Complement Factor B Inhibition or Deletion Is Not Sufficient to Prevent Neurodegeneration in a Murine Model of Glaucoma.

Purpose: Activation of the classical complement pathway is thought to contribute to the development and progression of glaucoma. The role of alternative complement or amplification pathways in glaucoma is not well understood. We evaluated complement factor B (FB) expression in postmortem human ocular tissues with or without glaucoma and the effect of FB inhibition and deletion in a mouse ocular hypertensive model of glaucoma induced by photopolymerized hyaluronic acid glycidyl methacrylate (HAGM). Methods: Human CFB mRNA in human eyes was assessed by RNAscope and TaqMan. HAGM model was performed on C57BL6/J mice. The effect of FB in HAGM model was evaluated with an oral FB inhibitor and Cfb-/- mice. Complement mRNA and proteins in mouse eyes were assessed by TaqMan and western blot, respectively. Results: CFB mRNA in human glaucomatous macular neural retina and optic nerve head was upregulated. Cfb mRNA is also upregulated in the HAGM model. Oral FB inhibitor, ED-79-GX17, dosed daily at 200 mg/kg for 3 days after intraocular pressure (IOP) induction in wild-type mice showed complement inhibition in ocular tissues and significantly inhibited systemic complement levels. Daily dosing of ED-79-GX17 for 30 days or Cfb deletion was also unable to prevent retinal ganglion cell or axon loss 30 days after IOP induction in mice. Conclusion: The alternative complement component FB may not substantially contribute to RGC loss in the HAGM mouse glaucoma model despite upregulation of Cfb expression and activation of the alternative pathway. The relevance of these findings to human glaucoma remains to be determined.

Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

A sulfonate ligand-defected Zr-based metal-organic framework for the enhanced selective removal of anionic dyes.

In this work, we introduce a novel defective analogue of the representative 6-connected zirconium-based metal-organic framework (MOF-808), by employing 5-sulfoisophthalic acid monosodium salt (H2BTC-SO3Na) as a defect inducer via a mixed-linker approach. The structural integrity and different physicochemical properties were investigated by various characterization techniques, including powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nitrogen physisorption at 77 K. Additionally, proton nuclear magnetic resonance (1H-NMR), energy-dispersive X-ray (EDX), and inductively coupled plasma optical emission spectroscopy (ICP-OES) were employed to confirm the presence of 6.9 mol% of the 5-sulfoisophthalate ligand within the highly crystalline MOF-808 structure. The defective material exhibited significant enhancements in the removal efficiency of various organic dyes, including approximately 64% and 77% for quinoline yellow and sunset yellow, and 56% and 13% for rhodamine B and malachite green, compared to its pristine counterpart. Importantly, the defective MOF-808 showed a remarkable selectivity toward anionic species in binary-component dyes comprising both anionic and cationic dyes.

Palliative procedures for malignant gastric outlet obstruction: a network meta-analysis.

BACKGROUND: The optimal treatment for malignant gastric outlet obstruction (GOO) remains uncertain. This systematic review aimed to comprehensively investigate the efficacy and safety of four palliative treatments for malignant GOO: gastrojejunostomy, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), stomach-partitioning gastrojejunostomy (PGJ), and endoscopic stenting. METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform for randomized controlled trials (RCTs) and cohort studies comparing the four treatments for malignant GOO. We included studies that reported at least one of the following clinical outcomes: clinical success, 30-day mortality, reintervention rate, or length of hospital stay. Evidence from RCTs and non-RCTs was naïve combined to perform network meta-analysis through the frequentist approach using an inverse variance model. Treatments were ranked by P score. RESULTS: This network meta-analysis included 3617 patients from 4 RCTs, 4 prospective cohort studies, and 32 retrospective cohort studies. PGJ was the optimal approach in terms of clinical success and reintervention (P scores: 0.95 and 0.90, respectively). EUS-GE had the highest probability of being the optimal treatment in terms of 30-day mortality and complications (P scores: 0.82 and 0.99, respectively). Cluster ranking to combine the P scores for 30-day mortality and reintervention indicated the benefits of PGJ and EUS-GE (cophenetic correlation coefficient: 0.94; PGJ and EUS-GE were in the same cluster). CONCLUSION: PGJ and EUS-GE are recommended for malignant GOO. PGJ could be the alternative choice in centers with limited resources or in patients who are unsuitable for EUS-GE.

Highest 3-month international normalized ratio (INR): a predictor of bleeding following ultrasound-guided liver biopsy.

OBJECTIVES: To determine whether international normalized ratio (INR), bilirubin, and creatinine predict bleeding risk following percutaneous liver biopsy. METHODS: A total of 870 consecutive patients (age 53 ± 14 years; 53% (459/870) male) undergoing non-targeted, ultrasound-guided, percutaneous liver biopsy at a single tertiary center from 01/2016 to 12/2019 were retrospectively reviewed. Results were analyzed using descriptive statistics and logistic regression models to evaluate the relationship between individual and combined laboratory values, and post-biopsy bleeding risk. Receiver operating characteristic (ROC) curves and area under ROC (AUC) curves were constructed to evaluate predictive ability. RESULTS: Post-biopsy bleeding occurred in 2.0% (17/870) of patients, with 0.8% (7/870) requiring intervention. The highest INR within 3 months preceding biopsy demonstrated the best predictive ability for post-biopsy bleeding and was superior to the most recent INR (AUC = 0.79 vs 0.61, p = 0.003). Total bilirubin is an independent predictor of bleeding (AUC = 0.73) and better than the most recent INR (0.61). Multivariate regression analysis of the highest INR and total bilirubin together yielded no improvement in predictive performance compared to INR alone (0.80 vs 0.79). The MELD score calculated using the highest INR (AUC = 0.79) and most recent INR (AUC = 0.74) were similar in their predictive performance. Creatinine is a poor predictor of bleeding (AUC = 0.61). Threshold analyses demonstrate an INR of > 1.8 to have the highest predictive accuracy for bleeding. CONCLUSION: The highest INR in 3 months preceding ultrasound-guided percutaneous liver biopsy is associated with, and a better predictor for, post-procedural bleeding than the most recent INR and should be considered in patient risk stratification. CLINICAL RELEVANCE STATEMENT: Despite correction of coagulopathic indices, the highest international normalized ratio within the 3 months preceding percutaneous liver biopsy is associated with, and a better predictor for, bleeding and should considered in clinical decision-making and determining biopsy approach. KEY POINTS: • Bleeding occurred in 2% of patients following ultrasound-guided liver biopsy, and was non-trivial in 41% of those patients who needed additional intervention and had an associated 23% 30-day mortality rate. • The highest INR within 3 months preceding biopsy (AUC = 0.79) is a better predictor of bleeding than the most recent INR (AUC = 0.61). • The MELD score is associated with post-procedural bleeding, but with variable predictive performance largely driven by its individual laboratory components.

Diagnostic Accuracy of the FRAIL Scale, Groningen Frailty Indicator, Tilburg Frailty Indicator, and PRISMA-7 for Frailty Screening Among Older Adults in Community Settings: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the diagnostic accuracy of four questionnaire-based tools (i.e., the FRAIL scale, Groningen Frailty Indicator [GFI], Tilburg Frailty Indicator [TFI], and PRISMA-7) for screening frailty in older adults. RESEARCH DESIGN AND METHODS: The 4 databases comprising the Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, and ProQuest were searched from inception to June 20, 2023. Study quality comprising risks of bias and applicability was assessed via a QUADAS-2 questionnaire. A bivariate network meta-analysis model and Youden's index were performed to identify the optimal tool and cutoff points. RESULTS: In total, 20 studies comprising 13 for FRAIL, 7 for GFI, 6 for TFI, and 5 for PRISMA-7 were included. Regarding study quality appraisal, all studies had high risks of bias for study quality assessment domains. Values of the pooled sensitivity of the FRAIL scale, GFI, TFI, and PRISMA-7 were 0.58, 0.74, 0.66, and 0.73, respectively. Values of the pooled specificity of the FRAIL scale, GFI, TFI, and PRISMA-7 were 0.92, 0.77, 0.84, and 0.86, respectively. The Youden's index was obtained for the FRAIL scale with a cutoff of 2 points (Youden's index = 0.65), indicating that the FRAIL scale with a cutoff of 2 points was the optimal tool for frailty screening in older adults. DISCUSSION AND IMPLICATIONS: The FRAIL scale comprising 5 self-assessed items is a suitable tool for interview older adults for early frailty detection in community settings; it has the advantages of being short, simple, and easy to respond to.

A review of the extraction methods and advanced applications of lignin-silica hybrids derived from natural sources.

The global trend of increasing energy demand along the large volume of wastewater generated annually from the paper pulping and cellulose production industries are considered as serious dilemma that may need to be solved within these current decades. Within this discipline, lignin, silica or lignin-silica hybrids attained from biomass material have been considered as prospective candidates for the synthesis of advanced materials. In this study, the roles and linking mechanism between lignin and silica in plants were studied and evaluated. The effects of the extraction method on the quality of the obtained material were summarized to show that depending on the biomass feedstocks, different retrieval processes should be considered. The combination of alkaline treatment and acidic pH adjustment is proposed as an effective method to recover lignin-silica with high applicability for various types of raw materials. From considerations of the advanced applications of lignin and silica materials in environmental remediation, electronic devices and rubber fillers future valorizations hold potential in conductive materials and electrochemistry. Along with further studies, this research could not only contribute to the development of zero-waste manufacturing processes but also propose a solution for the fully exploiting of by-products from agricultural production.

Female Genital Tuberculosis.

Female genital tuberculosis (FGTB) is an important cause of morbidity and infertility worldwide. Mycobacterium tuberculosis most commonly spreads to the genital tract from a focus elsewhere in the body and affects the bilateral fallopian tubes and/or endometrium. Many patients with FGTB have indolent disease and are only diagnosed after evaluation for infertility. Women may present with menstrual irregularities, lower abdominal or pelvic pain, or abnormal vaginal discharge. Given the low sensitivity of diagnostic tests, various composite reference standards are used to diagnose FGTB, including some combination of endoscopic findings, microbiological or molecular testing, and histopathological evidence in gynecological specimens. Early treatment with a standard regimen of a 2-month intensive phase with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by a 4-month continuation phase with isoniazid and rifampin, is recommended to prevent irreversible organ damage. However, even with treatment, FGTB can lead to infertility or pregnancy-related complications, and stigma is pervasive.

Imaging evaluation of the pediatric mediastinum: new International Thymic Malignancy Interest Group classification system for children.

Mediastinal masses are commonly identified in the pediatric population with cross-sectional imaging central to the diagnosis and management of these lesions. With greater anatomical definition afforded by cross-sectional imaging, classification of mediastinal masses into the traditional anterior, middle and posterior mediastinal compartments - as based on the lateral chest radiograph - has diminishing application. In recent years, the International Thymic Malignancy Interest Group (ITMIG) classification system of mediastinal masses, which is cross-sectionally based, has garnered acceptance by multiple thoracic societies and been applied in adults. Therefore, there is a need for pediatric radiologists to clearly understand the ITMIG classification system and how it applies to the pediatric population. The main purpose of this article is to provide an updated review of common pediatric mediastinal masses and mediastinal manifestations of systemic disease processes in the pediatric population based on the new ITMIG classification system.

Cardiology clinic patient attitudes toward and potential personal utility of genetic testing: Findings from a unique multiracial clinical sample.

As more is understood about the hereditary nature of disease risk, the utility of genetic testing within cardiovascular medicine is increasingly being explored. Although testing may afford more personalized risk stratification, there is a paucity of information regarding patient knowledge, attitudes, and beliefs toward genetic testing among cardiology patients. Participants (n = 530) recruited primarily from a cardiology clinic filled out a 41-item written questionnaire assessing knowledge, beliefs, and attitudes toward genetic testing, motivators and detractors for considering genetic testing, and perceived likelihood for behavior change after hypothetical genetic testing risk stratification. Path analysis was used to test the hypothetical models predicting the likelihood of getting a genetic test and making behavior changes following genetic testing. The patient population was late-middle-aged (59.0 ± 14.5 years), majority women (61.5%), and about half reported having a bachelor's degree. 58.1% of participants self-identified as White, 25.7% as African American or Black, 6.8% as Spanish, Latino, or Hispanic, 3.0% as Asian or Pacific Islander, and 0.5% as Native American. Gender (being a woman) and more years of education were related to greater knowledge about genetic testing. Racial identity and years of education were related to beliefs about genetic testing. Beliefs, but not knowledge, were related to more positive attitudes and a higher likelihood of pursuing genetic testing. Positive attitudes were related to greater perceived personal control (PPC). Furthermore, attitudes and PPC were related to higher likelihood of lifestyle change after genetic testing. These results highlight the need to integrate the experiences of racialized communities into education/counseling efforts. Most educational counseling efforts lack a nuanced discussion of social determinants of health or beliefs. In addition to factual information, educational counseling must also address people's beliefs, concerns, and the intersecting experiences and identities, which shape patients' relationships with the evolving landscape of healthcare and personalized medicine.

Value of follow-up angiography: additional interventions in patients undergoing catheter-directed thrombolysis for massive and submassive pulmonary embolism.

PURPOSE: Catheter-directed thrombolysis (CDT) is an emerging, minimally invasive treatment for patients with massive and submassive pulmonary embolism (PE). The value of follow-up pulmonary angiography for evaluating improvement after CDT is limited by a paucity of large studies assessing its utility and role for additional intervention. The purpose of our study was to assess the role of next-day pulmonary angiography for CDT in patients with acute massive and submassive PE undergoing continuous pulmonary arterial pressure monitoring, and secondarily, determine factors that are correlated with a need for further therapy. METHODS: Patients who underwent CDT from 2006 to 2016 for massive and submassive PE were reviewed. Patient demographics, comorbidities, preprocedural lab results, noninvasive hemodynamic studies, and technical variables were recorded. Among patients receiving next-day angiography, those requiring further therapy, defined as continued CDT beyond the standard 24 hours (with or without catheter repositioning or exchange) and/or mechanical or suction thrombectomy were contrasted with those not requiring additional therapy to assess for the role of angiography and patient factors that correlate with need for further therapy. RESULTS: Thirty-two patients underwent CDT for massive (n=14) and submassive (n=18) PE. Eighteen (56.3%) were male, 14 (43.7%) were Caucasian, 18 (56.3%) were African-American, with a mean age of 66.2 years (range, 26-87 years). Of the 27 (84.4%) patients that underwent next-day pulmonary angiography, 16 (59.3%) did not require additional therapy and 11 (40.7%) did require additional therapy. Additional therapy included extended CDT beyond 24 hours (n=4), mechanical/suction thrombectomy (n=5), or both extended CDT and mechanical/suction thrombectomy (n=2). Younger age (50.1 vs. 62.2 years, P = 0.039) was correlated with a need for further therapy. Initial (40.7 vs. 34.8 mmHg, P = 0.248), next-day (31.5 vs. 26.3 mmHg, P = 0.259), and interval change (4.6 vs. 8.0 mmHg, P = 0.669) in pulmonary artery pressures were not statistically significant between patient subsets. Preprocedural right ventricular/left ventricular ratio (RV/LV) also did not differ significantly (1.74 vs. 1.75, P = 0.961). Thirty-day mortality was comparable (2 vs. 1, P = 0.332). CONCLUSION: Next-day pulmonary angiography is a useful method to identify patients needing additional therapy including extended CDT and/or mechanical or suction thrombectomy in acute PE management. Pulmonary arterial pressures and preprocedural RV/LV ratios were not found to be predicative of those requiring further intervention.

Prognostic performance of the Rapid Emergency Medicine Score (REMS) and Worthing Physiological Scoring system (WPS) in emergency department.

BACKGROUND: The Rapid Emergency Medicine Score (REMS) and Worthing Physiological Scoring system (WPS) have been developed for predicting in-hospital mortality in nonsurgical emergency department (ED) patients. The prognostic performance of the scoring systems in independent populations has not been clear. The aim of the study is to evaluate the prognostic accuracy of REMS and WPS systems in the estimation of 30-day mortality risk among medical patients in ED. METHODS: The study was designed as a prospective investigation, with the setting being the ED of the National Hospital of Can Tho, Vietnam. We enrolled medical patients aged 16+ years who met the study entry criteria. Clinical data were obtained as required for each scoring system. The primary outcome was mortality within 30 days since hospitalization. The association between each scoring system and mortality was assessed by the hazard ratio (HR) of the Cox's proportional hazard model. RESULTS: The study involved 1746 patients, average age 65.9 years (SD 17). During the period of follow-up, 172 patients (9.9 %) died. The risk of 30-day mortality was increased by 30 % for each additional REMS unit (HR: 1.28; 95 % confidence interval (CI): 1.23-1.34) and by 60 % for each additional WPS unit (HR: 1.6; 95 % CI: 1.5-1.7). The AUC of the REMS was 0.71 (95 % CI: 0.67-0.76) which was significantly lower than that of the WPS (0.80; 95 % CI: 0.76-0.83). CONCLUSIONS: Both REMS and WPS have good prognostic value in the prediction of death in ED patients. The WPS appeared to have a better prognostic performance than the REMS system.

GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling.

Dysregulated fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of human cancers. Aberrant activation of FGF receptor 2 (FGFR2) signaling, through overexpression of FGFR2 and/or its ligands, mutations, and receptor amplification, has been found in a variety of human tumors. We generated monoclonal antibodies against the extracellular ligand-binding domain of FGFR2 to address the role of FGFR2 in tumorigenesis and to explore the potential of FGFR2 as a novel therapeutic target. We surveyed a broad panel of human cancer cell lines for the dysregulation of FGFR2 signaling and discovered that breast and gastric cancer cell lines harboring FGFR2 amplification predominantly express the IIIb isoform of the receptor. Therefore, we used an FGFR2-IIIb-specific antibody, GP369, to investigate the importance of FGFR2 signaling in vitro and in vivo. GP369 specifically and potently suppressed ligand-induced phosphorylation of FGFR2-IIIb and downstream signaling, as well as FGFR2-driven proliferation in vitro. The administration of GP369 in mice significantly inhibited the growth of human cancer xenografts harboring activated FGFR2 signaling. Our findings support the hypothesis that dysregulated FGFR2 signaling is one of the critical oncogenic pathways involved in the initiation and/or maintenance of tumors. Cancer patients with aberrantly activated/amplified FGFR2 signaling could potentially benefit from therapeutic intervention with FGFR2-targeting antibodies.