Sepsis in obstetric care for the emergency clinician: A review.

Sepsis remains a leading cause of mortality among pregnant and recently pregnant patients, rendering it a subject of vital importance to emergency clinicians in the US. However, death by sepsis has been found to be largely preventable with prompt and appropriate intervention. This narrative review provides a summary of the physiologic, epidemiologic, and systemic factors specific to obstetric sepsis that contribute to delays in diagnosis and treatment. Additionally, it provides a framework for emergency department providers to approach infection identification, antimicrobial selection, and appropriate resuscitation prior to disposition.

Seroprevalence of transfusion transmissible infections (TTIS) among blood donors in SOS hospital Heliwa, Somalia.

Background: A transfusion-transmissible infection (TTI) refers to any infection that can be spread from one person to another through the injection of blood or blood products. The prevalence of these infections varies across countries, influenced by the disease burden within each population. To assess the severity of TTIs, the World Health Organization (WHO) has mandated pre-transfusion blood tests for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and syphilis. This study aimed to determine the seroprevalence and trends of TTIs among blood donors at SOS Hospital in Mogadishu, Somalia, from 2016 to 2022. Methods: A retrospective cross-sectional analysis was performed by examining SOS Hospital's blood bank records spanning from 2016 to 2022. The research included all blood donors screened for transfusion-transmissible infections (TTIs) during this period. Data obtained was input and analyzed utilizing Statistical Package for Social Science (SPSS) v.25.0 and Microsoft Excel 2010. Frequencies and percentages were calculated as part of the descriptive statistics. To analyze trends, Chi-square analysis was applied, and statistical significance between variables was determined using the p-value. Results: There was a total of 36,296 people donated blood during study period. The majority of blood donors were males (99.8 %), primarily aged between 25 and 44 years (80.4 %) with family donors constituting 80.8 % of the participants. Among 36,296 donors, 1087 (2.99 %) tested positive for transfusion-transmissible infections (TTIs), declining from 4.27 % in 2016 to 1.98 % in 2022. The Chi-Square test confirmed a highly significant reduction in TTIs from 2016 to 2022 (X2 = 57.625, p < 0.0001), indicating a decreasing trend over the seven-year period. Conclusion and recommendations: This study uncovers a moderate prevalence of transfusion-transmitted infections, indicating a notable decrease over time. Additionally, the findings underscore a gender disparity in blood donation, with replacement donors being predominant. It is imperative to conduct multi-center research endeavors to precisely identify the factors influencing transfusion-transmitted infections among blood donors.

[Patient monitoring strategy in a hand surgery university center labeled FESUM-Integration of postgraduate students: A prospective study]. / Stratégie de suivi des patients dans un centre SOS main universitaire labellisé FESUM-Intégration des étudiants de 3e cycle : une étude prospective.

INTRODUCTION: Federation of Hand Emergency Services (FESUM) is a European network of hand emergency centers (called SOS hand centers) in France, Belgium and Luxembourg. The FESUM network includes 64 SOS Hand centers in France. In our university hospital, the FESUM-certified SOS hand has been part of the plastic surgery department since 2001. It has included, since 2016, postgraduate students ("residents") training in hand surgery who participate independently in the patient follow-up. The objective of this study was to analyze the characteristics of this population of patients with hand injuries and their satisfaction with this mode of follow-up. The secondary objective was to study the characteristics of the patient population treated by our center. MATERIAL AND METHOD: We conducted a study on the follow-up of patients undergoing emergency hand surgery, prospective, single-center, declarative, anonymized, between May and October 2021 at the SOS main center of our university hospital at the "SOS Main" intern consultation. The demographic data, the main characteristics of the pathology, the elements of initial care and follow-up of the patients as well as their satisfaction were analyzed, as well as the satisfaction of the interns. RESULTS: We included 323 patients. The population of patients treated generally corresponded to a young man, manual worker, who was initially treated in an outpatient department or in an SOS Hand consultation. The lesions most often represented were fractures (24%), tendon wounds (18%) and wounds without damage to noble tissues (16%). Follow-up consultations took place mainly 15days after the emergency intervention, lasted on average 10minutes and did not present excessive delays. Patient (91.2%) and post-graduate student (87.2%) satisfaction was high. However, postoperative physiotherapy follow-up was insufficient, as was self-rehabilitation. CONCLUSION: The integration of post-graduate student in a university plastic surgery department into the care of SOS Hand patients seems beneficial for all those involved, and for their training. The characteristics of the follow-up consultations by the intern in autonomous supervision corresponded to the high quality standards of the FESUM. The patients showed a high satisfaction rate. Better valorization of this consultation in "office surgery" should be considered.

KRASG 12C-inhibitor-based combination therapies for pancreatic cancer: insights from drug screening.

Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options, emphasizing the urgent need for effective therapies. The predominant driver in PDAC is mutated KRAS proto-oncogene, KRA, present in 90% of patients. The emergence of direct KRAS inhibitors presents a promising avenue for treatment, particularly those targeting the KRASG12C mutated allele, which show encouraging results in clinical trials. However, the development of resistance necessitates exploring potent combination therapies. Our objective was to identify effective KRASG12C-inhibitor combination therapies through unbiased drug screening. Results revealed synergistic effects with son of sevenless homolog 1 (SOS1) inhibitors, tyrosine-protein phosphatase non-receptor type 11 (PTPN11)/Src homology region 2 domain-containing phosphatase-2 (SHP2) inhibitors, and broad-spectrum multi-kinase inhibitors. Validation in a novel and unique KRASG12C-mutated patient-derived organoid model confirmed the described hits from the screening experiment. Our findings propose strategies to enhance KRASG12C-inhibitor efficacy, guiding clinical trial design and molecular tumor boards.

Early defibrotide therapy and risk factors for post-transplant veno-occlusive disease/sinusoidal obstruction syndrome in childhood.

BACKGROUND: Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening complications of hematopoietic cell transplantation (HCT). METHODS: We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after transplantation, focusing on recent immunotherapies. A total of 111 pediatric patients who underwent HCT for malignant disease between February 2017 and March 2023 at Kyushu University Hospital were included. RESULTS: Among 111 patients of less than 20 years of age who underwent HCT for malignancy at a single institution between 2017 and 2023, VOD/SOS occurred in 25 (23%) patients. VOD/SOS developed more frequently in the post-DF era (2020-2023, n = 58) than in the pre-DF era (31% vs. 13%, p = .04). The proportion of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) was higher in the post-DF era than in the pre-DF era (44% vs. 8%, p = .04). Early DF therapy that was started at two European Society for Blood and Marrow Transplantation diagnostic criteria reduced the severity of VOD/SOS (p < .01) in comparison to non-early therapy started at less than two criteria. A multivariate analysis indicated that a history of cytokine release syndrome (odds ratio [OR] = 10.4, p = .01) and juvenile myelomonocytic leukemia (OR = 8.98, p = .04), but not an endothelial activation and stress index (EASIX) score of greater than 0.85, were independent risk factors for VOD/SOS. CONCLUSIONS: Early DF therapy improves the severity and survival outcomes of post-transplant VOD/SOS in children. However, its incidence is increasing in the era of immunotherapy for progressive diseases.

Conditional protein splicing of the Mycobacterium tuberculosis RecA intein in its native host.

The recA gene, encoding Recombinase A (RecA) is one of three Mycobacterium tuberculosis (Mtb) genes encoding an in-frame intervening protein sequence (intein) that must splice out of precursor host protein to produce functional protein. Ongoing debate about whether inteins function solely as selfish genetic elements or benefit their host cells requires understanding of interplay between inteins and their hosts. We measured environmental effects on native RecA intein splicing within Mtb using a combination of western blots and promoter reporter assays. RecA splicing was stimulated in bacteria exposed to DNA damaging agents or by treatment with copper in hypoxic, but not normoxic, conditions. Spliced RecA was processed by the Mtb proteasome, while free intein was degraded efficiently by other unknown mechanisms. Unspliced precursor protein was not observed within Mtb despite its accumulation during ectopic expression of Mtb recA within E. coli. Surprisingly, Mtb produced free N-extein in some conditions, and ectopic expression of Mtb N-extein activated LexA in E. coli. These results demonstrate that the bacterial environment greatly impacts RecA splicing in Mtb, underscoring the importance of studying intein splicing in native host environments and raising the exciting possibility of intein splicing as a novel regulatory mechanism in Mtb.

Anti-mutagenic agent targeting LexA to combat antimicrobial resistance in mycobacteria.

Antimicrobial resistance (AMR) is a serious global threat demanding innovations for effective control of pathogens. The bacterial SOS response, regulated by the master regulators, LexA and RecA, contributes to AMR through advantageous mutations. Targeting the LexA/RecA system with a novel inhibitor could suppress the SOS response and potentially reduce the occurrence of AMR. RecA presents a challenge as a therapeutic target due to its conserved structure and function across species, including humans. Conversely, LexA which is absent in eukaryotes, can be potentially targeted, due to its involvement in SOS response which is majorly responsible for adaptive mutagenesis and AMR. Our studies combining bioinformatic, biochemical, biophysical, molecular, and cell-based assays present a unique inhibitor of mycobacterial LexA, wherein we show that the inhibitor interacts directly with the catalytic site residues of LexA of Mycobacterium tuberculosis (Mtb), consequently hindering its cleavage, suppressing SOS response thereby reducing mutation frequency and AMR.

Effect of gamma irradiation on the proteogenome of cold-acclimated Kocuria rhizophila PT10.

The effects of ionizing radiation (IR) on the protein dynamics of cold-stressed cells of a radioresistant actinobacterium, Kocuria rhizophila PT10, isolated from the rhizosphere of the desert plant Panicum turgidum were investigated using a shotgun methodology based on nanoflow liquid chromatography coupled to tandem mass spectrometry. Overall, 1487 proteins were certified, and their abundances were compared between the irradiated condition and control. IR of cold-acclimated PT10 triggered the over-abundance of proteins involved in (1) a strong transcriptional regulation, (2) amidation of peptidoglycan and preservation of cell envelope integrity, (3) detoxification of reactive electrophiles and regulation of the redox status of proteins, (4) base excision repair and prevention of mutagenesis and (5) the tricarboxylic acid (TCA) cycle and production of fatty acids. Also, one of the more significant findings to emerge from this study is the SOS response of stressed PT10. Moreover, a comparison of top hits radio-modulated proteins of cold-acclimated PT10 with proteomics data from gamma-irradiated Deinococcus deserti showed that stressed PT10 has a specific response characterised by a high over-abundance of NemA, GatD, and UdgB.

Research Advancements in Salt Tolerance of Cucurbitaceae: From Salt Response to Molecular Mechanisms.

Soil salinization severely limits the quality and productivity of economic crops, threatening global food security. Recent advancements have improved our understanding of how plants perceive, signal, and respond to salt stress. The discovery of the Salt Overly Sensitive (SOS) pathway has been crucial in revealing the molecular mechanisms behind plant salinity tolerance. Additionally, extensive research into various plant hormones, transcription factors, and signaling molecules has greatly enhanced our knowledge of plants' salinity tolerance mechanisms. Cucurbitaceae plants, cherished for their economic value as fruits and vegetables, display sensitivity to salt stress. Despite garnering some attention, research on the salinity tolerance of these plants remains somewhat scattered and disorganized. Consequently, this article offers a review centered on three aspects: the salt response of Cucurbitaceae under stress; physiological and biochemical responses to salt stress; and the current research status of their molecular mechanisms in economically significant crops, like cucumbers, watermelons, melon, and loofahs. Additionally, some measures to improve the salt tolerance of Cucurbitaceae crops are summarized. It aims to provide insights for the in-depth exploration of Cucurbitaceae's salt response mechanisms, uncovering the roles of salt-resistant genes and fostering the cultivation of novel varieties through molecular biology in the future.

Surface-mutagenesis strategies to enable structural biology crystallization platforms.

A key prerequisite for the successful application of protein crystallography in drug discovery is to establish a robust crystallization system for a new drug-target protein fast enough to deliver crystal structures when the first inhibitors have been identified in the hit-finding campaign or, at the latest, in the subsequent hit-to-lead process. The first crucial step towards generating well folded proteins with a high likelihood of crystallizing is the identification of suitable truncation variants of the target protein. In some cases an optimal length variant alone is not sufficient to support crystallization and additional surface mutations need to be introduced to obtain suitable crystals. In this contribution, four case studies are presented in which rationally designed surface modifications were key to establishing crystallization conditions for the target proteins (the protein kinases Aurora-C, IRAK4 and BUB1, and the KRAS-SOS1 complex). The design process which led to well diffracting crystals is described and the crystal packing is analysed to understand retrospectively how the specific surface mutations promoted successful crystallization. The presented design approaches are routinely used in our team to support the establishment of robust crystallization systems which enable structure-guided inhibitor optimization for hit-to-lead and lead-optimization projects in pharmaceutical research.

SOS1 gene family in mangrove (Kandelia obovata): Genome-wide identification, characterization, and expression analyses under salt and copper stress.

BACKGROUND: Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+/H+ exchanger, is essential for plant salt tolerance. Salt damage is a significant abiotic stress that impacts plant species globally. All living organisms require copper (Cu), a necessary micronutrient and a protein cofactor for many biological and physiological processes. High Cu concentrations, however, may result in pollution that inhibits the growth and development of plants. The function and production of mangrove ecosystems are significantly impacted by rising salinity and copper contamination. RESULTS: A genome-wide analysis and bioinformatics techniques were used in this study to identify 20 SOS1 genes in the genome of Kandelia obovata. Most of the SOS1 genes were found on the plasma membrane and dispersed over 11 of the 18 chromosomes. Based on phylogenetic analysis, KoSOS1s can be categorized into four groups, similar to Solanum tuberosum. Kandelia obovata's SOS1 gene family expanded due to tandem and segmental duplication. These SOS1 homologs shared similar protein structures, according to the results of the conserved motif analysis. The coding regions of 20 KoSOS1 genes consist of amino acids ranging from 466 to 1221, while the exons include amino acids ranging from 3 to 23. In addition, we found that the 2.0 kb upstream promoter region of the KoSOS1s gene contains several cis-elements associated with phytohormones and stress responses. According to the expression experiments, seven randomly chosen genes experienced up- and down-regulation of their expression levels in response to copper (CuCl2) and salt stressors. CONCLUSIONS: For the first time, this work systematically identified SOS1 genes in Kandelia obovata. Our investigations also encompassed physicochemical properties, evolution, and expression patterns, thereby furnishing a theoretical framework for subsequent research endeavours aimed at functionally characterizing the Kandelia obovata SOS1 genes throughout the life cycle of plants.

Development of PROTACS degrading KRAS and SOS1.

The Kirsten rat sarcoma virus-son of sevenless 1 (KRAS-SOS1) axis drives tumor growth preferentially in pancreatic, colon, and lung cancer. Now, KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of KRAS. However, the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%, lasting for a mean period of 8 months. One approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras (PROTACs), which degrade the proteins of interest and exhibit much higher antitumor activity through multiple cycles of activity. Accordingly, PROTACs have been developed based on KRAS- or SOS1-directed inhibitors coupled to either von Hippel-Lindau (VHL) or Cereblon (CRBN) ligands that invoke the proteasomal degradation. Several of these PROTACs show increased activity in vitro and in vivo compared to their cognate inhibitors but their toxicity in normal tissues is not clear. The CRBN PROTACs containing thalidomide derivatives cannot be tested in experimental animals. Resistance to such PROTACS arises through downregulation or inactivation of CRBN or factors of the functional VHL E3 ubiquitin ligase. Although highly active KRAS and SOS1 PROTACs have been formulated their clinical application remains difficult.

ANZTCT practice statement: sinusoidal obstruction syndrome/veno-occlusive disease diagnosis and management.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication which can develop after haemopoietic stem cell transplantation (HSCT) and some antibody-drug conjugates. Several SOS/VOD diagnostic and management guidelines exist, with the most recent and refined being the European Society for Blood and Marrow Transplantation adult and paediatric guidelines. Timely diagnosis and effective management (including the availability of therapeutic options) significantly contribute to improved patient outcomes. In Australia and New Zealand, there is variability in clinical practice and access to SOS/VOD therapies. This review aims to summarise the current evidence for SOS/VOD diagnosis, prevention and treatment and to provide recommendations for SOS/VOD in the context of contemporary Australasian HSCT clinical practice.

Human Genetics of Semilunar Valve and Aortic Arch Anomalies.

Lesions of the semilunar valve and the aortic arch can occur either in isolation or as part of well-described clinical syndromes. The polygenic cause of calcific aortic valve disease will be discussed including the key role of NOTCH1 mutations. In addition, the complex trait of bicuspid aortic valve disease will be outlined, both in sporadic/familial cases and in the context of associated syndromes, such as Alagille, Williams, and Kabuki syndromes. Aortic arch abnormalities particularly coarctation of the aorta and interrupted aortic arch, including their association with syndromes such as Turner and 22q11 deletion, respectively, are also discussed. Finally, the genetic basis of congenital pulmonary valve stenosis is summarized, with particular note to Ras-/mitogen-activated protein kinase (Ras/MAPK) pathway syndromes and other less common associations, such as Holt-Oram syndrome.

The Multifaceted Actions of PVP-Curcumin for Treating Infections.

Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP-curcumin as a photosensitizer for antimicrobial photodynamic therapy (aPDT) as well as its potential to act as an adjuvant in antibiotic drug therapy. Gram-negative E. coli K12 and Gram-positive S. capitis were subjected to aPDT using various PVP-curcumin concentrations (1-200 µg/mL) and 475 nm blue light (7.5-45 J/cm2). Additionally, results were compared to aPDT using 415 nm blue light. Gene expression of recA and umuC were analyzed via RT-qPCR to assess effects on the bacterial SOS response. Further, the potentiation of Ciprofloxacin by PVP-curcumin was investigated, as well as its potential to prevent the emergence of antibiotic resistance. Both bacterial strains were efficiently reduced when irradiated with 415 nm blue light (2.2 J/cm2) and 10 µg/mL curcumin. Using 475 nm blue light, bacterial reduction followed a biphasic effect with higher efficacy in S. capitis compared to E. coli K12. PVP-curcumin decreased recA expression but had limited effect regarding enhancing antibiotic treatment or impeding resistance development. PVP-curcumin demonstrated effectiveness as a photosensitizer against both Gram-positive and Gram-negative bacteria but did not modulate the bacterial SOS response.

Membership-dependent polynomial fuzzy control of a positive discrete time system: A symbol transfer technique.

This work explores the polynomial fuzzy stabilization for positive systems. The traditional quadratic Lyapunov function and basic stability analysis may not be favourable for stability investigation due to the absence of the positivity property and membership functions. Therefore, a fuzzy co-positive polynomial Lyapunov-Krasovskii (FCPL) function which considers the positivity is proposed firstly through an imperfect premise matching (IPM) approach. Secondly, the symbol transfer technique which takes into account fuzzy membership knowledge relaxes the stability conditions. The number of symbols is reduced by two constraints: (1) the last and next moments of the membership functions of the FCPL function; (2) membership functions of the fuzzy model and the controller. Finally, the polynomial fuzzy controller with symbols is obtained. Two examples are implemented to verify the proposed methods.

Meta-analysis Driven Strain Design for Mitigating Oxidative Stresses Important in Biomanufacturing.

As the availability of data sets increases, meta-analysis leveraging aggregated and interoperable data types is proving valuable. This study leveraged a meta-analysis workflow to identify mutations that could improve robustness to reactive oxygen species (ROS) stresses using an industrially important melatonin production strain as an example. ROS stresses often occur during cultivation and negatively affect strain performance. Cellular response to ROS is also linked to the SOS response and resistance to pH fluctuations, which is important to strain robustness in large-scale biomanufacturing. This work integrated more than 7000 E. coli adaptive laboratory evolution (ALE) mutations across 59 experiments to statistically associate mutated genes to 2 ROS tolerance ALE conditions from 72 unique conditions. Mutant oxyR, fur, iscR, and ygfZ were significantly associated and hypothesized to contribute fitness in ROS stress. Across these genes, 259 total mutations were inspected in conjunction with transcriptomics from 46 iModulon experiments. Ten mutations were chosen for reintroduction based on mutation clustering and coinciding transcriptional changes as evidence of fitness impact. Strains with mutations reintroduced into oxyR, fur, iscR, and ygfZ exhibited increased tolerance to H2O2 and acid stress and reduced SOS response, all of which are related to ROS. Additionally, new evidence was generated toward understanding the function of ygfZ, an uncharacterized gene. This meta-analysis approach utilized aggregated and interoperable multiomics data sets to identify mutations conferring industrially relevant phenotypes with the least drawbacks, describing an approach for data-driven strain engineering to optimize microbial cell factories.

The DNA damage response of Escherichia coli, revisited: Differential gene expression after replication inhibition.

In 1967, in this journal, Evelyn Witkin proposed the existence of a coordinated DNA damage response in Escherichia coli, which later came to be called the "SOS response." We revisited this response using the replication inhibitor azidothymidine (AZT) and RNA-Seq analysis and identified several features. We confirm the induction of classic Save our ship (SOS) loci and identify several genes, including many of the pyrimidine pathway, that have not been previously demonstrated to be DNA damage-inducible. Despite a strong dependence on LexA, these genes lack LexA boxes and their regulation by LexA is likely to be indirect via unknown factors. We show that the transcription factor "stringent starvation protein" SspA is as important as LexA in the regulation of AZT-induced genes and that the genes activated by SspA change dramatically after AZT exposure. Our experiments identify additional LexA-independent DNA damage inducible genes, including 22 small RNA genes, some of which appear to activated by SspA. Motility and chemotaxis genes are strongly down-regulated by AZT, possibly as a result of one of more of the small RNAs or other transcription factors such as AppY and GadE, whose expression is elevated by AZT. Genes controlling the iron siderophore, enterobactin, and iron homeostasis are also strongly induced, independent of LexA. We confirm that IraD antiadaptor protein is induced independent of LexA and that a second antiadaptor, IraM is likewise strongly AZT-inducible, independent of LexA, suggesting that RpoS stabilization via these antiadaptor proteins is an integral part of replication stress tolerance.

SOS2-AFP2 module regulates seed germination by inducing ABI5 degradation in response to salt stress in Arabidopsis.

Soil salinity pose a significant challenge to global agriculture, threatening crop yields and food security. Understanding the salt tolerance mechanisms of plants is crucial for improving their survival under salt stress. AFP2, a negative regulator of ABA signaling, has been shown to play a crucial role in salt stress tolerance during seed germination. Mutations in AFP2 gene lead to increased sensitivity to salt stress. However, the underline mechanisms by which AFP2 regulates seed germination under salt stress remain elusive. In this study, we identified a protein interaction between AFP2 and SOS2, a Ser/Thr protein kinase known to play a critical role in salt stress response. Using a combination of genetic, biochemical, and physiological approaches, we investigated the role of the SOS2-AFP2 module in regulating seed germination under salt stress. Our findings reveal that SOS2 physically interacts with AFP2 and stabilizes it, leading to the degradation of the ABI5 protein, a negative transcription factor in seed germination under salt stress. This study sheds light on previously unknown connections within salt stress and ABA signaling, paving the way for novel strategies to enhance plant resilience against environmental challenges.

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill.

Hematopoietic stem cell transplantation (HSCT) remains a cornerstone in the management of patients with hematological malignancies. Endothelial injury syndromes, such as HSCT-associated thrombotic microangiopathy (HSCT-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (SOS/VOD), and capillary leak syndrome (CLS), constitute complications after HSCT. Moreover, endothelial damage is prevalent after immunotherapy with chimeric antigen receptor-T (CAR-T) and can be manifested with cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Our literature review aims to investigate the genetic susceptibility in endothelial injury syndromes after HSCT and CAR-T cell therapy. Variations in complement pathway- and endothelial function-related genes have been associated with the development of HSCT-TMA. In these genes, CFHR5, CFHR1, CFHR3, CFI, ADAMTS13, CFB, C3, C4, C5, and MASP1 are included. Thus, patients with these variations might have a predisposition to complement activation, which is also exaggerated by other factors (such as acute graft-versus-host disease, infections, and calcineurin inhibitors). Few studies have examined the genetic susceptibility to SOS/VOD syndrome, and the implicated genes include CFH, methylenetetrahydrofolate reductase, and heparinase. Finally, specific mutations have been associated with the onset of CRS (PFKFB4, CX3CR1) and ICANS (PPM1D, DNMT3A, TE2, ASXL1). More research is essential in this field to achieve better outcomes for our patients.