Microbial fermentation-based synthesis of nano-curcumin suggesting the role of pullulan in nano-formulation.

Curcumin is a multitargeting nutraceutical with numerous health benefits, however, its efficacy is limited due to poor aqueous solubility and reduced bioavailability. While nano-formulation has emerged as an alternative to encounter such issues, it often involves use of toxic solvents. Microbial synthesis may be an innovative solution to address this lacuna. Present study, for the first time, reports exploitation of Aureobasidium pullulans RBF4A3 for production of nano-curcumin. For this purpose, Aureobasidium pullulans RBF4A3 was inoculated in YPD media along with curcumin (0.1 mg/mL) and incubated for 24 h, 48 h, and 72 h. Subsequently, residual sugar, biomass, EPS concentration, curcumin concentration, and curcumin nanoparticle size were measured. As a result, nano-curcumin with an average particle size of 31.63 nm and enhanced aqueous solubility was obtained after 72 h. Further, investigations suggested that pullulan, a reducing polysaccharide, played a significant role in curcumin nano-formulation. Pullulan-mediated nano-curcumin formulation, with an average particle size of 24 nm was achieved with conversion rate of around 59.19 %, suggesting improved aqueous solubility. Additionally, the anti-oxidant assay of the resulting nano-curcumin was around 53.7 % per µg. Moreover, kinetics and thermodynamic studies of pullulan-based nano-curcumin revealed that it followed first-order kinetics and was favored by elevated temperature for efficient bio-conversion. Also, various physico-chemical investigations like FT-IR, NMR, and XRD reveal that pullulan backbone remains intact while forming curcumin nanoparticle. This study may open up new avenues for synthesizing nano-polyphenols through a completely green and solvent free process with plausible diverse applications.

Chronic total occlusion in non-ST elevation myocardial infarction - A multi-centre observational study.

OBJECTIVES: To evaluate the characteristics and outcomes of patients with a chronic total occlusion (CTO) in a Non-ST Elevation Myocardial Infarction (NSTEMI) cohort. BACKGROUND: There is limited data on the clinical characteristics, revascularisation strategies and outcomes of patients presenting with a NSTEMI and a CTO. METHODS: Retrospective analysis of a six-centre percutaneous coronary intervention (PCI) registry in the UK between January 2015 and December 2020 was performed. Patients with a NSTEMI with and without a CTO were compared for baseline characteristics and outcomes. RESULTS: There were 17,355 NSTEMI patients in total of whom 1813 patients had a CTO (10.4 %). Patients with a CTO were more likely to be older (CTO: 67.8 (±11.5) years vs. no CTO: 67.2 (±12) years, p = 0.04), male (CTO: 81.1 % vs.71.9 %, p < 0.0001) with a greater prevalence of cardiovascular risk factors. All-cause mortality at 30 days: HR 2.63, 95 % CI 1.42-4.84, p = 0.002 and at 1 year: HR: 1.87, 95 % CI 1.25-2.81, p = 0.003 was higher in the CTO cohort. CTO patients who underwent revascularisation were younger (Revascularisation 66.4 [±11.7] years vs. no revascularisation 68.4 [±11.4] years, p = 0.001). Patients with failed CTO revascularisation had lower survival (HR 0.21, 95 % CI 0.10-0.42, p < 0.0001). The mean time to revascularisation was 13.4 days. There was variation in attempt at CTO revascularisation between the 6 centres for (16 % to 100 %) with success rates ranging from 65 to 100 %. CONCLUSIONS: In conclusion, the presence of a CTO in NSTEMI patients undergoing PCI was associated with worse in-hospital and long-term outcomes.

Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease.

Aminophospholipids (aPL) such as phosphatidylserine are essential for supporting the activity of coagulation factors, circulating platelets, and blood cells. Phosphatidylthreonine (PT) is an aminophospholipid previously reported in eukaryotic parasites and animal cell cultures, but not yet in human tissues. Here, we evaluated whether PT is present in blood cells and characterized its ability to support coagulation. Several PT molecular species were detected in human blood, washed platelets, extracellular vesicles, and isolated leukocytes from healthy volunteers using liquid chromatography-tandem mass spectrometry. The ability of PT to support coagulation was demonstrated in vitro using biochemical and biophysical assays. In liposomes, PT supported prothrombinase activity in the presence and absence of phosphatidylserine. PT nanodiscs strongly bound FVa and lactadherin (nM affinity) but poorly bound prothrombin and FX, suggesting that PT supports prothrombinase through recruitment of FVa. PT liposomes bearing tissue factor poorly generated thrombin in platelet poor plasma, indicating that PT poorly supports extrinsic tenase activity. On platelet activation, PT is externalized and partially metabolized. Last, PT was significantly higher in platelets and extracellular vesicle from patients with coronary artery disease than in healthy controls. In summary, PT is present in human blood, binds FVa and lactadherin, supports coagulation in vitro through FVa binding, and is elevated in atherosclerotic vascular disease. Our studies reveal a new phospholipid subclass, that contributes to the procoagulant membrane, and may support thrombosis in patients at elevated risk.

Predictors of 1- and 12-month mortality in bifurcation coronary intervention: a contemporary perspective.

Aim: Bifurcation-PCI is performed frequently, although without extensive evidence to back up a definitive solution for its complexity. We set out to identify factors associated with 1- and 12-month mortality after bifurcation-PCI between 2017 and 2021 in our tertiary center in Wales, UK. Results: Of 732 bifurcation PCI cases (mean age 69; 25% female), 67% were in ACS, 42% were left main PCI and 25.3% involved two-stent strategy. 30-day and 12-month mortality were 1.9 and 8.2%, respectively. Age, diabetes, smoking and renal failure are associated with mortality after bifurcation-PCI, while the choice between provisional and 2-stent strategies did not impact mortality/TLR. Conclusion: Awareness of 'real-world' outcomes of bifurcation-PCI should be used for appropriate patient selection, technique planning and procedural consent.

Stent failure: the diagnosis and management of intracoronary stent restenosis.

INTRODUCTION: Despite advances in stent technology for percutaneous coronary intervention (PCI) in the treatment of coronary disease, these procedures can be complicated by stent failure manifested as intracoronary stent restenosis (ISR). Even with advances in stent technology and medical therapy, this complication is reported to affect around 10% of all percutaneous coronary intervention (PCI) procedures. Depending on stent type (drug-eluting versus bare metal), ISR has subtle differences in mechanism and timing and offers different challenges in diagnosing etiology and subsequent treatment options. AREAS COVERED: This review will be visiting the definition, pathophysiology, and risk factors of ISR. EXPERT OPINION: The evidence behind management options has been illustrated with the aid of real life clinical cases and summarized in a proposed management algorithm.

Self-assembled pH-stable gellan/κ-carrageenan bigel: Rheological studies and viscosity prediction by neural network.

The current study focused on analysing and predicting the effect of physicochemical parameters on the rheological properties of the novel polysaccharide-based bigel. This is the first study to report a bigel fabricated entirely from polysaccharides and develop a neural network to predict the modulation in its rheology. This bi-phasic gel had gellan and κ-carrageenan as the constitutive elements in the aqueous and the organic phase, respectively. Physicochemical studies revealed the influence of organogel in eliciting high mechanical strength and smooth surface morphology to the bigel. Furthermore, variation in physiochemical parameters indicated the bigel's inertness towards change in pH of the system. However, variation in temperature led to a noticeable change in the rheology of the bigel. It was observed that after gradual decline, the bigel regained its original viscosity as the temperature increased beyond 80 °C. Insights from this study can pave way for the development of highly-stable polysaccharide bigels.

Enhanced encapsulation efficiency and controlled release of co-encapsulated Bacillus coagulans spores and vitamin B9 in gellan/κ-carrageenan/chitosan tri-composite hydrogel.

The current study, for the first time, attempts to co-encapsulate Bacillus coagulans spores as probiotics and vitamin B9 in the polysaccharide-based matrix for their targeted delivery. Instead of vegetative cells, probiotic spores were chosen owing to their higher stability. The matrix, tri-composite hydrogel, was synthesized from gellan, κ-carrageenan, and chitosan through self-assembly devoid of chemical cross-linkers. Hence, it was found suitable for application in the co-encapsulation of bioactive compounds. The synthesized hydrogel showed remarkable encapsulation efficiency for folic acid and probiotic spores, both individually and in combination. At acidic pH, loaded hydrogel exhibited 28.42 % and 45.14 % release of spores and folic acid, respectively, which was comparatively lower than the trends observed under neutral and alkaline pH. These results were correlated with the release pattern observed during in vitro digestibility studies. Moreover, spore conversion to vegetative cells and its high colonization were observed in the simulated intestinal phase. Therefore, the matrix maintained viability and stability of co-encapsulated folic acid and bacterial spores in gastric pH while they were slowly released in the intestinal phase. These promising findings pave the way to develop a natural matrix for co-encapsulating various bioactive compounds and probiotics.

Long-term outcomes following intravascular lithotripsy (IVL) for calcified coronary lesions: A Real-World Multicenter European Study.

OBJECTIVES: To explore the long-term clinical outcomes following intravascular lithotripsy (IVL) in calcified coronary lesions from a real-world population. BACKGROUND: IVL is a relatively new but promising modality for treating coronary calcified lesions, but there is a dearth of long-term outcome data from real-world patients. METHODS: This was a multicenter, observational study in which we enrolled all patients treated with IVL from November 2018 to February 2021 from eight centers in Europe and the United Kingdom. Procedural success, complications, and clinical outcomes (cardiac death, target vessel myocardial infarction [TVMI], target lesion revascularization [TLR], and MACE [major adverse cardiac events, the composite of cardiac death, TVMI, and TLR]) were assessed. RESULTS: In total, 273 patients with a mean age of 72 ± 9.1 years were treated with IVL. Major comorbidities included diabetes mellitus (n = 110, 40%) and chronic kidney disease (n = 45, 16%). Acute coronary syndrome accounted for 48% (n = 132) of patients, while 52% (n = 141) had stable angina. De novo lesions and in-stent restenosis accounted for 79% and 21% of cases, respectively. Intravascular imaging was used in 33% (n = 90) of patients. An upfront IVL strategy was adopted in 34% (n = 92), while the rest were bailout procedures. Adjuvant rotational atherectomy ("RotaTripsy") was required in 11% (n = 31) of cases. The procedural success was 99%. During a median follow-up of 687 days (interquartile range: 549-787), cardiac death occurred in 5% (n = 14), TVMI in 3% (n = 8), TLR in 6% (n = 16), and MACE rate was 11% (n = 30). CONCLUSION: This is the largest multicenter registry with a long-term follow-up showing the remarkably high procedural success of IVL use in calcified coronary lesions with low rates of hard endpoints and MACE.

Microbial Polysaccharide-Based Nanoformulations for Nutraceutical Delivery.

In recent times, nutrition and diet have become prominent health paradigms due to sedentary lifestyle disorders. Preventive health care strategies are becoming increasingly popular instead of treating and managing diseases. A nutraceutical is an innovative concept that offers additional health benefits beyond its fundamental nutritional value. These nutraceuticals have the potential to reduce the exorbitant use of synthetic drugs because the modern medicine approach of treating diseases with high-tech, expensive supplements, and long-term consequences aggravates consumers. However, most nutraceuticals are plant-derived, making them susceptible to degradation and prone to chemical instability, poor solubility, unpleasant taste, and bioactivity loss before absorption to the targeted site. To counteract this problem, the bioavailability of these labile compounds can be maximized by encapsulating them in protective nanocarriers. It is crucial that nanoencapsulation technologies convert bioactive compounds into forms that can be easily combined with functional foods and beverages without adversely affecting their organoleptic properties. In recent years, nanoformulations using food-grade materials, such as polysaccharides, proteins, lipids, etc., have received considerable attention. Among them, microbial polysaccharides are biocompatible, nontoxic, and nonimmunogenic, and most of them are US-FDA approved and can undergo tailored modifications. The nanoformulation of microbial polysaccharide is a relatively new frontier which has several advantages over existing systems. The present article, for the first time, comprehensively reviews microbial polysaccharides-based nanodelivery systems for nutraceuticals and discusses various techno-commercial aspects of these nanotechnological preparations. Moreover, this has also attempted to draw a future research perspective in this area.

Predictors of 30-day and 12-month mortality in left main stem percutaneous coronary intervention 2016-2020: A study from two UK centers.

INTRODUCTION: Left main stem percutaneous coronary intervention (LMS-PCI) is a complex high-risk procedure which can be performed as an alternative to coronary artery bypass graft (CABG) procedure in surgical turn-down patients or where there is equipoise in percutaneous versus surgical strategies. Current guidelines suggest that PCI is an appropriate alternative to CABG in patients with unprotected LMS disease and low SYNTAX score. However, "real world" data on outcomes of LMS-PCI remain limited. This study aims to quantify and determine predictors of mortality following LMS-PCI. METHODS: Using local coronary angioplasty registries from two UK centers, all LMS-PCI cases were identified from 2016 to 2020. Descriptive statistics and multivariate logistic regressions were used to examine the association between baseline and procedural characteristics with 30-day and 12-month mortality. RESULTS: We identified 484 cases of LMS-PCI between 2016 and 2020. There was a year-on-year increase in the number of LMS-PCI, the highest being in 2020. Covariates associated with higher 30-day mortality were age (OR 1.07, 95% CI: 1.02-1.12) and shock preprocedure (OR 23.88, 95% CI: 7.90-72.20). Covariates associated with higher 12-month mortality were age (OR 1.04, 95% CI: 1.01-1.08), acute coronary syndrome (ACS) (OR 2.50, 95% CI: 1.08-5.80), renal disease (OR 5.24, 95% CI: 1.47-18.68), and shock preprocedure (OR 7.93, 95% CI: 3.30-19.05). Overall, 30-day and 12-month mortality in this contemporary data set were 9.5% and 16.7%, respectively, with significantly lower rates in elective cases (p < 0.01). CONCLUSIONS: Older age and cardiogenic shock preprocedure were associated with increased 30-day mortality after LMS-PCI. Twelve-month mortality was associated with older age, ACS presentation, preexisting renal disease, and cardiogenic shock preprocedure.

Isolation, purification, and characterization of a novel exopolysaccharide isolated from marine bacteria Brevibacillus borstelensis M42.

Marine microbes produce polysaccharides with unique physicochemical and functional properties that help them survive in harsh marine environments. However, only a handful of marine exopolysaccharides (EPSs) have been reported to date. The present study explored the seashore of Visakhapatnam, India, to report a novel exopolysaccharide designated as Br42 produced by Brevibacillus borstelensis M42. The isolate was identified through morphological, biochemical, phylogenetic, and genome sequencing analysis. The studies on fermentation kinetics revealed that EPS Br42 was a primary metabolite with a maximum production of 1.88 ± 0.02 g/L after 60 h when production broth was fortified with 2% glucose. Additionally, EPS Br42 was found to be a heteropolysaccharide consisting of glucose and galacturonic acid with a molecular weight of about 286 kDa. Interestingly, this molecule possesses industrially relevant functional properties such as water-holding (510 ± 0.35%), oil-holding (374 ± 0.12% for coconut oil and 384 ± 0.35% for olive oil), and swelling capacities (146.6 ± 5.75%). EPS Br42 could form an emulsion that was stable at a wide pH range for about 72 h and, in fact, performed better as compared to Span 20, a commercially used synthetic emulsifier. Moreover, this EPS was also found to be heat stable and exhibited non-Newtonian pseudoplastic behavior. These physicochemical and functional properties of polysaccharides suggest that the EPS Br42 has potential for multifarious industrial applications as an emulsifier, stabilizer, viscosifier, and binding agent.

Sirolimus-eluting stents with ultrathin struts versus everolimus-eluting stents for patients undergoing percutaneous coronary intervention: final three-year results of the TALENT trial.

BACKGROUND: In the TALENT study, the sirolimus-eluting ultrathin strut Supraflex stent was non-inferior to the XIENCE stent for a device-oriented composite endpoint (DoCE: defined as cardiac death, target vessel myocardial infarction [TV-MI], or clinically indicated target lesion revascularisation [CI-TLR]) at 12 months. AIMS: This study investigated the 3-year outcomes of the TALENT trial and long-term impact of ultrathin drug-eluting stents (DES), compared to the XIENCE everolimus-eluting thin stent. METHODS: The TALENT trial is a prospective, multicentre, randomised all-comers trial comparing the Supraflex sirolimus-eluting stent with the XIENCE everolimus-eluting stent, with planned follow-up for 3 years. RESULTS: The TALENT trial enrolled 1,435 patients (Supraflex n=720, XIENCE n=715) with 3-year follow-up data available in 97.8% in the Supraflex group, and in 98.9% in the XIENCE group. At 3 years, DoCE occurred in 57 patients (8.1%) in the Supraflex group, and in 66 patients (9.4%) in the XIENCE group (p=0.406). There were no significant between-group differences in rates of cardiac death, TV-MI or CI-TLR. The rates of definite or probable stent thrombosis were low and similar between groups (1.1% vs 1.4%; p=0.640). In a meta-analysis of long-term follow-up (3-5 years), ultrathin strut DES tended to reduce DoCE (relative risk 0.89 [0.79-1.01]; p=0.068), compared to thicker strut DES. The risks for cardiac death and definite or probable stent thrombosis were similar between ultrathin strut DES and thicker strut DES. CONCLUSIONS: At 3-year follow-up, the use of the Supraflex stent was at least as safe and efficacious as the XIENCE stent in an all-comers population. CLINICALTRIALS: gov: NCT02870140.

"RotaTripsy" for Severe Calcified Coronary Artery Lesions: Insights From a Real-World Multicenter Cohort.

OBJECTIVES: The aim of this study is to assess the feasibility, efficacy and safety of the "RotaTripsy" approach in severe calcified coronary artery lesions. BACKGROUND: Coronary lesions with a high calcium content represent a challenging scenario in interventional cardiology, requiring a proper lesion preparation. In this light, very little is known about the possibility to combine the benefits of rotational atherectomy and intravascular lithotripsy. METHODS: We retrospectively enrolled 34 patients from a real-word, multicenter, cohort of patients affected by severe calcified coronary artery lesions, which required the "RotaTripsy" to obtain a proper lesion preparation. In all the cases, rotational atherectomy and then intravascular lithotripsy were performed as a bail-out strategy following sub-optimal non-compliant balloon expansion. In 53% of the cases, the procedure was guided by intracoronary imaging findings. RESULTS: Procedural success was reported in all the cases, without any in-hospital major complication. Few major adverse clinical events were reported at mid-term follow-up. CONCLUSIONS: "RotaTripsy" can represent a valid therapeutic option for undilatable heavily calcified coronary artery lesions. Our findings demonstrate the feasibility, safety and efficacy of this approach.

Resource Constrained CVD Classification Using Single Lead ECG On Wearable and Implantable Devices.

Electrocardiogram (ECG) is one of the fundamental markers to detect different cardiovascular diseases (CVDs). Owing to the widespread availability of ECG sensors (single lead) as well as smartwatches with ECG recording capability, ECG classification using wearable devices to detect different CVDs has become a basic requirement for a smart healthcare ecosystem. In this paper, we propose a novel method of model compression with robust detection capability for CVDs from ECG signals such that the sophisticated and effective baseline deep neural network model can be optimized for the resource constrained micro-controller platform suitable for wearable devices while minimizing the performance loss. We employ knowledge distillation-based model compression approach where the baseline (teacher) deep neural network model is compressed to a TinyML (student) model using piecewise linear approximation. Our proposed ECG TinyML has achieved ~156x compression factor to suit to the requirement of 100KB memory availability for model deployment on wearable devices. The proposed model requires ~5782 times (estimated) less computational load than state-of-the-art residual neural network (ResNet) model with negligible performance loss (less than 1% loss in test accuracy, test sensitivity, test precision and test F1-score). We further feel that the small footprint model size of ECG TinyML (62.3 KB) can be suitably deployed in implantable devices including implantable loop recorder (ILR).

Green Synthesis of pH-Responsive, Self-Assembled, Novel Polysaccharide Composite Hydrogel and Its Application in Selective Capture of Cationic/Anionic Dyes.

Dyes are one of the most hazardous chemicals causing significant environmental pollution and affecting water quality. Majority of the existing methods for dye removal and degradation involve synthetic membranes and use of hazardous chemicals, further resulting in secondary pollution. The present study reports polysaccharide based novel composite hydrogel as biodegradable matrix for pH-responsive selective adsorption of cationic/anionic dyes. This membrane showed pH-responsive adsorption of methyl green (MG) and methyl orange (MO) with similar adsorption equilibrium, i.e., 315 and 276 mg g-1, respectively. Interestingly, selective adsorption at different pH has allowed separation of dye mixtures that holds incredible industrial importance for dyes recovery. The hydrogel matrix was able to completely separate MG, a model cationic dye at neutral pH from the dye mixture whereas, it was possible to remove 60% MO, a model anionic dye at acidic pH. Furthermore, comprehensive isothermal and kinetic studies of adsorption revealed that Freundlich isotherm describing the multilayer coverage and pseudo-second-order kinetics were followed. Thermodynamic studies indicated that the adsorption process was spontaneous and endothermic. In fact, the membrane was reusable for at least ten cycles and exhibited desorption efficiency of 80 and 60% for MO and MG, respectively, which may be further recycled to make the process environmentally sustainable. Overall, this study proposes an inexpensive, simple, biologically safe, and efficient adsorbent material for dye effluent treatment.

Recent advances in composite hydrogels prepared solely from polysaccharides.

The proliferating demand for sustainable, biodegradable, and biologically safe materials has triggered the development of polysaccharide-based hydrogels. The translation of research on single polysaccharide-based hydrogels into their desired clinical or industrial application is minimal. This is attributable to their lack of mechanical strength, inadequate stability, and constrained the possibility of their modulation to obtain the desired property. Polysaccharide-based composite hydrogels (PCHs) have proven their mantle to counteract this issue while expanding the horizons for their applications. PCHs can be fabricated by physical and/or chemical interlinking techniques, which entails the association of macromolecular chain linkages. The resulting composites can impart remarkably higher stability and elevate the suitability and efficiency of the system. Owing to these advantages, the research on PCHs has been gaining momentum. They are emerging as a lucrative alternative for the conventional molecules used for the fabrication of such materials. The review would initially focus on providing a detailed outlook for the various physical/chemical techniques involved in the preparation of PCHs. Subsequently, the characterization techniques used to understand the structural and chemical behavior of PCHs would be discussed. The article would also elaborate on the various fields of application and the possible areas for future research of PCHs.

Intravascular lithotripsy in calcified-coronary lesions: A real-world observational, European multicenter study.

BACKGROUND: The recently introduced intravascular lithotripsy (IVL) appears promising and relatively safer than conventional approaches when dealing with calcified lesions. Although there are published reports on this novel technology, data from the real world are limited. In this study, we aim to report on the experience of IVL from a real-world population derived from six European centers that undertake high-volume complex coronary interventions. METHODS AND RESULTS: We enrolled all patients treated with IVL between November 2018 and February 2020 at six centers. Procedural success and complications were assessed along with clinical outcomes, which included: cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR), and major adverse cardiac event (MACE) (composite of cardiac death, TVMI, and TLR). Hundred and ninety patients (200 lesions) with a mean age of 72 years were treated using IVL. Diabetes and chronic kidney disease were present in 50% (n = 95) and 16% (n = 30) of cases, respectively. Acute-coronary syndromes accounted for 91 (48%) of the cases. Most were de-novo lesions (77%; n = 154). Upfront use of IVL occurred in 26% of cases, while the rest were bail-out procedures due to inadequate predilatation with conventional balloons. Adjuvant rotational atherectomy was needed in 17% of cases. Procedural success was achieved in 99% of cases with a complication rate of 3%. During the median follow-up of 222 days, there was two cardiac deaths (1%), one case of TVMI (0.5%), 3 TLR (1.5%) taking the MACE rate to 2.6%. CONCLUSION: Use of IVL appears to be safe and effective in dealing with calcified-coronary lesions. A high success rate was observed with low procedural complications and event rates.

Hematopoietic Stem Cell Transplantation and Vasculopathy Associated With STAT3-Dominant-Negative Hyper-IgE Syndrome.

Dominant negative mutations in the transcription-factor STAT3 underlie the rare primary immunodeficiency Job's syndrome. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) has shown promise in correction of the underlying immunological defect, with one report suggesting HSCT can prevent development of wider connective tissue complications. Here, we report the case of a 26 year old male who developed an acute ST-elevation myocardial infarction due to coronary artery ectasia and thrombosis, occurring despite pediatric allogeneic HSCT for STAT3-HIES and a predicted 10-year conventional cardiovascular risk of 0.1%. Vasculopathy associated with STAT3-HIES may persist or arise following HSCT and can precipitate life-threatening complications. This has implications for counseling and vascular surveillance, and highlights the need for further studies to determine the risk, pathogenesis, and optimal management of the vasculopathy associated with STAT3-HIES.