to treat refractory AEO associated with blepharospasm. The postoperative outcomes and patient satisfaction were evaluated. RESULTS: Seven patients (mean ages 64.1 ± 3.9 years) of 14 eyelids in total had an average flap shortening distance of 24.4 ± 1.3 mm. During a mean follow-up of 31.6 ± 11.4 months, the average BTx dosage reduced from 58.6 ± 12. 1 units to 30.0 ± 8.2 units, with a mean injection interval decreasing from 2.3 ± 0.5 months to 4.1 ± 0.9 months (p < 0.05). Palpebral fissure height increased from 1.4 ± 0.5 mm to 7.9 ± 0.7 mm, and the disability scale decreased from 78.8% ± 7.2% to 12.6% ± 7.0% (p < 0.05). The postoperative BTx dosage and frequency were significantly reduced. All patients restored voluntary eyelid opening and reported high postoperative satisfaction (average Likert scale 4.6 ± 0.5). CONCLUSION: Extended FOOM flap shortening is an effective treatment to solve refractory AEO associated with blepharospasm.

Deep Learning Can Predict Bevacizumab Therapeutic Effect and Microsatellite Instability Directly from Histology in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) remains a significant cause of mortality among gynecologic cancers, with the majority of cases being diagnosed at an advanced stage. Before targeted therapies were available, EOC treatment relied largely on debulking surgery and platinum-based chemotherapy. Vascular endothelial growth factors have been identified as inducing tumor angiogenesis. According to several clinical trials, anti-vascular endothelial growth factor-targeted therapy with bevacizumab was effective in all phases of EOC treatment. However, there are currently no biomarkers accessible for regular therapeutic use despite the importance of patient selection. Microsatellite instability (MSI), caused by a deficiency of the DNA mismatch repair system, is a molecular abnormality observed in EOC associated with Lynch syndrome. Recent evidence suggests that angiogenesis and MSI are interconnected. Developing predictive biomarkers, which enable the selection of patients who might benefit from bevacizumab-targeted therapy or immunotherapy, is critical for realizing personalized precision medicine. In this study, we developed 2 improved deep learning methods that eliminate the need for laborious detailed image-wise annotations by pathologists and compared them with 3 state-of-the-art methods to not only predict the efficacy of bevacizumab in patients with EOC using mismatch repair protein immunostained tissue microarrays but also predict MSI status directly from histopathologic images. In prediction of therapeutic outcomes, the 2 proposed methods achieved excellent performance by obtaining the highest mean sensitivity and specificity score using MSH2 or MSH6 markers and outperformed 3 state-of-the-art deep learning methods. Moreover, both statistical analysis results, using Cox proportional hazards model analysis and Kaplan-Meier progression-free survival analysis, confirm that the 2 proposed methods successfully differentiate patients with positive therapeutic effects and lower cancer recurrence rates from patients experiencing disease progression after treatment (P < .01). In prediction of MSI status directly from histopathology images, our proposed method also achieved a decent performance in terms of mean sensitivity and specificity score even for imbalanced data sets for both internal validation using tissue microarrays from the local hospital and external validation using whole section slides from The Cancer Genome Atlas archive.