Laparoscopic versus open surgery in treating patients with gallbladder cancer: a systematic review and meta-analysis.

Background: Concerns over the security of laparoscopic radical operation for gallbladder cancer (GBC) persist. This systematic review and meta-analysis attempted to compare the safety and efficacy of laparoscopic surgery (LS) versus open surgery (OS) in the treatment of GBC. Methods: The PubMed, EMBASE, and Web of Science were searched from inception to July 18, 2022. Literature search, quality assessment, and data extraction were completed independently and in duplicate. Effect-size estimates expressed as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence interval (CI) were derived under the random-effects model. Results: A total of 27 independent studies including 2,868 participants were meta-analyzed. Significance was noted for intraoperative blood loss (WMD: -117.194, 95% CI: -170.188 to 64.201, P<0.001), harvested lymph nodes (WMD: -1.023, 95% CI: -1.776 to -0.269, P=0.008), postoperative hospital stay (WMD: -3.555, 95% CI: -4.509 to -2.601, P<0.001), postoperative morbidity (OR: 0.596, 95% CI: 0.407 to 0.871, P=0.008), overall survival rate at 2-year (OR: 1.524, 95% CI: 1.143 to 2.031, P=0.004), T2 survival at 1-year (OR: 1.799, 95% CI: 1.777 to 2.749, P<0.01) and 2-year (OR: 2.026, 95% CI: 1.392 to 2.949, P<0.001), as well as T3 survival at 1-year (OR: 2.669, 95% CI: 1.564 to 4.555, P<0.001) and 2-year (OR: 2.300, 95% CI: 1.308 to 4.046, P=0.004). Subgroup analyses revealed that ethnicity, incidental GBC, sample size, and follow-up period were possible sources of heterogeneity. There was a low probability of publication bias for all outcomes except postoperative morbidity. Conclusions: Our findings indicated that LS statistically had better 2-year survival rates, less intraoperative bleeding, shorter hospitalization times, and lower rates of complications than OS. However, the superiority and even the safety of LS still remain an open question due to the impact of incidental GBC, unaccounted heterogeneity, publication bias, lymph node dissection, and port-site metastasis.

2023 White Paper on Recent Issues in Bioanalysis: EU IVDR 2017/746 Implementation/Impact, IVD/CDx/CLIA Approved Assays, High Dimensional Cytometry, Multiplexing Technologies, LBA Tissue Analysis, Vaccine Study Endpoints, Cell-Based Assays for Biomarkers, Cell Therapy and Vaccines (PART 2 - Recommendations on Development & Validation of Biomarkers, IVD, CDx, Cell-Based, Flow Cytometry, Ligand-Binding and Enzyme Assays; Advanced Critical Reagents Strategies).

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on 19-23 June 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication (Part 2) covers the recommendations on Biomarkers, IVD/CDx, LBA and Cell-Based Assays. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 9 and 7 (2024), respectively.

Stereotactic radiotherapy vs whole brain radiation therapy in EGFR mutated NSCLC: Results & reflections from the prematurely closed phase III HYBRID trial.

BACKGROUND: All known randomized trials of stereotactic radiotherapy (SRT) versus whole brain radiotherapy (WBRT) for brain metastases (BMs) comprise mixed histologies. The phase III HYBRID trial (NCT02882984) attempted to evaluate the non-inferiority of SRT vs. WBRT specifically for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) BMs. METHODS: Inclusion criteria were ≤ 5 BMs (any size) from treatment-naïve EGFRm NSCLC. All patients started a first-generation tyrosine kinase inhibitor on the first day of WBRT (37.5 Gy/15 fractions) or SRT (25-40 Gy/5 fractions per tumor volume). The primary endpoint was 18-month intracranial progression-free survival (iPFS; intention-to-treat). RESULTS: The trial commenced in June 2015 and was closed in April 2021 after screening 208 patients but enrolling 85 (n = 41 WBRT, n = 44 SRT; median follow-up 31 and 36 months, respectively). Respectively, 9.5 % vs. 10.2 % of patients experienced intracranial progression at 18 months, and the median iPFS was 21.4 vs. 22.3 months (p > 0.05 for all). The SRT arm experienced higher overall survival and cognitive preservation (p < 0.05 for all). The most notable reason for low enrollment was patients not wishing to risk neurocognitive decline from WBRT. CONCLUSIONS: Although this phase III trial was underpowered, there was no evidence that SRT yielded outcome detriments compared to WBRT for EGFRm NSCLC BMs. Lessons from prematurely closed trials are valuable, as they often provide important experiential perspectives for investigators designing/executing future trials. In the current era, randomized trials involving WBRT without cognitive sparing measures may be at high risk of underaccrual; trial investigators are encouraged to carefully consider our experience when attempting to design such trials. However, trials of molecular-/biologically-stratified patients are highly recommended as the notion of "individualized medicine/oncology" continues to expand.

Prediction of Clinical Precision Chemotherapy by Patient-Derived 3D Bioprinting Models of Colorectal Cancer and Its Liver Metastases.

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient-derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d-bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient-derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient-derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.

Comparison of efficacy and safety of laparoscopic and open enucleation for liver hemangioma in the right hemi liver: a retrospective cohort study.

Background: Open enucleation (OE) is often performed for giant liver hemangioma (LH) because of its advantage in maximum preservation of functional liver parenchyma. Laparoscopic enucleation (LE) has been applied to LHs more frequently for its potential advantages in postoperative recovery and blood loss. However, to date, LE is still a difficult and complex surgical technique especially when the hemangioma is located in the right hemi liver. The aim of this study was to analyze whether LE is superior to OE for LH in the right hemi liver. Methods: Demographics and perioperative data of patients who underwent LE or OE for LH in the right hemi liver between May 2013 and July 2020 were collected. To decrease the selection bias, patients who underwent OE in first 2 years and those underwent LE in next 5 years by a same operation team were included. The data of sex, age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, largest tumor size, and removed tumor number were enrolled in the propensity score matching (PSM) method to compensate for differences in the baseline characteristics between LE and OE groups. The perioperative outcomes were compared between 2 matched groups after PSM method. Results: A total of 110 patients (36 LE vs. 74 OE) were matched by age, sex, BMI, ASA grade score, largest tumor size, removed tumor number and tumor location. Finally, 34 patients in each group were retained after PSM. There were no significant differences in operative time, estimated blood loss, amount of autologous transfusion, morbidity grade and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) on postoperative day 1 or 3 or 5. LE was associated with a significantly higher rate of use of the Pringle maneuver (P<0.001), shorter time to oral feeding (P<0.001) and shorter postoperative length of stay (P<0.001). Conclusions: For LHs in the right hemi liver, the perioperative safety of LE is not inferior to OE, and LE seems to achieves a faster recovery from surgery compared with OE.

Location of Hemangioma is an Individual Risk Factor for Massive Bleeding in Laparoscopic Hepatectomy.

BACKGROUND AND OBJECTIVES: The scope of laparoscopic surgery has expanded to encompass hepatic resections, specifically hepatic hemangioma. The most serious intraoperative complication is bleeding, often requiring laparotomy. Because risk factors associated with such massive blood loss have not been well evaluated, the intent of this retrospective study was to analyze these risk factors associated with laparoscopic resection of hepatic hemangiomas. METHODS: From June 1, 2011 to January 31, 2021, 140 consecutive patients underwent laparoscopic surgery for hepatic hemangioma in our hospital. According to quantity of intraoperative blood loss, they were divided into massive (≥ 800 ml) and minor blood loss (< 800 ml) groups. Perioperative data were analyzed by univariate and multivariate analyses with logistic regression to identify the risk factors for potential massive blood loss during laparoscopic resection. RESULTS: There were 24 and 116 patients in the massive and minor blood loss groups, respectively. Of four risk factors significantly associated with massive blood loss by univariate logistic regression analysis (location of hemangioma in the liver, postcaval or hepatic venous compression, hilar compression, and body mass index exceeding 28) the multifactorial logistic model identified only location in the liver of the hemangioma as statistically (P = 0.012) associated with intraoperative massive blood loss. CONCLUSIONS: Location of the hepatic hemangioma was the single statistically significant risk factor for massive blood loss during laparoscopic surgery for hepatic hemangioma. Of particular importance, location in Couinaud liver segments I, IVa, VII, and VIII necessitates precautions to mitigate the risk of massive blood loss.

Best practices for the development, analytical validation and clinical implementation of flow cytometric methods for chimeric antigen receptor T cell analyses.

Chimeric Antigen Receptor (CAR) T cells are recognized as efficacious therapies with demonstrated ability to produce durable responses in blood cancer patients. Regulatory approvals and acceptance of these unique therapies by patients and reimbursement agencies have led to a significant increase in the number of next generation CAR T clinical trials. Flow cytometry is a powerful tool for comprehensive profiling of individual CAR T cells at multiple stages of clinical development, from product characterization during manufacturing to longitudinal evaluation of the infused product in patients. There are unique challenges with regard to the development and validation of flow cytometric methods for CAR T cells; moreover, the assay requirements for manufacturing and clinical monitoring differ. Based on the collective experience of the authors, this recommendation paper aims to review these challenges and present approaches to address them. The discussion focuses on describing key considerations for the design, optimization, validation and implementation of flow cytometric methods during the clinical development of CAR T cell therapies.

Best practices for optimization and validation of flow cytometry-based receptor occupancy assays.

In the development of therapeutic compounds that bind cell surface molecules, it is critical to demonstrate the extent to which the drug engages its target. For cell-associated targets, flow cytometry is well-suited to monitor drug-to-target engagement through receptor occupancy assays (ROA). The technology allows for the identification of specific cell subsets within heterogeneous populations and the detection of nonabundant cellular antigens. There are numerous challenges in the design, development, and implementation of robust ROA. Among the most difficult challenges are situations where there is receptor modulation or when the target-antigen is expressed at low levels. When the therapeutic molecules are bi-specific and bind multiple targets, these challenges are increased. This manuscript discusses the challenges and proposes best practices for designing, optimizing, and validating ROA.

Survival benefits of simple versus extended cholecystectomy and lymphadenectomy for patients with T1b gallbladder cancer: An analysis of the surveillance, epidemiology, and end results database (2004 to 2013).

Although guidelines recommend extended surgical resection, radical resection and lymphadenectomy for patients with tumor stage (T)1b gallbladder cancer, these procedures are substantially underutilized. This population-based, retrospective cohort study aimed to evaluate treatment patterns and outcomes of 401 patients using the US Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013. Results showed that median overall survival (OS) was 69 months for lymphadenectomy patients and 37 months for those without lymphadenectomy. Lymphadenectomy also tended to prolong cancer-specific survival (CSS), although the differences were not statistically significant. OS and CSS were similar for patients who received simple cholecystectomy and extended surgical resection. Cox proportional hazards regression models revealed survival advantages in patients with stage T1bN0 gallbladder cancer compared to those with stage T1bN1, and patients who received simple cholecystectomy plus lymphadenectomy compared to those who did not receive lymph node dissection. In further analyses, patients undergoing simple cholecystectomy who had five or more lymph nodes excised had better OS and CSS than those without lymph node dissection. In conclusion, survival advantages are shown for patients with T1b gallbladder cancer undergoing surgeries with lymphadenectomy. Future studies with longer follow-up and control of potential confounders are highly warranted.

NOS1 expression promotes proliferation and invasion and enhances chemoresistance in ovarian cancer.

Nitric oxide (NO), an important chemical messenger, serves a dual role in tumor progression. Nitric oxide synthase isoform 1 (NOS1) was observed to be increasingly expressed in various types of cancer, and its expression has been associated with tumor progression. However, the level of NOS1 expression and the associated functions of NOS1 in human ovarian cancer remain undefined. Using gene expression profiles of ovarian cancer from the Gene Expression Omnibus (GEO) database, the present study revealed that NOS1 was increasingly expressed in ovarian cancer tissues. The present study investigated the level of NOS1 expression and its effects on in vitro cell function, including proliferation, migration and invasion as well as chemoresistance to cispatin (DDP) treatment in OVCAR3 cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the level of NOS1 mRNA expression varied in different ovarian cancer lines. However, immunoblotting indicated that the level of NOS1 protein expression was constitutively high in ovarian cancer cell lines. Treatment with NOS inhibitor NG-nitro-L-arginine methyl ester or transfection with NOS1 short hairpin RNA significantly inhibited cell proliferation, migration and invasion compared with the control, whereas the sensitivity of OVCAR3 cells to DDP treatment was increased. The results of the present study indicated that NOS1 promoted the function of ovarian cancer cells, including proliferation, invasion and chemoresistance, providing a potential target for ovarian cancer therapeutic.

An Integrative Approach to Inform Optimal Administration of OX40 Agonist Antibodies in Patients with Advanced Solid Tumors.

PURPOSE: The success of checkpoint blockade has led to a significant increase in the development of a broad range of immunomodulatory molecules for the treatment of cancer, including agonists against T-cell costimulatory receptors, such as OX40. Unlike checkpoint blockade, where complete and sustained receptor saturation may be required for maximal activity, the optimal dosing regimen and receptor occupancy for agonist agents is less well understood and requires further study. EXPERIMENTAL DESIGN: We integrated both preclinical and clinical biomarker data sets centered on dose, exposure, receptor occupancy, receptor engagement, and downstream pharmacodynamic changes to model the optimal dose and schedule for the OX40 agonist antibody BMS-986178 alone and in combination with checkpoint blockade. RESULTS: Administration of the ligand-blocking anti-mouse surrogate antibody OX40.23 or BMS-986178 as monotherapy or in combination with checkpoint blockade led to increased peripheral CD4+ and CD8+ T-cell activation in tumor-bearing mice and patients with solid tumors, respectively. OX40 receptor occupancy between 20% and 50% both in vitro and in vivo was associated with maximal enhancement of T-cell effector function by anti-OX40 treatment, whereas a receptor occupancy > 40% led to a profound loss in OX40 receptor expression, with clear implications for availability for repeat dosing. CONCLUSIONS: Our results highlight the value of an integrated translational approach applied during early clinical development to aggregate preclinical and clinical data in an effort to define the optimal dose and schedule for T-cell agonists in the clinic.

Neoplastic polyps in gallbladder: a retrospective study to determine risk factors and treatment strategy for gallbladder polyps.

BACKGROUND: Preoperative differentiation of malignant and premalignant gallbladder polyps (GBPs) from benign lesions is a key imperative to guide treatment decision-making. We aimed to characterize the various types of GBPs and sought to identify the risk factors for neoplastic polyps. Our findings may help optimize treatment strategy. METHODS: Retrospective analysis of 686 patients with post-cholecystectomy pathologically-proven GBPs between January 2003 and December 2016. The patients were classified into non-neoplastic polyp group, benign neoplastic polyp group, and adenoma canceration group. Clinical features, ultrasound findings, and results of laboratory investigations and histopathological examination were reviewed and compared between the groups. RESULTS: Out of 686 patients, 542 (79.0%) had non-neoplastic polyps, 134 (19.5%) had neoplastic polyps, and 10 (1.5%) had adenoma canceration. The mean age was 46.06±12.12 years; 383 (55.8%) patients were female. The median (25th percentile, 75th percentile) time between diagnosis and surgery in the cholesterol polyp group [24 (3.5, 60) months] was significantly longer than that in adenoma [12 (2, 60) months] and adenoma canceration [5 (0.475, 12) months] groups. The mean diameter was 1.14±0.61 cm (range, 0.5-8.4 cm). Three hundred twelve (45.5%) patients had solitary polyps and intralesional blood flow was observed in 41 (6.0%) patients. On univariate analysis, age >49.5 years, polyp size >1.15 cm, solitary polyp, intralesional blood flow, absence of symptoms, and lack of cholecystitis showed a significant association with adenoma. On multivariate analysis, polyp size (>1.15 cm), intralesional blood flow, and lack of cholecystitis were independent predictors of adenoma. CONCLUSIONS: Polyp size >1.15 cm, intralesional blood flow, and lack of cholecystitis were predictors of neoplastic polyps. Malignant transformation of adenoma may occur over a relatively short time.

IL­17A promotes CXCR2­dependent angiogenesis in a mouse model of liver cancer.

Serum interleukin (IL)­17A level is associated with higher microvessel density and poor prognosis in liver cancer. However, the specific mechanism underlying the role of IL­17A in liver cancer remains controversial. In the present study, the effect of IL­17A on liver cancer cells was examined. IL­17A had no evident impact on vascular endothelial growth factor A (VEGFA) production in HepG2 and Huh7.5 cells as determined by reverse transcription­quantitative PCR and ELISA, but it did stimulate angiogenic CXC chemokine secretion, including chemokine (C­X­C motif) ligand 1 (CXCL1), CXCL2, CXCL3, CXCL5, CXCL6 and CXCL8 in Huh7.5 cells and CXCL2 in HepG2 cells. In addition, the production of angiostatic chemokines such as CXCL10 was not affected. The supernatant of Huh7.5­IL17A cells promoted endothelial cell chemotaxis, which was attenuated by the C­X­C chemokine receptor type 2 (CXCR2) inhibitor SB225002. Although there was no role of IL­17A in promoting in vitro cell proliferation, IL­17A markedly increased the tumor growth of Huh7.5 cells in both subcutaneous and orthotopic xenograft models with increased vascularization. Taken together, these results demonstrated that IL­17A may stimulate chemokine­induced angiogenesis and promote tumor progression, independent of VEGF signaling. The CXCL­CXCR2 axis may be a novel target for the anti­angiogenesis treatment of liver cancer.

Clinicopathological characteristics and risk factors for recurrence of well-differentiated pancreatic neuroendocrine tumors after radical surgery: a case-control study.

BACKGROUND: Well-differentiated pancreatic neuroendocrine tumors (PanNETs) usually have a good prognosis; however, there are patients that experience recurrence after curative resection. AIM: To explore recurrence-related risk factors by analyzing clinicopathological data of PanNETs after radical surgery. METHODS: Clinical and pathological data from 47 patients with well-differentiated PanNETs at China-Japan Friendship Hospital from January 2012 to March 2016 were analyzed retrospectively. Univariate and multivariate analyses of the risk factors of PanNETs for postoperative recurrence were conducted. RESULTS: Among the 47 patients with well-differentiated PanNETs, there were 38 cases with non-functioning tumors, 9 cases with functional tumors (6 insulinomas, 1 gastrinoma, 1 glucagonoma, and 1 VIPomas). There are 17 cases (36.2%) in the pancreatic head, 17 (36.2%) in the body and tail, 9 (19.1%) in the tail, and 4 (8.5%) in the body. The median tumor size was 3.65 (IQR 2-5.5) cm. Fourteen cases (29.8%) were NET G1, and 33 cases (70.2%) were NET G2. In regard to the clinical stage, 9 (19.1%) cases were IA, 14 (29.8%) cases were IB, 7 (14.9%) cases were IIA, 14 (29.8%) cases were IIB, and 3 cases unknown. There were 17 patients who presented with postoperative recurrence. Univariate analysis showed that AJCC TNM staging, Ki67 index, vascular invasion, margin status, and the regional stage of the tumors are related to the recurrence of patients with PanNETs (p < 0.05). The results of multivariate analysis showed that Ki67 index ≥ 10% is an independent risk factor for the postoperative recurrence of PanNETs (p < 0.05). CONCLUSION: The Ki67 index ≥ 10% is an independent risk factor for recurrence in well-differentiated PanNETs after radical surgery, and close surveillance for these patients may be needed.

High-Throughput Analysis of Clinical Flow Cytometry Data by Automated Gating.

Advancements in flow cytometers with capability to measure 15 or more parameters have enabled us to characterize cell populations at unprecedented levels of detail. Beyond discovery research, there is now a growing demand to dive deeper into evaluating the immune response in clinical trials for immune modulating compounds. However, for high-volume, complex flow cytometry data generated in clinical trials, conventional manual gating remains the standard of practice. Traditional manual gating is resource intense and becomes a bottleneck and an impractical method to complete high volumes of flow cytometry data analysis. Current efforts to automate "manual gating" have shown that computational algorithms can facilitate the analysis of daunting multi-parameter data; however, a greater degree of precision in comparison with traditional manual gating is needed for wide-scale adoption of automated gating methods. In an effort to more closely follow the manual gating process, our automated gating pipeline was created to include negative controls (Fluorescence Minus One [FMO]) to enhance the reliability of gate placement. We demonstrate that use of an automated pipeline, heavily relying on FMO controls for population discrimination, can analyze multi-parameter, large-scale clinical datasets with comparable precision and accuracy to traditional manual gating.

Clinical features of idiopathic portal hypertension in China: A retrospective study of 338 patients and literature review.

BACKGROUND AND AIM: Idiopathic portal hypertension (IPH) refers to a relatively rare condition characterized by intrahepatic portal hypertension in the absence of underlying disease such as liver cirrhosis. METHODS: We retrospectively reviewed 338 patients with IPH that were diagnosed at the pathological consultation center of our hospital. RESULTS: The ratio of male to female patients was 1:1. Mean age at onset was 35.1 ± 16.5 years; male patients on average were 12 years younger than female patients at onset. The median duration from onset to IPH diagnosis was 12 months. In 50 patients, medication use may have been an etiological factor. The most common clinical manifestations were splenomegaly (91.3%) and hypersplenism (68.9%); 57.0% patients presented varicosis, while 25.1% patients had a history of variceal bleeding. Nodular regenerative hyperplasia was found in 22.2% liver biopsies. Among patients for whom laboratory data were available, 65.0%, 50.3%, and 71.4% patients presented leukopenia, anemia, and thrombocytopenia due to hypersplenism. Liver function was mostly in the compensated stage. Female patients showed worse leukopenia and anemia, while male patients were more likely to have abnormal serum transaminase and bilirubin levels. Sixty-seven patients received surgical or interventional treatment. CONCLUSIONS: High-quality liver biopsy, detailed clinical information, and expert pathologist are necessary for diagnosis of IPH. IPH can occur concurrently with other liver disease such as hepatitis and drug-induced liver injury. Medication appears to be an important etiological factor for IPH in China. Management approach was largely focused on treatment of portal hypertension and its complications.

A new perspective on perioperative coagulation management in a patient with congenital factor VII deficiency: A case report.

RATIONALE: Congenital factor VII (FVII) deficiency is a rare coagulopathy. There are little clinical data for congenital FVII deficiency and no evidence-based medicine guidelines for treatment. PATIENT CONCERNS: A 48-year-old woman with gallbladder stones suffered from intermittent abdominal pain for 2 months that was accompanied by an abnormally prolonged prothrombin time. DIAGNOSES: The woman was diagnosed as having cholecystolithiasis with cholecystitis and congenital FVII deficiency. INTERVENTION: Preoperative evaluation confirmed the necessity of recombinant activated factor VII (rFVIIa) replacement therapy. We monitored the plasma factor VII activity (FVII:C) and coagulation function, determined the half-life of rFVIIa in the patient, and administered personalized rFVIIa replacement therapy. OUTCOMES: Laparoscopic cholecystectomy was performed successfully, and the patient recovered well without any complications. LESSONS: The clinical manifestations and severity of bleeding in patients with congenital FVII deficiency can vary widely. The history of massive bleeding and plasma FVII:C are the decisive factors when implementing a replacement therapy. The actual half-life of rFVIIa can be determined from intensive monitoring results of plasma FVII:C at the beginning of replacement therapy, which could further guide the personalization of rFVIIa replacement therapy.

Voronoi Diagram and Crowdsourcing-Based Radio Map Interpolation for GRNN Fingerprinting Localization Using WLAN.

In the last decade, fingerprinting localization using wireless local area network (WLAN) has been paid lots of attention. However, this method needs to establish a database called radio map in the off-line stage, which is a labor-intensive and time-consuming process. To save the radio map establishment cost and improve localization performance, in this paper, we first propose a Voronoi diagram and crowdsourcing-based radio map interpolation method. The interpolation method optimizes propagation model parameters for each Voronoi cell using the received signal strength (RSS) and location coordinates of crowdsourcing points and estimates the RSS samples of interpolation points with the optimized propagation model parameters to establish a new radio map. Then a general regression neural network (GRNN) is employed to fuse the new and original radio maps established through interpolation and manual operation, respectively, and also used as a fingerprinting localization algorithm to compute localization coordinates. The experimental results demonstrate that our proposed GRNN fingerprinting localization system with the fused radio map is able to considerably improve the localization performance.