Primary central nervous system angiitis: a case report.

Introduction: Primary central nervous system angiitis is a rare idiopathic vasculitis that is limited to the central nervous system. It has a wide range of clinical presentations that can mimic other vasculopathies. Case presentation: A 24-year-old female patient presents with various non-specific neurological complaints in a progressive course. After a challenging diagnostic work-up, she was diagnosed by tissue biopsy to have primary central nervous system angiitis. Discussion: Although primary central nervous system angiitis has been reported increasingly recently, its pathogenesis is still unknown, and its diagnosis is still very challenging. No universal criteria have been adopted, and there is no laboratory test or imaging modality with sufficient sensitivity and specificity to confirm the diagnosis and exclude other mimickers. Conclusion: To prevent misdiagnosis, clinicians treating patients with suspected primary central nervous system angiitis should be aware of its differentials.

Recurrent Syncope and Cardiopulmonary Resuscitation Due to a Papillary Fibroelastoma.

Symptoms of papillary fibroelastomas are often related to thromboembolic events but are rarely caused by a mechanical impairment of blood supply by the tumor itself. We describe a case of a papillary fibroelastoma in a 91-year-old female patient leading to a cardiac arrest through intermittent occlusion of the left coronary artery.

Interpretation of Data from Translational Rodent Nerve Injury and Repair Models.

This article highlights the use of rodents as preclinical models to evaluate the management of nerve injuries, describing the pitfalls and value from rodent nerve injury and regeneration outcomes, as well as treatments derived from these rodent models. The anatomic structure, size, and cellular and molecular differences and similarities between rodent and human nerves are summarized. Specific examples of success and failure when assessing outcome metrics are presented for context. Evidence for translation to clinical practice includes the topics of electrical stimulation, Tacrolimus (FK506), and acellular nerve allografts.

Neuroendocrine neoplasms of the breast: a review of literature.

Primary neuroendocrine neoplasms (NENs) of the breast are characterized by neuroendocrine architectural and cytological features, which must be supported by immunohistochemical positivity for neuroendocrine markers (such as Chromogranin and Synaptophysin). According to the literature, making a diagnosis of primary neuroendocrine breast cancer always needs to rule out a possible primary neuroendocrine neoplasm from another site. Currently, the latest 2022 version of the WHO of endocrine and neuroendocrine neoplasms has classified breast NENs as well-differentiated neuroendocrine tumours (NETs) and aggressive neuroendocrine carcinomas (NECs), differentiating them from invasive breast cancers of no special type (IBCs-NST). with neuroendocrine features. The current review article describes six cases from our series and a comprehensive review of the literature in the field of NENs of the breast.

Ecotoxicological Research on the Toxic Impact of Zinc Oxide and Silver Nanoparticles on Oreochromis mossambicus.

Silver nanoparticles (AgNPs) and Zinc oxide nanoparticles (ZnONPs) have been widely used and are eventually been discharged into the natural aquatic ecosystem. The current study examined and correlated the toxicity of AgNPs and ZnONPs on the Mozambique tilapia, Oreochromis mossambicus. Lethal concentration (LC50) was determined with four different concentrations (0.05, 0.10, 0.15, and 0.20 mg/L) of AgNPs and ZnONPs; subsequently, the fishes were exposed to sublethal concentrations for a period of 21 days, and the oxidative stress and antioxidant and nonantioxidant parameters were studied. Results revealed oxidative stress evinced by increased lipid peroxidation (LPO) protein carbonyl activity (PCA), glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) activity, metallothionein (MT) activity, and reduced glutathione in chronic exposure compared with acute exposure. Nonspecific immunological characteristics such as lysozyme (LYZ), myeloperoxidase (MPO), and respiratory burst activity (RBA) were also noticed in the serum. Furthermore, severe histological damages including damages in telangiectasia and epithelial cell hyperplasia were found in the combined treated group with Ag and ZnONPs than in individual treatments. When Ag and ZnONPs were combined, a reduction in the accumulation of Ag was observed in the liver, which increased drastically in individual exposure. The current findings highlight the importance of taking into account the combined exposure and correlation of NPs, their bioavailability, and toxicity in the aquatic ecosystem.

Factors Influencing Bladder Perforation during Transurethral Resection of Bladder Cancer: A Comprehensive Analysis.

BACKGROUND: Bladder perforation (BP) is one of the important complications during transurethral resection of bladder tumour (TURBT). Additionally, multiple factors can contribute to BP. Here, we investigated the rates of BP, specifically in variant histology of bladder cancer (BC), and examined the clinical follow-up of relevant patients. METHODS: Of the 797 patients who underwent TURBT between 2015 and 2023, they were divided into two groups according to BP during the operation. Group 1 (n = 744) consisted of patients without BP, whereas Group 2 (n = 53) consisted of patients with BP. Demographic, operative, postoperative and follow-up data were investigated and analysed. Groups were examined in terms of causes of BP. Significance was set at p < 0.05. RESULTS: A significantly higher rate of BP was found in patients operated with bipolar energy (p = 0.027) than in their counterparts. In multivariable analysis, the presence of the obturator reflex during TURBT was significantly associated with an increased risk of BP (p < 0.001). We observed a statistically significant increase in the rate of BP in patients with a history of previous intravesical Bacillus Calmette-Guérin (BCG) therapy (p = 0.023). Variant histology was reported in 32 patients (4%). However, we could not find any statistically significant relationship between the development of BP and the variant histology of BC (p = 0.641). CONCLUSIONS: Multiple factors can affect BP during TURBT. Understanding the factors associated with BP is crucial for improving patient safety and outcomes. According to the results of the present study, the energy source, the presence of obturator reflex during TURBT and intravesical BCG therapy may increase BP. Nevertheless, the presence of variant histology was not significantly associated with BP.

Automated determination of 8-OHdG in cells and tissue via immunofluorescence using a specially created antibody.

Despite powerful DNA repair systems, oxidative damage/modification to DNA is an inevitable side effect of metabolism, ionizing radiation, lifestyle habits, inflammatory pathologies such as type-2 diabetes or metabolic syndrome, cancer and natural aging. One of the most common oxidative DNA modifications is 8-OHdG (8­hydroxy-2'-deoxyguanosine), which is the most widely used marker in research and clinical diagnostics. 8-OHdG is easily and specifically detectable in various samples such as urine, plasma, cells and tissues via a large variety of methods like ELISA, HPLC, chromatographic methods, and immunochemistry. Formed by oxidation of guanine and being representative for the degree of DNA damage, 8-OHdG can be also used as biomarker for risk assessment of various cancers as well as degenerative diseases. Here, we present a highly specific, self-developed 8-OHdG antibody in successful comparison to a commercially one, tested in cells (FF95, HCT116, and HT22) and intestinal tissue, focusing on automatized evaluation via fluorescence/confocal microscopy.

Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase.

BACKGROUND: Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted. AIM: To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy. METHODS: The clinical and laboratory data of 1532 untreated CHB patients were collected, and all patients had least once liver biopsy from January 2015 to December 2021. The significant differences among different phases of CHB infection were compared with t-test, and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis. RESULTS: Among 1532 untreated CHB patients, 814 (53.13%) patients were in the indeterminate phase. Significant liver histological changes (defined as biopsy score ≥ G2 and/or ≥ S2) were found in 488/814 (59.95%) CHB patients in the indeterminate phase. Significant liver histological changes were significant differences among different age, platelets (PLTs), and alanine aminotransferase (ALT) subgroup in indeterminate patient. Multivariate logistic regression analysis indicated that age ≥ 40 years old [adjust odd risk (aOR), 1.44; 95% confidence interval (CI): 1.06-1.97; P = 0.02], PLTs ≤ 150 × 109/L (aOR, 2.99; 95%CI: 1.85-4.83; P < 0.0001), and ALT ≥ upper limits of normal (aOR, 1.48; 95%CI: 1.08, 2.05, P = 0.0163) were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase. CONCLUSION: Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase, and additional strategies are urgently required for the management of these patients.

Does an untreated peri-implant dehiscence defect affect the progression of peri-implantitis?: A preclinical in vivo experimental study.

OBJECTIVE: To investigate the early impact of plaque accumulation in a buccal dehiscence defect on peri-implant marginal bone resorption. MATERIALS AND METHODS: In six male Mongrel dogs, four dental implants were placed in the posterior maxilla on both sides (two implants per side). Based on the group allocation, each implant was randomly assigned to one of the following four groups to decide whether buccal dehiscence defect was prepared and whether silk ligation was applied at 8 weeks post-implant placement for peri-implantitis induction: UC (no defect without ligation); UD (defect without ligation); LC (no defect with ligation); and LD (defect with ligation) groups. Eight weeks after disease induction, the outcomes from radiographic and histologic analyses were statistically analyzed (p < .05). RESULTS: Based on radiographs, the exposed area of implant threads was smallest in group UC (p < .0083). Based on histology, both the distances from the implant platform to the first bone-to-implant contact point and to the bone crest were significantly longer in the LD group (p < .0083). In the UD group, some spontaneous bone fill occurred from the base of the defect at 8 weeks after implant placement. The apical extension of inflammatory cell infiltrate was significantly more prominent in the LD and LC groups compared to the UC group (p < .0083). CONCLUSION: Plaque accumulated on the exposed implant surface had a negative impact on maintaining the peri-implant marginal bone level, especially when there was a dehiscence defect around the implant.

Timely Review and Communication of Histopathology Reports Following Appendicectomy: Insights from a Two-Cycle Clinical Audit.

INTRODUCTION: Appendicectomy is the most frequent emergency general surgical procedure. Prior research highlights the importance of histopathology analysis after appendicectomy which is the practice in many countries including the United Kingdom (UK), aiming to prevent any oversight of vital findings and the avoidance of potential delays in patient care. Our primary objective was to audit the extent to which surgeons adhere to the NHS England patient safety guidelines from 2016 when it comes to timely reviewing and effectively communicating histopathology results to patients and/or their general practitioners following appendicectomy procedures. Our secondary objective was to amend practice, if deemed necessary, following the implementation of agreed-upon protocols, with the expected improvements being observable in the second cycle of the audit. METHODS: In our two-cycle audit, we performed a retrospective analysis using online patient records from a single centre in the UK. The initial cycle involved cases of emergency appendectomies carried out consecutively for suspected appendicitis from April 2018 to June 2019. Following the clinical governance meeting and the implementation of recommendations, the second audit cycle covered cases between September 2020 and October 2020. RESULTS: In the first cycle, among 418 laparoscopic appendectomies, 207 (49.52%) and 47 reports (11.24%) were reviewed within a 15-day and a 16-30-day window, respectively, following the online availability of histopathology results. Notably, 116 reports (27.75%) remained unreviewed by surgeons, and only 67 (16.02%) of these reports documented communication with patients and/or their general practitioners. In the second cycle, involving 49 patients, 38 reports (77.55%) were reviewed within the first 15 days, and 10 reports (20.4%) were reviewed between 16-30 days. Among these, 16 reports (32.65%) documented communication with patients and/or their general practitioners. CONCLUSIONS: Our adherence to the aforementioned guidance was poor prior to this audit. This two-cycle audit highlighted the need for improvement in the timely review and communication of histopathology reports following appendectomy at our centre. The second cycle showed promising progress, suggesting that changes implemented between the cycles had a positive impact. Nevertheless, continuous efforts may be required to enhance and sustain adherence to these vital patient safety guidelines.

Effect of benralizumab on histopathology and inflammatory signatures in a clinical cohort of eosinophilic esophagitis.

A preliminary report from the recent phase 3 trial of benralizumab, a monoclonal antibody that binds to interleukin-5 receptor alpha (IL5Rα), in patients with EoE revealed that medication use led to tissue eosinophil eradication but did not meet the clinical endpoint of symptom resolution. Here, we characterized the clinical, endoscopic, histologic, and transcriptional changes in patients with active EoE following benralizumab treatment. We retrospectively examined patients with EoE treated with benralizumab at the University of Utah (n = 11) and reviewed reported clinical symptoms, circulating and tissue eosinophilia, and endoscopic and histologic scores. Gene expression profiles from available esophageal tissue from benralizumab-treated patients were compared to those from patients with remission EoE (n = 5), active EoE (n = 10), and controls (n = 22). Benralizumab treatment resulted in partial symptom improvement and significant reduction in tissue eosinophilia, and endoscopic and histologic disease scoring (P < 0.01). Histologic score reductions were driven by eosinophil feature scores, while scores for epithelial features (basal cell hyperplasia and dilated intercellular spaces) were similar to those in active EoE. The gene signatures in benralizumab-treated patients mimicked those of active EoE (e.g. upregulation of POSTN, CDH26, CCL26, and downregulation of DSG1). RNA profiles and pathways support histologic findings of impaired epithelial function that persists despite benralizumab treatment. In conclusion, despite eosinophil eradication, patients treated with benralizumab had persistent epithelial injury at the histologic and transcriptional level. In this cohort, benralizumab therapy failed to eradicate inflammation and epithelial dysfunction showing that interleukin-5 receptor alpha blockade monotherapy is insufficient to control EoE.

The prevalence and rate of undiagnosed celiac disease in an adult general population, the Trøndelag Health Study, Norway.

BACKGROUND & AIMS: This study aimed to determine the total prevalence of celiac disease (CeD), including undiagnosed cases, in a population-based study of adults screened for CeD. METHODS: The study utilized the fourth Trøndelag Health Study (HUNT4), conducted in 2017-2019, where 56,042 adult (aged >20 years) residents of Nord-Trøndelag County, Norway, participated. Serum samples from 54,505 participants were analysed for anti-transglutaminase 2 immunoglobulin A and G. Seropositive individuals were invited for a clinical assessment, including upper endoscopy with duodenal biopsies. Previously diagnosed and seronegative CeD cases were identified through linkage to hospital records and the Norwegian Patient Registry. RESULTS: The rate of CeD seropositivity was 2.0% (1107/54,505). Out of these, 724 individuals attended the clinical assessment. Additionally, the hospital records and registry identified individuals with a known CeD diagnosis, that were seronegative or without serology in HUNT4 or seropositive in HUNT4 but did not participate in the clinical assessment. In total, the study confirmed a new CeD diagnosis after participation in HUNT4 in 470 individuals and a known CeD diagnosis before participation in HUNT4 in 383 individuals. The total biopsy-confirmed prevalence of CeD was 1.5% (853/56,042), and the ratio of new, previously undiagnosed CeD cases (after HUNT4) to known, previously diagnosed CeD cases (before HUNT4) was 1.2:1 (470/383). CONCLUSION: The total prevalence of CeD in this population-based study of adults in Norway was high and many individuals were previously undiagnosed. Detection of CeD should be improved, as early diagnosis is crucial for effective management and prevention of complications.

Comparative evaluation of thermal impact of 980nm diode laser on soft tissue using irrigation and non-irrigation systems: A histomorphometric study.

Background: Diode laser is one of the most captivating technologies in dental practice. In periodontics, when used at appropriate settings, it possesses the best properties for selective surgical and nonsurgical procedures such as subgingival calculus removal without a thermal change of the root surface, and also provides tissue surface sterilization. However, lasers always produce a certain amount of thermal damage to the soft tissues. Therefore, this study aimed to comparatively evaluate the thermal impact of 980-nm diode laser incisions, when used with irrigation versus nonirrigation systems. Materials and Methods: The study was conducted on 24 gingival tissue samples obtained from the goat's mandible and maxilla. The samples were divided into two groups of 12 samples each, and laser incisions were given in 4 power settings, using 980-nm diode laser in super short pulse mode, with and without saline irrigation. Martius Scarlet Blue staining technique was used to prepare the histological slides. Then, slides were examined under a research microscope (Olympus CX 21), and the pictures of the slides were taken by mounting the camera onto the microscope mobile mount. The microscopic images hence obtained were analyzed for the depth and width of the incisions, area of carbonization, necrosis, and reversible damage, using the Digimizer image analysis software. Results: The results of this study demonstrated that the mean incision depth was higher (592.49 ± 180.97, P < 0.05), with less carbonization (25.52 ± 29.21, P = 0.00) and less necrosis (311.63 ± 156.441, P < 0.05) in the laser incisions with irrigation, as compared to the laser incisions given without irrigation system. Conclusion: Within the limitations of this study, it can be concluded that using an irrigation system causes less collateral damage while maintaining the incising efficiency of the diode laser. Further studies with a higher sample size, controlled irrigation systems, and incision techniques are needed to evaluate the efficiency of diode lasers for the clinical explanation of the results.

Computerized metric assessment of glandular tissue volume within the peripheral zone of the prostate using combined magnetic resonance imaging and histopathology: Possible pathophysiological implications on prostate cancer development.

PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are prevalent urological ailments in elderly males. Numerous clinical studies have revealed an invert association between BPH/prostate size and PCa growth. This study investigates the association between prostate size and total glandular tissue volume of the peripheral zone (GVPZ) using a unique blend of magnetic resonance imaging (MRI) and histo-anatomical imaging technique. MATERIALS AND METHODS: Patients were selected who underwent both radical prostatectomy and preoperative MRI scans. MRI scans provided quantitative measurements of prostatic zone dimensions, while histo-anatomical slides yielded quantitative data on glandular density of the peripheral zone (PZ) using imaging software. Integration of MRI and histopathology enabled the assessment of the GVPZ. Statistical analysis identified relationships between total prostate volume (TPV) and GVPZ. RESULTS: Seventy-two patients were selected and 40 cc was determined to be the optimal cutoff for small-to-moderate versus large prostates. Once the two subgroups in TPV were formed, the relationship between TPV and GVPZ was found to be highly significant (p<0.001). CONCLUSIONS: The combination of MRI and histopathology offers a novel approach for precise quantification of glandular tissue within the prostatic PZ. This study corroborates the hypothesis of PZ compression via an enlarging transition zone in larger BPH prostates, resulting in PZ glandular atrophy. Given that most PCa originates in the PZ, these results shed light on the potential protective role of larger BPH prostates against PCa growth.

Diffuse-Type Histology Is Prognostic for All Siewert Types of Gastroesophageal Adenocarcinoma.

PURPOSE: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. MATERIALS AND METHODS: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. RESULTS: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. CONCLUSIONS: Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.

Newly revealed anatomy of the bucinator muscle: An anatomical and histological study.

BACKGROUND: Current anatomical knowledge of the origin of the bucinator muscle (BM), i.e., long thin attachments on the maxilla and mandible and the pterygomandibular raphe (PMR), is not supported by anatomical dissection of this muscle. The aim of this study was therefore to investigate the detailed morphology of the BM and associated structures and to discuss its function. METHODS: The anatomy of the BM and related structures was investigated in 15 cadaveric heads using a surgical microscope and histological analysis. RESULTS: The inferior fibers of the BM originated from a small retromolar area (internal oblique line), which shared a common tendon with the deep tendon of the temporalis. The superior fibers of the BM originated from the maxillary tuberosity. The middle fibers originated the pterygoid hamulus. No PMR was identified in any of the specimens, but the border between the BM and superior pharyngeal constrictor muscle (SC) was clear because the muscle fibers followed different directions. Some horizontal fibers were continuous between the BM and SC. CONCLUSIONS: Our results suggest the need to revise established accounts of the origins of the bucinator (the maxillary tuberosity, conjoint tendon of the temporalis, and pterygoid hamulus without a pterygomandibular raphe. It also needs to be noted that some of its fibers merge directly with the SC.

Rice body synovitis in pediatrics: three different case reports.

Rice body synovitis (RBS) is a rare disease, especially in children. Rheumatoid disorders and tuberculosis are the first two reasons for the formation of the RB. The diagnosis is mainly based on imaging and histopathological features. Herein, we report three cases of RBS in children diagnosed with congenital synovial chondromatosis, tuberculosis (unconfirmed), and ANA -positive juvenile idiopathic arthritis. Clinical features, radiographic findings, pathophysiology, treatment process, and prognosis were reviewed and documented meticulously to enhance cognition in this population and provide some references for clinicians in diagnosing and treating the disease.

The Effect of Osteotomy Preparation Technique and Implant Diameter on Primary Stability and Bone-implant Interface of Short Implants (6 mm).

PURPOSE: To evaluate the effect of osteotomy preparation technique and implant diameter on primary stability and bone-implant interface of short implants (6mm), when placed in bone with high degree of cancellous content. MATERIAL AND METHOD: 90 short (S) implants (6 mm) divided in nine groups based on width (Narrow 4.2 mm, Regular 4.8 mm, Wide 5.4 mm) (N,R,W) and osteotomy preparation (Standard, Osteotome, Osseodensification) (ST, OT, OD) and placed in porcine tibia plateau bone samples: Group SN-ST; Group SN-OT; Group SN-OD; Group SRST; Group SR-OT; Group SR-OD; Group SW-ST; Group SW-OT and Group SW-OD. Insertion torque and Implant Stability Quotient (ISQ) were measured. Four implants from each group SNST, SN-OT, SN-OD were evaluated histomorphometrically. RESULTS: Insertion torque was significantly higher for implants of Group SW-OD compared to Group SW-ST (50.00 ±14.14 Ncm vs 28.00 ±10.85 Ncm, p= 0.005) and Group SW-OT compared to Group SW-ST (46.87 ±17.10 Ncm vs 28.00 ±10.85 Ncm, p=0.026). Insertion torque was significantly higher for implants of Group SW-OD compared to Group SN-OD (50.00 ±14.14 Ncm vs 31.5 ±15.82 Ncm, p=0.04). No significant differences were observed for the percentage of bone, marrow space and connective tissue in contact to the implant surface between studied groups. CONCLUSION: Osteotomy preparation technique at sites with high degree of cancellous content can influence the implant insertion torque for short and wide implants (5.4x6mm). Implant width can influence the insertion torque of short implants placed with the osseodensification technique.

Histological improvements following energy restriction and exercise: The role of insulin resistance in resolution of MASH.

BACKGROUND & AIMS: Metabolic-dysfunction associated steatohepatitis (MASH) is one of the most common liver diseases worldwide and is characterized by multi-tissue insulin resistance. The effects of a 10-month energy restriction and exercise intervention on liver histology, anthropometrics, plasma biochemistries, and insulin sensitivity were compared to standard of care (control) to understand mechanisms that support liver health improvements. METHODS: Following medical diagnosis of MASH, subjects were randomized to treatment (n=16) or control (n=8). Liver fat (MRS), 18-hour plasma biochemical measurements, and isotopically-labeled hyperinsulinemic-euglycemic clamps were completed pre- and post-intervention. Body composition and cardiorespiratory fitness (VO2peak) were also measured mid-intervention. Treatment subjects were counseled to reduce energy intake and completed supervised, high-intensity interval training (3x/week) for 10 months. Control subjects continued physician-directed care. RESULTS: Treatment induced significant (P<0.05) reductions in body weight, fat mass, and liver injury, while VO2peak (P<0.05) and fatty acid (NEFA) suppression (P=0.06) were improved. Both groups exhibited reductions in total energy intake, HbA1c, hepatic insulin resistance, and liver fat (P<0.05). Compared to control, treatment induced a two-fold increase in peripheral insulin sensitivity which was significantly related to higher VO2peak and resolution of liver disease, despite no group differences in peripheral insulin sensitivity. CONCLUSIONS: Exercise and energy-restriction elicited significant and clinically-meaningful treatment effects on liver health, potentially driven by a redistribution of excess nutrients to skeletal muscle, thereby reducing hepatic nutrient toxicity. Clinical guidelines should emphasize the addition of aerobic exercise in lifestyle treatments for the greatest histologic benefit in individuals with advanced MASH. CLINICAL TRIAL NUMBER: NCT03151798.