Paradigm Shift of Interventional Strategies and Outcomes for Acute Limb Ischemia Post-Pandemic.

PURPOSE: We performed a large-scale comparison of patients treated for acute limb ischemia (ALI) in the pre-COVID (2017-2019) and COVID (2020-2022) eras to evaluate changes in interventional strategies and compare factors associated with adverse outcomes. We sought to characterize patient outcomes in an evolving ALI treatment algorithm in response to pandemic-associated presentation delays and rapid technological advancements in mechanical thrombectomy (MT). METHODS: Using the TriNetX global research network, we conducted a multicenter query across 80 health care organizations (HCOs) spanning 4 countries for patients treated for ALI. Propensity score matching was performed to account for comorbidities. Risk of adverse outcomes within 30 days was calculated for each era, including re-intervention (RI30), major/minor amputation, and death. Patients were then stratified by initial intervention: open revascularization (OR), MT, or catheter-directed thrombolysis and adjunctive endovascular procedures alone (CDT/EP). Risk of adverse outcomes was compared between treatment groups of the same era. RESULTS: After propensity score matching, the pre-COVID era and COVID era cohorts included 7344 patients each. COVID era patients experienced a statistically significant higher risk of 30-day mortality (RR=1.211, p=0.027). Mechanical thrombectomy interventions were performed more frequently in the COVID era (RR=1.314, p<0.0001). Comparing outcomes between treatment groups, MT patients required RI30 more than OR patients (pre-COVID: RR=2.074, p=0.006; COVID: RR=1.600, p=0.025). Open revascularization patients had higher 30-day mortality (pre-COVID: RR=2.368, p<0.0001; COVID: RR=2.013, p<0.0001) and major amputations (pre-COVID: RR=2.432, p<0.0001; COVID: RR=2.176, p<0.0001) than CDT/EP. Pre-COVID CDT/EP patients were at higher risk for RI30 (RR=1.449, p=0.005) and minor amputations (RR=1.500, p=0.010) than OR. The MT group had higher major amputation rates than CDT/EP (pre-COVID: RR=2.043, p=0.019; COVID: RR=1.914, p=0.007). COVID-era MT patients had greater 30-day mortality (RR=1.706, p=0.031) and RI30 (RR=1.544, p=0.029) than CDT/EP. CONCLUSION: Significant shifts toward an MT-based approach have been observed in the last 3 years. Although MT required more RI30 than OR, there was no associated consequence of mortality and limb salvage. The increased mortality seen among COVID-era patients could be explained by delayed presentation, as well as poorly understood pro-thrombogenic or pro-inflammatory mechanisms related to the first waves of COVID. More research is necessary to determine an optimal treatment algorithm. CLINICAL IMPACT: Comorbid risk factors and severity of ischemia must be carefully considered before selecting an interventional strategy to prevent adverse outcomes and maximize limb salvage. Open revascularization strategies are associated with increased mortality and limb loss compared to less-invasive thrombolytic therapy alone. Mechanical thrombectomy (MT)-based approaches have been increasingly used in the last 3 years. Patients receiving MT are more likely to require reintervention within 30 days.

Sex-Related Disparities in Acute Limb Ischemia Treatment Outcomes.

BACKGROUND: Although a substantial impetus behind disparities research in healthcare exists, those that are sex-related within vascular surgery outcomes are largely unexplored. Consequently, published guidelines lack specificity when it comes to treating male and female patients with vascular disease. Disparities related to patients suffering from chronic limb-threatening ischemia have been broached, although no extensive studies assessing disparities in acute limb ischemia treatment outcomes have come to the forefront. In this study, our aim is to identify and quantify sex-related disparities as they pertain to interventions for acute limb ischemia. METHODS: Using the TriNetX global research network, we conducted a multicenter query across 48 healthcare organizations spanning 5 countries for patients treated for acute limb ischemia. We determined the number of male and female patients that received one of the following interventions: open revascularization, percutaneous mechanical thrombectomy, or catheter-directed thrombolysis and/or adjunctive endovascular procedures. Propensity score matching was performed to account for comorbidities. Risk of adverse outcomes within 30 days was calculated for each sex, including reintervention, major amputation, and death. Risk of adverse outcomes was then compared between treatment groups of the same sex and between sexes. Type-I errors were reduced through utilization of the Holm-Bonferroni method to correct P values. RESULTS: Within our study, we noted several important findings. Females were more likely to receive catheter-directed thrombolysis and/or adjunctive endovascular procedures (P = 0.001) than males. There were no significant differences in the rates of open revascularization or percutaneous mechanical thrombectomy between males and females. Overall, females were more likely to die within 30 days (P < 0.0001) and greater number of males required reintervention within 30 days (P < 0.0001). Analyzing outcomes within individual treatment groups, females undergoing open revascularization or catheter-directed thrombolysis and/or adjunctive endovascular intervention demonstrated a profound increase in mortality within 30 days of intervention (P = 0.0072 and P = 0.0206, respectively), but these differences were not reflected in the percutaneous mechanical thrombectomy group. Limb salvage rates in females were higher than males overall although there were no significant sex differences within any treatment groups specifically. CONCLUSIONS: In conclusion, there was a significantly higher risk of death in females across all treatment groups in the studied timeframe. Limb salvage rates were higher for females in the open revascularization (OR) treatment group, while males were more likely to require a reintervention across all treatment groups. By evaluating these disparities, we can provide greater insight into personalized treatment for patients presenting with acute limb ischemia.

Dietary starch promotes hepatic lipogenesis in barramundi (Lates calcarifer).

Barramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.

Effect of glycerol feed-supplementation on seabass metabolism and gut microbiota.

Dietary glycerol supplementation in aquaculture feed is seen as an alternative and inexpensive way to fuel fish metabolism, attenuate metabolic utilization of dietary proteins and, subsequently, reduce nitrogen excretion. In this study, we evaluated the impact of dietary glycerol supplementation on nitrogen excretion of European seabass (Dicentrarchus labrax) and its effects on metabolite profile and bacterial community composition of gut digesta. These effects were evaluated in a 60-day trial with fish fed diets supplemented with 2.5% or 5% (w/w) refined glycerol and without glycerol supplementation. Nuclear magnetic resonance spectroscopy and high-throughput 16S rRNA gene sequencing were used to characterize the effects of glycerol supplementation on digesta metabolite and bacterial community composition of 6-h postprandial fish. Our results showed that ammonia excretion was not altered by dietary glycerol supplementation, and the highest glycerol dosage was associated with significant increases in amino acids and a decrease of ergogenic creatine in digesta metabolome. Concomitantly, significant decreases in putative amino acid degradation pathways were detected in the predicted metagenome analysis, suggesting a metabolic shift. Taxon-specific analysis revealed significant increases in abundance of some specific genera (e.g., Burkholderia and Vibrio) and bacterial diversity. Overall, our results indicate glycerol supplementation may decrease amino acid catabolism without adversely affecting fish gut bacterial communities.Key points• Glycerol can be an inexpensive and energetic alternative in fish feed formulations.• Glycerol did not affect nitrogen excretion and gut bacteriome composition.• Glycerol reduced uptake of amino acids and increased uptake of ergogenic creatine.• Glycerol reduced putative amino acid degradation pathways in predicted metagenome.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Correction to: Suspension syndrome: a potentially fatal vagally mediated circulatory collapse-an experimental randomized crossover trial.

The original version of this article unfortunately contained a mistake. Information was missing in the acknowledgements section. The correct information is given below.

Suspension syndrome: a potentially fatal vagally mediated circulatory collapse-an experimental randomized crossover trial.

PURPOSE: Suspension syndrome describes a potentially life-threatening event during passive suspension on a rope. The pathophysiological mechanism is not fully understood and optimal treatment unknown. We aimed to elucidate the pathophysiology and to give treatment recommendations. METHODS: In this experimental, randomized crossover trial, 20 healthy volunteers were suspended in a sit harness for a maximum of 60 min, with and without prior climbing. Venous pooling was assessed by measuring the diameter of the superficial femoral vein (SFV), lower leg tissue oxygenation (StO2) and by determining localized bioelectrical impedance. Hemodynamic response was assessed by measuring heart rate, blood pressure, stroke volume, and left ventricular diameters. Signs and symptoms of pre-syncope were recorded. RESULTS: Twelve (30%) out of 40 tests were prematurely terminated due to pre-syncopal symptoms (mean 44.7 min, minimum 13.4, maximum 59.7). SFV diameter increased, StO2 and the capacitive resistance of the cells decreased indicating venous pooling. Heart rate and blood pressure did not change in participants without pre-syncope. In contrast, in participants experiencing pre-syncope, heart rate and blood pressure dropped immediately before the event. All symptoms dissolved and values returned to normal within 5 min with participants in a supine position. CONCLUSIONS: Sudden pre-syncope during passive suspension in a harness was observed in 30% of the tests. Blood pools in the veins of the lower legs; however, a vagal mechanism finally leads to loss of consciousness. Time to pre-syncope is unpredictable and persons suspended on a rope should be rescued and put into a supine position as soon as possible.

Controversies and evidence for cardiovascular disease in the diverse Hispanic population.

OBJECTIVE: Hispanics account for approximately 17% of the U.S. POPULATION: They are one of the fastest growing racial/ethnic groups, second only to Asians. This heterogeneous population has diverse socioeconomic conditions, making the prevention, diagnosis, and management of vascular disease difficult. This paper discusses the cultural, racial, and social aspects of the Hispanic community in the United States and assesses how they affect vascular disease within this population. Furthermore, it explores risk factors, medical and surgical treatments, and outcomes of vascular disease in the Hispanic population; generational evolution of these conditions; and the phenomenon called the Hispanic paradox. METHODS: A systematic search of the literature was performed to identify all English-language publications from 1991 to 2014 using PubMed, which draws from the National Institutes of Health and U.S. National Library of Medicine, with the words "cardiovascular disease," "prevalence," "vascular," and "Hispanic." An additional search was performed using "cardiovascular disease and Mexico," "cardiovascular disease and Cuba," "cardiovascular disease and Puerto Rico," and "cardiovascular disease and Latin America" as well as for complications, management, outcomes, surgery, vascular disease, and Hispanic paradox. The resulting publications were queried for generational data (spanning multiple well-defined age groups) regarding cardiovascular disease, and cross-references were obtained from their bibliographies. Results are segmented by country of origin. RESULTS: Compared with non-Hispanic whites, Hispanics face higher risks of cardiovascular diseases because of a high prevalence of high blood pressure, obesity, diabetes mellitus, and ischemic stroke. However, the incidence of peripheral arterial disease and carotid disease appears to be significantly lower than in whites. The Hispanic paradox (lower mortality in spite of higher cardiovascular risk factors) may relate to challenges in ascribing life expectancy and cause of death in this diverse population. Low socioeconomic status and high prevalence of concomitant diseases negatively influence the outcomes of all patients, independent of being Hispanic. CONCLUSIONS: Understanding the cultural diversity in Hispanics is important in terms of targeting preventive measures to modify cardiovascular risk factors, which affect development and outcomes of vascular disease. The available literature regarding vascular disease in the Hispanic population is limited, and further longitudinal study is warranted to improve health care delivery and outcomes in this group.

Detection of IgG3 antibodies specific to the human immunodeficiency virus type 1 (HIV-1) p24 protein as marker for recently acquired infection.

Reducing the risk of human immunodeficiency virus type 1 (HIV-1) transmission is still a public health priority. The development of effective control strategies relies on the quantification of the effects of prophylactic and therapeutic measures in disease incidence. Although several assays can be used to estimate HIV incidence, these estimates are limited by the poor performance of these assays in distinguishing recent from long-standing infections. To address such limitation, we have developed an assay to titrate p24-specific IgG3 antibodies as a marker of recent infection. The assay is based on a recombinant p24 protein capable to detect total IgG antibodies in sera using a liquid micro array and enzyme-linked immunosorbent assay. Subsequently, the assay was optimised to detect and titrate anti-p24 IgG3 responses in a panel of sequential specimens from seroconverters over 24 months. The kinetics of p24-specific IgG3 titres revealed a transient peak in the 4 to 5-month period after seroconversion. It was followed by a sharp decline, allowing infections with less than 6 months to be distinguished from older ones. The developed assay exhibited a mean duration of recent infection of 144 days and a false-recent rate of ca. 14%. Our findings show that HIV-1 p24-specific IgG3 titres can be used as a tool to evaluate HIV incidence in serosurveys and to monitor the efficacy of vaccines and other transmission control strategies.

Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies.

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. METHODS: Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. OBJECTIVE: The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

Aflatoxin contamination in nuts marketed in Italy: preliminary results.

BACKGROUND: Aflatoxins (AFs) are one of the main groups of mycotoxins produced by molds. Nuts, although recognized as a food with health benefits, are frequently contaminated by AFs. STUDY DESIGN: In this preliminary study we evaluated the contamination by total AFs and AFB1 in different types of nuts from different countries marketed in Apulia. METHODS: Overall, 124 samples (almonds, apricot kernels, chestnuts, hazelnuts, peanuts, pistachios, walnuts and Brazil nut) were analyzed using an High-Performance Liquid Chromatography system. RESULTS: Twenty samples (16.1%) were contaminated with AFs of which 55% were non-compliant, according to Reg. 165/2010. The median values (µg/kg) of total AFs and AFB1 were 16.6 and 15.1, respectively. Pistachios appeared more susceptible to AF contamination than the other nuts, with levels of total AFs ranging from 8.8 to 387.3 µg/kg and of AFB1 from 8.2 to 354.5 µg/kg. The majority of contaminated samples came from Asia and AF contamination was different in the various Asiatic sub-regions: regardless of the type of nuts, samples from Western Asia were the least contaminated. CONCLUSIONS: As geographical origin may influence the risk of contamination, in order to protect human health, customer countries should increase AF monitoring in nuts coming from those countries with favorable environments for the growth of aflatoxigenic molds or with less strict regulations.

Development of potent class II transactivator gene delivery systems capable of inducing de novo MHC II expression in human cells, in vitro and ex vivo.

Class II transactivator (CIITA) induces transcription of major histocompatibility complex (MHC) II genes and can potentially be used to improve genetic immunotherapies by converting non-immune cells into cells capable of presenting antigens to CD4+ T cells. However, CIITA expression is tightly controlled and it remains unclear whether distinct non-immune cells differ in this transactivator regulation. Here we describe the development of gene delivery systems capable of promoting the efficient CIITA expression in non-immune cell lines and in primary human cells of an ex vivo skin explant model. Different human cell types undergoing CIITA overexpression presented high-level de novo expression of MHC II, validating the delivery systems as suitable tools for the CIITA evaluation as a molecular adjuvant for gene therapies.

New oral targeted therapies for metastatic breast cancer disrupt the traditional patients' management-A healthcare providers' view.

Although a cure still cannot be expected for metastatic breast cancer, thanks to progressive advances in treatments, life expectancy has been increasing over the past 15 years. This study aims to present the impact on the organisation of patients' management of newly released oral targeted therapies dedicated to metastatic breast cancer and the obstacles to their diffusion. Our work is based on the analysis of 40 semi-structured interviews, conducted with oncology healthcare professionals in three regions of France (2015-2016). It shows three main results. First, the prescription of an oral targeted therapy requires greater collaboration between healthcare professionals than traditional intravenous oncology drugs, which may be challenging. Second, there remain many barriers to the dissemination of oral targeted therapies. Third, taking an oral targeted therapy keeps the patient away from the hospital facility and asks for a strong therapeutic alliance. The management of oral targeted therapies is time-consuming for medical oncologists and disrupts the traditional care pathway. The multiplication of actors involved in patients' management reinforces the slowdown in the deployment and acceptance of therapeutic innovations. More players equal a higher risk of slowdown. Questioning and re-designing hospital organisation and management modalities towards this type of care are critical.

Prevention and treatment of skin lesions associated with non-invasive mechanical ventilation. Recommendations of experts. / Prevención y tratamiento de las lesiones cutáneas asociadas a la ventilación mecánica no invasiva. Recomendaciones de expertos.

INTRODUCTION: In the last two decades, non-invasive mechanical ventilation (NIV) has been consolidated as an initial strategy for the management of respiratory failure in critical adult and paediatric patients. OBJECTIVES: To identify risk factors and preventive strategies to reduce the incidence of skin lesions associated with clinical devices (LESADIC) related to NIV, as well as the most effective treatment for injuries that cannot be avoided. METHODOLOGY: Review in the MEDLINE, CINAHL and Cochrane databases of studies published in the last 10years to reach consensus through an expert panel. RESULTS: Knowledge about how to measure correct mask size and protection of the skin with foam or hydrocolloids dressings are factors related to the incidence of LESADIC, as it conditions the degree of pressure-friction and shear that the interface exerts on the skin. The interface that causes fewer LESADIC and is better tolerated is the face mask. When there are injuries, the first thing is to remove the interface that causes pressure on damaged skin, recommending a Helmet® hood as an alternative, treating the infection, managing the exudate and stimulating perilesional skin. CONCLUSIONS: The mask of choice is the facial, always using foam or hydrocolloid dressings on the nasal bridge. Evaluate the condition of the skin under the interface and harness every 4hours (recommended) and 11hours (maximum). Evaluate the rotation strategy of the interface at 24hours if the NIV is still needed on an ongoing basis.

Diagnostic, therapeutic and health-care management protocol in thyroid surgery: a position statement of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

PURPOSE: The diagnostic, therapeutic and health-care management protocol (Protocollo Gestionale Diagnostico-Terapeutico-Assistenziale, PDTA) by the Association of the Italian Endocrine Surgery Units (U.E.C. CLUB) aims to help treat the patient in a topical, rational way that can be shared by health-care professionals. METHODS: This fourth consensus conference involved: a selected group of experts in the preliminary phase; all members, via e-mail, in the elaboration phase; all the participants of the XI National Congress of the U.E.C. CLUB held in Naples in the final phase. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. RESULTS: A clear and concise style was adopted to illustrate the reasons and scientific rationales behind behaviors and to provide health-care professionals with a guide as complete as possible on who, when, how and why to act. The protocol is meant to help the surgeon to treat the patient in a topical, rational way that can be shared by health-care professionals, but without influencing in any way the physician-patient relationship, which is based on trust and clinical judgment in each individual case. CONCLUSIONS: The PDTA in thyroid surgery approved by the fourth consensus conference (June 2015) is the official PDTA of U.E.C. CLUB.

Classification of dependence-related skin lesions: a new proposal.

A new theoretical framework on the development of pressure ulcers and other dependence-related lesions requires continued in-depth analysis of their conceptual bases. This study reports the historical background, definitions, and production mechanisms of these lesions, describing the differential pathognomonic features of pressure and/or shear ulcers, moisture-associated skin damage, and lesions from rubbing or friction. It also discusses the combined/multifactorial lesions that can be found in the clinical setting. Finally, it presents the new classification of these lesions proposed by the Spanish Pressure Ulcers and Chronic Wounds Advisory Panel.

Targets for Ibrutinib Beyond B Cell Malignancies.

Ibrutinib (Imbruvica™) is an irreversible, potent inhibitor of Bruton's tyrosine kinase (BTK). Over the last few years, ibrutinib has developed from a promising drug candidate to being approved by FDA for the treatment of three B cell malignancies, a truly remarkable feat. Few, if any medicines are monospecific and ibrutinib is no exception; already during ibrutinib's initial characterization, it was found that it could bind also to other kinases. In this review, we discuss the implications of such interactions, which go beyond the selective effect on BTK in B cell malignancies. In certain cases, the outcome of ibrutinib treatment likely results from the combined inhibition of BTK and other kinases, causing additive or synergistic, effects. Conversely, there are also examples when the clinical outcome seems unrelated to inhibition of BTK. Thus, more specifically, adverse effects such as enhanced bleeding or arrhythmias could potentially be explained by different interactions. We also predict that during long-term treatment bone homoeostasis might be affected due to the inhibition of osteoclasts. Moreover, the binding of ibrutinib to molecular targets other than BTK or effects on cells other than B cell-derived malignancies could be beneficial and result in new indications for clinical applications.