Review: Livestock cell types with myogenic differentiation potential: Considerations for the development of cultured meat.

With the current environmental impact of large-scale animal production and societal concerns about the welfare of farm animals, researchers are questioning whether we can cultivate animal cells for the purpose of food production. This review focuses on a pivotal aspect of the cellular agriculture domain: cells. We summarised information on the various cell types from farm animals currently used for the development of cultured meat, including mesenchymal stromal cells, myoblasts, and pluripotent stem cells. The review delves into the advantages and limitations of each cell type and considers factors like the selection of the appropriate cell source, as well as cell culture conditions that influence cell performance. As current research in cultured meat seeks to create muscle fibers to mimic the texture and nutritional profile of meat, we focused on the myogenic differentiation capacity of the cells. The most commonly used cell type for this purpose are myoblasts or satellite cells, but given their limited proliferation capacity, efforts are underway to formulate myogenic differentiation protocols for mesenchymal stromal cells and pluripotent stem cells. The multipotent character of the latter cell types might enable the creation of other tissues found in meat, such as adipose and connective tissues. This review can help guiding the selection of a cell type or culture conditions in the context of cultured meat development.

[Advances in the application of intragastric flora in the diagnosis and treatment of gastric cancer].

Gastric cancer is one of the major causes of cancer-related deaths worldwide, and infection with Helicobacter pylori and EBV, smoking and a salt-heavy diet have been shown to be risk factors for the development of gastric cancer. Currently, numerous research has demonstrated that differences in the structure of the gastric flora can be exploited to distinguish the different stages of gastric mucosal lesions and to predict the progression of gastric cancer. Therefore, a new biomarker is presented for the diagnosis of gastric cancer based on the structural differences of the gastric flora. Gastric flora has also potential in the treatment of gastric cancer. The application of non-H. pylori flora to modulate immune cells may increase the sensitivity of tumour cells for chemotherapy, improve the efficacy of immune checkpoint inhibitors and significantly prolong the survival of patients. This review of advances in the application of gastric flora in the diagnosis and treatment of gastric cancer is aimed at providing a reference and basis for future research in this field.

[From exposure to control: the application of allergen component-resolved diagnosis in the clinical management of cockroach allergies].

Cockroaches are one of the most common indoor allergens worldwide, and exposure to cockroach allergens (such as the insect body, debris, and secretions) can trigger severe allergic rhinitis and(or) asthma. Currently, the World Health Organization (WHO)/International Union of Immunological Societies (IUIS) has identified 32 allergenic components in cockroaches, but none of these allergens have shown a clear immunodominance. The sensitization rate to cockroach allergens shows significant variability across different regions and populations and exhibits cross-reactivity with various invertebrates, increasing the complexity of clinical diagnosis and treatment. This article delves into the "Molecular Allergology User's Guide 2.0"(MAUG 2.0) published by the European Academy of Allergy and Clinical Immunology (EAACI) and the research progress on cockroach allergies both domestically and internationally. It elucidates the crucial role of allergen component diagnostic technology in enhancing the diagnosis and treatment of cockroach-induced allergic diseases, efficiently assisting clinicians in identifying common sensitizations and cross-reactivities, thereby offering patients more accurate diagnoses and personalized treatment plans.

Dynamics for High-Sensitivity Detection of Free Radicals in Primary Bronchial Epithelial Cells upon Stimulation with Cigarette Smoke Extract.

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is caused by chronic exposure to toxic particles and gases, such as cigarette smoke. Free radicals, which are produced during a stress response to toxic particles, play a crucial role in disease progression. Measuring these radicals is difficult since the complex mixture of chemicals within cigarette smoke interferes with radical detection. We used a new quantum sensing technique called relaxometry to measure free radicals with nanoscale resolution on cells from COPD patients and healthy controls exposed to cigarette smoke extract (CSE) or control medium. Epithelial cells from COPD patients display a higher free radical load than those from healthy donors and are more vulnerable to CSE. We show that epithelial cells of COPD patients are more susceptible to the damaging effects of cigarette smoke, leading to increased release of free radicals.

The history of thrombotic thrombocytopenic purpura research: a narrative review.

Background and Objective: Thrombotic thrombocytopenic purpura (TTP) is a rare but debilitating thrombotic microangiopathy that results from severe deficiency of the enzyme ADAMTS13. The disorder was first described in the early 20th century, but the pathophysiology of the disease has only been elucidated in the past three decades. In this narrative review, we will summarize the milestone moments in the history of TTP research and discovery. Methods: We searched literature using PubMed from 1924 to 2023 using the following free text searches: "thrombotic thrombocytopenic purpura", "Moschcowitz disease", and "thrombotic microangiopathy". We found 6,917 peer-reviewed articles and sorted through these for relevant literature pertinent to the review. A total of 46 articles were included for review and the remainder were excluded. Key Content and Findings: The history of TTP research was reviewed, with a sampling of major events in the evolution of the understanding of the pathophysiology and treatment of the disease discussed here. There remains much to be learned about the nature of the disease in order to develop more specific and less harmful treatments. Conclusions: An overview of the major discoveries that have led to our current understanding of TTP reveals the results of collaboration of multiple groups of physicians and scientists through the past century, with additional breakthroughs likely to occur in the future because of that same collaborative spirit.

Readmissions Following Endovascular Thoracic and Thoracoabdominal Aortic Repairs in The Vascular Implant Surveillance and Interventional Outcomes Network (VISION).

OBJECTIVES: Investigate readmission rates, diagnoses associated with readmission, and associations with mortality through 90-days post-operatively after elective endovascular thoracic and thoracoabdominal aortic repair overall and by extent of coverage. METHODS: A cohort of index elective non-traumatic endovascular thoracic and thoracoabdominal aortic cases from 2010-2018 was derived from the Vascular Implant Surveillance and Interventional Outcomes Network. Cohort readmissions within 90-days postoperative were examined both overall and by Crawford extent (CE) of aortic coverage. Postoperative mortality was examined by reason for readmission and CE. RESULTS: The cohort consisted of 2,093 patients who underwent endovascular thoracic and thoracoabdominal aortic repair (1,541 CE 0A/0B; 240 CE 1-3; 312 CE 4-5). Cumulative risk for 90-day readmission was 34.3% in CE 0A/0B repairs, 33.4% in CE4-5 repairs and 47.4% in CE 1-3 repairs. Compared to CE 0A/B, patients with CE 1-3 repairs experienced an increased risk of readmission within 90 days postoperatively after adjusting for preoperative factors (aHR 1.27(1.00,1.61) while the readmission risk for CE 4-5 repairs did not differ significantly (aHR 0.83 (0.64,1.06). Significant risk factors for 90-day readmission included COPD, dialysis dependence, limited ambulation, visceral/spinal ischemia, and in-hospital stroke. Discharge to home was protective against readmission (HR 0.65, CI 0.54-0.79). Patients with a readmission within 90-days had a 7.89-fold increase in 90-day mortality (HR 7.84; 5.17, 11.9) compared to those not readmitted. CONCLUSIONS: Increasing extent of endovascular thoracic and thoracoabdominal aortic repair was associated with higher 90-day readmission rates. Readmission for all CE was associated with near 8-fold increased risk of mortality. Risk factors associated with increased risk for readmission included pulmonary insufficiency, renal disease, and poor functional status. These findings can inform stakeholders about investment of resources to improve processes of care that both target prevention and mitigate risk of readmission after elective endovascular thoracic and thoracoabdominal aortic repair.

Exploring Putative Causal Associations between Diet and Periodontal Disease Susceptibility.

INTRODUCTION: Dietary factors may play an important role in periodontal health. However, current evidence from observational studies remains inconclusive. OBJECTIVE: This study aimed to investigate the causal relationships between dietary exposures and periodontal disease risks using Mendelian randomization analysis. METHODS: Large-scale genome-wide association study summary statistics for 20 dietary factors were obtained from the MRC-IEU consortium. Multivariable and univariable 2-sample Mendelian randomization analyses were performed to assess the causal effects of each dietary exposure on 6 periodontal outcomes, including gingivitis and periodontitis. RESULTS: Genetically predicted higher dried fruit intake was significantly associated with reduced risks of acute gingivitis (odds ratio [OR]: 0.02; 95% confidence interval [CI]: 0.00-0.42; P = 0.01) and bleeding gums (OR: 0.96; 95% CI: 0.93-0.99; P = 0.01). Higher fresh fruit and water intake showed protective effects against chronic gingivitis (OR: 0.18; 95% CI: 0.04-0.91; P = 0.04 and OR: 0.15; 95% CI: 0.04-0.53; P = 0.00) and bleeding gums (OR: 0.95; 95% CI: 0.92-0.981; P = 0.00 and OR: 0.98; 95% CI: 0.96-0.99; P = 0.02). Alcohol intake frequency and processed meat intake were risk factors for bleeding gums (OR: 1.01; 95% CI: 1.00-1.02; P = 0.01 and OR: 1.05; 95% CI: 1.01-1.08; P = 0.00) and painful gums (OR: 1.01; 95% CI: 1.00-1.01; P = 0.00 and OR: 1.02; 95% CI: 1.01-1.03; P = 0.00). Most of the causal relationships between genetic predisposition to the specified dietary factors and periodontal diseases remained statistically significant (P < 0.05) after adjusting for genetic risks associated with dentures, smoking, and type 2 diabetes in multivariable Mendelian randomization models. CONCLUSIONS: The findings suggest potential protective effects of higher fruit and water intake against gingivitis and other periodontal problems, while alcohol and processed meat intake may increase the risks of periodontal disease. Our study provides preliminary causal evidence on the effects of diet on periodontal health and could inform prevention strategies targeting dietary habits to improve oral health. KNOWLEDGE TRANSFER STATEMENT: This study suggests that fruit and water intake may protect against periodontal disease, while alcohol and processed meats increase risk, informing dietary guidelines to improve oral health.

Novel mechanisms of action of emerging therapies of hereditary thrombotic thrombocytopenic purpura.

INTRODUCTION: Hereditary thrombotic thrombocytopenic purpura (hTTP) is caused by deficiency of plasma ADAMTS13 activity, resulting from ADAMTS13 mutations. ADAMTS13 cleaves ultra large von Willebrand factor (VWF), thus reducing its multimer sizes. Hereditary deficiency of plasma ADAMTS13 activity leads to the formation of excessive platelet-VWF aggregates in small arterioles and capillaries, resulting in hTTP. AREAS COVERED: PubMed search from 1956 to 2024 using thrombotic thrombocytopenic purpura and therapy identified 3,675 articles. Only the articles relevant to the topic were selected for discussion, which focuses on pathophysiology, clinical presentations, and mechanisms of action of emerging therapeutics for hTTP. Current therapies include infusion of plasma, or coagulation factor VIII, or recombinant ADAMTS13. Emerging therapies include anti-VWF A1 aptamers or nanobody and gene therapies with adeno-associated viral vector or self-inactivated lentiviral vector or a sleeping beauty transposon system for a long-term expression of a functional ADAMTS13 enzyme. EXPERT OPINION: Frequent plasma infusion remains to be the standard of care in most parts of the world, while recombinant ADAMTS13 has become the treatment of choice for hTTP in some of the Western countries. The success of gene therapies in preclinical models may hold a promise for future development of these novel approaches for a cure of hTTP.

[The pathological characteristics and prognostic analysis of medullary thyroid microcarcinoma].

Objectives: To analyze the clinical characteristics and prognosis of medullary thyroid microcarcinoma (MTMC). Methods: A case series studies. The clinical data of patients with medullary thyroid carcinoma (MTC) diagnosed by postoperative pathology and with complete follow-up data who were initially treated in Tianjin Medical University Cancer Hospital from January 2013 to December 2019 were retrospectively analyzed. There were a total of 170 cases, including 70 males and 100 females, aged (49.7±12.3) years old. Among them, there were 61 patients with MTMC. They were divided into group A (with a maximum tumor idameter of ≤0.5 cm, n=13) and group B (with a maximum tumor diameter >0.5~≤1.0 cm, n=48) based on whether the maximum diameter of the tumor was >0.5 cm. Analysis was conducted on their pathological results and prognosis. Results: Among the MTC, MTMC accounted for 26.4% (61/231) with 26 males and 35 females aged Mï¼»Q1，Q3ï¼½51.0 (41.0, 59.0) years. Among the MTMC patients, 57.4% (35/61) were in stage Ⅰ, 16.4% (10/61) were in stage Ⅲ, and 26.2% (16/61) were in stage Ⅳ. For MTMC with a maximum diameter of≤0.5 cm and a maximum diameter of >0.5-≤1.0 cm, there was no statistically significant difference between the two groups in terms of gender, age, mixed cancer, invasion of glandular lobes, multifocal, central lymph node metastasis, lateral neck lymph node metastasis rate and other pathological characteristics(both P>0.05). In terms of prognosis, the recurrence free survival time of MTMC patients was 83.1 (68.0, 97.0) months. Among them, structural tumor recurrence occurred in 5 patients (8.2%) after surgery, and 1 patient (1.6%) died. The expected 5-year and 10-year survival rates were 93.4% and 89.0%, respectively. There was no statistically significant difference in recurrence free survival time among MTMC patients, MTC patients with a maximum diameter of >1.0-≤2.0 cm, and MTC patients with a maximum diameter of >2.0 cm (all P>0.05). Conclusion: MTMC has strong invasiveness, and although the prognosis of most MTMCs is relatively good, the risk of long-term recurrence and death is still high.

[Changes of hemodynamic parameters in normal pregnant women and their relationship with maternal basic characteristics].

Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

Nuclear mTOR Signaling Orchestrates Transcriptional Programs Underlying Cellular Growth and Metabolism.

mTOR is a central regulator of cell growth and metabolism in response to mitogenic and nutrient signals. Notably, mTOR is not only found in the cytoplasm but also in the nucleus. This review highlights direct involvement of nuclear mTOR in regulating transcription factors, orchestrating epigenetic modifications, and facilitating chromatin remodeling. These effects intricately modulate gene expression programs associated with growth and metabolic processes. Furthermore, the review underscores the importance of nuclear mTOR in mediating the interplay between metabolism and epigenetic modifications. By integrating its functions in nutrient signaling and gene expression related to growth and metabolism, nuclear mTOR emerges as a central hub governing cellular homeostasis, malignant transformation, and cancer progression. Better understanding of nuclear mTOR signaling has the potential to lead to novel therapies against cancer and other growth-related diseases.

[Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma].

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

[A study on the distribution characteristics of peripheral retinal defocus in children and adolescents].

Objective: To explore the distribution characteristics of peripheral retinal defocus in children and adolescents. Methods: This cross-sectional study included 500 individuals aged 3 to 18 years, who visited the People's Hospital of Lincang, the First Affiliated Hospital of Dali University and Dali Ophthalmology Hospital between January and December 2021. Data of the right eye of each participant was analyzed. There were 226 males (45.20%) and 274 females (54.80%), with an average age of (10.79±3.79) years. All participants underwent post-cycloplegic refraction, optical biometry, and intraocular pressure measurement to obtain spherical equivalent, average corneal curvature, axial length, and intraocular pressure. Multispectral refraction topography was performed to obtain topographic maps and values at various field angles and orientations of peripheral retinal defocus. Based on multispectral refraction topography, peripheral retinal defocus values were categorized as crater type, hemilateral upturn type, saddle type, and relatively flat type. The distribution of different refractive states was analyzed. Results: The spherical equivalent of the 500 participants was(-1.51±2.61) D, axial length was (24.10±1.28) mm, and average corneal curvature was (43.20±1.22) D. Among the 500 eyes, 382 exhibited hyperopic peripheral retinal defocus values, with 316 eyes (82.72%) being myopic. Myopic peripheral retinal defocus values were observed in 118 eyes, with 15 eyes (12.72%) being myopic. Among different types of peripheral retinal defocus values, 112 eyes (22.4%) exhibited a crater type, 153 eyes (30.6%) exhibited a hemilateral upturn type, 107 eyes (21.4%) exhibited a saddle type, and 128 eyes (25.6%) exhibited a flat type. The proportion of myopia was 82.14% (92 eyes), 69.28% (106 eyes), 60.75% (65 eyes), and 3.90% (5 eyes), respectively. The peripheral retinal defocus values at 15°, 30°, and 45° were (0.01±0.08) D, (0.06±0.21) D, and (0.20±0.37) D, respectively. The peripheral retinal defocus values at temporal, inferior, nasal, and superior locations were (0.58±0.69) D, (0.52±0.63) D, (0.21±0.64) D, and (-0.26±0.67) D, respectively. Notably, the superior primarily manifested as myopic, while the others were predominantly hyperopic. Conclusions: Approximately three-fourths of children and adolescents exhibit hyperopic peripheral retinal defocus values, with a higher prevalence of myopia in this subgroup. The hyperopia peripheral retinal defocus value increases with the distance from the retina to the macula. The peripheral retinal defocus values between superior and inferior, nasal and temporal locations are asymmetrical, with the temporal hyperopic peripheral retinal defocus value being most prominent and the superior myopic peripheral retinal defocus value being most evident.

[Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis].

OBJECTIVE: To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. METHODS: C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. RESULTS: Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = -3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = -0.723, P > 0.05), TNF-α (t = -0.659, P > 0.05), IL-4 (t = -0.263, P > 0.05), IL-10 (t = -0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = -4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = -1.902, P > 0.05), IL-4 (t = -1.333, P > 0.05), IL-10 (t = -1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). CONCLUSIONS: During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

A machine learning approach to predict mortality due to immune-mediated thrombotic thrombocytopenic purpura.

Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models. Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index. Methods: We analyzed variables available at the time of initial presentation, including demographics, symptoms, and laboratory findings. We developed our model using gradient boosting machine, a machine learning ensemble method based on classification trees, implemented in the R package gbm. Results: In our cohort (n = 419), the French score predicted mortality with an area under the receiver operating characteristic curve of 0.63 (95% CI: 0.50-0.77), sensitivity of 0.35, and specificity of 0.84. Our gradient boosting machine model selected 8 variables to predict acute mortality with a cross-validated area under the receiver operating characteristic curve of 0.77 (95% CI: 0.71-0.82). The 2 cutoffs corresponded to sensitivities of 0.64 and 0.50 and specificities of 0.76 and 0.87, respectively. Conclusion: The USTMA Mortality Index was acceptable for predicting mortality due to acute iTTP in the USTMA registry, but not sensitive enough to rule out death. Identifying patients at high risk of iTTP-related mortality may help individualize care and ultimately improve iTTP survival outcomes. Further studies are needed to provide external validation. Our model is one of many recent examples where machine learning models may show promise in clinical prediction tools in healthcare.