Multi-institutional Study Research Articles

Clinical findings and prognostic factors for immediate survival in 33 dogs undergoing surgery for biliary peritonitis.

To report demographics, clinical signs, physical examination, diagnostic test results, surgical findings, and prognostic factors for in-hospital postoperative mortality following biliary peritonitis surgery in dogs. Retrospective, multi-institutional cohort study. Thirty-three client-owned dogs. The medical records of dogs that underwent surgery for biliary peritonitis between 2015 and 2021 were reviewed. Dogs were included if they had a definitive diagnosis of biliary peritonitis and a surgery report. Information on demographics, clinical signs and duration, physical examination findings, laboratory and diagnostic imaging results, surgery, perioperative medical treatment, and complications for each patient was obtained. Statistical analyses were performed to identify risk factors that affected survival. Cholecystectomy was the procedure most frequently performed (31/33, 94%). The overall mortality rate was 36% (12/33). Survival was affected negatively by hyperbilirubinemia (p = .049), administration of vasopressors (p = .002), renal dysfunction (p = .008), and number of postoperative complications (p = .005). A mortality rate of 50% was observed in dogs with a total bilirubin level greater than 60.5 μmol/L. There was no difference in mortality rate between septic and nonseptic biliary effusions. New prognostic factors associated with in-hospital postoperative mortality in dogs treated surgically for biliary peritonitis were identified, while others that had been reported previously were confirmed. A preoperative bilirubin threshold value associated with a 50% mortality was identified. Additional information that could help to predict survival in dogs with biliary peritonitis has been provided. However, further research is warranted.

Impact of Age in Single-Level Versus Multilevel Airway Compromise: A Multi-Institutional Review.

Examine the association between age and treatment outcomes in conditions causing single- versus multilevel airway restriction. Multi-institutional retrospective cohort study. Tertiary laryngology centers. Participants included younger (18-64 years) and geriatric (≥65 years) adults with posterior glottic stenosis (PGS), multilevel airway stenosis (MLAS), and bilateral vocal fold paralysis (BVFP). Subgroup demographics, comorbidities, type, and etiology of airway compromise were described. Associations between age and primary outcome variables (i.e., tracheostomy and decannulation rates, number of surgeries performed, time between surgeries, and change in quality-of-life patient-reported outcome measures [PROMs]) were evaluated. Statistical analyses included independent t tests, χ2, Fisher's exact, or Mann-Whitney tests. In 158 patients [96 younger (30 PGS, 29 MLAS, 37 BVFP) and 62 geriatric (24 PGS, 9 MLAS, 29 BVFP)], age differences were not significant for gender (P = .990), tracheostomy placement (70% vs 66%, P = .629), or decannulation success (40% vs 24%, P = .091) in younger versus geriatric groups, respectively. In younger patients, MLAS was more common (30.2% vs 14.5%, P = .024), and BVFP patients were more likely to decannulate (50% vs 12%, P = .017). Geriatric patients were more likely to have a history of prior radiation (26% vs 10%, P = .016), stenosis due to malignancy (23% vs 9%, P = .022), and fewer overall surgeries (median 1 vs 3, P = .003). Median PROMs were comparable between age subgroups (P > .05). Younger adults underwent more surgeries, but overall comorbidities, tracheostomy decannulation rates, and PROMs were comparable between groups. Age does not negatively impact treatment outcomes and should not be a deterrent in treatment decision-making.

A Novel Liver Metastasis Score for Patients Undergoing Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: A Multi-institutional Study.

Liver metastasis impacts survival in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs); however, current guidelines lack consensus on post-resection surveillance and adjuvant therapy. A comprehensive risk stratification tool is needed to guide personalized management. We aimed to develop and validate a predictive model for liver metastasis risk after surgical resection of GEP-NETs that incorporates pathological factors and adjuvant therapy. Patients with GEP-NETs who underwent surgical resection with curative intent at three major Chinese hospitals (2010-2022) were identified. Univariable and multivariable Cox regression analysis identified independent risk factors of liver metastasis. The liver metastasis score (LMS) was developed using weighted risk factors and validated by tenfold cross-validation. Among the 724 patients included in the analytic cohort, liver metastasis occurred in 66 patients (9.1%) at a median of 36 months; patients with liver metastasis had a worse 5-year overall survival (no liver metastasis 63.6% vs. liver metastasis 95.8%; p<0.001). Independent predictors were Ki-67 index (hazard ratio [HR] 10.36 for Ki-67 3-20%, HR 18.30 for Ki-67 >20%, vs. <3%), vascular invasion (HR 5.03), lymph node metastases (HR 2.24), and lack of adjuvant therapy (HR 3.03). The LMS demonstrated excellent discrimination (C-index 0.888) and stratified patients into low, intermediate, and high-risk relative to 5-year risk of liver metastasis: 2.9%, 20.8%, and 49.7%, respectively (p<0.001). The novel LMS effectively predicted the risk of liver metastasis after surgical resection of GEP-NETs. This validated model can help guide personalized surveillance and adjuvant treatment strategies, potentially improving outcomes for high-risk patients.

Evidence and Multi-institutional Prospective Observational Study of Radiotherapy for Metastatic Bone Tumor

Evidence and Multi-institutional Prospective Observational Study of Radiotherapy for Metastatic Bone Tumor

A large scale multi institutional study for radiomics driven machine learning for meningioma grading

This study aims to develop and evaluate radiomics-based machine learning (ML) models for predicting meningioma grades using multiparametric magnetic resonance imaging (MRI). The study utilized the BraTS-MEN dataset’s training split, including 698 patients (524 with grade 1 and 174 with grade 2–3 meningiomas). We extracted 4872 radiomic features from T1, T1 with contrast, T2, and FLAIR MRI sequences using PyRadiomics. LASSO regression reduced features to 176. The data was split into training (60%), validation (20%), and test (20%) sets. Five ML algorithms (TabPFN, XGBoost, LightGBM, CatBoost, and Random Forest) were employed to build models differentiating low-grade (grade 1) from high-grade (grade 2–3) meningiomas. Hyperparameter tuning was performed using Optuna, optimizing model-specific parameters and feature selection. The CatBoost model demonstrated the best performance, achieving an area under the receiver operating characteristic curve (AUROC) of 0.838 [95% confidence interval (CI): 0.689–0.935], precision of 0.492 (95% CI: 0.371–0.623), recall of 0.838 (95% CI: 0.689–0.935), F1 score of 0.620 (95% CI: 0.495–0.722), accuracy of 0.729 (95% CI: 0.650–0.800), an area under the precision-recall curve (AUPRC) of 0.620 (95% CI: 0.433–0.753), and Brier score of 0.156 (95% CI: 0.122-0.200). Other models showed comparable performance, with mean AUROCs ranging from 0.752 to 0.784. The radiomics-based ML approach presented in this study showcases the potential for non-invasive and pre-operative grading of meningiomas using multiparametric MRI. Further validation on larger and independent datasets is necessary to establish the robustness and generalizability of these findings.

Normal values and distribution of ventricular global longitudinal strain in 513 healthy fetuses measured by two-dimensional speckle-tracking echocardiography: a multi-institutional cohort study.

This study aimed to determine the normal reference values and distribution of global longitudinal strain (GLS) in the right and left ventricles of healthy Japanese fetuses during pregnancy. This multi-institutional cohort study included healthy Japanese fetuses during normal pregnancies without maternal or fetal complications between 18 and 40weeks of gestation. Two-dimensional fetal echocardiographic images of the four-chamber view with a high frame rate were acquired and stored as DICOM clips. Data were collected and analyzed in a central laboratory to measure the left ventricular (LV) and right ventricular (RV) GLS using two-dimensional speckle tracking. In total, 513 fetuses were enrolled. The mean LV-GLS and RV-GLS were - 24.3% ± 3.5% and - 23.5% ± 3.7%, respectively. The magnitude of the GLS, with normal limits in both ventricles, decreased with advancing gestation. LV values were r = 0.34 (95% confidence interval, 0.27-0.42) and p < 0.0001; RV values were r = 0.33 (95% confidence interval, 0.25-0.41) and p < 0.0001. The normal values of healthy Japanese fetuses in healthy pregnancies is the first to be established by the large-scale, multi-institutional cohort study as LV-GLS of 24.3% ± 3.5% and RV-GLS of - 23.5% ± 3.7%, respectively. This can serve as a basic reference for assessing the cardiac functions in Japanese fetuses with various heart diseases.

Outcome of 21 dogs treated for the portocaval subtype of extrahepatic portosystemic shunts.

To assess outcomes of dogs with side-to-side portocaval extrahepatic portosystemic shunts (PC-EHPSS) and poor portal perfusion to the liver treated with medical management alone (MM) or surgical attenuation (SA). Multi-institutional retrospective study. A total of 21 dogs with PC-EHPSS (14/21 MM and 7/21 SA). Medical records were reviewed, and data was collected on dogs <12 kg with PC-EHPSS treated with MM or SA between June 2008 to June 2021. Signalment, clinical signs, postoperative complications, bloodwork values, long-term clinical outcome, survival, and owner reported quality of life were recorded. Of 21 dogs included, 10 were mixed breeds and 14 were females. Median age at time of presenting clinical signs was 163 days. At final follow-up examination (median 1119 days), all SA and 6/14 MM dogs were alive, with a median survival time of 2138 days following treatment onset. In surviving MM dogs, outcome was fair in 3/6 and poor in 3/6. In SA dogs with long-term follow-up, outcome was fair in 5/6, and poor in 1/6. A greater proportion of SA dogs had improved bloodwork parameter values at final follow-up examination, and the mean relative change in final bloodwork values was higher when compared to MM dogs. These findings demonstrate that SA has improved clinical outcomes to MM for PC-EHPSS; however, SA clinical outcomes appear worse than those previously reported for other EHPSS. This information may have implications for expected outcomes in other EHPSS subtypes associated with severely diminished portal perfusion.

Cushing’s Myopathy in Dogs: Prevalence, Clinical Abnormalities, and Response to Treatment

A distinct myotonia is a muscle disorder that may occur secondary to excess corticosteroids (hyperadrenocorticism, HAC, or Cushing’s disease) and is associated with electrodiagnostic abnormalities on electromyography (EMG). Clinically these disorders cause muscle stiffness, weakness, atrophy, and/or contractures, which can severely limit the quality of life of those affected. To date, there are very few published data regarding the onset, development, and treatment of hyperadrenocorticism-associated myotonia/pseudomyotonia. This is a multi-institutional retrospective study describing the clinical signs, diagnosis, and treatment of HAC-associated myotonia/pseudomyotonia. We found that this disorder was and continues to be rare. It most commonly occurs in adult dogs with chronic steroid exposure secondary to pituitary-dependent HAC. No cases of adrenal dependent HAC were identified in this population. In addition to muscle stiffness, dermatologic disease and liver enzyme abnormalities were common. A wide variety of therapeutic strategies, including polypharmacy and physical rehabilitation, were implemented, with little success. Analgesics were the most frequently administered type of medication.

The Significance of Comprehensive Metabolic Phenotypes in Cancer Risk: A Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

The present study investigated the relationship between metabolic phenotypes and the risk of cancer in a Japanese population using the criteria of metabolic phenotypes based on an examination and those based on questionnaires. We used data from 25,357 subjects for examination-based analyses and those from 53,042 subjects for questionnaire-based analyses in the Japan Multi-Institutional Collaborative Cohort Study. Metabolic phenotypes were defined by classifying subjects according to their BMI (obesity: BMI ≥25 kg/m2; normal weight: BMI <25 kg/m2) and the number of metabolic abnormalities. Metabolic abnormalities were defined according to metabolic syndrome components of the Joint Interim Statement Criteria for examination-based analyses and self-reported histories of diabetes, dyslipidemia, and hypertension for questionnaire-based analyses. Cox proportional hazards regression analyses adjusted for potential confounders were performed for total and site-specific cancer incidence according to metabolic phenotypes. Metabolically unhealthy obesity (MUHO) was significantly associated with cancer incidence in both examination-based [HR (95% CI): 1.17 (1.01-1.36)] and questionnaire-based analyses [HR (95% CI): 1.15 (1.04-1.26)]. Regarding site-specific cancer in questionnaire-based analyses, metabolically healthy obesity and MUHO were associated with colorectum and liver cancers in all subjects and with breast cancer in female subjects. Subjects with a metabolically unhealthy normal weight had a higher risk of pancreatic cancer. Moreover, MUHO was associated with corpus uteri cancer in female subjects. This prospective cohort study suggests that metabolic phenotypes are important risk factors for total and some site-specific cancers in Japanese adults.

Random Forest Prognostication of Survival and 6-Month Outcome In Pediatric Patients Following Decompressive Craniectomy For Traumatic Brain Injury

There is a dearth of literature regarding prognostic and predictive factors for outcome following pediatric decompressive craniectomy (DC) following traumatic brain injury (TBI). The aim of this study was to develop a random forest machine learning algorithm to predict outcomes following DC in pediatrics. This is a multi-institutional retrospective study assessing the 6-month postoperative outcome in pediatric patients that underwent DC. We developed a machine learning model using classification and survival random forest algorithms (CRF and SRF respectively) for the prediction of outcomes. Data was collected on clinical signs, radiographic studies, and laboratory studies. The outcome measures for the CRF were mortality and good or bad outcome based on Glasgow Outcome Scale (GOS) at 6-months. A GOS score of 4 or higher indicated a good outcome. The outcomes for the SRF model assessed mortality at during the follow-up period. A total of 40 pediatric patients were included. There was a hospital mortality rate of 27.5%, and 75.8% of survivors had a good outcome at 6-month follow up. The CRF for 6-month mortality had a ROC AUC of 0.984; whereas, the 6-month good/bad outcome had a ROC AUC of 0.873. The SRF was trained at the 6-month timepoint with a ROC AUC of 0.921. CRF and SRF models successfully predicted 6-month outcomes and mortality following DC in pediatric TBI patients. These results suggest random forest models may be efficacious for predicting outcome in this patient population.

Prophylactic Antimicrobials for Prevention of Febrile Neutropenia in Tumour-Bearing Dogs Treated With Lomustine.

CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosurea), lomustine, is an oral alkylating agent in the nitrosourea subgroup. The dose-limiting toxicity of CCNU is neutropenia most frequently documented 7 days after its administration. Use of prophylactic antimicrobials to prevent chemotherapy-related febrile neutropenia (FN) and its associated morbidity and mortality has been well-documented in human oncology, but this information is limited in the veterinary literature. The purpose of this multi-institutional retrospective study was to assess whether antimicrobial prophylaxis reduced the risk of FN approximately 7 days after CCNU administration in tumour-bearing dogs. A secondary goal was to identify risk factors for fever development in neutropenic dogs. Two hundred dogs were included in the study. One hundred and fifty-three dogs (76.5%) were neutropenic at the first post-CCNU recheck. One hundred and six (69.3%) dogs received prophylactic antimicrobials and 47 (30.7%) did not. Of the 106 dogs on prophylactic antimicrobials, 8 (7.5%) developed FN. Of the 47 dogs in the no-prophylactic antimicrobials group, 4 (8.5%) developed FN. Use of prophylactic antimicrobials did not reduce the risk of development of FN (p = 0.84). Older age (> 9 y), lower weight and body surface area, and pre-treatment with chemotherapy or radiation therapy were significantly associated with development of FN (p = 0.009, p = 0.023, p = 0.015 and p = 0.01). Patients with a lower absolute neutrophil count, and a higher VCOG-CTCAE v2 neutropenia grade were also at an increased risk of developing FN (p = 0.01, p < 0.001). Additional studies may help establish guidelines for antimicrobial prophylaxis in dogs treated with CCNU, especially for those at high-risk for FN.

Delays in Treatment for Temporal Encephaloceles and Cerebrospinal Fluid Leaks.

Lateral skull base defects (LSBD) pose a diagnostic challenge; however, early recognition and treatment are important to avoid sequelae. This study examines the impact of health care disparities associated with time to diagnosis and treatment for patients with LSBD. Multi-institutional retrospective cohort study at four U.S. tertiary centers from 2000 to 2022. Adult patients with a primary diagnosis of CSF leak or encephalocele were included. Multivariate regressions used to analyze how age, sex, race/ethnicity, insurance, language, zip code, distance to medical center, referral patterns, diagnostic workup, and clinical course affected time to diagnosis and treatment. In 127 patients with LSBD, mean time to treatment of CSF leak or encephalocele was 13.9 months. On average, patients waited 10.6 months from initial assessment to diagnosis and saw 2 providers prior to diagnosis. Approximately 91% (115) of patients had a CT scan, and 75% (95) had an MRI. Imaging did not influence time to treatment. Older age, public insurance, and number of providers seen were associated with delays. Non-English speakers (5% of 127) encountered treatment delays, although this was not statistically significant. Fifty-eight (46%) people had private insurance. The average traveled distance for care was 62.6 miles. Clinical presentation, race, zip code, imaging, myringotomy, beta-2 transferrin, and ED workup were not found to be associated with delays to care. There are significant delays in diagnosis and management of LSBD. Referral patterns did influence care. Health care disparities did not impact care; however, disparities and language barriers need to be studied further to determine contributions to delays in care.

Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma.

Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM). To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM. This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS). In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02). Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.

Diagnostic incidence and pitfalls of rete testis hyperplasia and hyaline globules in a multi-institutional study of 348 testicular germ cell tumors.

The concept of rete hyperplasia with hyaline globules simulating testicular yolk sac tumor was first reported in a mostly retrospective review over 30 years ago. Nonetheless, we continue to encounter examples where this scenario resulted in misdiagnosis. Herein, we sought to investigate the incidence of rete hyperplasia/hyaline globules in germ cell tumors and their associated subtypes and hypothesize an etiology. A consecutive series of 348 germ cell tumor orchiectomies was evaluated for the presence of rete hyperplasia and hyaline globules, with clinicopathologic features recorded. The incidence of rete hyperplasia and/or hyaline globules in our cohort was 30%, with 56% of specimens with rete hyperplasia containing concomitant hyaline globules. Hyaline globules were more often identified in specimens with nonfocal rete hyperplasia (78%) vs focal rete hyperplasia (22%). Absence of a yolk sac tumor component was seen in over half (61%) of orchiectomies with concurrent rete hyperplasia/hyaline globules (n = 105), inclusive of tumors with "pure" subtypes (ie, pure seminoma, pure teratoma, or pure embryonal carcinoma). Of these 105 specimens, rete invasion was seen in only 48%; notably, Paneth cell-like metaplasia was identified in efferent ductules/epididymis in 13%. Rete hyperplasia and hyaline globules are not uncommon findings in the setting of germ cell tumors (including occurrences in various pure/mixed germ cell tumors) and can show striking overlap with yolk sac tumor. We hypothesize that these histologic pitfalls evolve secondary to testicular obstruction by the tumor mass. Recognition of and distinguishing this morphologic mimicry is fundamental to guide appropriate clinical management.

Beyond the Bite: Exploring Mental Health of Dental Faculty in Pakistan– a multi-institutional study

IntroductionMental health issues are being reported increasingly amongst healthcare staff and students globally. The aim of this study was to investigate the frequency of common mental health issues amongst dental faculty members at multiple institutions in Pakistan.MethodsFollowing approval from the institutional ethics review board, dental faculty members at 14 dental institutions were invited to participate in an online survey based on globally validated scales for mental health problems including the Patient Health Questionnaire (PHQ-9), and the Depression, Anxiety, and Stress Scale (DASS-21). Two open-ended questions were included in the survey to identify perceived factors contributing to poor mental health and recommendations for improving institutional support.ResultsA total of 200 faculty members out of provided their responses to the survey questionnaire but complete responses were provided by 183 participants which included 120 (65.57%) females, and 63 (34.43%) males. The total number of faculty members at the participating institutions was 426 and 183 responses translated into an overall response rate of 43%. Most participants were in the 31–40 years age-group (n = 81, 44.26%) followed by 25–30 year (n = 51, 22.87%) and 41–50 years (n = 40, 21.86%). The mean score on PHQ-9 was 6.51 (SD ± 5.4) while the mean DASS-21 score was 13.04 (SD ± 10.95). PHQ-9 Depression, and DASS-21 Depression, Anxiety, and Stress scores were all significantly positively correlated for the whole sample, and within each subgroup of each demographic factor. Job-related workload, lack of institutional support, financial limitations, and poor work life balance were identified as the main factors contributing adversely to the mental health of the participants.DiscussionThis study provides useful insights into the scale of mental health status amongst dental faculty members at 14 institutions in Pakistan. Underlying factors affecting the mental health of faculty members adversely were identified and recommendations are provided to address these challenges.

Prophylactic Local Antibiotics for Tissue Expansion (PLATE) Improve Breast Reconstruction Outcomes.

Infection following tissue expander (TE) breast reconstruction is frequent and impactful. Preliminary reports demonstrate value of local antibiotic delivery for implant salvage and prophylactic potential. Herein is a multi-institutional retrospective study employing surgeon-crafted tobramycin-vancomycin PMMA plates (PLATE) during TE implantation for infection prophylaxis. The authors hypothesized the intervention would be associated with fewer infections compared to historical practice. In 2021, surgeons at three institutions began independently offering PLATE for primary TE breast reconstructions. After independent IRB approvals, data were retrospectively collected for PLATE subjects and pre-intervention cohorts of equivalent sizes. Subjects were followed for seven months, or to second stage removal. The primary outcome, complication requiring readmission/reoperation, was compared between aggregated cohorts. Analysis included logistic modeling and Kaplan-Meyer survival. The aggregate sample included 183 intervention subjects (292 breasts) and 183 controls (301 breasts), each with 5+/-2-month follow-up. Overall, complications were significantly less frequent with PLATE (13.1% vs 21.9%, p<0.01*). This was driven by significantly fewer infections (4.8% vs 12.6%, p<0.01*) with no difference in rates of tissue necrosis, seroma, or other complications (p>0.05). In multivariable regression, the intervention was associated with significantly reduced odds of any complication (OR=0.53, 95%CI: [0.3-0.93]) and infection (OR=0.22, 95%CI: [0.08-0.50]). Kaplan-Meyer curves demonstrated significant longitudinal reduction in complication and infection (p<0.01*) without notable rebound throughout dissipation of the antibiotic eluent. Prophylactic employment of intraoperatively-crafted PLATE during TE implantation was associated with significant infection reduction without increase in local or systemic complications. This reproducible tool may be highly valuable in alloplastic breast reconstruction.

Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among the 440 patients with Ki-67 staining, 22% had high Ki-67 (Ki-67 >20%). The median progression-free survival (PFS) for patients with high Ki-67 was 5.4 years compared to 7.0 years for patients with low Ki-67 (HR = 1.45, 95%CI = 1.03–2.05). Ki-67 > 20% strongly correlated with high LDH level. The risk of HT was higher in patients with increased Ki-67 than those without (5-year risk, 9.8% vs 3.87%, p = 0.01). Twelve percent of patients had LC reported on biopsy with 6% having >10% LC. The presence of LC was associated with high Ki-67 (p < 0.001), but not associated with shorter PFS or overall survival (OS). The cumulative risk for HT was higher in patients with LC compared to those without LC (5-year risk, 9.4% vs 2.9%, p = 0.04). Receipt of anthracycline-based therapy did not impact PFS or OS in either group. Ki-67 staining >20% was a prognostic factor for worse survival and strongly correlated with elevated LDH. Novel therapies should be investigated for their potential ability to overcome the high-risk features in MZL. Our data reinforce the importance of obtaining biopsies at relapse or progression, particularly in patients with baseline high Ki-67 and increased LCs, given their increased risk for HT.

A multi-institutional study on Ultrasound image analysis for staging HBV-derived liver fibrosis: a potential non-invasive alternative to liver stiffness measurement

Background: Liver stiffness measurement is principal for staging liver fibrosis but not included in routine examinations. We investigated whether comparable diagnostic performance can be achieved by mining ultrasound images and developing a novel serum index (NSI). Methods: Texture features were extracted from ultrasound images. Spearman correlation and logistics regression selected independent variables for significant (F≥2) and advanced (F≥3) fibrosis. We compared the diagnostic performance of transient elastography (TE), ultrasound image biomarker (UIB), conventional serum indices (APRI, FIB-4, GPR), and NSI in 365 chronic hepatitis B patients. Results: Among patients, 52.1% had significant fibrosis and 24.2% had advanced fibrosis. PLT, GGT, prealbumin, and globulin were incorporated into NSI. In the validation group, TE achieved the best performance (AUC: 0.765 [0.690-0.849] for significant fibrosis; 0.812 [0.745-0.878] for advanced fibrosis), followed by UIB (AUC: 0.712 [0.629-0.795]; 0.678 [0.595-0.763]) and NSI (AUC: 0.630 [0.534-0.725]; 0.659 [0.572-0.745]), outperforming conventional indices. Conclusions: Texture analysis enhances ultrasound's diagnostic utility, but TE remains superior. When TE is unavailable, ultrasound image analysis and NSI, incorporating prealbumin, can serve as alternative tools for fibrosis staging.

Comparison of computed tomography findings between perianal tumors originating from the anal sacs and perianal glands in dogs.

Tumors originating from the anal sacs and perianal glands are common tumors of the perianal region. However, differentiation of perianal tumors based on CT findings remains challenging because perianal tumors can show overlapping CT characteristics. Therefore, this retrospective, multi-institutional study aimed to identify the CT findings that can differentiate between tumors originating from the anal sacs and perianal glands in canines. Twenty dogs were included, with nine apocrine gland anal sac adenocarcinomas (AGASACAs), six perianal gland adenomas, three perianal gland carcinomas, and two perianal gland epitheliomas. The tumor CT features included the tumor growth pattern, tumor shape, cystic changes within the tumor, contrast enhancement pattern, displacement of the anus, and identification of the anal sacs. The prevalences of suspected metastatic lymphadenopathy of the iliosacral lymph centers and lung metastases were evaluated. The tumor volumes and values normalized to body weight were also assessed. The tumor growth patterns differed significantly between AGASACAs and perianal gland tumors. AGASACAs mostly showed unilateral growth, whereas perianal gland tumors mostly exhibited bilateral growth. CT features, except for the tumor growth pattern, failed to show significant differences between tumors arising from the anal sacs and those arising from the perianal glands. Although histopathological diagnosis remains the gold standard, this study's findings suggest that CT analysis of tumor growth patterns may help differentiate AGASACAs from perianal gland tumors.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Fifteen lesions (3-42mm) were identified, predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AML contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four AL contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included ulceration, thrombosis, inflammation, myxoid change, senescent nuclei, and extramedullary hematopoiesis; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin, desmin, and/or caldesmon) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AML. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.