Citations

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health threat, potentially leading to chronic liver disease and liver cancer. Current guidelines recommend using the Fibrosis-4 score for initial identification of subjects at risk of future complications. We formulate a novel population screening strategy based on the Steatosis-Associated Fibrosis Estimator (SAFE) score, recently developed for MASLD risk stratification in primary care. METHODS: We interrogated the National Health and Nutrition Examination Survey data, 2017–20, in which a sample of subjects representative of US civilian population underwent vibration-controlled transient elastography (VCTE). The current guideline and a new, SAFE-based proposal were applied to these data to project the number of subjects to be diagnosed with liver fibrosis gauged by liver stiffness measurement (LSM), including significant (LSM ≥8 kPa) and advanced (LSM ≥12 kPa) fibrosis, as well as the number of VCTEs to be performed. RESULTS: In the survey data, 2,691 subjects, projecting to 75.8 million US adults, were found to have MASLD, of whom 11% had LSM 8–12 kPa and 6% LSM ≥12 kPa. When the current guideline was applied, 18.1 million VCTEs would be needed to diagnose 3.5 million subjects with LSM ≥8 kPa and 1.7 million subjects with LSM ≥12 kPa. In comparison, a new approach based on the SAFE score would detect 4.9 million with LSM ≥8 kPa and 2.5 million subjects with LSM ≥12 kPa (37% and 45% improvement over the current guideline, respectively), while requiring 5.0 million fewer VCTEs (28% reduction). DISCUSSION: The proposed population risk stratification approach using the SAFE score is simpler and substantially more effective, yielding more subjects with liver fibrosis while requiring less resources compared with the currently recommended algorithm.

ABSTRACT Background: Neutrophil extracellular traps (NETs), and its formation and release, known as NETosis, may play a role in the initiation of thrombin generation (TG) in trauma. The objective of this study was to assess whether trauma patients, who develop symptomatic venous thromboembolism (VTE), have increased levels of plasma citrullinated histone H3 (CitH3) and accelerated TG kinetics. Methods: Patients presenting to a level I trauma center as trauma activations had samples collected within 12 h of time of injury, alongside healthy volunteers (HV). CitH3 was measured by enzyme-linked immunosorbent assay, and TG data were measured using a TG analyzer, comparing results between patients developing symptomatic VTE versus those who did not, within 90 days of injury. Data were expressed as median and quartiles (Q1, Q3), and tested using Wilcoxon rank-sum or Fisher’s exact test, or 1-sample test of Spearman’s correlation, P < 0.05 considered significant. Results: 39 trauma patient samples were analyzed (10 with and 29 without VTE), and compared to 15 HV samples. CitH3 levels in patients who developed VTE were significantly greater as compared to those who did not (12.8 ng/mL [7.1, 30.8]; 3.0 ng/mL [1.8,6.8], P = 0.024), with levels in both groups greater compared to HV (1.2 [0.3, 4.1], P = 0.003, P = 0.012), respectively. TG profiles were accelerated in patients developing VTE, with differences in peak height (337.6 nM [304.4, 356.0]; 231.8 nM [180.2, 281.8], P = 0.008), endogenous thrombin potential (1718.5 nM*min [1,500, 1794]; 1208.5 nM*min [1,072, 1,417], P = 0.003) and velocity index (213.2 nM/min [162.3, 260.5]; 124.3 nM/min [93.2, 223.1], P = 0.03), respectively. Conclusion: Trauma patients developing VTE exhibit increased NETosis, measured by increased CitH3 levels and accelerated TG early after injury, outlining an area for further understanding VTE after trauma.

Abstract Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies. In this study, we investigated zebrafish mutants of IFT140 , a newly identified ADPKD gene, and observed phenotypes similar to those seen in mammalian models, including kidney cysts and bone defects. Using efficient microhomology-mediated end joining (MMEJ)-based genome editing technology, we demonstrated that ift140 CRISPRants recapitulate mutant phenotypes while bypassing the early lethality of the mutants to allow for renal cyst analysis in adult fish. In addition to cilia defects, non-cilia phenotypes, such as disrupted cell polarity and aberrant microtubule stabilization in kidney epithelial cells, may also contribute to ift140 -associated cystogenesis. Importantly, the ability to detect ift140 -associated renal cysts with ease allowed us to develop an F0-based genetic screen to identify potential protective modifiers. A pilot screen of sixteen genes previously linked to dysregulated signaling pathways in ADPKD revealed both known and novel modifiers, including mtor and ulk1a . Inhibition of mtor and ulk1a reversed both cilia-related and non-cilia-related abnormalities. In summary, our study underscores the potential of using zebrafish as a model for the efficient discovery of genetic modifiers of kidney cysts.

IntroductionUnilateral sphenoid sinus opacification on computed tomography is caused by a variety of pathologies including inflammatory and infectious sinusitis, benign and malignant tumors, and encephaloceles. The purpose of this study was to report craniofacial pain locations and outcomes in inflammatory unilateral sphenoid sinusitis (USS) patients who underwent endoscopic sinus surgery (ESS).MethodsA multi‐institutional retrospective cohort study was conducted on all adult patients who had ESS for USS from 2015 to 2022. Patient demographics, presenting symptoms and nasal endoscopy findings, extent of surgical dissection, and craniofacial pain locations and outcomes were recorded. Exclusion criteria included age <18 years, non‐inflammatory etiology, immunodeficiency, invasive fungal sinusitis, lack of follow‐up, lack of preoperative pain location, and neoplasia. Descriptive statistics were calculated.ResultsOf 57 patients with USS, 44 (77.2%) reported craniofacial pain at one or more locations. Retrobulbar (n = 19, 43.2%) was the most common pain location followed by frontal (n = 17, 38.6%) and occipital (n = 10, 22.7%). Surgical intervention resulted in pain resolution in 33/44 patients (75%), with a mean follow‐up of 83.7 (±97.8) days. There were no significant associations between presenting symptoms, imaging findings, endoscopy, surgical extent, or final pathology and the presence or resolution of facial pain (p > 0.05).ConclusionIn USS patients, the most common craniofacial pain locations were retrobulbar, occipital, and frontal, with a minority being vertex. Based on short‐term follow‐up, ESS resolved the craniofacial pain in 75% of cases. There were no clinical variables that predicted the presence or resolution of craniofacial pain.Level of Evidence4 Laryngoscope, 135:1915–1919, 2025

ObjectiveTo examine implementation of virtual reality (VR) and Fitbit wearable activity devices in postoperative recovery.MethodsThis was a prospective, 4‐arm, randomized controlled trial of patients undergoing inpatient head and neck surgery at a tertiary academic center from November 2021 to July 2022. Patients were randomized to Control, VR, Fitbit, or combined VR + Fitbit groups. Patients in the VR groups were brought VR headsets to use throughout each day, and patients in the Fitbit groups wore Fitbit devices and were encouraged to achieve 2,000 daily steps. The primary outcome was average daily opioid use, measured as milligram morphine equivalents (MME).ResultsThere were 80 patients included. The majority of patients were male (68.8%), and mean age was 58.8 ± 14.4 years. Only the combined VR + Fitbit cohort was associated with reduced average daily opioid use (VR + Fitbit: 8.8 [20.6] MME vs. Control: 26.4 [37.4] MME, p = 0.02). Patients in intervention groups also had higher hospital satisfaction (p = 0.02). VR was utilized 26% of the time it was provided, with mean use time of 23.8 ± 7.8 min. Mean post‐VR subjective pain reduction was 1.0 ± 1.3, and there were three mild adverse events of neck or nasal discomfort. Among the Fitbit groups, there were no adverse events and daily step counts ≥2,000 steps were achieved 45% of the time.ConclusionImplementation of VR and wearable activity devices in postoperative recovery appears well tolerated and may facilitate further development of Enhanced Recovery After Surgery (ERAS) protocols, though there are challenges to maximizing device usage.Level of Evidence2 Laryngoscope, 135:2044–2050, 2025

Leuprolide acetate is commonly used to reduce the size of myomas before surgery. Initially, it stimulates pituitary gonadotropin secretion, followed by sustained suppression of gonadal function. However, the impact on pregnancy outcomes from inadvertent exposure remains unclear. This case involves a woman in her 30s, multiparous, with a 20-week-sized leiomyoma, who received two doses of 3.75 mg subcutaneous leuprolide acetate, 15 days after menstruation, 4 weeks apart. An ultrasound, conducted 2 weeks after the last dose, accidentally revealed a viable intrauterine pregnancy at 8+6 weeks gestation. Her pregnancy progressed without complications, culminating in a term caesarean delivery without fetal anomalies. She opted for a total hysterectomy with bilateral salpingectomy 6 months later. Despite unclear teratogenic effects, evidence suggests that leuprolide acetate does not significantly impact pregnancy outcomes.

Aims . To identify the most common reasons for consultation to a large specialty breast pathology service at a major institution. To provide insight into the overall challenges in practicing breast pathology. Methods . The anatomic pathology database at one institution was searched for all breast consultations received in 2021, excluding in-house patients and patients who were transferring care. Results . A total of 553 patients met the criteria ( n = 553) from a variety of academic and private practices. For each patient, the paperwork from the submitting institution was reviewed to identify the specific question, and subsequently classified into 14 categories. The reason for the consultation request was not provided for 78 (14%) patients, and a review of the outside diagnoses, where applicable, was performed. In summary, the top 5 reasons for consultation were: (1) assistance with classification of atypical intraductal epithelial proliferations (32%); (2) evaluation for the presence of (micro-)invasive carcinoma (14%); (3) evaluation of fibroepithelial (12%), (4) papillary (11%), and (5) spindle cell lesions (7%). Conclusion . We show an ongoing educational and practice gap for pathologists who most commonly struggle with classifying atypical precursor lesions, specifically when these are small and focal, or bordering on intraductal carcinoma (32%, 177/553). The second most common reason for consultation was classifying invasive carcinomas as microinvasive and subtypes (total of 20.4%, 113/553). As such, our data supports the continued need for rigid and clear criteria for diagnosing threshold lesions (namely atypical hyperplasias) and intraductal carcinoma of the breast.

ObjectiveSpondyloarthritis (SpA) is the most common extraintestinal manifestation of inflammatory bowel disease (IBD). The application of screening tools to detect SpA in patients with IBD may lead to earlier recognition of SpA and affect treatment decisions.MethodsA combination of two previously described SpA screening questionnaires, the Detection of Arthritis in Inflammatory Bowel Disease (DETAIL) and IBD Identification of Spondyloarthritis Questionnaire (IBIS‐Q), was administered to consecutive patients with IBD attending IBD specialty clinics in six US academic medical centers. Demographic data, IBD, and rheumatology history were extracted by chart review.ResultsA total of 669 patients were analyzed. The median age was 40 years (interquartile range [IQR] 30–54) with a median disease duration of 12 years (IQR 6–22) and moderate to severe IBD based on medication exposure and history of bowel surgery. A total of 81 patients (12%) carried a diagnosis of an inflammatory rheumatic disease, whereas 75 (11%) had consulted a rheumatologist during the previous year. Using published cutoffs, 180 out of 669 patients (27%) screened positive with DETAIL, 266 (40%) with IBIS‐Q, and 275 (41%) with either questionnaire. Axial symptoms were more frequently reported than peripheral musculoskeletal complaints. Notably, 189 out of 275 (69%) screen‐positive patients had neither a documented inflammatory rheumatic disease diagnosis nor a visit with a rheumatologist within the past year.ConclusionA substantial proportion of patients with IBD have symptoms suggestive of SpA, and many of these may have undiagnosed SpA. The IBIS‐Q questionnaire appears to identify more potential SpA cases than DETAIL. Strategies are needed to prioritize rheumatology consultations for those patients with IBD who are most likely to benefit.

PURPOSE Management of locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal excision. Recently, total neoadjuvant treatment (TNT) has gained attention. In developing countries, patients with rectal cancer often present at advanced stages. This study assesses treatment patterns and outcomes in LARC at a largest referral center in Ethiopia. MATERIALS AND METHODS A cross-sectional study was conducted on 100 patients with LARC treated at Tikur Anbessa Specialized Hospital from January 2020 to September 2022. RESULTS The median age at diagnosis was 45.5 years (range, 20-86), with 51% male. Of the patients, 81% had no previous oncologic treatment and 75.3% was discussed in a multidisciplinary tumor board. Up-front surgery was planned for 44.4% of patients, whereas 22.2% and 8.6% were assigned to TNT and NACRT, respectively. Among 81 treatment-naïve patients, 79 were triaged for surgery, but only 47 (59.5%) underwent surgery, achieving an 89.9% R0 resection rate. Of 36 up-front planned surgeries, 35 proceeded as planned, whereas only 12 of 43 (28%) planned after neoadjuvant treatment underwent surgery. Neoadjuvant chemotherapy (NACT) was given to 37% of patients, with 16.7% (5 of 30) undergoing subsequent surgery. Radiotherapy was given to 24.2% of participants, with 56.25% undergoing surgery. Short-course radiotherapy (SCRT) was given to two patients. Only 14.8% completed all planned treatments, with radiation waiting time (median, 10 months) being the main impediment. CONCLUSION Timely administration of neoadjuvant treatment is not possible in most resource-limited settings. Because of better treatment completion, up-front surgery looks a more viable option than NACT in these situations. Extended waiting time for radiotherapy can be mitigated by opting for alternatives like SCRT in selected patients.