A Multidisciplinary Assessment of ChatGPT's Knowledge of Amyloidosis: Observational Study.

BACKGROUND: Amyloidosis, a rare multisystem condition, often requires complex, multidisciplinary care. Its low prevalence underscores the importance of efforts to ensure the availability of high-quality patient education materials for better outcomes. ChatGPT (OpenAI) is a large language model powered by artificial intelligence that offers a potential avenue for disseminating accurate, reliable, and accessible educational resources for both patients and providers. Its user-friendly interface, engaging conversational responses, and the capability for users to ask follow-up questions make it a promising future tool in delivering accurate and tailored information to patients. OBJECTIVE: We performed a multidisciplinary assessment of the accuracy, reproducibility, and readability of ChatGPT in answering questions related to amyloidosis. METHODS: In total, 98 amyloidosis questions related to cardiology, gastroenterology, and neurology were curated from medical societies, institutions, and amyloidosis Facebook support groups and inputted into ChatGPT-3.5 and ChatGPT-4. Cardiology- and gastroenterology-related responses were independently graded by a board-certified cardiologist and gastroenterologist, respectively, who specialize in amyloidosis. These 2 reviewers (RG and DCK) also graded general questions for which disagreements were resolved with discussion. Neurology-related responses were graded by a board-certified neurologist (AAH) who specializes in amyloidosis. Reviewers used the following grading scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. Questions were stratified by categories for further analysis. Reproducibility was assessed by inputting each question twice into each model. The readability of ChatGPT-4 responses was also evaluated using the Textstat library in Python (Python Software Foundation) and the Textstat readability package in R software (R Foundation for Statistical Computing). RESULTS: ChatGPT-4 (n=98) provided 93 (95%) responses with accurate information, and 82 (84%) were comprehensive. ChatGPT-3.5 (n=83) provided 74 (89%) responses with accurate information, and 66 (79%) were comprehensive. When examined by question category, ChatGTP-4 and ChatGPT-3.5 provided 53 (95%) and 48 (86%) comprehensive responses, respectively, to "general questions" (n=56). When examined by subject, ChatGPT-4 and ChatGPT-3.5 performed best in response to cardiology questions (n=12) with both models producing 10 (83%) comprehensive responses. For gastroenterology (n=15), ChatGPT-4 received comprehensive grades for 9 (60%) responses, and ChatGPT-3.5 provided 8 (53%) responses. Overall, 96 of 98 (98%) responses for ChatGPT-4 and 73 of 83 (88%) for ChatGPT-3.5 were reproducible. The readability of ChatGPT-4's responses ranged from 10th to beyond graduate US grade levels with an average of 15.5 (SD 1.9). CONCLUSIONS: Large language models are a promising tool for accurate and reliable health information for patients living with amyloidosis. However, ChatGPT's responses exceeded the American Medical Association's recommended fifth- to sixth-grade reading level. Future studies focusing on improving response accuracy and readability are warranted. Prior to widespread implementation, the technology's limitations and ethical implications must be further explored to ensure patient safety and equitable implementation.

Hospitalizations and Mortality From Myasthenia Gravis: Trends From 2 US National Datasets

BACKGROUND AND OBJECTIVES: Myasthenia gravis (MG) is a rare neuromuscular disorder where IgG antibodies damage the communication between nerves and muscles, leading to muscle weakness that can be severe and have a significant impact on patients' lives. MG exacerbations include myasthenic crisis with respiratory failure, the most serious manifestation of MG. Recent studies have found MG prevalence increasing, especially in older patients. This study examined trends in hospital admissions and in-hospital mortality for adult patients with MG and readmissions and postdischarge mortality in older (65 years or older) adults with MG. METHODS: Data from the Nationwide Inpatient Sample (NIS), an all-payer national database of hospital discharges, were used to characterize trends in hospitalizations and in-hospital mortality related to MG exacerbations and MG crisis among adult patients aged 18 years or older. The Medicare Limited Data Set, a deidentified, longitudinal research database with demographic, enrollment, and claims data was used to assess hospitalizations, length of stay (LOS), readmissions, and 30-day postdischarge mortality among fee-for-service Medicare beneficiaries aged 65 years or older. The study period was 2010-2019. Multinomial logit models and Poisson regression were used to test for significance of trends. RESULTS: Hospitalization rates for 19,715 unique adult patients and 56,822 admissions increased from 2010 to 2019 at an average annualized rate of 4.9% (MG noncrisis: 4.4%; MG crisis: 6.8%; all p < 0.001). Readmission rates were approximately 20% in each study year for both crisis and noncrisis hospitalizations; the in-hospital mortality rate averaged 1.8%. Among patients aged 65 years or older, annualized increases in hospitalizations were estimated at 5.2%, 4.2%, and 7.7% for all, noncrisis, and crisis hospitalizations, respectively (all p < 0.001). The average LOS was stable over the study period, ranging from 11.3 to 13.1 days, but was consistently longer for MG crisis admissions. Mortality among patients aged 65 years or older was higher compared with that in all patients, averaging 5.0% across each of the study years. DISCUSSION: Increasing hospitalization rates suggest a growing burden associated with MG, especially among older adults. While readmission and mortality rates have remained stable, the increasing hospitalization rates indicate that the raw numbers of readmissions-and deaths-are also increasing. Mortality rates are considerably higher in older patients hospitalized with MG.

Safety and outcomes with efgartigimod use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice.

INTRODUCTION/AIMS: Multiple novel therapies have been approved for patients with myasthenia gravis. Our aim is to describe the early experience of efgartigimod use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG). METHODS: This multicenter retrospective study included AChR+ve gMG patients from five major neuromuscular centers who were treated with efgartigimod and had both pre- and post-efgartigimod myasthenia gravis activities of daily living (MG-ADL) scores. Information regarding MG history, concomitant treatment(s), MG-ADL and other MG-specific measures, laboratory data, and adverse events were recorded. RESULTS: A total of 37 patients (M:23, F:14) with a mean age of 65.56 (±14.74) y were included in this cohort. A total of 36/37 patients completed at least one cycle and 28 patients completed at least two cycles of efgartigimod. A total of 72% (26/36) of patients had a clinically meaningful reduction (≥2 point change) in MG-ADL after the completion of the first cycle of efgartigimod (mean pre-efgartigimod 8.02) (±3.09) versus post-efgartigimod 4.33 (±3.62). Twenty-five percent (9/36) achieved minimal symptom expression status after one cycle and 25% (7/28) after the second cycle. Treatment benefit was sustained after cycle 2. Three out of four patients with thymoma in this cohort had clinically significant reductions in MG-ADL scores. Immunoglobulin G (IgG) levels decreased by about 60% (n = 10). One patient had a relapse of Clostridium difficile infection resulting in the discontinuation of therapy. Four patients had mild side effects. DISCUSSION: Efgartigimod led to clinically meaningful improvement in MG-ADL in diverse AChR+ve gMG patients but treatment frequency to achieve optimal symptom control needs to be explored.

Impact of social determinants of health on individuals living with generalized myasthenia gravis and implications for patient support programs.

Introduction: Social determinants of health (SDOH) are important contributors to health outcomes, and better understanding their impact on individuals diagnosed with rare, chronic diseases with high burden and unmet need is critical. Characterizing SDOH burden can help improve the design of patient support programs (PSPs), using targeted approaches to remove barriers to access. Methods: This study used a mixed-methods strategy employing a quantitative survey, which was designed based on qualitative interviews, to understand the unmet needs and awareness/utilization of PSPs among individuals living with generalized myasthenia gravis (gMG) and experiencing SDOH barriers. The survey was completed by 38 individuals living with gMG, of which the majority were non-White/Caucasian, unemployed, low income, and enrolled in public insurance. Common SDOH challenges, awareness/utilization of available PSPs, and unmet needs were identified. Results: Financial and mental health concerns were the most common among individuals living with gMG and experiencing SDOH barriers throughout diagnosis, accessing treatment, initiating treatment, and continuing treatment. Awareness and utilization of existing support services were low, especially when accessing treatment. Educational, financial, and personalized support with high "human touch" were commonly perceived as the most valuable resources. Implications: To better serve the needs of individuals with gMG experiencing SDOH barriers, PSPs should use a targeted approach to offer services tailored to harder-to-reach populations. Further, providers, advocacy groups, manufacturers, and public organizations in the gMG ecosystem should strengthen collaborations with PSPs to enable individuals living with gMG to access the services they need to improve their health outcomes.

Molecular Characterization of Germin-like Protein Genes in Zea mays (ZmGLPs) Using Various In Silico Approaches.

Germin (GER) and germin-like proteins (GLPs) play an important role in various plant processes. Zea mays contains 26 germin-like protein genes (ZmGLPs) located on chromosomes 2, 4, and 10; most of which are functionally unexplored. The present study aimed to characterize all ZmGLPs using the latest computational tools. All of them were studied at a physicochemical, subcellular, structural, and functional level, and their expression was predicted in plant development, against biotic and abiotic stresses using various in silico approaches. Overall, ZmGLPs showed greater similarity in their physicochemical properties, domain architecture, and structure, mostly localized in the cytoplasmic or extracellular regions. Phylogenetically, they have a narrow genetic background with a recent history of gene duplication events on chromosome 4. Functional analysis revealed novel enzymatic activities of phosphoglycolate phosphatase, adenosylhomocysteinase, phosphoglycolate phosphatase-like, osmotin/thaumatin-like, and acetohydroxy acid isomeroreductase largely mediated by disulfide bonding. Expression analysis revealed their crucial role in the root, root tips, crown root, elongation and maturation zones, radicle, and cortex with the highest expression being observed during germination and at the maturity levels. Further, ZmGLPs showed strong expression against biotic (Aspergillus flavus, Colletotrichum graminicola, Cercospora zeina, Fusarium verticillioides, and Fusarium virguliforme) while limited expression was noted against abiotic stresses. Concisely, our results provide a platform for additional functional exploration of the ZmGLP genes against various environmental stresses.

Ferroptosis in Haematological Malignancies and Associated Therapeutic Nanotechnologies.

Haematological malignancies are heterogeneous groups of cancers of the bone marrow, blood or lymph nodes, and while therapeutic advances have greatly improved the lifespan and quality of life of those afflicted, many of these cancers remain incurable. The iron-dependent, lipid oxidation-mediated form of cell death, ferroptosis, has emerged as a promising pathway to induce cancer cell death, particularly in those malignancies that are resistant to traditional apoptosis-inducing therapies. Although promising findings have been published in several solid and haematological malignancies, the major drawbacks of ferroptosis-inducing therapies are efficient drug delivery and toxicities to healthy tissue. The development of tumour-targeting and precision medicines, particularly when combined with nanotechnologies, holds potential as a way in which to overcome these obstacles and progress ferroptosis-inducing therapies into the clinic. Here, we review the current state-of-play of ferroptosis in haematological malignancies as well as encouraging discoveries in the field of ferroptosis nanotechnologies. While the research into ferroptosis nanotechnologies in haematological malignancies is limited, its pre-clinical success in solid tumours suggests this is a very feasible therapeutic approach to treat blood cancers such as multiple myeloma, lymphoma and leukaemia.

Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials.

An increasing number of clinical trials are enrolling patients with myasthenia gravis (MG). A lack of standardization in the performance of outcome measures leads to confusion among site research teams and is a source of variability in clinical trial data. MGNet, the NIH-supported Rare Disease Clinical Research Network for MG, views standardization of MG outcome measures as a critical need. To address this issue, a group of experts summarized key outcome measures used in MG clinical trials and a symposium was convened to address issues contributing to outcome measure variability. Consensus recommendations resulted in changes to outcome measure instructions and, in some cases, modifications to specific instruments. Recommended changes were posted for public commentary before finalization. Changes to the MG-Activities of Daily Living, MG-Quality of Life-15r, and MG-Impairment Index were limited to adding details to the administration instructions. Recommendations for proper positioning of participants and how to score items that could not be performed because of non-MG reasons were provided for the MG Composite. The Quantitative MG (QMG) score required the most attention, and changes were made both to the instructions and the performance of certain items resulting in the QMG-Revised. The Postintervention Status was believed to have a limited role in clinical trials, except for the concept of minimal manifestation status. As a next step, training materials and revised source documents, which will be freely available to study teams, will be created and posted on the MGNet website. Further studies are needed to validate changes made to the QMG-Revised.

Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study.

BACKGROUND: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating autoimmune disease. New treatments for this disease are needed because conventional therapies have limitations, such as side-effects (eg, increased infection risk) or inadequate control of symptoms. Rozanolixizumab is a neonatal Fc receptor blocker that might provide a novel therapeutic option for myasthenia gravis. We aimed to assess the safety and efficacy of rozanolixizumab for generalised myasthenia gravis. METHODS: MycarinG is a randomised, double-blind, placebo-controlled, adaptive phase 3 study done at 81 outpatient centres and hospitals in Asia, Europe, and North America. We enrolled patients (aged ≥18 years) with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) autoantibody-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America class II-IVa), a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 3 (non-ocular symptoms), and a quantitative myasthenia gravis score of at least 11. Patients were randomly assigned (1:1:1) to receive subcutaneous infusions once a week for 6 weeks of either rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg, or placebo. Randomisation was stratified by AChR and MuSK autoantibody status. Investigators, patients, and people assessing outcomes were masked to random assignments. The primary efficacy endpoint was change from baseline to day 43 in MG-ADL score, assessed in the intention-to-treat population. Treatment-emergent adverse events (TEAEs) were assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03971422) and EudraCT (2019-000968-18); an open-label extension study has been completed (NCT04124965; EudraCT 2019-000969-21) and another is underway (NCT04650854; EudraCT 2020-003230-20). FINDINGS: Between June 3, 2019, and June 30, 2021, 300 patients were assessed for eligibility, of whom 200 were enrolled. 66 (33%) were randomly assigned to rozanolixizumab 7 mg/kg, 67 (34%) to rozanolixizumab 10 mg/kg, and 67 (34%) to placebo. Reductions in MG-ADL score from baseline to day 43 were greater in the rozanolixizumab 7 mg/kg group (least-squares mean change -3·37 [SE 0·49]) and in the rozanolixizumab 10 mg/kg group (-3·40 [0·49]) than with placebo (-0·78 [0·49]; for 7 mg/kg, least-squares mean difference -2·59 [95% CI -4·09 to -1·25], p<0·0001; for 10 mg/kg, -2·62 [-3·99 to -1·16], p<0·0001). TEAEs were experienced by 52 (81%) of 64 patients treated with rozanolixizumab 7 mg/kg, 57 (83%) of 69 treated with rozanolixizumab 10 mg/kg, and 45 (67%) of 67 treated with placebo. The most frequent TEAEs were headache (29 [45%] patients in the rozanolixizumab 7 mg/kg group, 26 [38%] in the rozanolixizumab 10 mg/kg group, and 13 [19%] in the placebo group), diarrhoea (16 [25%], 11 [16%], and nine [13%]), and pyrexia (eight [13%], 14 [20%], and one [1%]). Five (8%) patients in the rozanolixizumab 7 mg/kg group, seven (10%) in the rozanolixizumab 10 mg/kg group, and six (9%) in the placebo group had a serious TEAE. No deaths occurred. INTERPRETATION: Rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses. Both doses were generally well tolerated. These findings support the mechanism of action of neonatal Fc receptor inhibition in generalised myasthenia gravis. Rozanolixizumab represents a potential additional treatment option for patients with generalised myasthenia gravis. FUNDING: UCB Pharma.

The optimal approach of EBUS-FNA rapid on-site evaluation (ROSE): a five-year experience from a large academic medical center.

INTRODUCTION: Rapid on-site evaluation (ROSE) performed during endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA) has shown significant value. However, ROSE may not be available for some pulmonary centers. Performing ROSE can be challenging and stressful due to time constrains for preparing, staining and reviewing the cytology slides between passes. MATERIALS AND METHODS: A retrospective cytology report review of EBUS-FNA procedures performed between October 2014 and May 2019 revealed 516 cases that were included in the study. The number of passes for each procedure was documented. The adequacy rates were assessed at 4 different study points; ≤3 passes, ≤5 passes, at odd passes only, and the even passes only. The study groups results were compared to the overall ROSE and the final cytology adequacy. RESULTS: The overall ROSE interpretation was adequate in 370 (71.7%) and inadequate in 146 (28.3%). After reviewing the Papanicolaou stained slides and cell blocks, the final cytology results were adequate in 473 (91.7%) and inadequate in 43 (8.3%) of the cases. The number of passes per procedure ranged from 1 to 17. Our results showed that ROSE evaluation of the first 5 passes during the EBUS-FNA procedure could achieve the similar adequacy rate compared to the overall ROSE evaluation of all the passes. CONCLUSIONS: To achieve the most benefits of ROSE and to reduce the procedure time for EBUS-FNA, we recommend performing ROSE for ≤5 passes depending on the adequacy, and save all additional passes for cell blocks preparation if more than 5 passes are attempted.

Plasmablastic Lymphomas: Characterization of Tumor Microenvironment Using CD163 and PD-1 Immunohistochemistry.

This study aims to characterize the tumor microenvironment of plasmablastic lymphoma (PBL) in regard to the quantities of CD163(+) tumor associated macrophages (TAM) and PD1(+) tumor infiltrating lymphocytes (TIL). This article also reviews the existing knowledge of the role of PD-1/PD-L1 pathway in the tumor microenvironment of hematopoietic neoplasms, discusses potential mechanisms to explain our findings, and outlines areas for future studies. We performed CD163 and PD1 immunohistochemical studies in 11 cases classified as plasmablastic lymphoma, and recorded the percentages of positive TAMs and TILs. Based on previous studies, cut off values of ≥30% and >5% were used to classify the cases into high TAMs and TILs, respectively. We determined that the majority of cases (8 of 11, or 73%) had high percentage of TAMs, while only a minority had high percentage of TILs (3 of 11, or 27%). Our data shows a trend towards a negative correlation between TAMs and TILs (p=0.08), and a predominance of the pattern TAMhigh/TILlow (7 of 11, or 63%) compared to other patterns. The microenvironment of plasma-blastic lymphoma tends to show high percentage of TAMs (≥30%) combined with low percentage of TILs (≤5%). Additional studies are needed to determine the clinical significance of TILs and the influence of EBV and HIV infections on numbers of TILs in PBL. As high microenvironment TAMs have been associated with high microenvironment PD-L1 in other hematopoietic malignancies, our data supports the need for future studies on the expression of PD-L1 in PBL.

Update on immune-mediated therapies for myasthenia gravis.

With the exception of thymectomy, immune modulatory treatment strategies and clinical trials in myasthenia gravis over the past 50 y were mainly borrowed from experience in other nonneurologic autoimmune disorders. The current experimental therapy paradigm has significantly changed such that treatments directed against the pathological mechanisms specific to myasthenia gravis are being tested, in some cases as the initial disease indication. Key advances have been made in three areas: (i) the expanded role and long-term benefits of thymectomy, (ii) complement inhibition to prevent antibody-mediated postsynaptic membrane damage, and (iii) neonatal Fc receptor (FcRn) inhibition as in vivo apheresis, removing pathogenic antibodies. Herein, we discuss these advances and the potential for these newer therapies to significantly influence the current treatment paradigms. While these therapies provide exciting new options with rapid efficacy, there are anticipated challenges to their use, especially in terms of a dramatic increase in cost of care for some patients with myasthenia gravis.

Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial.

Importance: Many patients with generalized myasthenia gravis (gMG) have substantial clinical disability, persistent disease burden, and adverse effects attributable to chronic immunosuppression. Therefore, there is a significant need for targeted, well-tolerated therapies with the potential to improve disease control and enhance quality of life. Objective: To evaluate the clinical effects of zilucoplan, a subcutaneously (SC) self-administered macrocyclic peptide inhibitor of complement component 5, in a broad population of patients with moderate to severe gMG. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled phase 2 clinical trial at 25 study sites across North America recruited participants between December 2017 and August 2018. Fifty-seven patients were screened, of whom 12 did not meet inclusion criteria and 1 was lost to follow-up after randomization but before receiving study drug, resulting in a total of 44 acetylcholine receptor autoantibody (AChR-Ab)-positive patients with gMG with baseline Quantitative Myasthenia Gravis (QMG) scores of at least 12, regardless of treatment history. Interventions: Patients were randomized 1:1:1 to a daily SC self-injection of placebo, 0.1-mg/kg zilucoplan, or 0.3-mg/kg zilucoplan for 12 weeks. Main Outcomes and Measures: The primary and key secondary end points were the change from baseline to week 12 in QMG and MG Activities of Daily Living scores, respectively. Significance testing was prespecified at a 1-sided α of .10. Safety and tolerability were also assessed. Results: The study of 44 patients was well balanced across the 3 treatment arms with respect to key demographic and disease-specific variables. The mean age of patients across all 3 treatment groups ranged from 45.5 to 54.6 years and most patients were white (average proportions across 3 treatment groups: 78.6%-86.7%). Clinically meaningful and statistically significant improvements in primary and key secondary efficacy end points were observed. Zilucoplan at a dose of 0.3 mg/kg SC daily resulted in a mean reduction from baseline of 6.0 points in the QMG score (placebo-corrected change, -2.8; P = .05) and 3.4 points in the MG Activities of Daily Living score (placebo-corrected change, -2.3; P = .04). Clinically meaningful and statistically significant improvements were also observed in other secondary end points, the MG Composite and MG Quality-of-Life scores. Outcomes for the 0.1-mg/kg SC daily dose were also statistically significant but slower in onset and less pronounced than with the 0.3-mg/kg dose. Rescue therapy (intravenous immunoglobulin or plasma exchange) was required in 3 of 15, 1 of 15, and 0 of 14 participants in the placebo, 0.1-mg/kg zilucoplan, and 0.3-mg/kg zilucoplan arms, respectively. Zilucoplan was observed to have a favorable safety and tolerability profile. Conclusions and Relevance: Zilucoplan yielded rapid, meaningful, and sustained improvements over 12 weeks in a broad population of patients with moderate to severe AChR-Ab-positive gMG. Near-complete complement inhibition appeared superior to submaximal inhibition. The observed safety and tolerability profile of zilucoplan was favorable. Trial Registration: ClinicalTrials.gov Identifier: NCT03315130.

Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience.

Yttrium-90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000-patient cohort acquired over a 15-year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child-Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention-to-treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty-three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty-eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5-80.3) months, BCLC B 25.0 (CI, 17.3-30.5) months, and BCLC C 15.0 (CI, 13.8-17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21-30.2) months, BCLC B 15.0 (CI, 12.3-19.0) months, and BCLC C 8.0 (CI, 6.8-9.5) months. Forty-nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. CONCLUSION: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first-line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).

Appraisal of the Preparedness of Midwives and Nurses in Bahrain to Conduct Early Screening for Zika Virus Infection in Pregnant Women.

OBJECTIVE: To appraise the awareness and knowledge levels of midwives and nurses concerning early screening for Zika virus (ZIKV) infection among pregnant women attending health care facilities in Bahrain. METHODS: This was a cross-sectional, purposely chosen study of Bahraini and expatriate midwives, nurses, and supervisors employed in gynecology/obstetrics and labor wards of Salmanya hospital, a maternity hospital, 4 private hospitals, and health centers in Bahrain. The chosen individuals were invited to participate in a survey on awareness and knowledge of early screening for ZIKV infection. RESULTS: Of 266 midwives and nurses employed in the study sites, 170 (64%) consented to participate in the study. Of those who agreed to participate, 76 were midwives and 94 were nurses. Admittedly, 39% of midwives and nurses were unaware of ZIKV infection. The grand mean knowledge score in the study was 39%. Expatriate midwives and nurses scored better than did Bahrainis (P<0.001). The grand mean knowledge scores of evening and night shift duty participants were significantly higher than those of the day duty participants. CONCLUSIONS: The awareness and knowledge scores of midwives and nurses concerning ZIKV infection were inadequate, which supported our hypothesis. By harnessing modern technology and support systems, lifelong learning can be used as a means to enhance preparedness for public health crises such as ZIKV. (Disaster Med Public Health Preparedness. 2018;12:7-13).

Comparative study of post-transplant outcomes in hepatocellular carcinoma patients treated with chemoembolization or radioembolization.

PURPOSE: To analyze long-term outcomes in patients bridged/downstaged to orthotopic liver transplantation (OLT) by transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y90) for hepatocellular carcinoma (HCC). METHODS: 172 HCC patients who underwent OLT after being treated with transarterial liver-directed therapies (LDTs) (Y90: 93; TACE: 79) were identified. Pre-LDT and pre-OLT clinical/imaging/laboratory characteristics including United Network for Organ Sharing (UNOS) staging and alpha-fetoprotein values (AFP) were tabulated. Post-OLT HCC recurrence was assessed by imaging follow-up per standard of care. Recurrence-free (RFS) and overall survival (OS) were calculated. Uni/multivariate and sub-stratification analyses were performed. RESULTS: Time-to-OLT was longer in the Y90 group (Y90: 6.5 months; TACE: 4.8 months; p=0.02). With a median post-OLT follow-up of 26.1 months (IQR: 11.1-49.7), tumor recurrence was found in 6/79 (8%) TACE and 8/93 (9%) Y90 patients. Time-to-recurrence was 26.6 (CI: 7.0-49.5) and 15.9 months (CI: 7.8-46.8) for TACE and Y90, respectively (p=0.48). RFS (Y90: 79 months; TACE: 77 months; p=0.84) and OS (Y90: 57% alive at 100 months; TACE: 84.2 months; p=0.57) were similar. 54/155 patients (Y90: 29; TACE: 25) were downstaged to UNOS T2 or less. RFS hazard ratios for patients downstaged to ≤T2 versus those that were not were 0.6 (CI: 0.33-1.1) and 1.7 (CI: 0.9-3.1) respectively (p=0.13). 17/155 patients (Y90: 8; TACE: 9) that were >T2 were downstaged to UNOS T2 or less (within transplant criteria). Distribution (unilobar/bilobar), AFP, and pre-transplant UNOS stage affected RFS on univariate analyses. CONCLUSION: Despite longer time-to-OLT for Y90 patients, post-OLT outcomes were similar between patients bridged or downstaged by TACE or Y90. A trend towards improved RFS for downstaged patients was identified.

Transarterial approaches to primary and secondary hepatic malignancies.

Transarterial therapies in the setting of primary and secondary liver malignancies are becoming an essential part of the oncology landscape. Most patients with hepatic malignancies are not candidates for curative surgical intervention, thereby warranting exploration of alternative means of treatment that preserves quality of life while providing clinical benefit. Herein, the data for intra-arterial chemoinfusion, transarterial chemoembolization, drug-eluting beads, and radioembolization are discussed in the setting of malignancies within the liver; outcome data relating to survival, time-to-progression, time-to-recurrence, and adverse events are presented. Further data regarding different treatment paradigms for hepatocellular carcinoma, metastatic colorectal carcinoma, neuroendocrine tumours, and intrahepatic cholangiocarcinoma are also provided. In light of these and forthcoming data, transarterial therapies seem to offer a viable treatment pathway for select populations of patients.

Locoregional therapy of hepatocellular carcinoma.

Hepatocellular carcinoma can be treated using minimally invasive, image-guided, catheter-based or percutaneous techniques. Such procedures offer compelling clinical outcomes with a favorable side-effect profile in a population of patients who are poor candidates for surgical or systemic treatment. This article discusses key data regarding the effectiveness of locoregional therapies in treating these patients. Disease-specific treatment is discussed in the context of hepatocellular carcinoma, with additional data discussed in the context of transplantation. As rapid innovation occurs in the realm of oncology, interventional oncology represents a safe, effective alternative that continues to generate impressive data that could potentially change treatment paradigms.

Pretransplant Portal Vein Recanalization-Transjugular Intrahepatic Portosystemic Shunt in Patients With Complete Obliterative Portal Vein Thrombosis.

BACKGROUND: Chronic, obliterative portal vein (PV) thrombosis (PVT) represents a relative contraindication to liver transplantation (LT) in some centers. When PV thromboembolectomy is not feasible, alternative techniques (portacaval hemitransposition, portal arterialization, multivisceral transplantation) are associated with suboptimal outcomes. In cases where a chronically thrombosed PV has become obliterated, we developed PV recanalization (PVR)-transjugular intrahepatic portosystemic shunt (TIPS) to potentiate LT. We evaluated the impact of PVR-TIPS on liver function, transplant eligibility, and long-term outcomes after LT. METHODS: Forty-four patients with chronic obliterative main PVT were identified during our institutional LT selection committee. After joint imaging review by transplant surgery/radiology, these patients underwent PVR-TIPS to potentiate transplant eligibility. Patients were followed by hepatology/transplant until LT, and ultimately in posttransplant clinic. The TIPS venography and serial ultrasound/MRI were used subsequently to document PV patency. RESULTS: The main PV (MPV) was completely thrombosed in 17 of 44 (39%) patients; near complete (>95%) occlusion was noted in 27 of 44 (61%) patients. Direct transhepatic and transsplenic punctures were required in 11 of 43 (26%) and 3 of 43 (7%) cases, respectively. Technical success was 43 of 44 (98%) cases. At PVR-TIPS completion, persistence of MPV thrombus was noted in 33 of 43 (77%) cases. One-month TIPS venography demonstrated complete resolution of MPV thrombosis in 22 of 29 (76%) without anticoagulation. Thirty-six patients were listed for transplantation; 18 (50%) have been transplanted. Eighty-nine percent MPV patency rate and 82% survival were achieved at 5 years. CONCLUSIONS: The PVR-TIPS may be considered for patients with obliterative PVT who are otherwise appropriate candidates for LT. The high rate of MPV patency post-TIPS placement suggests flow reestablishment as the dominant mechanism of thrombus resolution.