Citations

Importance Given the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed. Objective To examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population. Design, Setting, and Participants This cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023. Exposure Regular statin use. Main Outcomes and Measures Primary outcomes were liver disease and HCC development as well as liver-associated death. Results A total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P < .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02). Conclusions and Relevance This cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

Background: Nasal septal perforation repair is commonly attempted utilizing bilateral nasal mucosal flaps supported with an interposition graft. Objectives: To compare the failure rates for bilateral flap repairs utilizing four different autologous interposition grafts. Methods: This is a retrospective review of a single surgeon's bilateral flap perforation repairs supported with an autologous interposition graft. Study inclusion over the 18-year review period required at least one examination 1 month after surgery. Repair failure rates were calculated and compared for each graft type, and logistic regression was performed for multivariate analysis. Results: For the 356 study patients, median (range) age was 51 years (14–81) and 63.0% were women. Mean (range) perforation length was 13.9 mm (1–45). Median (range) at last follow-up was 11.2 months (1–192). Graft types used (percentage of patients and failure rate) were temporalis fascia (58.7/4.4), septal cartilage (23.3/7.3), auricular perichondrium (13.8/4.1), and septal bone (4.2/6.7) ( p > 0.05). Conclusion: There was no significant difference in bilateral mucosal flap perforation repair failure rate when either a temporalis fascia, septal cartilage, auricular perichondrium, or septal bone interposition graft was used.

Hepatic angiosarcomas are aggressive malignant tumors of the liver with variable morphology. One of the rare morphologies is that of the sinusoidal growth pattern, which is challenging to diagnose because of its subtle imaging and morphologic findings. This retrospective study characterizes the clinical, histologic, and immunohistochemical features of sinusoidal hepatic angiosarcomas. Thirteen cases were included in the study, comprising 12 (92.3%) needle core biopsies and 1 wedge biopsy; one of the needle biopsies also had a subsequent resection specimen available for review. Multiple biopsies were needed to make the diagnosis in 4 cases. At least moderate sinusoidal dilatation was seen in 53.8% of cases. Increased cellularity within the sinusoids was seen at both low-power and high-power magnification (69.2% and 84.6%, respectively). Cytologic atypia ranged from mild to marked. Multinucleated tumor cells were present in most cases (10/13 cases) but were often sparse. Mitotic activity was identified in 5/13 cases. ERG immunostains were more reliable than CD31 and CD34 in identifying the tumor cells. Ki-67 proliferative index ranged from 5% to 30%. p53 immunostains were available in 9 cases and c-MYC in 7 cases; they were positive in 62.5% and 33.3% of cases, respectively and had a mutually exclusive staining pattern. In summary, this rare pattern of hepatic angiosarcoma is challenging to diagnose but has distinctive morphologic findings that can be supplemented with immunostains to establish the diagnosis.

Abstract Disease Overview Polycythemia vera (PV) is a JAK2 ‐mutated myeloproliferative neoplasm characterized by clonal erythrocytosis; other features include leukocytosis, thrombocytosis, splenomegaly, pruritus, constitutional symptoms, microcirculatory disturbances, and increased risk of thrombosis and progression into myelofibrosis (post‐PV MF) or acute myeloid leukemia (AML). Diagnosis A working diagnosis is considered in the presence of a JAK2 mutation associated with hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women; morphologic confirmation by bone marrow examination is advised but not mandated. Cytogenetics Abnormal karyotype is seen in 15%–20% of patients with the most frequent sole abnormalities being +9 (5%), loss of chromosome Y (4%), +8 (3%), and 20q− (3%). Mutations Over 50% of patients harbor DNA sequence variants/mutations other than JAK2 , with the most frequent being TET2 (18%) and ASXL1 (15%). Prognostically adverse mutations include SRSF2, IDH2, RUNX1 , and U2AF1 , with a combined incidence of 5%–10%. Survival and Prognosis Median survival is ⁓15 years but exceeds 35 years for patients aged ≤40 years. Risk factors for survival include older age, leukocytosis, abnormal karyotype, and the presence of adverse mutations. Twenty‐year risk for thrombosis, post‐PV MF, or AML are ⁓26%, 16% and 4%, respectively. Risk Factors for Thrombosis Two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors). Additional predictors for arterial thrombosis include cardiovascular risk factors and for venous thrombosis higher absolute neutrophil count and JAK2 V617F allele burden. Treatment Current goal of therapy is to prevent thrombosis. Periodic phlebotomy, with a hematocrit target of <45%, combined with once‐ or twice‐daily aspirin (81 mg) therapy, absent contraindications, is the backbone of treatment in all patients, regardless of risk category. Cytoreductive therapy is reserved for high‐risk disease with first‐line drugs of choice being hydroxyurea and pegylated interferon‐α and second‐line busulfan and ruxolitinib. In addition, systemic anticoagulation is advised in patients with venous thrombosis history. Additional Treatment Considerations At the present time, we do not consider a drug‐induced reduction in JAK2 V617F allele burden, which is often incomplete and seen not only with peg‐IFN but also with ruxolitinib and busulfan, as an indicator of disease‐modifying activity, unless accompanied by cytogenetic and independently‐verified morphologic remission. Accordingly, we do not use the specific parameter to influence treatment choices. The current review also includes specific treatment strategies in the context of pregnancy, splanchnic vein thrombosis, pruritus, perioperative care, and post‐PV MF.

Lipoprotein(a) [Lp(a)] is a lipid molecule with atherogenic, inflammatory, thrombotic, and antifibrinolytic effects, whose concentrations are predominantly genetically determined. The association between Lp(a) and cardiovascular diseases (CVDs) has been well-established in numerous studies, and the ability to measure Lp(a) levels is widely available in the community. As such, there has been increasing interest in Lp(a) as a therapeutic target for the prevention of CVD. The impact of the currently available lipid-modifying agents on Lp(a) is modest and heterogeneous, except for the monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), which demonstrated a significant reduction in Lp(a) levels. However, the absolute reduction in Lp(a) to significantly decrease CVD outcomes has not been definitely established, and the magnitude of the effect of PCSK9i seems insufficient to directly reduce the Lp(a)-related CVD risk. Therefore, emerging therapies are being developed that specifically aim to lower Lp(a) levels and the risk of CVD, including RNA interference (RNAi) agents, which have the capacity for temporary and reversible downregulation of gene expression. This review article aims to summarize the effects of Lp(a) on CVD and to evaluate the available evidence on established and emerging therapies targeting Lp(a) levels, focusing on the potential reduction of CVD risk attributable to Lp(a) concentrations.

Background The Woven EndoBridge (WEB) has been specifically developed to manage wide neck bifurcation intracranial aneurysms. A wide range of aneurysm occlusion rates and device-related complications are reported in different papers, and a lack of collective evidence in this regard. Objective To clarify the long-term efficacy and safety outcomes of intracranial aneurysm treatment with WEB devices. Methods A systematic literature search was performed on PubMed, Scopus, Web of Science, and Embase databases on April 25, 2023. Considering the eligibility criteria, all the studies reporting the outcomes of the intracranial aneurysm treatment with WEB device at 1 and/or more than 1 year were included. Data elements of interest were extracted and analyzed using R software version 4.2.1. Results Twenty-seven articles were included. Complete occlusion rate was 56.85%, 67.10%, and 56.34% at one year, beyond one year, and at/beyond two years of follow-up, respectively. Adequate occlusion rate was 87.11% at one year, 91.16% beyond one year, and 88.87% at/beyond two years of follow-up. WEB compression and aneurysm recurrence rates increased from 17.62% and 0.58% at one year to 42.59% and 18.99% beyond one year of follow-up, respectively. An increase in retreatment rate from 3.45% at one year to 7.15% beyond one year of follow-up was found. Conclusion The current study supports the long-term efficacy of WEB devices for the treatment of intracranial aneurysms. However, an increase in WEB compression, aneurysm recurrence, and retreatment rates beyond one year reveals the importance of follow-ups after the first year of WEB placement.

Assess agreement of hypernasality and audible nasal emission (ANE) ratings between audio-recordings and a clinic setting. Cross-sectional study using retrospective clinical recordings. Audio-recording ratings by two trained speech language pathologists. Percent agreement and intra- and inter-rater reliability of perceptual ratings. Intra-rater reliability (AC2) of 167 audio-recorded speech samples for the primary and secondary raters, respectively, was 0.82 and 0.79 for hypernasality; for ANE, it was 0.57 and 0.75. Inter-rater reliability was 0.77 for hypernasality and 0.63 for ANE. When comparing ratings made from audio-recording versus the original clinical ratings, intra-rater reliability was 0.85 and 0.61 (primary and secondary rater, respectively) for hypernasality and 0.21 and 0.34 for ANE. Ratings for hypernasality made from audio recordings were consistent with clinical evaluation, while ratings of ANE were not. ANE ratings made from audio recordings may not be a valid measure of velopharyngeal insufficiency speech characteristics.