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Genitofemoral (GF) neuralgia refers to pain and sensory complaints in the region innervated by the GF nerve. It is a rarely reported condition, often due to iatrogenic causes following inguinal surgeries. In refractory forms, diagnostic reassessment is required to look for possible entrapment of the GF nerve. Here we describe a patient who underwent appendectomy and subsequently developed severe debilitating pain in the region of the right GF nerve. Our patient underwent a second laparoscopic surgery with clip removal, resulting in rapid recovery.

Sentinel lymph node biopsies are recommended for staging in node-positive breast cancer patients who become clinically node-negative after neoadjuvant therapy. Current guidelines support the omission of an axillary lymph node dissection if 3 negative sentinel nodes are retrieved during surgery. Consequently, the utility of routine clip placement in biopsied nodes prior to neoadjuvant chemotherapy and the necessity of targeted removal of these clipped nodes is in question. There are various methods for retrieving clipped nodes. We describe a case in which an intraoperative radiograph of a mastectomy specimen identified a clipped node that had not been localized with targeted axillary dissection in a patient with breast cancer. Pathology revealed persistent nodal positivity after neoadjuvant therapy, resulting in an escalation in care and a complete axillary dissection. We review the current literature on nodal clipping, and discuss the importance of localizing clipped nodes and the impact it can have on management.

Objective: Limited data on the treatment and outcomes of patients with intracranial aneurysms (ICAs) in the (coronavirus disease 2019) COVID-19 era is available. Our objective was hence to investigate the impact of the pandemic on the overall complication rate and postprocedural ischemic strokes specifically, in patients treated for ICAs. Methods: The National Inpatient sample database was used. The main outcomes were the occurrence of postprocedural ischemic strokes, as well as death, non-routine discharge, total charges (US dollars), and length of stay (days). Propensity score matching was applied to compare the pre- and COVID-19 periods. Trends were assessed using piecewise joinpoint regression with the Mann-Kendall test. Results: A total of 57,715 patients were included in the study. The mean age was 65 years, with most of the patients (69.9 %) being females. After matching, no differences in length of stay (p = 0.266), non-home discharge (p = 0.475), and in-hospital mortality rates (p = 0.305) between the two periods were found. However, the overall complication rate was significantly higher during the pandemic (31.1 % vs. 28.3 %; p

Introduction: Rupture of intracranial aneurysms is the most frequent cause of subarachnoid hemorrhage and is associated with high morbidity. Recommendations for preventive treatment of unruptured aneurysms (UIAs) remain controversial due to inconsistent data on their natural history and the risks associated with treatment. The awareness of being diagnosed with one or more UIAs can provoke feelings of anxiety and psychosocial distress. Therefore, the impact of management on a patients’ health perception and quality of life (QoL) is an essential factor to be considered in the treatment decision-making process. Objective: The aim of this study was to assess and compare QoL in patients diagnosed with one or more UIAs depending on their treatment as well as their pre- or postoperative status. Material and methods: Demographic and clinical data as well as results of the 15D quality of life (15D QoL) questionnaire of 189 patients were prospectively collected and retrospectively analyzed. Patients were categorized into different subgroups, depending on their treatment modalities (conservative, microsurgery or endovascular treatment) and their pre- or postoperative status at the time of completion of the questionnaire. Statistical analysis was performed to compare the different subgroups. Results: Conservatively treated patients had similar mean 15D QoL scores as preoperative patients. Despite an initial postoperative QoL reduction and a trend towards recovery and even an improvement of QoL in the long term after UIA occlusion, neither clinically relevant nor statistically significant differences between preoperative and postoperative mean 15D QoL scores were observed. Conclusions: Health-related QoL does not significantly change after treatment of UIAs when compared to the preoperative period. Further studies are needed to confirm long-term postoperative quality of life changes as well as treatment-related influencing factors on patients’ quality of life.

Introduction: Large and Giant intracranial aneurysms (LGIAs) have become the paradigm for which endovascular techniques do not provide satisfactory results. Yet, microsurgery is followed by non-negligible rates of morbimortality. This scenario may have changed since the introduction of flow-diversion devices. Research question: Contemporary and standardised revision on microsurgical and endovascular results, with emphasis on anterior circulation LGIAs. Materials and methods: A systematic literature search was conducted in two databases (PubMed and Embase) on treatment outcomes of LGIAs of the anterior circulation, after the introduction of flow-diverters 2008/01/01, till 2023/05/20. Small case series (15% of posterior circulation aneurysms, and studies not reporting clinical and/or angiographic outcomes were excluded. Results: 44 relevant studies (observational cohorts) were identified, including 2923 LGIAs predominantly from anterior circulation. Mean follow-up 22 (±20) months. 1494 (51%) LGIAs were treated endovascularly and 1427 (49%) microsurgically. According to the random effects model, pooled rates of favourable clinical outcomes were 85.8% (CI 95% 82.6–88.4), complete occlusion 69.4% (CI 95% 63.7–7.46), complications 19.6% (CI 95%16–23.9) and mortality 5.6% (CI 95% 4.4–7.1). Focusing on type of treatment, occlusion rates are higher with microsurgical (842/993, 85% vs 874/1,299, 67%), although good outcomes are slightly more frequent with endovascular (1045/1,135, 92% vs 1120/1,294, 87%). Discussion and conclusions: According to contemporary data about occlusion rates, functional outcomes, and complications, primary or secondary treatment of LGIAs of the anterior circulation seems justified. Microsurgical occlusion rates are higher in LGIAs. An expert consensus on reporting complications and management strategies is warranted.

Zero-shot remote sensing scene classification aims to solve the scene classification problem on unseen categories and has attracted numerous research attention in the remote sensing field. Existing methods mostly use shallow networks for visual and semantic feature learning, and the semantic encoder networks are usually fixed during the zero-shot learning process, thus failing to capture powerful feature representations for classification. In this work, we introduced a vision-language model for remote sensing scene classification based on contrastive vision-language supervision. Our method is capable of learning semantic-aware visual representations using a contrastive vision-language loss in the embedding space. By pretraining on large-scale image–text datasets, our baseline method shows good transferring ability on remote sensing scenes. To enable model training in zero-shot settings, we introduced a pseudo-labeling technique that can automatically generate pseudo labels from unlabeled data. A curriculum learning strategy is developed to boost the performance of zero-shot remote sensing scene classification with multiple stages of model finetuning. We conducted experiments on four benchmark datasets and showed considerable performance improvement on both zero-shot and few-shot remote sensing scene classification. The proposed RS-CLIP method achieved a zero-shot classification accuracy of 95.94%, 95.97%, 85.76%, and 87.52% on the novel classes of UCM-21, WHU-RS19, NWPU-RESISC45, and AID-30 datasets respectively. Our code will be released at https://github.com/lx709/RS-CLIP.

The prevalence of cardiovascular disease, tumors, and other chronic illnesses has been steadily rising in recent years. Researchers have recently been employing cross-modal large-scale models and natural language generation models to address the significant visual and textual disparities in medical report generation tasks. However, these training processes presents challenges, such as difficulties matching cross-modal information and generating specialized medical terminology. To tackle these issues, we propose a Multifocal Region-Assisted Report Generation Network (MRARGN) to enhance cross-modal information matching. Specifically, we integrate a pre-trained ResNet-50 with multi-channel and attention mechanisms for trainable X-ray image representation. We then combine our proposed memory response matrix with OpenAI's contrastive pre-training results to construct a dynamic knowledge graph that stores lesion features and their corresponding texts. Finally, we incorporate attention mechanisms and forget gate units to generate comprehensive textual descriptions for different lesions, using an image and report alignment loss. We conduct ablation experiments on the IU-Xray and MIMIC-CXR datasets to evaluate our approach. The experimental results demonstrate that our proposed MRARGN outperforms most state-of-the-art approaches, including their own variants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The evolution of sophisticated technology has brought about the rise of endoscopic strategies for managing iatrogenic esophageal perforation. This approach is reserved for stable patients with limited contamination. The most commonly performed procedures are reviewed, focusing on procedural steps and outcomes. Esophageal stenting remains the most widely implemented strategy with promising success rates. Clipping, endoluminal vacuum therapy, and suturing are also viable options. Patient selection and further study are paramount to establishing this less invasive strategy as a more standard approach., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recently, the US Food and Drug Administration (FDA) approved the first small interfering RNA (siRNA) drug, marking a significant milestone in the therapeutic use of RNA interference (RNAi) technology. However, off-target gene silencing by siRNA remains one of the major obstacles in siRNA therapy. Although siRNA off-target effects caused by a mechanism known for microRNA (miRNA)-mediated gene repression have been extensively discussed, whether RNAi can cause unintended cleavage through the effector protein AGO2 at sites harboring partially complementary sequences to the siRNA remains unknown. Here, we report a strategy to establish a comprehensive picture of siRNA cleaved and noncleaved off-targets by performing SpyCLIP using wild-type and catalytically inactive AGO2 mutants in parallel. Additionally, we investigated naturally occurring cleavage events mediated by endogenous miRNAs using the same strategy. Our results demonstrated that AGO2 SpyCLIP is a powerful method to identify both the cleaved and noncleaved targets of siRNAs, providing valuable information for improving siRNA design rules.

This article provides an overview of the techniques for closure of the mucosal entry point following advanced procedures in the third space. The outbreak of natural orifice transluminal endoscopic surgery (NOTES) has significantly impacted the treatment of various benign and malignant conditions. Reliable and secure closure of the mucosal entrance is essential for avoiding serious adverse events. Although small defects are typically closed using through-the-scope clips (TTSCs) or over-the-scope clips (OTSCs), challenges may occur with larger or transmural defects. Alternative methods, such as specialised stitches and full-thickness suturing systems, have been developed to address these challenges with promising results. Each method has its own pros and cons, and the choice of closure technique depends on various factors such as anatomical location, endoscopist expertise, costs, and clinical context. By understanding the technical specifications of each closure device, endoscopists can make decisions that enhance patient outcomes and minimise the risk of complications associated with the approximation of defect edges. Continued research is essential to optimise the evolution of newer closure devices and techniques for advancing NOTES., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pial arteriovenous fistula (pAVF) is a rare intracranial vascular lesion. In pAVF, there is direct connection between one or more arterial supply and venous drainage without intervening nidus. We present a case of pAVF with multiple fistulous points and vein of Galen dilation which underwent microsurgical complete clip in one stage.

Introduction: To safely perform the clipping procedure, surgeons must familiarize themselves with correct handling of the instruments. If the clip is not properly loaded or fully inserted in the jaws of the applier, the clipping procedure may cause aneurysmal laceration. Case illustration: A 49-year-old man presented with severe headache and was admitted to another hospital. The patient underwent clipping surgery at that hospital by the author (H.K.), because patient transfer to our hospital carried the risk of aneurysm rupture caused by unstable blood pressure. The condition of the clip and applier was not confirmed by the surgeon before using it. When the surgeon brought the clip close to the aneurysm and opened the clip blade, the clip suddenly and forcefully popped out from the applier immediately and hit the aneurysm dome, resulting in rupture of the aneurysm. Conclusion: This accidental phenomenon is rare but dangerous. Vascular neurosurgeons must always be aware of the importance of the clip being accurately seated in the applier.

The nuclear cap-binding complex (CBC) stimulates processing reactions of capped RNAs, including their splicing, 3′-end formation, degradation, and transport. CBC effects are particular for individual RNA families, but how such selectivity is achieved remains elusive. Here, we analyze three main CBC partners known to impact different RNA species. ARS2 stimulates 3′-end formation/transcription termination of several transcript types, ZC3H18 stimulates degradation of a diverse set of RNAs, and PHAX functions in pre-small nuclear RNA/small nucleolar RNA (pre-snRNA/snoRNA) transport. Surprisingly, these proteins all bind capped RNAs without strong preferences for given transcripts, and their steady-state binding correlates poorly with their function. Despite this, PHAX and ZC3H18 compete for CBC binding and we demonstrate that this competitive binding is functionally relevant. We further show that CBC-containing complexes are short lived in vivo, and we therefore suggest that RNA fate involves the transient formation of mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis.

Objective: Flow diverters are a promising new tool in the neurosurgeon's arsenal for aneurysm management. We sought to quantify the trends of flow diversion in comparison to traditional endovascular coiling and surgical clip ligation techniques in the United States from 2010 to 2020 with an emphasis on aneurysm location and preferences in usage for ruptured versus unruptured aneurysms., Methods: In this large cross-sectional study, patients aged 18 and older within the MARINER database were analyzed. Descriptive characteristics were calculated for all included patients. χ 2 tests were used to compare categorical variables. P values < 0.05 were statistically significant., Results: A total of 45,542 procedures were conducted in the United States from 2010 to 2020 (clipping: 14,491; coiling: 28,840; flow diversion: 2211). The Southern United States had the largest operative volume across all 3 intervention types, closely followed by the Midwest. Aneurysms of the middle cerebral artery were mostly clipped, whereas coiling and flow diversion techniques were most utilized for anterior communicating and posterior communicating artery aneurysms. Flow diversion is growing most rapidly in the treatment of unruptured aneurysms, though there were also significant increases in usage for ruptured aneurysm treatment from 2019 to 2020., Conclusions: Flow diverters have gained significant traction in the treatment for both unruptured and ruptured aneurysms. In the coming years, the indications and use of flow diversion will undoubtedly grow further, but excitement over their application should be tempered by the safety and efficacy data that continues to emerge., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objective: Although randomized controlled trials have compared surgery versus endovascular treatment for intracranial aneurysms, the literature is sparse in terms of subgroup analysis for anterior communicating artery (ACoA) aneurysm management. This systematic review and meta-analysis sought to compare surgical versus endovascular treatment for ACoA aneurysms., Methods: Medline, PubMed, and Embase were searched from inception to December 12, 2022. Primary outcomes were post-treatment modified Rankin Scale (mRS) >2 and mortality. Secondary outcomes were aneurysm obliteration, retreatment and recurrence, rebleeding, technical failure, vessel rupture, aneurysmal subarachnoid hemorrhage-related hydrocephalus, symptomatic vasospasm, and stroke., Results: Eighteen studies yielded 2368 patients, from which 1196 (50.5%) and 1172 (49.4%) patients underwent surgery and endovascular treatment, respectively. The odds ratio (OR) of mortality was similar in total (OR = 0.92 [0.63-1.37], P = 0.69), ruptured (OR = 0.92 [0.62-1.36], P = 0.66), and unruptured cohorts (OR = 1.58 [0.06-39.60], P = 0.78). The OR of mRS > 2 was similar in total (OR = 0.75 [0.50-1.13], P = 0.17), ruptured (OR = 0.77 [0.49-1.20], P = 0.25), and unruptured cohorts (OR = 0.64 [0.21-1.96], P = 0.44). The OR of obliteration was higher with surgery in the total (OR = 2.52 [1.49-4.27], P = 0.0008) and ruptured cohorts (OR = 2.61 [1.33-5.10], P = 0.005) and unruptured group (OR = 3.46 [1.30-9.20], P = 0.01). The OR of retreatment was lower with surgery in the total (OR = 0.37 [0.17-0.76], P = 0.007) and ruptured cohorts (OR = 0.31 [0.11-0.89], P = 0.03), thought it was similar in the unruptured group (OR = 0.51 [0.08-3.03], P = 0.46). The OR of recurrence was lower with surgery in the total (OR = 0.22 [0.10, 0.47], P = 0.0001), ruptured (OR = 0.16 [0.03, 0.90], P = 0.04), and mixed (un) ruptured cohorts (OR = 0.22 [0.09-0.53], P = 0.0009). The OR of rebleeding in ruptured group was similar (OR = 0.66 [0.29-1.52], P = 0.33). The ORs of other outcomes were similar., Conclusions: ACoA aneurysms may be safely treated with either surgery or endovascular treatment, although microsurgical clipping demonstrates higher obliteration rates and lower rates of retreatment and recurrence., (Published by Elsevier Inc.)

A chemiluminescent immunoassay is commonly employed to measure adrenocorticotrophic hormone (ACTH) concentrations to assist pituitary pars intermedia dysfunction diagnosis. In a previous study, seasonally-dependent assay cross-reactivity to endogenous equine corticotropin-like intermediate lobe peptide (CLIP, ACTH 18-39) was suspected. The present study aimed to demonstrate binding of endogenous equine CLIP to the capture antibody of the ACTH chemiluminescent immunoassay. Liquid chromatography - mass spectrometry (LCMS) methods were optimised to identify selected ions from synthetic human ACTH, α-melanocyte stimulating hormone (α-MSH, ACTH 1-17) and CLIP. Synthetic ACTH and CLIP bound to the capture antibody of the chemiluminescent ACTH assay, but α-MSH did not. Equine endogenous CLIP was detected by LCMS in pony plasma taken in the autumn and could be eluted from the capture antibody of the ACTH chemiluminescent immunoassay. Further research is required to enable quantification of CLIP. Equine CLIP may alter measured ACTH concentrations in vivo., (Copyright © 2023. Published by Elsevier Inc.)

Background: Intracranial aneurysms (IAs) are dilatations of the cerebral arteries, whose treatment is commonly based on the implant of a metallic clip on the aneurysm neck. Despite the dissection and understanding of the surgical anatomy of the IA when often only parts of it are visible, the choice of the ideal clip to be used is one of the surgical difficulties. Although current imaging tests guarantee IA visualization, currently there is no planning method that allows for a real three-dimensional (3D) visualization for optimal choice of clip prior to surgery. The aim of this study is to evaluate whether IA biomodels generated by additive manufacturing methods are useful for surgical clip selection in microsurgeries for IA., Methods: Three-dimensional (3D) IA biomodels of 10 patients with IA were evaluated using computerized tomography, surgical microscope, and 3D printer. The research was divided into 4 phases as follows: development of the 3D biomodels, evaluation of the biomodel dimensional characteristics, surgical planning evaluation with the biomodel and its clipping effectiveness, and evaluation of the actual surgical simulation process within the models., Results: Ten 3D biomodels were obtained, made of a malleable and hollow part, formed by the IA and related arteries, and another rigid part, mimicking the skull and other arteries of the skull base. Based on these 3D models, 10 clips were chosen during the surgical planning, and all exactly matched the clip characteristics used during the actual surgeries. The surgical simulation with the biomodels performed by 2 neurosurgeons still in training obtained 100% accuracy in the identification of the clips that were eventually used during the actual surgeries., Conclusions: 3D biomodels generated by additive manufacturing methods were effective for surgical clip selection in microsurgeries for IA, reducing surgical time, increasing cerebral angioarchitecture understanding, and providing more safety in this type of surgery., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Lee is a speaker and consultant for Abbott Structural and Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objective: The diagnosis of unruptured intracranial aneurysms (UIAs) is being made more frequently in elderly patients. The goal of this study is to evaluate complications and clinical outcome in patients ≥ 60 years-old who underwent clipping of UIAs., Methods: We performed a retrospective cohort study. Clinical outcome (modified Rankin scale score) was determined at the latest clinical follow-up. Complications and outcomes were compared between age groups (60-69, 70-80) and subgroups (60-64, 65-69, 70-74, and >75)., Results: The study population consisted of 255 patients (range 60-80 years-old) who underwent 262 clipping procedures for UIAs. Mean follow-up duration was 15.6 months (± 27.5). Major complications occurred in 20 patients (7.6%) and mortality in 3 patients (1.1%). Medical complications occurred in 26 patients (10%). Mean length of hospital-stay was 4.7 days (± 5.8). 89.6% were discharged to home. 87.8% had a favorable clinical outcome. The 70-80 age group had significantly more complications (P = 0.03) than the 60-69 group and a significantly longer hospital stay (6.02 vs. 4.3 days, P = 0.04). The older group was less likely to discharge to home and more likely to require rehabilitation (P = 0.002). Favorable clinical outcome did not significantly differ between the two groups (85.7% vs. 88.4%, P = 0.56). There was a trend for increasing complications from the younger to older subgroups (P = 0.008) and a reduction in the likelihood to discharge to home (P < 0.0001). The rate of ultimate favorable clinical outcome did not differ significantly between subgroups (P = 0.79)., Conclusion: Although complications, length of hospital-stay, and discharge to non-home destinations increase with older age, the majority of patients ≥ 60 may have favorable clinical outcomes., (Copyright © 2021. Published by Elsevier B.V.)

Localization of metastatic axillary lymph nodes in breast cancer patients is an increasingly common procedure performed by radiologists. In 2014, the National Comprehensive Cancer Network guidelines stated that "clinically positive axillary lymph node (s) should be sampled by FNA or core biopsy and clipped with image-detectable marker; clipped lymph nodes must be removed if FNA or core biopsy was positive prior to neoadjuvant therapy". Since then, multiple studies have further supported targeted axillary surgery after neoadjuvant chemotherapy (NAC), with excision of the clipped metastatic axillary node in addition to the sentinel node (s). Requests for image guided localization of clipped axillary nodes will continue to increase and likely become the standard of care. However, when lymph nodes have decreased in size after NAC, or when small deep lymph nodes are sampled, the clipped node can be difficult to identify under ultrasound at the time of localization. When the target node is questionable, we have found it valuable to place an intermediary clip, and use an axillary mammographic view to confirm this intermediary clip co-localizes with the intended target. With this confirmation, safe, accurate localization can then be performed. We describe 3 cases of intermediary clip placement facilitating successful localization of previously clipped axillary lymph nodes., (Copyright © 2020. Published by Elsevier Inc.)

Ideal management of unruptured intracranial aneurysms (UIAs) and ruptured intracranial aneurysms (RIAs) is a controversial issue. Over the last few decades, a significant paradigm shift has occurred away from open microsurgical clipping toward endovascular coil embolization. Multiple studies have been performed with mixed results. Some studies suggest that endovascular treatment produces better clinical and functional outcomes, but is associated with increased need for retreatment. Other studies report increased durability in aneurysms treated with microsurgical clipping, but that clipping may be associated with worse functional outcomes in some cases. Further complicating the dialogue are variable costs associated with different treatment modalities, including country-dependent cost differences. Here we provide a review of some of the major studies comparing open surgery versus endovascular treatment for both RIAs and UIAs to distill their key findings and corresponding implications for clinical practice. We relate these research results to our institution's experience with RIAs and UIAs and describe our approach to treatment of these conditions. Finally, we discuss implications of the paradigm shift for both open and endovascular surgery, including educational initiatives directed toward preserving important microsurgical tenets in the setting of diminishing surgical volume., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Since the introduction of endovascular treatment for cerebral aneurysms, hospitals in which subarachnoid hemorrhage is treated show different availability and/or preferences towards both treatment modalities. The main aim is to evaluate the clinical and angiographic results according to the hospital's treatment preferences applied., Methods: This study was conducted based on use of the subarachnoid hemorrhage database of the Vascular Pathology Group of the Spanish Neurosurgery Society. Centers were classified into 3 subtypes according to an index in the relationship between endovascular and surgical treatment as: endovascular preference, high endovascular preference, and elevated surgical preference. The clinical results and angiographic results were evaluated among the 3 treatment strategies., Results: From November 2004 to December 2017, 4282 subarachnoid hemorrhage patients were selected for the study: 630 (14.7%) patients from centers with surgical preference, 2766 (64.6%) from centers with endovascular preference, and 886 (20.7%) from centers with high endovascular preference. The surgical preference group obtained the best angiographic results associated with a greater complete exclusion (odds ratio: 1.359; 95% confidence interval: 1.025-1.801; P = 0.033). The surgical preference subgroup obtained the best outcome at discharge (65.45%), followed by the high endovascular preference group (61.5%) and the endovascular preference group (57.8%) (odds ratio: 1.359; 95% confidence interval: 1.025-1.801; P = 0.033)., Conclusions: In Spain, there is significant variability in aneurysm exclusion treatment in aneurysmal subarachnoid hemorrhage. Surgical centers offer better results for both surgical and endovascular patients. A multidisciplinary approach and the maintenance of an elevated quality of surgical competence could be responsible for these results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

RNA-protein interactions play a critical role in post-transcriptional gene regulation. Characterizing these interactions in their native context has been challenging; however, advances in RNA sequencing and mass spectrometrybased proteomics combined with innovative chemical biological tools have heralded the development of robust strategies for performing biochemistry on a cellular scale. Herein, we review recent advances in the development and application of proteomic and transcriptomic approaches to profile cellular RNA-protein interactions, focusing on sequencing-based strategies and proteomic analysis of RNA-binding proteins, as well as approaches to address the role of RNA modifications in protein-RNA binding events., Competing Interests: Conflict of interest statement None declared., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aging is characterized by significant immune remodeling at both cellular and molecular levels, also known as immunosenescence. Older adults often manifest a chronic low-grade inflammatory phenotype. These age-related immune system changes have increasingly been recognized not only to lead to immune functional decline and increased vulnerability to infections, but also to play an important role in many chronic conditions such as frailty in older adults. In addition to sex as an important biological factor, chronic viral infections including that by human immunodeficiency virus (HIV) and cytomegalovirus (CMV) are all known to have major impact on the aging immune system. This article provides an overview of our current understanding of aging immunity, sex, inflammation, frailty, and HIV and CMV infections., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aneurysm clips are indispensable tools in the armamentarium of vascular neurosurgeons. The history of the development of aneurysm clips is witness to ingenuity and tenacity in treating a potentially devastating disease. Few know the stories of their innovators and the inspiration behind their designs. Hence, we present this historical vignette in an attempt to shed more light on the pioneers who shaped the evolution of aneurysm clips as we know them. A comprehensive literature search was performed using PubMed, Google Scholar, Google Books, and library historical archives, as well as personal communications with relatives, colleagues, and institutions of the surgeon-designers. We present the following aneurysm clip innovators and chronicle their biographies and contributions: Herbert Olivecrona (1891-1980), Frank Mayfield (1908-1991), Charles Drake (1920-1998), Joseph McFadden (1920-present), Thoralf Sundt Jr. (1930-1992), William M. Lougheed (1923-2004), William B. Scoville (1906-1984), Milton D. Heifetz (1921-2015), Gazi Yaşargil (1925-present), Kenichiro Sugita (1932-1994), and Robert Spetzler (1944-present). Although this compilation of eponymous clips is by no means complete, we hope that it provides an informative historical perspective and an inspiration for aspiring neurosurgeons. The history of aneurysm surgery, an entity once deemed inoperable, teaches us the importance of innovation in medicine., (Copyright © 2019. Published by Elsevier Inc.)

Background: Complications after coiling of large, giant, and thrombosed aneurysms because of increased mass effect on surrounding structures have been widely reported. A case of bilateral blindness after incomplete coil embolization of a small anterior cerebral artery aneurysm is rare. We review the potential mechanisms, clinical progression, and proper treatment needs., Case Description: A 50-year-old man was urgently admitted with subarachnoid hemorrhage. Digital subtraction angiography (DSA) showed a ruptured aneurysm of the A1 segment, anterior cerebral artery. An endovascular coil occlusion was performed without an additional device. The visual acuity of patient slowly decreased from the 13th day after endovascular intervention. His visual acuity improved after steroid therapy but then deteriorated again. DSA showed an enlarged aneurysm, and an urgent craniotomy was performed for optic nerve decompression. The patient finally became bilaterally blind, although hyperbaric oxygen, neurotrophy drugs, and other supporting treatment was given., Conclusions: Incomplete aneurysm coiling may result in bilateral blindness, even at a small anterior cerebral artery. Early DSA, steroid therapy, and secondary craniotomy for nerve decompression should be considered promptly for improving clinical outcome before nerve atrophy, although sometimes single steroid therapy is effective., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: We aimed to summarize our microsurgical treatment results for large (10-25 mm) and giant (≥25 mm) intradural internal carotid artery (ICA) aneurysms over a 7-year period at a single institution and to describe our detailed strategy., Patients and Methods: We reviewed the records of 68 patients with 69 aneurysms, including large and giant intradural ICA aneurysms, treated using microsurgical techniques from January 2008 to December 2014. We used adenosine-induced cardiac standstill or retrograde suction decompression for some aneurysm clipping cases and performed bypass surgery if needed., Results: Fifty-eight large and giant ICA aneurysms (84%) were treated with direct clipping, including 6 aneurysms (9%) clipped using adenosine-induced cardiac standstill and 10 aneurysms (14%) clipped using suction decompression. Eleven unclippable aneurysms (16%) were trapped with extracranial-intracranial bypass. Good or excellent results (modified Rankin Scale scores 0-2) were obtained in 47 patients with unruptured aneurysms (92%) and in 14 patients with ruptured aneurysms (82%) at the 6-month follow-up. Of 17 patients with visual disturbances before treatment, 11 (65%) had improved vision after surgical treatment. A remnant sac was found in 20 cases (29%) on digital subtraction angiography performed immediately postoperatively. At the median follow-up of 22 months, we encountered 3 recurrent aneurysm cases (5%) among the 58 aneurysms that were followed up., Conclusion: Our study demonstrated that microsurgical treatment of large and giant intradural ICA aneurysms remains competitive to flow-diverting treatment, if the surgeon is prepared to perform multifarious surgical methods, including adenosine administration, retrograde suction decompression, and bypass vascular anastomosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Treatment of arteriovenous malformations (AVMs) is currently performed at specialized neurosurgical centers well equipped with microscopes with green filters, neurosurgical catheterization laboratories, and experienced neurosurgical teams. Patients in whom AVMs are diagnosed at smaller hospitals should be referred to such specialized centers. This case report describes the unavoidable worst-case scenario of an emergency unplanned surgical excision of an undiagnosed ruptured AVM with large hematoma., Case Description: A 26-year-old man was brought to the emergency department with episodes of seizures and sudden loss of consciousness. His Glasgow Coma Scale score was 5. He had anisocoria. Computed tomography of the head showed right occipital hematoma with mass effect and herniation. Suspected diagnosis was spontaneous tumor or hypertensive bleed. Emergency surgery was performed. Intraoperatively, ruptured AVM was found. After explaining to family members about nonavailability of conventional instruments (i.e., microscope, clips, indocyanine green), we planned for excision of AVM with available resources., Conclusions: Postoperatively the patient recovered satisfactorily with right-side vision loss. He underwent cranioplasty after 6 weeks. In such a worst-case scenario, remaining calm, following basic surgical steps, using blood transfusion, and employing lateral thinking regarding using available resources can result in satisfactory management of the patient., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The use of microsurgery for aneurysm clipping has decreased considerably in recent years. This study was conducted to demonstrate the safety and effectiveness of surgical treatment of intracranial aneurysms even in less-developed countries., Methods: This study was a retrospective review of the medical records of 320 patients with 416 aneurysms treated with microsurgical clipping at a single neurosurgical center in Brazil between 2008 and 2016. We evaluated postoperative outcomes using the modified Rankin Scale (mRS) at the time of hospital discharge, treatment efficacy by digital subtraction angiography (DSA) performed postoperatively, and mortality., Results: The 320 patients with aneurysms included 228 patients with ruptured aneurysms and 92 with unruptured aneurysms. Overall, 81 (26.3%) had a poor outcome (mRS score >2), and the other 227 (73.4%) had a good outcome. The presence of a ruptured aneurysm was a statistically significant factor for poor outcome (P < 0.001) and mortality (P < 0.015). Giant and large aneurysms were also associated with poor outcome (P = 0.004). When analyzed separately, unruptured aneurysms with poor outcome were only associated with aneurysm size. Among the patients with ruptured aneurysms, those with Hunt and Hess (HH) grade >2 on hospital admission had unfavorable outcomes (P < 0.0001). Among the patients who underwent postoperative DSA, 207 (89.8%) had complete aneurysm occlusion and 24 (10.2%) had residual aneurysms, with reoperation required in 8 cases., Conclusions: Microsurgical treatment of intracranial aneurysms is an effective and safe method., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Breast cancer patients who present with nodal metastasis receive neoadjuvant chemotherapy (NAC) with increasing frequency and can have complete pathologic response after treatment. In this clinical scenario, sentinel node mapping and biopsy are gaining acceptance instead of axillary dissection to avoid morbidity. Biopsy proven positive lymph nodes must be reliably excised and examined after NAC to further decrease the false negativity rate of sentinel lymph node (SLN) surgery. The standard method for axillary staging in breast cancer patients even after NAC is SLN biopsy (SLNB) with a radioisotope, blue dye, or both (dual technique). Currently, preoperative axillary staging with ultrasound and biopsy, along with placement of an image-detectable marker to be removed at the time of definitive surgery is recommended. In this study, we evaluated some methods of SLNB for patients treated with NAC like indocyanine green fluorescence, superparamagnetic iron oxide nanoparticles, indigocarmine blue dye, contrast-enhanced ultrasound using microbubbles, and tattooing. Some methods are also needed to ensure that the initially biopsy proven positive node is removed at the time of surgery to be carefully evaluated for residual disease after chemotherapy like clip placement to the suspected or involved nodes before NAC, and removing the clipped node with the guidance of 125I-labeled radioactive seed or guide wires., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Previously we introduced two novel NMR experiments for small molecules, the so-called ASAP-HSQC and ALSOFAST-HSQC (Schulze-Sünninghausen et al., 2014), which allow the detection of heteronuclear one-bond correlations in less than 30s at natural abundance. We propose an improved symmetrized pulse scheme of the basic experiment to minimize artifact intensities and the combination with non-uniform sampling to enable the acquisition of conventional HSQC spectra in as short as a couple of seconds and extremely 13 C-resolved spectra in less than ten minutes. Based on steady state investigations, a first estimate to relative achievable signal intensities with respect to conventional, ASAP-, and ALSOFAST-HSQC experiments is given. In addition, we describe several extensions to the basic pulse schemes, like a multiplicity-edited version, a revised symmetrized CLIP-ASAP-HSQC, an ASAP-/ALSOFAST-HSQC sequence with broadband BIRD-based 1 H, 1 H decoupling, and a symmetrized sequence optimized for water suppression. Finally, RF-power considerations with respect to the high duty cycle of the experiments are given., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: This study aimed to assess the clinical and radiologic outcomes after neurosurgical treatment of large and giant aneurysms of the middle cerebral artery (MCA). In addition, we aimed to identify risk factors for unfavorable outcomes., Methods: This retrospective study included 105 patients with 106 large or giant MCA aneurysms treated with neurosurgical methods, including microsurgery and endovascular treatment, over a 15-year period., Results: The mean aneurysm size was 15.3 ± 7.1 mm. Ten (9.4%) were giant aneurysms. The MCA bifurcation was the most common aneurysm site, followed by the MCA trunk and distal MCA. Aneurysm clipping was the most common treatment method, followed by clipping or trapping with bypass surgery and endovascular treatment. However, acute cerebral infarction was the most common complication (16.0%), poor outcomes (modified Rankin Scale score, 3-6) developed in 12.3% of aneurysms after treatment, and 6.6% of treated aneurysms needed retreatment. Multivariate analysis showed that independent risk factors for acute cerebral infarction after treatment were aneurysms located on the MCA trunk and 2 or more underlying diseases. Initial presentation with subarachnoid hemorrhage and complications during treatment were independent risk factors for poor outcomes. In addition, endosaccular coiling was an independent risk factor for retreatment., Conclusions: Neurosurgical management should be considered a priority for large and giant MCA aneurysms because of the high rupture rate and clinical symptoms. However, treatment outcomes remain unsatisfactory. Therefore, tailored management with consideration of risk factors for unfavorable outcomes should be implemented., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: In an era of continued advancements in endovascular treatment of cerebral aneurysms, novel developments concerning microsurgical clipping are sparse. The Lazic aneurysm clip system represents such an advancement. The applier has a malleable shaft and is designed to minimally obstruct the view of the surgical field. The purpose of this study was to illustrate the transition to this new aneurysm clip system in an established cerebrovascular practice., Methods: We retrospectively reviewed all aneurysms treated with microsurgical clipping using the Lazic aneurysm clip system in 1 cerebrovascular practice in the United States from January 2009 to June 2016., Results: Between 2009 and 2016, a total of 973 aneurysms underwent surgical clipping. The Lazic clip system was used in 191 (19.6%) aneurysms (maximum diameter, 5.6 ± 3.8 mm) in 181 patients. The middle cerebral artery was the most frequent location (25.7%) followed by posterior communicating artery (20.9%). There was a continuous increase in the percentage of aneurysms treated with the Lazic clip system from 6% in 2009 to 98% in 2016. The proportion of posterior circulation aneurysms treated with Lazic clips decreased, whereas the middle cerebral artery location increased. There were a total of 11 complications (5.8%), but no instances of clip malfunction., Conclusions: In the largest series to date, the Lazic clip system proved to be safe and efficacious and presents an interesting alternative to established aneurysm clip systems. This study illustrates the transition of an established cerebrovascular practice to the Lazic clip system., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Few studies have addressed the effect of treatment of unruptured intracranial aneurysm (UIA) on cognitive function., Objective: Neuropsychological assessment after UIA treatment is underreported, and prospective trials have repeatedly been demanded. In 2014, we conducted a prospective controlled study to evaluate the differences in cognitive processing caused by the treatment of anterior circulation UIAs., Patients and Methods: Thirty patients were enrolled until September 2015. Ten patients received endovascular aneurysm occlusion (EV), 10 patients were treated microsurgically (MS), and 10 patients with surgically treated degenerative lumbar spine disease (LD) served as control. All patients underwent extended standardized neuropsychological assessment before (t 1 ) and 6 weeks after treatment (t 2 ). Tests included verbal, visual, and visuospatial memory, psychomotor functioning, executive functioning, and its subdomains verbal fluency and cognitive flexibility. We statistically evaluated intragroup and intergroup changes., Results: Intragroup comparisons and group-rate analysis showed no significant impairment in overall neuropsychological performance, either postinterventionally or postoperatively. However, the postoperative performance in cognitive processing speed, cognitive flexibility, and executive functioning was significantly worse in the MS group than in the EV (P = 0.038) and LD group (P = 0.02). Compared with the EV group, patients with MS showed significant postoperative impairment in a subtest for auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. EV P = 0.011). The MS group trended toward posttreatment impairment in subtests for verbal fluency and semantic memory (Regensburg Word Fluency Test; MS vs. EV P = 0.083) and in auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. LD P = 0.06)., Conclusions: Our preliminary data showed no effect of anterior circulation UIA treatment on overall neuropsychological function but impaired short-term executive processing in surgically treated patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Unruptured paraophthalmic aneurysms present unique challenges, and the ideal management remains unknown., Methods: We performed a pooled analysis of single-center experiences to compare the risks and effectiveness involving patients with unruptured paraophthalmic aneurysms treated with clipping, coiling alone, stent-assisted coiling, and flow-diversion. The MEDLINE database was searched and thirty-three series (including our institutional experience) were included., Results: Clipping caused more intracranial hemorrhage (ICH) and neurologic complications (NCs) than coiling alone (ICH: odds ratio [OR] = 3.058, P = 0.013; NC: OR = 5.809, P < 0.001), stent-assisted coiling (ICH: P = 0.018; NC: OR = 7.367, P < 0.001), and flow-diversion (ICH: P = 0.006; NC: OR = 16.954, P < 0.001). Clipping also caused more unfavorable visual outcomes than both coiling alone (OR = 3.037, P = 0.001) and stent-assisted coiling (OR = 6.055, P = 0.005). Clipping resulted in a lower reoperation rate than coiling alone in large/giant aneurysm group, which approached statistical significance (OR = 0.133, P = 0.057). Clipping, stent-assisted coiling, and flow-diversion all showed higher occlusion rates compared with coiling alone (OR [clipping vs. coiling alone] = 2.852, P ≤ 0.001; OR [coiling alone vs. stent-assisted coiling] = 0.302, P = 0.003; OR [coiling alone vs. flow-diversion] = 0.400, P = 0.013). Flow-diversion showed comparative complication rate, clinical outcomes, and angiographic result compared with stent-assisted coiling. No significant differences were found among all 4 treatment modalities on mortality and poor outcome., Conclusions: Endovascular therapies have benefits over surgical clipping in terms of fewer intracranial hemorrhage complications, fewer NCs, and lower unfavorable visual outcome rate. Flow diversion showed comparative safety and effectiveness to stent-assisted coiling, and they both achieved better radiologic results than coiling alone. Further validation by randomized cohort studies is still needed to provide robust evidence., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Middle cerebral artery (MCA) aneurysms represent 20% of intracranial aneurysms. Most (80%) of them are located on the sylvian bifurcation, the seat of hemodynamic turbulence flow. Morbidity and mortality related to surgery of MCA aneurysms are not negligible. MCA vascularization areas are important eloquence functional territorial of Brain tissue. Indocyanine green videoangiography assistance (ICG-VA) is an emergent tool for intraoperative assessment of aneurysmal occlusion and for checking a possible stenosant clip in vascular area. The purposes of this study were to evaluate the safety of clipping procedure in terms of morbidity, mortality, and efficiency of aneurysm occlusion without using ICG-VA, recurrence and bleeding/rebleeding at short and long terms, and angiographic and clinical follow-ups., Material and Methods: This study is a monocentric retrospective study performed at Pitié-Salpêtrière-Charles Foix Hospital Center, reporting clinical and angiographic follow-up of consecutive patients treated for MCA aneurysms (ruptured and unruptured) by clipping procedures. From 2002-2012, 251 consecutive patients were admitted at the author's institution for treatment of 263 MCA aneurysms (163 ruptured and 100 unruptured). Procedure-related death and complications were systematically assessed without video-angiography availability. The degree of aneurysms exclusion was evaluated according to the Raymond-Roy scale after the procedure and at long-term angiographic follow-up (mean delay = 36 months)., Results: The death rate related to aneurysmal exclusion procedure was 1.2%. The major complication rate related to surgery was 5.3%. Postprocedure, an aneurysm occlusion rate Raymond-Roy grade A or B was 95.6%. Neither recanalization controlled clipped aneurysms nor re-aneurysmal rupture was observed in the long-term clinical follow-up (mean time = 83.5 months). The institution's series of surgical outcomes reported 95.6% of complete exclusion and 4.5% incomplete procedures without ICG-VA. A clip of repositioning rate was estimated at 15% when ICG-VA was used., Conclusion: Surgical management is relatively safe for patients, with an acceptable complication rate in the era when ICG-VA was not yet available. Indeed, the main source of procedural ischemia microsurgery is stenosant clip. To limit the occurrence of malposition, the author's center began using ICG-VA a few months ago and expects to reduce its rate of incomplete occlusion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: One of the most important technical problems in surgery to repair aneurysms is the presence of a hard/calcified neck. In this situation, various techniques can be used for proper clipping. In addition to well-known techniques, we have used a different technique for more than 10 years. This technique probably also has been used by other neurosurgeons, but we could not find any publications about it in the English literature. Therefore, we would like to report the details of this technique and our own experience., Methods: More than 600 anterior circulation aneurysms were clipped between January 2003 and December 2014. It was necessary to apply this technique in 25 aneurysms because of a hard/calcified neck. This series was reviewed retrospectively. If the hard-calcified plaque at the neck does not allow for full closure of the clip and the known techniques are not sufficient for clipping, we carefully and slowly compress the aneurysm clip itself at the neck with a hemostatic clamp. The hard plaque usually is crushed with this technique, and full closure of the clip is immediately obtained., Results: Complete occlusion of the neck was achieved in 16 aneurysms (64%) with this technique. Technique-related complication developed as intraoperative rupture of the aneurysm in two patients (8%). However, this complication was managed with other techniques in both cases. No distal thromboembolism developed in any patient., Conclusions: Our aneurysm clip compression technique may be a viable option in surgery of aneurysms with hard-calcified neck., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To examine first-time neonatal intensive care unit (NICU) mothers' perceptions of the initial effect and stress of their birth experiences and hospitalizations of their infants and what facilitated or hindered the development of their maternal roles within the context of the NICU., Design: A qualitative descriptive design., Setting: A 57-bed, tertiary NICU in Chicago., Participants: Twenty-three mothers of very low birth weight (VLBW) infants hospitalized in the NICU., Methods: Participants were a subset of a larger longitudinal mixed-method study of psychological distress in 69 mothers of VLBW infants. Mothers were interviewed using an adaptation of the Clinical Interview for Parents of High-Risk Infants (CLIP) approximately 6 weeks after the births of their infants. Data were analyzed using conventional content analysis., Results: Mothers characterized the infants' births and hospitalizations as a time of overwhelming change culminating in a new perspective on life. Primary themes were loss, stress and anxiety, adapting, resilience, peer support, and "I'm a NICU Mom." Mothers rated peer support as the most facilitative and supportive aspect of developing the maternal role in the NICU., Conclusion: Peer support and role modeling by NICU-based breastfeeding peer counselors helped the mothers throughout every stage of their infants' hospitalizations, from giving them hope, to helping them begin to develop maternal identity, to providing anticipatory guidance about taking their infants home. Talking points are provided for nurses who work in NICUs without dedicated peer support to help mothers establish a healthy mother/infant relationship., (© 2015 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.)

Object: To understand the relationship between the parent artery and its distal arteries, blood vessels running through the subarachnoid space need to be extensively dissected, which is time-consuming. We examined the efficacy of temporary clipping with the indocyanine green (ICG) technique (target-controlled infusion (TCI) technique), in which the parent artery is occluded using a temporary clip, and ICGV (videoangiography) is performed to clarify the relationship between the distal M4 and proximal M2., Methods: Thirteen radial artery grafts (RAGs) for internal carotid aneurysm underwent TCI to confirm the relationship between M2 and cortical M4. To monitor the perfusion pressure of the cortical middle cerebral artery, superficial temporal artery (STA) to M4 anastomosis was performed before RA-M2 anastomosis. We performed anastomosis of the recipient of STA- M4 that was distal and downstream of the M2 segment that is the recipient of RA-M2 anastomosis. To select the proper recipient M4 of the STA-M4 anastomosis, the ICGV image range was set sufficiently wide to accommodate the possibility that the distal artery was not the one anticipated. ICGV followed complete occlusion by temporary clipping of the recipient M2., Results: In 2 of the 13 cases, the relationship between the M2 and M4 could not be clarified., Conclusions: In cases with developed collateral circulation or small perfusion area of the occluded M2, it was difficult to ascertain the relationship by TCI. Nevertheless, TCI was useful in 11 of the 13 cases, suggesting that unnecessary dissection in the subarachnoid space may be reduced using this technique., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In the past, the treatment of iatrogenic gastrointestinal perforations was limited to surgical management or to medical observation. Natural Orifice Transluminal Endoscopic Surgery (NOTES) has paved the way towards the development of reliable endoscopic closure techniques, which can be applicable in accidental perforations of the gastrointestinal tract. When endoscopic treatment is feasible, hemoclips are preferred in smaller perforations, while over-the-scope-clips or a combination of hemoclips, endoloops, and glue are used in larger ones. Endoscopic stitching is rarely utilized, and endoscopic stapling has been practically abandoned. The use of self-expandable covered stents can be considered in the esophagus and duodenum. Broad spectrum antibiotics are recommended in most cases. Clinical follow-up in a medico-surgical unit is mandatory and surgical intervention should not be delayed more than 24h if clinical or biological worsening occurs. Imaging with oral contrast medium is advisable before resumption of oral feeding in the case of large perforations., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: No approved therapy is available for patients with advanced hepatocellular carcinoma (HCC) who fail first-line therapy. The prognosis of these patients, especially those eligible for clinical trials of second-line therapy, is unclear., Methods: All patients who participated in clinical trials of first-line systemic therapy for metastatic or locally advanced HCC in a referral center of Taiwan between 2005 and 2011 were included. Their clinicopathologic characteristics, when the first-line treatment failed, were analyzed and correlated with the overall survival (OS) from the date of first-line treatment failure., Results: A total of 192 patients were included. Before the start of the first-line therapy, all patients had Child-Pugh class A liver reserves and Cancer of the Liver Italian Program (CLIP) scores ≤4. After the failure of the first-line therapy, the median OS of the entire group was 4.0 months. Patients with Child-Pugh class A liver reserves, when the first-line treatment failed, had significantly better OS than patients with Child-Pugh class B or C liver reserves (median, A vs. B vs. C=7.5 vs. 1.3 vs. 1.0 month, p<0.001). According to the key eligibility criteria of 3 published clinical trials for second-line therapy, 41%-56% of patients were potentially eligible. Compared to patients who were ineligible for clinical trials, potentially eligible patients had longer OS with a median of 7.8-8.6 months., Conclusions: Patients with advanced HCC who failed first-line therapy could have substantially improved prognosis if they had Child-Pugh A liver reserves or were potentially eligible for clinical trials., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: The serum cell death parameters M30 and M65 and the macrophage activation marker sCD163 (soluble CD163) are elevated in patients with acute and chronic liver diseases. However, their diagnostic and prognostic potential in patients with hepatocellular carcinoma (HCC) has not yet been investigated., Methods: Serum levels of M30, M65, and sCD163 were measured in two cohorts of HCC patients and a cohort of cirrhotic patients. The parameters were compared between patients with and without HCC and the overall survival (OS) times according to M30, M65, and sCD163 were assessed., Results: M30 and M65 levels were higher in HCC patients than in cirrhotic patients (both p < 0.001). M65 was an independent parameter for non-invasive identification of HCC patients by logistic regression analysis and could supplement AFP (alpha-fetoprotein) and abdominal ultrasound in non-invasive detection of HCC patients. High M65 serum levels as well as high sCD163 concentrations were associated with an impaired prognosis in univariate Cox regression analysis. The sCD163 level was associated with OS independently of the CLIP (Cancer of the Liver Italian Program) score, the BCLC (Barcelona Clinic Liver Cancer) stage, and the CRP (C-reactive protein) level in a multivariate Cox regression model., Conclusions: Serum M65 has the potential as a new diagnostic parameter for HCC and serum sCD163 is a new prognostic parameter in HCC patients., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)