New perspectives in hepatocellular carcinoma surveillance after hepatitis C virus eradication.

Achieving a sustained virologic response (SVR) through direct-acting antivirals for hepatitis C virus (HCV) infection significantly reduces the long-term risk of hepatocellular carcinoma (HCC), particularly in patients with advanced fibrosis (F3) or cirrhosis (F4). However, despite this improvement, the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate. This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively, especially at advanced fibrosis (F3), and the unclear cost-effectiveness, modality, frequency, and duration of HCC surveillance in individuals with SVR but without cirrhosis. These factors contribute to significant variations in surveillance guidelines recommended by different professional societies. Therefore, there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians. This review article evaluates the existing data, addresses ongoing controversies, and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV.

Metapipeline-DNA: A Comprehensive Germline & Somatic Genomics Nextflow Pipeline.

Summary: DNA sequencing is becoming more affordable and faster through advances in high-throughput technologies. This rise in data availability has contributed to the development of novel algorithms to elucidate previously obscure features and led to an increased reliance on complex workflows to integrate such tools into analyses pipelines. To facilitate the analysis of DNA sequencing data, we created metapipeline-DNA, a highly configurable and extensible pipeline. It encompasses a broad range of processing including raw sequencing read alignment and recalibration, variant calling, quality control and subclonal reconstruction. Metapipeline-DNA also contains configuration options to select and tune analyses while being robust to failures. This standardizes and simplifies the ability to analyze large DNA sequencing in both clinical and research settings. Availability: Metapipeline-DNA is an open-source Nextflow pipeline under the GPLv2 license and is freely available at https://github.com/uclahs-cds/metapipeline-DNA.

Changes in use of acute and preventive medications for migraine after erenumab initiation over 12 months: A United States retrospective cohort study.

OBJECTIVE: To assess changes in real-world use of acute and preventive medications for migraine over a 12-month follow-up period in the United States following initiation of the anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb) erenumab. BACKGROUND: Early assessments of real-world use of acute and preventive medications for migraine after initiation of erenumab have been limited to 6 months of follow-up. METHODS: This retrospective cohort study used data from the IQVIA open-source longitudinal prescription (LRx) and medical (Dx) claims databases. Adult patients with an initial claim (index date) for erenumab between May 2018 and April 2020 were identified. RESULTS: Among 201,176 patients who met inclusion criteria, the mean (standard deviation [SD]) age was 47.5 (13.8) years and 85.6% (n = 172,153) were female. Most patients used one or more acute (88.4%; n = 177,795) and one or more traditional preventive (86.1%; n = 173,225) medications during the 12-month pre-index period. Adherence to erenumab (proportion of days covered [PDC] ≥0.80) was 40.2% (n = 80,927) with an overall mean (SD) PDC of 0.60 (0.34). Among all patients, 70.0% (n = 140,809) discontinued erenumab. After accounting for 24.7% (n = 49,720) of patients who restarted erenumab, discontinuation without reinitiation was observed in 45.3% (n = 91,089) of total patients. Switching to a different anti-CGRP pathway mAb was observed in 13.1% (n = 26,446) of total patients. Among 177,795 patients with pre-index use of one or more acute migraine medication class, 86.5% (n = 153,788) had post-index use of the same class, and 56.7% (87,134/153,788) of them discontinued one or more class of acute medication in the 12-month follow-up period. Similarly, among 173,225 patients with pre-index use of one or more traditional migraine preventive medication class, 67.7% (n = 117,274) had post-index use of the same class, and 46.7% (54,790/117,274) of them discontinued one or more class of traditional preventive medication in the 12-month follow-up period. CONCLUSIONS: In this long-term study, we observed the discontinuation of both acute and preventive medications for migraine post-erenumab initiation.

Demographic and Academic Characteristics of Orthopaedic Shoulder and Elbow Division Chiefs in the United States.

INTRODUCTION: Division Chiefs (DCs) and department leadership play an integral role within the service, and in the department as a whole. The goal of this study was to assess the demographics and academic characteristics of the leadership in orthopedic shoulder and elbow services across academic centers in the United States and comment on the diversity within these leadership positions. METHODS: Academic medical centers were identified using the FRIEDA database. DCs were identified using the hospitals' respective websites where data such as sex, race/ethnicity, academic rank, fellowship institution, and time since graduating fellowship. Scopus database was used to determine individual h-indices. RESULTS: Of 198 academic programs identified, 49 were found to have a DC of the orthopedic shoulder and elbow division. An additional 26 programs were noted to have a shoulder and elbow division, but were not found to have a DC of the division. These DCs were mostly White (n=43, 87.8%), with only 6 identified DCs with a different ethnicity. Forty-five of the DCs (91.8%) were male and 4 were female (8.2%). The average time out of fellowship was 20.7 years and the average h-index was 18.9. More than 20% of the DCs trained at Columbia's Neer shoulder and elbow Fellowship. Six DCs were current or past president of ASES and 5 DCs completed the ASES traveling fellowship. CONCLUSIONS: There is a paucity of available research on demographic and leadership characteristics in academic orthopedic shoulder and elbow. Shoulder and elbow DC had average h-index of 18.9 and 20% trained at one fellowship. There also opportunities for increased gender/racial/ethnic diversity among the leadership of shoulder and elbow divisions.

Recent advancements in management for noncolorectal, nonneuroendocrine hepatic metastases.

BACKGROUND: Owing to the heterogeneity of underlying primary tumors, noncolorectal, nonneuroendocrine metastases to the liver (NCNNMLs), although relatively rare, pose major challenges to treatment and long-term management. Despite being considered the gold standard for colorectal cancer liver metastases, the role of surgical resection for NCNNML remains controversial. Furthermore, advancements in locoregional treatment modalities, such as ablation and various chemotherapeutic modalities, have contributed to the treatment of patients with NCNNML. METHODS: This was a comprehensive review of literature that used Medline/PubMed, Google Scholar, the Cochrane Library, and the Web of Science, which were accessed between 2014 and 2024. RESULTS: NCNNMLs are rare tumor entities with varied presentation and outcomes. A multidisciplinary approach, which includes chemotherapy, surgery, and interventional radiologic techniques, can be implemented with good results. CONCLUSION: Given the complex nature of NCNNML, its management should be highly individualized and multidisciplinary. Locoregional treatments, such as surgical resection and/or ablation, may be more appropriate for select patients and should be offered as a viable therapeutic option for a subset of individuals.

Venous thromboembolism: exploring incidence and utility of screening in individuals with dual diagnosis.

OBJECTIVES: The development of venous thromboembolism (VTE) is a common complication following spinal cord injury (SCI) and brain injury (BI), leading to significant morbidity and mortality. The purpose of this study was to explore the incidence of VTE in patients with the dual diagnosis (DD) of SCI and concomitant BI using ultrasonography. DESIGN: Retrospective study. SETTING: Acute rehabilitation hospital. PARTICIPANTS: Thirty-one individuals admitted for DD rehabilitation who were routinely screened for VTE with ultrasound on admission. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Retrospective chart review was performed to identify whether patients were found to have DVT or PE at the following three time points: in acute care prior to admission to rehabilitation, at time of admission diagnosed via screening examination, and after admission to rehabilitation during the inpatient stay via post screening examinations. Retrospective chart review was also performed to identify incidence of bleeding. RESULTS: 67.7% of individuals were found to have DVTs at any timepoint. Of these DVTs, 22.6% were identified in acute care, 48.4% on admission to rehabilitation, and 16.1% during the course of rehabilitation stay. Of those who were placed on therapeutic anticoagulation due to admission diagnosis of VTE, 25% developed recurrent DVT and 12.5% had bleeding complications. No cases of PE were observed in this study population. CONCLUSIONS: This study found a high incidence of DVT for the DD population at all three timepoints with a high proportion identified via screening ultrasonography on admission to rehabilitation. Further research is needed to investigate the incidence of VTE and utility of screening ultrasonography in this population.

Abiotic and biotic factors jointly influence the contact and environmental transmission of a generalist pathogen.

The joint influence of abiotic and biotic factors is important for understanding the transmission of generalist pathogens. Abiotic factors such as temperature can directly influence pathogen persistence in the environment and will also affect biotic factors, such as host community composition and abundance. At intermediate spatial scales, the effects of temperature, community composition, and host abundance are expected to contribute to generalist pathogen transmission. We use a simple transmission model to explain and predict how host community composition, host abundance, and environmental pathogen persistence times can independently and jointly influence transmission. Our transmission model clarifies how abiotic and biotic factors can synergistically support the transmission of a pathogen. The empirical data show that high community competence, high abundance, and low temperatures correlate with high levels of transmission of ranavirus in larval amphibian communities. Discrete wetlands inhabited by larval amphibians in the presence of ranavirus provide a compelling case study comprising distinct host communities at a spatial scale anticipated to demonstrate abiotic and biotic influence on transmission. We use these host communities to observe phenomena demonstrated in our theoretical model. These findings emphasize the importance of considering both abiotic and biotic factors, and concomitant direct and indirect mechanisms, in the study of pathogen transmission and should extend to other generalist pathogens with the capacity for environmental transmission.

Characterizing drug-induced epidermal necrolysis in a pediatric cohort.

This study aims to characterize the timeline and clinical features of onset, progression, and management of drug-induced epidermal necrolysis in pediatric patients. Sixteen pediatric patients were retrospectively identified and selected if under age 18 years at admission with one identified culprit drug exposure. Culprit drugs were antiepileptics (12/16, 75%) and antibiotics (4/16, 25%). Notably, anti-epileptic drugs (AED) had delayed onset and reported dose escalations that precipitated symptom onset; thus, patients prescribed AED with or without planned dose escalations should be monitored for prodromal symptoms longer than the typical onset window.

Neurorehabilitation with vagus nerve stimulation: a systematic review.

Objective: To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). Methods: Data sources: PubMed, EMBASE, SCOPUS, and Cochrane. Study selection: Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery. Data extraction: Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically. Data synthesis: Twenty-nine studies were included; 11 were animal models of stroke, TBI, and SCI, and eight involved humans with stroke. While there was heterogeneity in methods of delivering VNS with respect to rehabilitation therapy in animal studies and human non-invasive studies, a similar methodology was used in all human-invasive VNS studies. In animal studies, pairing VNS with rehabilitation therapy consistently improved motor outcomes compared to controls. Except for one study, all human invasive and non-invasive studies with controls demonstrated a trend toward improvement in motor outcomes compared to sham controls post-intervention. However, compared to non-invasive, invasive VNS, studies reported severe adverse events such as vocal cord palsy, dysphagia, surgical site infection, and hoarseness of voice, which were found to be related to surgery. Conclusion: Our review suggests that VNS (non-invasive or invasive) paired with rehabilitation can improve motor outcomes after stroke in humans. Hence, VNS human studies are needed in people with TBI and SCI. There are risks related to device implantation to deliver invasive VNS compared to non-invasive VNS. Future human comparison studies are required to study and quantify the efficacy vs. risks of paired VNS delivered via different methods with rehabilitation, which would allow patients to make an informed decision. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=330653.

Robotic management of huge hepatic angiomyolipoma: A case report and literature review.

Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal liver tumor encountered in Asia, primarily in females, and can be found within the right hepatic lobe, but also in other areas of the liver. Immunohistochemically, HAMLs are characteristically positive for human melanoma black-45 antigen (HMB-45) and can histochemically vary in the composition of angiomatous, lipomatous, and myomatous tissue, together with the presence of epithelioid cells. In this case report, we discuss a previously healthy patient presenting with bloating and previously documented concern of liver lesions, found to have HAML confirmed by surgical pathology. Surgery was decided, as HAMLs greater than 10 cm are at risk of rupture. This is one of the first documented cases of HAML resected through robot-assisted bisegmentectomy and cholecystectomy, and therefore, intraoperative images have been included to assist in the planning of future robotic cases.

Disparities in Cancer Mortality among Disaggregated Asian American Subpopulations, 2018-2021.

Federal, state, and institutional data collection practices and analyses involving Asian Americans as a single, aggregated group obscure critical health disparities among the vast diversity of Asian American subpopulations. Using from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Causes of Death database, we conducted a cross-sectional study using data on disaggregated Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, other Asians) between 2018 and 2021. We examine deaths from 22 cancer types and in situ, benign neoplasms, identified using ICD-10 codes C00-C97 and D00-D48. Overall, our study comprised 327,311 Asian American decedents, with a mean age of death at 70.57 years (SD=2.79), wherein females accounted for approximately half of the sample (n=36,596/73,207; 49.99%). Notably, compared to the aggregated Asian American reference group, we found higher proportions of deaths from total cancers among Chinese (25.99% vs. 22.37% [ref]), Korean (25.29% vs. 22.37% [ref]), and Vietnamese (24.98% vs. 22.37% [ref]) subgroups. In contrast, total cancer deaths were less prevalent among Asian Indians (17.49% vs. 22.37% [ref]), Japanese (18.90% vs. 22.37% [ref]), and other Asians (20.37% vs. 22.37% [ref]). We identified further disparities by cancer type, sex, and age. Disaggregated data collection and analyses are imperative to understanding differences in cancer mortality among Asian American subgroups, illustrating at-risk populations with greater granularity. Future studies should aim to describe the association between these trends and social, demographic, and environmental risk factors.

Animal Bites and Attacks.

This text serves to familiarize readers with animal bites and attacks. Topics include appropriate management of animal bite wounds, postexposure prophylaxis for possible rabies exposures, and unique infectious diseases transmitted through animal vectors. Large mammal attacks are discussed, in addition to the management of smaller animal attacks and exposures.

Multiple myeloma incidence and mortality trends in the United States, 1999-2020.

Multiple myeloma (MM) is a plasma cell disorder accounting for approximately 10% of hematologic malignancies. There is limited epidemiological evidence regarding the long-term trends and disparities in MM in the US. We conducted a multiple time point cross-sectional study using MM incidence rate data from the Surveillance, Epidemiology, and End Results (SEER) database and mortality data from the CDC Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Cause of Death database between 1999 and 2020. During this period, MM incidence has steadily increased, while MM mortality has steadily decreased, with substantial racial and ethnic disparities. Non-Hispanic Black individuals exhibited the highest incidence rates, which consistently rose from 12.02 (95% CI 10.54, 13.64) in 1999 to 14.20 (95% CI 12.93, 15.55) per 100,000 population by 2020. Non-Hispanic American Indian/Native Alaskans and Asian/Pacific Islanders demonstrated the lowest incidence rates of 5.59 (95% CI 2.69, 10.04) and 3.56 (95% CI 2.94, 4.27) per 100,000 population in 1999 to 5.76 (95% CI 3.49, 8.90) and 3.92 (95% CI 3.46, 4.42) per 100,000 population, respectively, by 2020. Disparities by gender, age, US census region, and rurality were observed, underscoring the importance of targeted, equity-centered interventions and MM screening initiatives for at-risk populations.

Comprehensive review of clinical presentation, diagnosis, management, and prognosis of ruptured hepatocellular carcinoma.

BACKGROUND: Spontaneous rupture of hepatocellular carcinoma (rHCC) is a life-threatening complication that occurs in 3 % to 15 % of patients with hepatocellular carcinoma (HCC). This review aimed to discuss the most recent updates in the epidemiology, pathophysiology, risk factors, diagnosis as well as presentation, management, and prognostic factors of rHCC. METHODS: A comprehensive systematic review was conducted using Medline/PubMed and Web of Science databases with the end of search date being December 1, 2023 regarding rHCC diagnosis, imaging, and management. RESULTS: Achieving adequate hemostasis and stabilization of the patient remains the primary objective in the management of patients with rHCC. In earlier studies, the mortality rate in the acute phase of rHCC was reported to be 25 % to 75 %. However, more recent studies have demonstrated that transcatheter arterial embolization (TAE)/transcatheter arterial chemoembolization (TACE) followed by elective hepatectomy in select patients may offer improved survival benefits and decrease perioperative complications compared with TAE/TACE alone or emergent/1-stage hepatectomy. CONCLUSION: Although the prognosis for rHCC remains the worst among causes of death related to HCC, more recent studies have demonstrated that improved short- and long-term patient outcomes may be achieved through active surveillance efforts for HCC combined with advanced multimodal diagnostic tools and multidisciplinary management strategies.

BTN1A1 is a novel immune checkpoint mutually exclusive to PD-L1.

BACKGROUND: While Programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockade is a potent antitumor treatment strategy, it is effective in only limited subsets of patients with cancer, emphasizing the need for the identification of additional immune checkpoints. Butyrophilin 1A1 (BTN1A1) has been reported to exhibit potential immunoregulatory activity, but its ability to function as an immune checkpoint remains to be systematically assessed, and the mechanisms underlying such activity have yet to be characterized. METHODS: BTN1A1 expression was evaluated in primary tumor tissue samples, and its ability to suppress T-cell activation and T cell-dependent tumor clearance was examined. The relationship between BTN1A1 and PD-L1 expression was further characterized, followed by the development of a BTN1A1-specific antibody that was administered to tumor-bearing mice to test the amenability of this target to immune checkpoint inhibition. RESULTS: BTN1A1 was confirmed to suppress T-cell activation in vitro and in vivo. Robust BTN1A1 expression was detected in a range of solid tumor tissue samples, and BTN1A1 expression was mutually exclusive with that of PD-L1 as a consequence of its inhibition of Janus-activated kinase/signal transducer and activator of transcription signaling-induced PD-L1 upregulation. Antibody-mediated BTN1A1 blockade suppressed tumor growth and enhanced immune cell infiltration in syngeneic tumor-bearing mice. CONCLUSION: Together, these results confirm that the potential of BTN1A1 is a bona fide immune checkpoint and a viable immunotherapeutic target for the treatment of individuals with anti-PD-1/PD-L1 refractory or resistant disease, opening new avenues to improving survival outcomes for patients with a range of cancers.

Adamantinoma of the Ulnar Shaft Reconstructed With a Vascularized Free Fibula.

We describe a 36-year-old man with a long-standing diagnosis of ulnar fibrous dysplasia with associated fracture of the ulna. He presented with a growing and increasingly tender forearm mass and was diagnosed with adamantinoma of the ulna, for which he underwent wide resection of the ulnar diaphysis followed by reconstruction with a vascularized fibula autograft. This case serves to emphasize the importance of performing a stepwise workup for the diagnosis of osseous neoplasms even in cases with long-standing diagnoses. [Orthopedics. 2024;47(2):e102-e105.].

Effects of circulating endothelial microvesicles isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide production.

Circulating endothelial cell-derived microvesicles (EMVs) have been shown to be elevated with obesity and associated with endothelial dysfunction; however, their direct effect on endothelial cells is unknown. The experimental aim of this study was to determine the effect of EMVs isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide (NO) production. EMVs (CD144+ microvesicles) were identified, enumerated, and isolated from plasma by flow cytometry from 24 sedentary adults: 12 normal-weight adults [8 M/4 F; age: 55 ± 6 yr; body mass index (BMI): 24.3 ± 0.7 kg/m2; EMV: 144 ± 53 EMVs/µL] and 12 adults with obesity (6 M/6 F; 59 ± 7 yr; BMI: 31.0 ± 1.1 kg/m2; EMV: 245 ± 89 EMVs/µL). Human umbilical vein endothelial cells were cultured and treated with EMVs from either normal-weight adults or adults with obesity. EMVs from obese adults induced significantly higher release of interleukin (IL)-6 (108.2 ± 7.7 vs. 90.9 ± 10.0 pg/mL) and IL-8 (75.4 ± 9.8 vs. 59.5 ± 11.5 pg/mL) from endothelial cells vs. EMVs from normal-weight adults, concordant with greater intracellular expression of phosphorylated NF-κB p65 (Ser536; active NF-κB) [145.0 ± 34.1 vs. 114.5 ± 30.4 arbitrary units (AU)]. Expression of phosphorylated p38-MAPK (15.4 ± 5.7 vs. 9.2 ± 2.5 AU) and active caspase-3 (168.2 ± 65.5 vs. 107.8 ± 40.5 AU), markers of cell apoptosis, was higher in cells treated with obesity-related EMVs. Phosphorylated endothelial nitric oxide synthase (eNOS) (Ser1177) expression (23.5 ± 7.2 vs. 34.7 ± 9.7 AU) and NO production (6.9 ± 1.4 vs. 8.7 ± 0.7 µmol/L) were significantly lower in the cells treated with EMVs from obese adults. These data indicate that circulating EMVs from adults with obesity promote a proinflammatory, proapoptotic, and NO-compromised endothelial phenotype. Circulating EMVs are a potential mediator of obesity-related endothelial dysfunction.NEW & NOTEWORTHY In the present study, we determined the effect of circulating endothelial cell-derived microvesicles (EMVs) isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide (NO) production in vitro. Circulating EMVs harvested from adults with obesity promoted a proinflammatory, proapoptotic, and NO-compromised endothelial phenotype. Elevated circulating EMVs in adults with obesity, independent of other cardiometabolic risk factors, are a potential novel systemic mediator of obesity-related endothelial dysfunction and vascular risk.

Development of a Hypercoagulable-Hypofibrinolytic State Early After Spinal Cord Injury.

OBJECTIVES: To determine whether spinal cord injury (SCI) is associated with adverse changes in coagulation and fibrinolytic factors that underlie thrombogenesis and contribute to atherothrombotic events such as myocardial infarctions (MIs) and strokes. DESIGN: Cross-sectional study. SETTING: Neurorehabilitation hospital and general community. PARTICIPANTS: Thirty young and middle-aged (20-58 years) adults (N=30) were studied: 14 non-injured community dwelling adults. (11M/4F) and 16 with subacute tetraplegic motor complete SCI during initial inpatient rehabilitation (13M/3F; time since injury: 11.8±5.3 wk). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Circulating markers of coagulation [von Willebrand factor (vWf) and factors VII, VIII, and X], the fibrinolytic system [tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) antigen and activity], and fibrin formation (D-dimer) were determined by enzyme immunoassay. RESULTS: Thirty young and middle-aged (20-58 years) adults were studied: 14 non-injured (11M/4F) and 16 with subacute tetraplegic motor complete SCI (13M/3F; time since injury: range 4-25 wk). Circulating levels of coagulation factors VII, VIII, and X were significantly higher (∼20%-45%; P<.05) in the adults with SCI than non-injured adults, whereas vWf was similar between groups. Fibrinolytic markers were adversely disrupted with SCI with t-PA antigen, PAI-1 antigen and PAI-1 activity were markedly higher (∼50%-800%; P<.05) in adults with SCI compared with non-injured adults. The molar concentration ratio of active t-PA to PAI-1 was significantly higher (∼350%) in adults with SCI. Concordant with coagulation cascade activation and fibrinolytic system inhibition, D-dimer concentrations were markedly ∼70% higher (P<.05) in adults with SCI compared with non-injured adults. CONCLUSIONS: Subacute tetraplegic motor complete SCI is associated with a prothrombotic hemostatic profile. Adverse changes in the coagulation cascade and fibrinolytic system appear to occur early after injury and may contribute to the increased atherothrombotic risk in adults living with SCI.