An improved attention module based on nnU-Net for segmenting primary central nervous system lymphoma (PCNSL) in MRI images1.

BACKGROUND: Accurate volumetric segmentation of primary central nervous system lymphoma (PCNSL) is essential for assessing and monitoring the tumor before radiotherapy and the treatment planning. The tedious manual segmentation leads to interindividual and intraindividual differences, while existing automatic segmentation methods cause under-segmentation of PCNSL due to the complex and multifaceted nature of the tumor. OBJECTIVE: To address the challenges of small size, diffused distribution, poor inter-layer continuity on the same axis, and tendency for over-segmentation in brain MRI PCNSL segmentation, we propose an improved attention module based on nnUNet for automated segmentation. METHODS: We collected 114 T1 MRI images of patients in the Huashan Hospital, Shanghai. Then randomly split the total of 114 cases into 5 distinct training and test sets for a 5-fold cross-validation. To efficiently and accurately delineate the PCNSL, we proposed an improved attention module based on nnU-Net with 3D convolutions, batch normalization, and residual attention (res-attention) to learn the tumor region information. Additionally, multi-scale dilated convolution kernels with different dilation rates were integrated to broaden the receptive field. We further used attentional feature fusion with 3D convolutions (AFF3D) to fuse the feature maps generated by multi-scale dilated convolution kernels to reduce under-segmentation. RESULTS: Compared to existing methods, our attention module improves the ability to distinguish diffuse and edge enhanced types of tumors; and the broadened receptive field captures tumor features of various scales and shapes more effectively, achieving a 0.9349 Dice Similarity Coefficient (DSC). CONCLUSIONS: Quantitative results demonstrate the effectiveness of the proposed method in segmenting the PCNSL. To our knowledge, this is the first study to introduce attention modules into deep learning for segmenting PCNSL based on brain magnetic resonance imaging (MRI), promoting the localization of PCNSL before radiotherapy.

Lian-Mei-Yin formula alleviates diet-induced hepatic steatosis by suppressing Yap1/FOXM1 pathway-dependent lipid synthesis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.

Prognostic models for patients suffering a heart failure with a preserved ejection fraction: a systematic review.

The purpose of this study was to systematically review the development, performance, and applicability of prognostic models developed for predicting poor events in patients with heart failure with preserved ejection fraction (HFpEF). Databases including Embase, PubMed, Web of Science Core Collection, the Cochrane Library, China National Knowledge Infrastructure, Wan Fang, Wei Pu, and China Biological Medicine were queried from their respective dates of inception to 1 June 2023, to examine multivariate models for prognostic prediction in HFpEF. Both forward and backward citations of all studies were included in our analysis. Two researchers individually used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist to extract data and assess the quality of the models using the Predictive Mode Bias Risk Assessment Tool (PROBAST). Among the 6897 studies screened, 16 studies derived and/or validated a total of 39 prognostic models. The sample size ranges for model development, internal validation, and external validation are 119 to 5988, 152 to 1000, and 30 to 5957, respectively. The most frequently employed modelling technique was Cox proportional hazards regression. Six studies (37.50%) conducted internal validation of models; bootstrap and k-fold cross-validation were the commonly used methods for internal validation of models. Ten of these models (25.64%) were validated externally, with reported the c-statistic in the external validation set ranging from 0.70 to 0.96, while the remaining models await external validation. The MEDIA echo score and I-PRESERVE-sudden cardiac death prediction mode have been externally validated using multiple cohorts, and the results consistently show good predictive performance. The most frequently used predictors identified among the models were age, n-terminal pro-brain natriuretic peptide, ejection fraction, albumin, and hospital stay in the last 5 months owing to heart failure. All study predictor domains and outcome domains were at low risk of bias, high or unclear risk of bias of all prognostic models due to underreporting in the area of analysis. All studies did not evaluate the clinical utility of the prognostic models. Predictive models for predicting prognostic outcomes in patients with HFpEF showed good discriminatory ability but their utility and generalization remain uncertain due to the risk of bias, differences in predictors between models, and the lack of clinical application studies. Future studies should improve the methodological quality of model development and conduct external validation of models.

How I do it? Surgical clipping of a large right internal carotid artery-superior hypophyseal artery aneurysm.

BACKGROUND: Microsurgery alone often proves to be challenging in treating paraclinoid internal carotid artery (ICA) aneurysms, which are known for their complex anatomy. METHOD: A 53-year-old female with a large right ICA-superior hypophyseal artery (SHA) aneurysm underwent clipping repair. Mixed reality technology was utilized in the preoperative planning and anatomical study. During the surgery, the anterior clinoid process was removed intradurally to improve access to the aneurysm neck. The aneurysm was then secured with a long curved clip. The patient's recovery was successful without any complications. CONCLUSION: This report aims to shed light on the intricacies involved in clipping ICA-SHA aneurysms.

Measurement properties of assessment tools of Kinesophobia in patients with cardiovascular disease: A systematic review.

Objectives: This study aimed to evaluate the measurement properties and methodological quality of assessment tools for Kinesophobia among patients with cardiovascular disease and provide a reference for healthcare professionals in selecting high-quality assessment tools. Methods: A systematic search was performed on specific databases: Embase, the Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang database, China Biological Medicine disc, CINAHL, and China Science and Technology Journal Database, from inception to April 1, 2023. The researchers retrieved studies on the measurement attributes of the exercise fear scale in patients with cardiovascular diseases. They also traced back the references of the included studies to supplement relevant literature. According to the inclusion and exclusion criteria, screening and data extraction were independently undertaken by two reviewers. Two researchers individually used the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) Risk of Bias Checklist to assess the methodological quality of the scale, applied the COSMIN criteria to evaluate the measurement properties of the scale, and used a modified Grading, Recommendations, Assessment, Development, and Evaluation system to assess the certainty of evidence. Results: Seventeen studies were identified that reported the psychometric properties of six patient reported outcome measurement tools (included different languages version) The methodological quality of content validity was adequate in only two studies, the remaining patient-reported outcome measures demonstrated doubtful content validity. Limited information on cross-cultural validity/measurement invariance, measurement error, and responsiveness was retrieved. The Swedish version and the Chinese version of the Tampa Scale for Kinesiophobia Heart were graded "A." The remaining instruments were graded "B." Conclusions: The methodological and measurement attributes of the Swedish and Chinese versions of the Tampa Scale for Kinesiophobia Heart are relatively high quality and can be tentatively recommended. The measurement properties of the remaining scales remain to be verified.

A model of pregnancy-associated malaria for inducing adverse pregnancy outcomes in ICR mouse.

BACKGROUND: Based on understanding of placental pathological features and safe medication in pregnancy-associated malaria (PAM), establishment of a stable pregnant mouse infection model with Plasmodium was urgently needed. METHODS: ICR mice with vaginal plugs detected were randomly divided into post-pregnancy infection (Malaria+) and uninfected pregnancy (Malaria-) cohorts. Age-matched mice that had not been mated were infected as pre-pregnancy infection group (Virgin control), which were subsequently mated with ICR males. All mice were inoculated with 1 × 106Plasmodium berghei ANKA-infected RBCs by intraperitoneal injection, and the same amount of saline was given to Malaria- group. We recorded the incidence of adverse pregnancy outcomes and the amounts of offspring in each group. RESULTS: The Virgin group mice were unable to conceive normally, and vaginal bleeding, abortion, or stillbirth appeared in the Malaria+ group. The incidence of adverse pregnancy outcomes was extremely high and statistically significant compared with the control (Malaria-) group (P < 0.05), of which placenta exhibited pathological features associated with human gestational malaria. CONCLUSIONS: The intraperitoneal injection of 1 × 106Plasmodium berghei ANKA-infected RBCs could establish a model of pregnancy-associated malaria in ICR mouse.

The compound artemisinin-hydroxychloroquine ameliorates bleomycin-induced pulmonary fibrosis in rats by inhibiting TGF-ß1/Smad2/3 signaling pathway.

Pulmonary fibrosis (PF) is a lethal disease characterized by a progressive decline in lung function. Currently, lung transplantation remains the only available treatment for PF. However, both artemisinin (ART) and hydroxychloroquine (HCQ) possess potential antifibrotic properties. This study aimed to investigate the effects and mechanisms of a compound known as Artemisinin-Hydroxychloroquine (AH) in treating PF, specifically by targeting the TGF-ß1/Smad2/3 pathway. To do this, we utilized an animal model of PF induced by a single tracheal drip of bleomycin (BLM) in Sprague-Dawley (SD) rats. The PF animal models were administered various doses of AH, and the efficacy and safety of AH were evaluated through pulmonary function testing, blood routine tests, serum biochemistry tests, organ index measurements, and pathological examinations. Additionally, Elisa, western blotting, and qPCR techniques were employed to explore the potential molecular mechanisms of AH in treating PF. Our findings reveal that AH effectively and safely alleviate PF by inhibiting BLM-induced specific inflammation, reducing extracellular matrix (ECM) deposition, and interfering with the TGF-ß1/Smad2/3 signaling pathway. Notably, the windfall for this study is that the inhibition of ECM may initiate self-healing in the BLM-induced PF animal model. In conclusion, AH shows promise as a potential therapeutic drug for PF, as it inhibits disease progression through the TGF-ß1/Smad2/3 signaling pathway.

How we do it: the double keyhole micro-endoscopic combined complex pituitary adenoma surgery.

BACKGROUND: Surgical removal of complex pituitary adenomas (PA) is a technically challenging procedure. To ensure safe and efficient surgery, we employ the micro-endoscopic combination technique. METHOD: In this study, we present our approach to the removal of a complex PA using the micro-endoscopic combination strategy. We describe our surgical setup and workflow in detail. CONCLUSION: Our experience with this case highlights the effectiveness of the micro-endoscopic combination technique in the management of complicated skull base surgeries with good teamwork and cooperation.

Spliceosome component Usp39 contributes to hepatic lipid homeostasis through the regulation of autophagy.

Regulation of alternative splicing (AS) enables a single transcript to yield multiple isoforms that increase transcriptome and proteome diversity. Here, we report that spliceosome component Usp39 plays a role in the regulation of hepatocyte lipid homeostasis. We demonstrate that Usp39 expression is downregulated in hepatic tissues of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) subjects. Hepatocyte-specific Usp39 deletion in mice leads to increased lipid accumulation, spontaneous steatosis and impaired autophagy. Combined analysis of RNA immunoprecipitation (RIP-seq) and bulk RNA sequencing (RNA-seq) data reveals that Usp39 regulates AS of several autophagy-related genes. In particular, deletion of Usp39 results in alternative 5' splice site selection of exon 6 in Heat shock transcription factor 1 (Hsf1) and consequently its reduced expression. Importantly, overexpression of Hsf1 could attenuate lipid accumulation caused by Usp39 deficiency. Taken together, our findings indicate that Usp39-mediated AS is required for sustaining autophagy and lipid homeostasis in the liver.

How we do it? The surgical resection of a medial parietal arteriovenous malformation under multimodal imaging technology-guided hybrid operation.

BACKGROUND: This report described the surgical resection of a challenging medial parietal lobe arteriovenous malformation (AVM) using the hybrid operation theater with a multimodal imaging-guided technology. METHOD: A 29-year-old male was admitted to treat a ruptured medial parietal AVM. The deep and diffusive compartment of the nidus was embolized before resection. Preoperatively and intraoperatively, mixed reality technology with multimodality imaging was utilized for surgical planning and navigation. The nidus was totally resected and confirmed by intraoperative angiography. The patient recovered without sequella. CONCLUSION: We hope this report provides new insights into applying multimodal imaging technology-guided hybrid operation for brain AVM.

Assessment of the anti-inflammatory mechanism of quercetin 3,7-dirhamnoside using an integrated pharmacology strategy.

Pouzolzia zeylanica (L.) Benn. is a Chinese herbal medicine widely used for its anti-inflammatory and pus-removal properties. To explore its potential anti-inflammatory mechanism, quercetin 3,7-dirhamnoside (QDR), the main flavonoid component of P. zeylanica (L.) Benn., was extracted and purified. The potential anti-inflammatory targets of QDR were predicted using network analysis. These potential targets were verified using molecular docking, molecular dynamics simulations, and in vitro experiments. Consequently, 342 potential anti-inflammatory QDR targets were identified. By analyzing the intersection between the protein-protein interaction and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified several potential protein targets of QDR, including RAC-alpha serine/threonine-protein kinase (AKT1), Ras-related C3 botulinum toxin substrate 1 (RAC1), nitric oxide synthase 3 (NOS3), serine/threonine-protein kinase mTOR (mTOR), epidermal growth factor receptor (EGFR), growth factor receptor-bound protein 2 (GRB2), and endothelin-1 receptor (EDNRA). QDR has anti-inflammatory activity and regulates immune responses and apoptosis through chemokines, Phosphatidylinositol 3-kinase 3(PI3K)/AKT, cAMP, T-cell receptor, and Ras signaling pathways. Molecular docking analysis showed that QDR has good binding abilities with AKT1, mTOR, and NOS3. In addition, molecular dynamics simulations demonstrated that the protein-ligand complex systems formed between QDR and AKT1, mTOR, and NOS3 have high dynamic stability, and their protein-ligand complex systems possess strong binding ability. In RAW264.7 macrophages, QDR significantly inhibited lipopolysaccharides (LPS)-induced inducible nitric oxide synthase expression, nitric oxide (NO) release and the generation of proinflammatory cytokines IL-6, IL-1ß, and TNF-α. QDR downregulated the expression of p-AKT1(Ser473)/AKT1 and p-mTOR (Ser2448)/mTOR, and upregulated the expression of NOS3, Rictor, and Raptor. This indicates that the anti-inflammatory mechanisms of QDR involve regulation of AKT1 and mTOR to prevent apoptosis and of NOS3 which leads to the release of endothelial NO. Thus, our study elucidated the potential anti-inflammatory mechanism of QDR, the main flavonoid found in P. zeylanica (L.) Benn.

How I do it? Preoperative Microsoft HoloLens 2 planning-assisted surgical clipping of a fetal posterior cerebral artery aneurysm.

BACKGROUND: The treatment of intracranial aneurysms has predominantly shifted towards endovascular strategies, but complex cases still necessitate microsurgery. Preoperative stimulation can be beneficial for inexperienced young neurosurgeons in preparing for safe microsurgery. METHOD: A 72-year-old female with a left irregular fetal posterior cerebral artery (PCA) aneurysm underwent clipping repair. Microsoft HoloLens 2, utilizing mixed reality technology, was employed for preoperative stimulation and anatomical study. During the operation, we successfully identified the planned relationship between the aneurysm and the fetal PCA. The patient was cured without any complications. CONCLUSION: We hope that this report will highlight the significance of Microsoft HoloLens 2 in microsurgical planning and education.

Ablation treatment of hepatocellular carcinoma: a bibliometric analysis.

Objective: Ablation is a common treatment for hepatocellular carcinoma (HCC). This study aimed to assess research trends in the ablation treatment of HCC using bibliometric analysis. Methods: Publications between January 1, 1993 and December 31, 2022 were retrieved from the Web of Science database. The bibliometrix package from R software, CiteSpace, VOSviewer and an online analytical platform were used for data analysis and plotting. Results: A total of 4,029 publications were retrieved from the Web of Science database between 1993 and 2022. The annual growth rate of publication numbers was 10.14%. China had the largest number of publications in the field of HCC ablation. China and the United States of America have the most notable cooperation. Sun Yat-sen University had the largest number of publications in the field of HCC ablation. The most relevant journals were Hepatology, Journal of Hepatology, Gastroenterology, and Radiology. High-frequency keywords mainly focused on "therapy," "resection," "radiofrequency ablation" and "survival". Conclusions: With the increase in related publications, the research direction of ablation treatment of HCC is mainly focused on "therapy," "resection," "radiofrequency ablation" and "survival", and the ablation treatment method has gradually changed from percutaneous ethanol injection to radiofrequency ablation and microwave ablation. Irreversible electroporation may become the main method of ablation therapy in the future.

GB1a Activates SIRT6 to Regulate Lipid Metabolism in Mouse Primary Hepatocytes.

Lipid accumulation, oxidative stress, and inflammation in hepatocytes are features of nonalcoholic fatty liver disease (NAFLD). Garcinia biflavonoid 1a (GB1a) is a natural product capable of hepatic protection. In this study, the effect of GB1a on anti-inflammatory, antioxidant, and regulation of the accumulation in HepG2 cells and mouse primary hepatocytes (MPHs) was investigated, and its regulatory mechanism was further explored. The result showed that GB1a reduced triglyceride (TG) content and lipid accumulation by regulating the expression of SREBP-1c and PPARα; GB1a reduced reactive oxygen species (ROS) and improved cellular oxidative stress to protect mitochondrial morphology by regulating genes Nrf2, HO-1, NQO1, and Keap1; and GB1a reduced the damage of hepatocytes by inhibiting the expression of inflammatory cytokines interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65. The activities of GB1a were lost in liver SIRT6-specific knockout mouse primary hepatocytes (SIRT6-LKO MPHs). This indicated that activating SIRT6 was critical for GB1a to perform its activity, and GB1a acted as an agonist of SIRT6. It was speculated that GB1a may be a potential drug for NAFLD treatment.

KNOWLEDGE, ATTITUDES, AND PRACTICES TOWARD MALARIA AND ANTIMALARIAL MASS DRUG ADMINISTRATION AMONG HEADS OF HOUSEHOLDS IN VILLAGES ON GRANDE COMORE ISLAND, THE COMOROS.

Knowledge, attitudes, and practices (KAP) surveys on malaria and antimalarial mass drug administration (MDA) have not received much attention in the Union of the Comoros. This study is a household-based cross-sectional survey using a multi-stage sampling technique aiming at investigating KAP toward malaria and antimalarial MDA with artemisinin-piperaquine among heads of households on Grande Comore Island, the largest island of the Comoros. A predefined structured questionnaire containing socio-demographic characteristics and questions about malaria and antimalarial MDA was administered to 1,368 randomly selected heads of households from 10 malaria-endemic villages on Grande Comore Island. The results showed that 81.4% of the heads of households knew that malaria is a transmissible disease, 77.6% recognized mosquitoes as the vectors of malaria, and 70.8% recognized fever as one of the frequent symptoms of malaria; 40.8% of respondents remembered the name of the antimalarial drug used for MDA, and 62.1% remembered the color of the antimalarial tablets; and 65.1% chose to go to a public health center to seek treatment as their first option within 24 hr of the onset of initial malaria symptoms. This study found that most heads of households had a reasonable level of knowledge about malaria and antimalarial MDA. However, only 7.3% obtained full points on all knowledge-related questions. Misconceptions about malaria cause, transmission, diagnostic method, and antimalarial MDA exist in the community of Grande Comore Island. As the Comoros continues to put great efforts to go toward malaria elimination, the community's KAP on malaria and antimalarial MDA is crucial to guarantee the community's long-term adherence to malaria elimination interventions and could become key to guaranteeing malarial elimination in the Comoros. Therefore, there is a great need to improve malaria prevention awareness through strengthening malaria education and promoting behavioral change. Heads of households should be the core target of malaria education and behavioral change for malaria elimination.

How we do it? Performing a protective superficial temporal artery-middle cerebral artery bypass with endoscopic transnasal cavernous sinus lesion operation.

BACKGROUND: To describe the concept of a protective superficial temporal artery-middle cerebral artery (STA-MCA) bypass performed prior to endoscopic transnasal cavernous sinus (CS) lesion resection in order to reduce the risk of perioperative cerebral ischemia due to internal carotid artery (ICA) vasospasm, occlusion, and even injury. METHOD: We illustrated the procedure of a 14-year-old female accepting a protective STA-MCA bypass with endoscopic transnasal CS lesion resection. CONCLUSION: A protective bypass may be a prophylactic strategy in selected endoscopic transnasal CS surgery cases, particularly where the diagnosis is uncertain, or the risk of ICA injury or occlusion is high.

KMO in the promotion of tumor development and progression in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers and an important medical problem with poor prognosis. The role of messenger RNA (mRNA) has been broadly researched in the progression of different human cancers. Microarray analysis has demonstrated that kynurenine 3-monooxygenase (KMO) expression is lower in HCC, but the mechanism of KMO in regulating the development of HCC remains unknown. Methods: Through comprehensive bioinformatics analysis of GSE101728 and GSE88839, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) network analysis, gene expression, and overall survival (OS) analysis, KMO was selected as the candidate molecular marker in HCC. The expression of KMO at the protein and RNA level was evaluated by Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, the cell proliferation, migration, invasion, and apoptosis, and the protein levels of epithelial-mesenchymal transition (EMT) markers were examined with Cell Counting Kit 8 (CCK-8) assays, Transwell assay, flow cytometry, and WB. Results: Through comprehensive bioinformatics analysis, we found that the low expression of KMO in HCC is not conducive to a good prognosis of HCC. Then, through in vitro cell experiments, we found that low expression of KMO promoted HCC proliferation, invasion, metastasis, EMT, and cell apoptosis. Additionally, hsa-miR-3613-5p was found to be highly expressed in HCC cells and could negatively regulate the expression of KMO. Moreover, hsa-miR-3613-5p was found to be the target microRNA (miRNA) of KMO according to qRT-PCR verification. Conclusions: KMO plays an important role in the early diagnosis, prognosis, occurrence, and development of liver cancer, and may target miR-3613-5p to function. This represents a novel insight into understanding the molecular mechanisms of HCC.

Ultrafast Doppler Imaging of Brain Arteriovenous Malformation.

Ultrafast ultrasound Doppler imaging offers a new and advantageous intraoperative method for brain lesions. Compared to the conventional color Doppler ultrasound system, the ultrafast Doppler allows us to image hemodynamics in small vasculature in an unprecedented high spatio-temporal resolution without using contrast agent. This report presents an intraoperative ultrafast ultrasound Doppler image of a 53-year-old male with a language eloquent area brain arteriovenous malformation. The advanced ultrafast Doppler method provides the nidus vasculature hemodynamics with a spatial resolution of 300 µm at thousands of framerates per second. The image also demonstrates that no abnormal vessels infiltrated the eloquent gyrus as the piamatral small vessels outlined the intact boundary. Successful removal of the nidus with full language function preservation highlights the potentials of ultrafast Doppler imaging to improve diagnostic capabilities and surgical outcomes for patients with intracranial lesions.

How I do it? Basilar bifurcation and left anterior choroidal artery aneurysms clipping.

BACKGROUND: Despite advancements in endovascular techniques, microsurgical treatment for posterior circulation aneurysms remains challenging. METHOD: This report highlights the successful clipping surgery of a 17-year-old female patient with an aneurysm located at the basilar artery (BA) bifurcation and left anterior choroidal artery (AChoA). To improve exposure, the posterior communicating artery was transected. A straight fenestrated clip was then placed to repair the BA bifurcation aneurysm, followed by a curved mini clip for the AChoA aneurysm. CONCLUSION: This report demonstrates the nuances of microsurgery in the treatment of select complex cases, which can benefit from microsurgery to achieve optimal treatment outcomes.