Overall, 91.3% of all cases were managed as out-patient cases and were eligible for follow-up appointments. The rate of out-patient follow-up at 72 ± 12 h in the older patients was significantly higher (43.2%) than in the younger adult patients (32.4%) . Regarding the clinical/treatment outcomes, the rates of coagulopathy, antivenom administration, and hospital admission were not statistically different between both groups.We compared older and younger adults envenomated by the green pit viper (GPV) with regard to the following: follow-up compliance, elapsed time between envenomation and emergency department (ED) visit, and clinical/treatment outcomes. This was a two-site retrospective cohort study. We searched hospital electronic medical databases between January 2011 and December 2021. Patients aged 15 and above were eligible if they had a history of snakebite and had at least two VCT and/or platelet count results in their medical records. After the search, 1550 medical records were reviewed and 760 cases were found to be eligible for analysis. In total, 205 cases (27.0%) were ≥60 years old. The median ages in the younger and older groups were 40 (26–51) and 68 (64–75) years, respectively. The median elapsed times from bite to the ED were 47 (30–118) vs. 69 (35–150) min ( Trimeresurus albolabris (the white-lipped pit viper) and T macrops (the big-eyed pit viper) [Snakebites are still an issue in Thailand’s public health system. In 2018, the Department of Disease Control released a report that an average of 5035 people were bitten by venomous snakes per year between 2009 and 2018. When the snake could be identified, for the year 2018, the green pit viper was found to be the most common at 31.9% [t viper) . One majt viper) ,7. To fot viper) ,11.3; (4) severe local swelling or impending compartment syndrome; (5) compartment syndrome [Regarding treatment, after a GPV bite patient arrives in the ED, blood should be taken for a venous clotting time (VCT) or 20 WBCT (20 min whole blood clotting time), and a complete blood count, including platelet count, at the least. The following criteria are used for antivenom administration and admission: (1) systemic bleeding; (2) VCT lasting more than 20 min, or unclotted blood at 20 min (20WBCT), or INR ≥ 1.2; (3) platelets < 100,000 /mmsyndrome ,13,14. IAs of 2015, Thailand has an aging society, with seniors over 60 accounting for 15% of the overall population. It is expected that by 2035 Thailand will have become even more of an aged society, with more than 30% of the population over 60 ,17.In a survey study that collected data from national surveys of older people from three countries in Southeast Asia, Myanmar, Vietnam, and Thailand, it was revealed that percentages of solo living in older adults have been rising. From this study, compared with two decades ago, solo living among older people in Thailand was found to have increased more dramatically compared with Myanmar and Vietnam. It was found that 16% of older Thai people had no children and that, for those who had children, 40% of their children lived somewhere else and not close to them. Being alone can restrict personal assistance when it is in need . It is uVery few studies exist at present regarding snakebites in this vulnerable population and even fewer have compared follow-up compliance and clinical/treatment outcomes among younger adults and older ones. In this study, we aimed to compare follow-up compliance, elapsed time from bite to emergency department visit, clinical symptoms, and clinical/treatment outcomes between the younger and older adults in our study who had been bitten by green pit vipers.Between January 2011 and December 2021, 1550 cases were diagnosed with ICD10 X20, X27, or X29. From a total of 1550 cases, 790 cases were excluded due to not meeting the inclusion criteria or meeting at least one of the exclusion criteria . Finallyp-value < 0.001). Overall, the frequency of undetermined bites was low at 5.1%. The remaining 94.9% of bites were further classified as definite GPV bites (43.0%), probable GPV bites (22.6%), or possible GPV bites (29.3%) . The median elapsed time from bite to ED arrival was significantly shorter, by 22 min, among the younger patients as compared with the older patients. The majority in both groups were bitten outdoors around the house or away from the house, even in the older adults. Younger adults were bitten more often in the feet (67.2%), whereas the most common site of bites in older adults was the hands (45.9%), and the difference was significant . A younger patient had anaphylaxis  from envenomation upon arrival at the ED. No one had wheezing.The degrees of local reactions, including hemorrhagic blebs and wound necrosis, between the two groups were similar. Systemic signs and symptoms were also not different. Abnormal or systemic bleeding was not found at all in either group, even though more of the older patients had taken antiplatelets, anticoagulants, or both , a fourth time at 48 ± 12 h, and a fifth time at 72 ± 12 h after the bite. Blood test results were not significantly different between younger and older patients. Most patients who were bitten by a green pit viper were treated in the ED and then discharged home for out-patient follow-up appointments (91.3%). Only 8.8% of patients with GPV bites were admitted due to risk of systemic bleeding or coagulopathy. A total of 39 cases were administered antivenom. None of the bitten cases in either age group underwent any invasive procedure or any kind of surgical intervention for treatment. None of the patients received vasopressors. No one received blood components because nobody had systemic bleeding. There were no deaths in this study.p-value = 0.01) or excluding  undetermined bite cases , where toxicology rotation and consultation were available on a daily basis . Surprisingly, the older patients had better compliance with follow-up. Older patients might have had more available time for follow-up appointments compared with the younger adults, since the older patients were likely retired from work , unlike the younger adults, who may be busy with daily living, such as working for income or taking care of children or spouses. The older patients in this study might still be quite active as well, since most of the bites occurred outdoors around the house or outside away from the house . This might be because it was mandatory for all residents to consult a medical toxicologist for envenomation and intoxication review at Vajira Hospital. Medical toxicology consultation as well as residency toxicology rotation became available at Vajira Hospital in October 2012. If a patient was lost to follow-up, the in-service medical toxicologist would ask resident rotators to call the patient to come back to the ED for follow-up. This might be a reason that the follow-up rate at Vajira Hospital was significantly higher than that at Taksin Hospital. This was supported by a study “Assessing the effect of a medical toxicologist in the care of rattlesnake-envenomated patients”; medical toxicologist care can be advantageous for those bitten by venomous snakes [The rate of complete follow-up at Vajira Hospital was significantly higher than the rate of complete follow-up at Taksin Hospital   data registry . Most of macrops . From thre (<1%) . 3 [3 [Adverse clinical outcomes, such as abnormal laboratory results, bleeding tendency, or compartment syndrome, were not found in this study  and were3 . However3 [3 . This al3 [3 ,25. The 3 [3 . If any No invasive procedures or surgical interventions or worsening cases that needed blood components or vasopressor drugs were seen in the admission cases. There was no mortality at all among those admitted to the hospitals, as in other reports ,10,27.Since this study was conducted retrospectively, there were some limitations. First, there were insufficient data for a number of medical records; especially in the early years of data collection, registration of ICD10 did not match the patient history, and there were some missing medical records. Some information that could be explanatory for compliance and elapsed time since bite to ED arrival, such as functional status or frailty score for the older patients, living status , and mode of arrival, could not be identified. Sixty-five percent of patients did not complete follow-up to day 3 , and thiOlder adults took more time to reach the ED after a GPV bite but had a higher rate of completed follow-up at 72 ± 12 h. Even though the older patients had more underlying diseases, they had favorable outcomes that were similar to outcomes in the younger patients. This was a two-site retrospective cohort study. We searched the electronic medical databases of two hospitals, one university hospital (900 beds with tertiary care) and one university-affiliated hospital (500 beds with secondary care) in Bangkok using the ICD10  codes X20, X27, and X29 between January 2011 and December 2021. Patients aged 15 years and above were eligible for this study if they had a history of snakebite and had at least two VCT and/or platelet count results. We excluded cases with a known type of animal bite that was clearly identified as being not from a GPV, such as a bite from a cobra, a non-venomous snake, or a non-venomous animal. Patients with insufficient data in the medical records or those with missing medical records were also excluded. The following data were collected: general information, such as sex, age, geographic location of bite, underlying disease, tetanus vaccination history, use of antiplatelets/anticoagulants, bite site, date and time of bite, date and time of ED arrival, initial vital signs, clinical manifestations, and severity of local reaction. For the investigation, we collected VCT or 20WBCT, platelet count, PT/INR, and fibrinogen level (if available). For treatment and outcomes, the following were collected: ED disposition, antivenom administration, admission status, final hospital discharge status, administration of blood components, unplanned ED revisit, surgical intervention, invasive procedure , and need for vasoactive drugs. We had six research assistants review and collect data from these electronic medical records. All six research assistants were trained for data extraction using a standardized data collection form. We tested them for inter-rater reliability using Cohen’s weighted kappa statistics for ordinal scale, and these were more than 0.8 from 10 medical records for bite scene (0.87), type of snake (0.9), bite site (1), skin bleb appearance (1), local reaction (0.88), and management at the ED (0.86), before the data collection. In addition, all 6 assistants were blinded to the objectives of the study; this was decided in an attempt to eliminate selection bias during data collection. This study was approved by the Institutional Review Board of the Faculty of Medicine, Vajira Hospital, and the Ethics Committee of the Bangkok Metropolitan Administration (COA 076/2564).Younger adults: Patients aged 15–59 years old.Older adults: Patients aged ≥60 years old.Severity of local reaction grading: 1: minimal swelling or no swelling, 2: swelling involves not more than 1 major joint, 3: swelling involves more than 1 major joint but fewer than 2 major joints, 4: swelling involves more than 2 major joints.GPV bite: A patient was deemed bitten by a GPV when one of the following criteria was met: (1) definite GPV bite: the patient brought in a green pit viper snake for identification or the patient described the snake as having a green body with a red or red-brown tail; (2) probable GPV bite: the patient was bitten by a snake, but could not describe the snakes details, and 2 fang marks were found with signs of local reaction, such as redness or swelling, or there was bleeding from bite marks, and the patient did not have muscle weakness, which is a symptom of neurotoxic snakebites, especially those of cobras, which can be found in Bangkok, and, in addition, if the patient did not see the animal and whether it was a snake but the patient had 2 fang marks with a local reaction and he/she received GPV antivenom because he/she showed signs of systemic effects ; 3) possible GPV bite: the patient did not see the animal and whether it was a snake but had 2 fang marks with a local reaction and the patient did not have muscle weakness, which is a symptom of neurotoxic snakes (cobras). In this group, the patient did not receive the GPV antivenom even if he/she had mild coagulopathy/thrombocytopenia. For criterion 2, abnormal bleeding or coagulopathy/thrombocytopenia after an animal bite in Bangkok, especially in our catchment area, is only possible with GPV envenomation  possible.Undetermined bite: The patient did not know that he/she was bitten by an animal and only one fang mark or no fang mark was clearly seen. We included this group in this study due to our concern that patients might have been bitten by a GPV without seeing it, as might have happened if it was too dark to identify the snake or if they were bitten in a clump of grass. In addition, we usually treated these patients and had them follow-up as if they were bitten by a GPV because the most concerning envenomation in Bangkok is that from the GPV due to the risk of coagulopathy and systemic bleeding.Anaphylaxis: Patients had any of these characteristics after bite:Skin or mucosal symptoms, such as rash, itching, swollen mouth, puffy eyes, red skin, along with respiratory symptoms or hypotension or inadequate blood supply, such as syncope, or urination.At least 2 of the following symptoms: skin or mucosal manifestations/respiratory symptoms/hypotension or symptoms of poor tissue perfusion/gastrointestinal symptoms.Hypotension after bite without an alternative explanation, such as coagulopathy with systemic bleeding.Elapsed time: The length of time the patient was bitten up to the time he/she was triaged in the ED.Completion for out-patient follow-up: According to the guidelines for management of green pit viper bites published by the Ministry of Public Health of Thailand in 2004, patients are scheduled for a total of 3 follow-up appointments at 24, 48, and 72 h after bite by a GPV. If the patient comes for follow-up all 3 times , he/she is considered to have had a complete follow-up. We set a time interval of ±12 h because sometimes patients are busy at the time scheduled for the follow-up and are unable to come to their visit on time. Moreover, sometimes when a bite occurs at an unusual time, such as 3 a.m., a follow-up at 3 a.m. seems inappropriate for patients, relatives, and ED providers. Therefore, providing a window of follow-up appointments of ±12 h each day seemed more appropriate.-3, fibrinogen < 100 mg/dL, or INR >1.2;Abnormal blood test for coagulation: (coagulopathy): VCT > 20 min, or abnormal 20WBCT (unclotted blood at 20 min), platelet count less than 100,000 cells/mm-Administration of antivenom: patient received GPV antivenom (F(ab’)2) produced by the Queen Saovabha Memorial Institute (QSMI) if he/she had coagulopathy or abnormal bleeding or signs of impending compartment syndrome/compartment syndrome . The dos-Administration of blood components: patient received blood components due to abnormal bleeding from the GPV bite;-If patient had surgical intervention: patient underwent any of the following: incision and drainage, wound debridement, fasciotomy, or limb amputation;-If patient had an invasive procedure: patient underwent or received any of the following: intubation, central vein catheterization, or hemodialysis;-If vasopressors were administered: patient received an intravenous infusion of any vasopressor drugs  to improve hemodynamics.Clinical outcome: Patient had severe envenomation when he/she had any of the following: -ED revisit: In case of out-patient follow-up, the patient had an ED revisit when he/she returned to the ED without an appointment within 72 ± 12 h;-Discharge status: In case the patient was admitted to the hospital as an inpatient. The patient’s final status after being treated in the hospital was described as: (1) alive with complete recovery; (2) alive with disability (such as limb loss); (3) alive with permanent neurological deficits, such as muscle weakness ; (4) dead ; or (5) against medical advice.Treatment outcomes included: t-test or the Mann–Whitney U test, with a significance p-value of < 0.05.Quantitative data, such as age, elapsed time from snakebite to ED arrival, pain score, and test results, were reported using means (SDs) or medians . We compared differences in those continuous data between patients over 60 years old and those under 60 years old using the Student’s Qualitative data, such as sex, underlying diseases, geographic location of the bite, bite site body part, bleeding tendency status, and receipt of antivenom, were reported using percentages. We compared the differences in these qualitative data between the elderly (over 60 years old) and the younger (under 60 years old) patients using the chi-squared test or Fisher’s exact test, where appropriate. Data were collected using Microsoft Excel 2019 . Data were analyzed using IBM SPSS Statistics for Windows, Version 26.0 .


Psoriasis is a chronic systemic inflammatory disease that primarily affects the skin and is associated with multiple comorbidities with a considerable reduction in quality of life of affected patients. One-third of psoriasis cases begin in childhood and are associated with significant medical comorbidities such as obesity, metabolic syndrome, arthritis, and psychiatric disorders. In addition, because of its chronic nature and frequent relapses, psoriasis tends to require long-term treatment. Treatment of pediatric psoriasis usually involves the same methods used for adults. However, most treatments for pediatric psoriasis are used off-label, and research in this regard is still lacking. Targeted therapies involving the use of newly developed biologic drugs are also increasingly being applied to childhood psoriasis. This review summarizes the clinical features of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and biological treatments of pediatric psoriasis. Psoriasis (PsO) is a multifactorial immune-mediated inflammatory disease, with a chronic relapsing remitting course, which affects 2–3% of the worldwide population. It is characterized by aberrant T cell activity causing hyperproliferation of epidermal keratinocytes, with development of erythematous skin plaques covered by a silvery or micaceous scale ,2. PlaquTreatment options available today are the result of years of research into the pathogenesis of the disease which led to the definition of treatments with increasingly specific molecular targets resulting in high efficacy and a reduced number of side effects ,10,11.The aim of this paper is, through a narrative review of the literature, to analyze the pathogenetic features of pediatric psoriasis and the latest biologic treatments available for the management of this condition.This narrative review was based on the general approach of the biomedical narrative review construction that involves four key steps: 1—identify keywords; 2—conduct research; 3—review abstract and articles; 4—document results .To identify keywords, a brainstorming approach, involving the entire research group, was used. The research team consisted of two dermatologists with expertise in psoriasis pathophysiology, two dermatologists with expertise in psoriasis therapy, and two dermatologists with expertise in pediatric psoriasis. Two among them also had specific expertise in literature review methodology. During the first meeting, the research team selected the topic, identified the scope, constructed the title, and selected the keywords as follows: “pediatric psoriasis”, “pediatric psoriasis AND pathophysiology”, “pediatric psoriasis AND therapy”, pediatric psoriasis AND treatment”, “pediatric psoriasis AND biologic treatment”.An extensive search for eligible articles was conducted on the following databases: National Library of Medicine PubMed, and Scopus. The references list of selected studies was scanned to find additional records. Inclusion criteria: studies reporting on pediatric psoriasis, published in the English language, published between 1990 and 2020, abstract available. No restriction on the design of the study was considered, and randomized controlled trials, case-control studies, cross-sectional studies, case reports and series, and review articles were included.The selection of the relevant data published in the literature took place in three steps. In the first step, two researchers  independently selected the articles based on the title. Any disagreement was solved by consulting a senior investigator (A. Offidani). The second step consisted of evaluating the abstracts. At least three members of the research team  independently assessed each abstract. The research team resolved all discrepancies through consensus. Linguistic revision was performed by E. Martina.All sources with similar data/level of evidence were analyzed, collected, and grouped. The main text was structured into subsections. New evidence-based points were summarized and major points for future research and practice were defined.Two macro topics emerged from the literature review: “pathophysiology of pediatric psoriasis” and “the use of biologic drugs in pediatric psoriasis”.The pathogenesis of pediatric psoriasis involves a complex interaction between the immune system and the two main factors that influence the onset and exacerbation of the disease: environmental factors and genetic predisposition. Approximately one-third of patients with psoriasis have a first-degree relative with the condition, emphasizing the influence of genetics ,14.Environmental factors are involved in the expression of the disease. The most frequent of these include: high stress when reaching the age to start school, detachment from parents, mild mechanical trauma (Koebner phenomenon), drugs and infections . RegardiPediatric psoriasis patients exhibited a distinct difference in the expression of interleukin (IL)-17 and IL-22 compared to that of healthy pediatric controls and adult psoriasis patients . Indeed,Biologic drugs have revolutionized the treatment of moderate to severe plaque psoriasis due to their high efficacy and relative side effects.Several biologic agents have recently been approved for use in pediatric psoriasis. Compared with other systemic therapies, which are commonly used off-label in children, biologics are very convenient because they have better dosing protocols and require less laboratory testing. In addition, because they are targeted drugs, the risk of systemic toxicity may be lower . There aTNF-α inhibitors have been used to treat rheumatoid arthritis, TNF 1-associated fever, juvenile idiopathic arthritis, ulcerative colitis, and Crohn’s disease in children for more than a decade . Data onA phase 3 clinical trial is currently underway to evaluate the efficacy and safety of certolizumab pegol in the treatment of moderate to severe chronic plaque psoriasis in study participants aged 6 to 11 and 12 to 17 years , but no AdalimumabAdalimumab is a fully human anti TNF-α monoclonal antibody. In Europe, adalimumab has been approved for the treatment of psoriasis in children and adolescents (aged ≥ 4 years) who have had an insufficient reaction to topical therapy and phototherapy. While adalimumab is FDA-approved for children with Crohn’s disease (6 years or older) and Juvenile Idiopathic Arthritis (JIA) (2 years or older), it is not approved for pediatric psoriasis indication in the USA ,24. AdalInfection was one of the common side effects, but there was no significant difference among the groups ,26.EtanerceptEtanercept is a recombinant protein that blocks TNF- α from binding to its receptor . It is tIn 2008, 211 patients with moderate to severe plaque psoriasis aged 4 to 17 years were treated for 12 weeks with etanercept at a dosage of 0.8 mg/kg or placebo, followed by an open-label duration of 24 weeks and a second randomization to 36 weeks to examine the effects of treatment discontinuation in a randomized, double-blind, phase 3 clinical trial . PASI 75InfliximabInfliximab is a chimeric monoclonal antibody that binds to human TNF-α and prevents it from binding to its receptor in both soluble and membrane-bound forms . Many coAnother class of drugs widely used for the treatment of plaque psoriasis is those that target interleukins 12 and 23, cytokines that are at the top of the inflammatory cascade that causes psoriasis. There is currently only one drug approved for pediatric use, which targets both IL-12 and IL-23 (ustekinumab). Three other drugs, guselkumab, risankizumab and tildrakizumab, are currently in phase 3 trials for pediatric use .UstekinumabUstekinumab is a fully human monoclonal antibody targeting the IL-12 and IL-23 axis and is efficient for psoriasis and psoriatic arthritis. Specifically, it binds to the p-40 subunit of both IL-12 and IL-23 so that they subsequently cannot bind to their receptors [Ustekinumab is FDA- and EMA-approved for treatment of moderate to severe psoriasis in children aged 6 years and older ,42. DosiIn the phase 3 CADMUS Jr study, patients with moderate to severe plaque psoriasis, aged 6 years to less than 12 years, received ustekinumab. After 12 weeks, 77% of patients achieved a Physician’s Global Assessment (PGA) 0/1 response. In addition, 84% of patients achieved a PASI 75 response and 64% achieved a PASI 90 response . The resThe CADMUS and CADMUS Jr clinical trials showed that ustekinumab was well-tolerated in children with plaque psoriasis. The most common AEs were nasopharyngitis, upper respiratory tract infection and pharyngitis. No cases of opportunistic infections or malignancy were reported ,42.GuselkumabGuselkumab is a fully human IgG1λ monoclonal antibody that selectively targets the unique p19 subunit of human IL-23 without binding IL-12. It is approved for the treatment of plaque psoriasis in adults by both the FDA and EMA ,45,46,47Presently, no study on the efficacy and safety of the IL-23 antibody for pediatric patients has been published. A study is now being conducted (NCT03451851) to evaluate the efficacy and safety of guselkumab in relation to etanercept and placebo in pediatric patients with chronic plaque psoriasis .RisankizumabRisankizumab is an IgG1k monoclonal antibody that, like guselkumab, binds the p-19 subunit of IL-23 and is the latest anti-IL-23 drug approved for the treatment of moderate to severe plaque psoriasis in adults. The latest head-to-head phase 3 trial and a recent meta-analysis provided further evidence of the superior efficacy of risankizumab compared to adalimumab for treatment of moderate to severe psoriasis ,52. A stTildrakizumabTildrakizumab is an IgG1k monoclonal antibody that, like the other two anti-IL-23, binds the p19 subunit of the IL-23. Among the IL-23 p19 inhibitors and also in comparison to IL-17 inhibitors, tildrakizumab seems to have slightly lower efficacy in terms of PASI scores for the treatment of plaque psoriasis in adult patients . Pooled IL-17A is considered, along with IL-23, the most important target of plaque psoriasis therapy and has been recognized as the critical effector cytokine in psoriasis. Presently, the three approved IL-17 pathway inhibitors are secukinumab and ixekizumab, both IL-17A inhibitors, and brodalumab, which targets the IL-17-receptor A (IL-17RA). Several RCTs, sustained by real-life data, proved the efficacy and safety of these treatments, showing higher rates of complete or almost complete clearance compared to TNF-alfa inhibitors and ustekinumab ,49. SecuSecukinumabSecukinumab is a fully human IgG1κ monoclonal anti-IL-17A antibody. It is currently approved by the FDA and EMA for the treatment of pediatric plaque psoriasis in children up to 6 years old. The phase 3 study that enabled the drug’s approval showed that both doses of secukinumab, a low dose and a high dose, had superior efficacy compared with placebo in PASI 90 response (72.5% and 67.5% vs. 2.4%), PASI 75 response (80.0% and 77.5% vs. 14.6%) and IGA at week 12.The response trend was maintained until week 52 . Safety profiles were similar to those in adult studies with secukinumab: the most common (incidence ≥ 10%) AEs reported up to week 52 were nasopharyngitis (23.5% with any low dose of secukinumab and 26.0% with any high dose of secukinumab vs. 26.8% with etanercept) and headache (10.2% and 10.0% vs. 9.8%) [IxekizumabIxekizumab is a humanized IgG4 monoclonal antibody that selectively binds to IL-17A, approved by the FDA and EMA for the treatment of adults and children six years and older with moderate to severe plaque psoriasis. The double-blind, randomized, placebo-controlled phase 3 IXORA-PEDS study addressed the high-affinity monoclonal antibody to IL-17A ixekizumab in pediatric psoriasis . IxekizuBrodalumabBrodalumab, a recombinant fully human monoclonal IgG2 antibody with high affinity to human interleukin (IL)-17RA, is approved for the treatment of moderate to severe plaque psoriasis in adults. The EMBRACE study, a phase 3 trial that aims to investigate the efficacy and safety compared with placebo, and the safety compared with ustekinumab of brodalumab in adolescents with moderate to severe plaque psoriasis, is currently underway (NCT04305327). The study will also evaluate whether brodalumab affects the development of vaccination-induced immune responses .Phase 3 studies performed in adults have fully demonstrated the efficacy and safety of the drug in the treatment of plaque psoriasis . ConsistPediatric psoriasis is a common disorder that often begins in childhood. In a questionnaire survey of 5600 individuals with psoriasis , approximately one-third reported onset of disease during the first two decades of life and 10% reported onset prior to the age of 10 years .In addition, children with psoriasis are more likely to present with psoriasis involving the face, scalp, or intertriginous skin than adults, and it is known that involvement of these areas affects the patient’s DLQI and requires urgent treatment .Pediatric psoriasis is associated with an increased risk of various comorbidities, including obesity and other cardiovascular risk factors, arthritis, and psychiatric disorders .Obesity and metabolic syndrome appear to be the most common comorbidities of pediatric psoriasis. Population-based studies have found increased rates of hyperlipidemia and lipid peroxidation, hypertension and diabetes in psoriatic children ,63,64,65However, although psoriasis is independently associated with an increased risk of metabolic syndrome, this risk appears to be largely driven by obesity .All of this makes adequate treatment of pediatric psoriasis critical. Currently, biological therapy appears to be the only systemic therapy, besides phototherapy, approved for pediatric use. Other treatments, such as methotrexate and cyclosporine, although they have been used in children for years, in fact have an off-label indication and are not without side effects .The literature and clinical practice tend to increase the use of biologics, with 25% of children with psoriasis treated with these drugs . In deteMoreover, biologic drugs, compared with other systemic treatments such as methotrexate and cyclosporine, require less rigid treatment schedules, have fewer adverse effects, less need for monitoring, and greater efficacy . HoweverCurrently, there are several biologic drugs approved for use in pediatric psoriasis. In addition to anti-TNF-α, of which etanercept certainly appears to be the most studied with regard to safety in the pediatric population, drugs targeting IL-17 (secukinumab and ixekizumab) are also approved to date, and other drugs such as brodalumab, which targets the IL-17 receptor, and anti-IL-23 drugs are under investigation. The efficacy of these drugs appears to be non-inferior to anti-TNF alpha, and, as far as currently approved drugs are concerned, the safety profile is similar . CurrentPsoriasis in children poses a number of challenges. It has age-specific clinical features, the appearance of which can change over time. Most treatment modalities for adult psoriasis have been used off-label for pediatric psoriasis. Although studies have been limited, recent research has proposed a difference in TNF-α, IL-17, IL-22 expressions in pediatric psoriasis patients compared with those in adult psoriasis patients. Biologics, as targeted therapy, are also gradually being used for pediatric psoriasis with great efficacy and a similar safety profile as adults. It is reasonable to assume that a more targeted therapeutic approach for pediatric psoriasis will be guided by the unique immunophenotypic characteristics of psoriasis in children, characteristics that are not fully known and need to be better investigated. Thus, we believe that further studies are needed to identify the different pathogenetic processes in pediatric psoriasis.


N6-methyladenosine (m6A), an essential post-transcriptional modification in eukaryotes, is closely related to the development of pathological processes in neurological diseases. Notably, spinal cord injury (SCI) is a serious traumatic disease of the central nervous system, with a complex pathological mechanism which is still not completely understood. Recent studies have found that m6A modification levels are changed after SCI, and m6A-related regulators are involved in the changes of the local spinal cord microenvironment after injury. However, research on the role of m6A modification in SCI is still in the early stages. This review discusses the latest progress in the dynamic regulation of m6A modification, including methyltransferases (“writers”), demethylases (“erasers”) and m6A -binding proteins (“readers”). And then analyses the pathological mechanism relationship between m6A and the microenvironment after SCI. The biological processes involved included cell death, axon regeneration, and scar formation, which provides new insight for future research on the role of m6A modification in SCI and the clinical transformation of strategies for promoting recovery of spinal cord function. N6-methyladenosine (m6A) modification, a type of posttranscriptional modification, has been confirmed to be involved in the post-transcriptional regulation of gene . It was Spinal cord injury (SCI), a catastrophic condition resulting from a combination of factors, is associated with high rates of disability and fatality and always reduces patient quality of life and imposes a financial burden on families . NotablyIn this review, we summarize the current state of research on m6A modification and emphasize the regulatory mechanism of this type of modification in various pathological processes associated with dysfunction of the nervous system after injury and subsequent tissue repair after SCI to provide a theoretical basis for future research on SCI.Since the discovery of m6A modification, researchers have continued to explore its mechanism and function. With the emergence of various sequencing technologies, such as m6A-seq, MeRIP-seq, m6A-CLIP, and m6A-sensitive HRM analysis, etc., it has been found that m6A modification is ubiquitous in coding and non-coding RNAs . The depIntracellular RNA methylation often requires co-catalysis by various enzymes, which are named “writers” . The metin vitro and in vivo (In addition to Mettl3/14, the role of other writers is also worth exploring. First, WTAP plays a regulatory role in the methylase complex, linking the complex to RNA, and deletion of WTAP results in in aberrant gene expression and alternative splicing . Recent  in vivo . A study in vivo .in vivo and in vitro (Demethylases can remove methyl groups from nucleotides, and the discovery of m6A demethylases, generally known as “erasers,” reveals that the m6A modification of RNA may be reversed dynamically . FTO andin vitro . In addiin vitro .AlkB homolog 5, another enzyme capable of reversing m6A modification, has also been implicated in posttranscriptional RNA regulation, including mRNA splicing, stability, export and RNA metabolism . InactivEukaryotes produce a variety of proteins that can bind to the m6A modification site and affect RNA translation, splicing, and disintegration and other biological processes . These pYTHDF2 interacts with the m6A modification site on RNA, increasing the likelihood of RNA degradation . YTHDF2 The nervous system is a multicellular network, and the close interactions among numerous nerve cells, such as neurons and glial cells, is essential for the coordination of its functions . Direct Recent studies have also reported that after SCI, the levels of m6A as well as writers, such as mettl3 and mettl14, in tissues rise dramatically and specific knockout of methylase can alleviate the severity of SCI . This inThe structural and functional integrity of the spinal cord are the foundations for proper physiological activity . HoweverProgrammed cell death is tightly linked to m6A modification . Apoptosin vitro, as Mettl14 can promote the conversion of pri-miR-375 to miR-375, which is related to apoptosis and inhibits neural recovery (Recently, several studies have shown that methylation regulators can influence cell survival after SCI by regulating m6A levels . Haoyu Wrecovery . In addirecovery . EEF1A2 recovery .The above experiments show that the regulation of cell death after SCI, particularly neuronal apoptosis, is influenced by RNA m6A modification, providing a new direction for reducing cellular dysfunction and promoting functional recovery. However, apoptosis is not the only cause of cell loss after injury, and previous studies have shown that other forms of PCD, such as ferroptosis, autophagy, and necroptosis, also mediate cell death after SCI . There hAnother cause of functional deficiency following SCI is the disruption of spinal nerve continuity . Unfortuin vitro when METTL14 is knocked out, as is the capacity to increase the axon length in vivo. In addition to that in the peripheral nervous system, Pten deletion-induced axonal regeneration in CNS neurons is considerably impeded following METTL14 loss. Furthermore, the YTHDF1 reader is required for injury-induced protein translation and axonal regeneration in neurons (in vitro and in vivo, and knock out of these proteins might enhance axonal development (In the nervous system, regeneration of neuronal axons is likewise affected by m6A modification. Following sciatic nerve damage, the levels of m6A-tagged transcripts associated with axonal regeneration are increased in mouse dorsal root neurons, facilitating axonal regeneration. Primary neurite length is considerably decreased  neurons . Additio neurons . After i neurons . Interes neurons . In addielopment . To goveelopment .Recently, m6A modification was shown to have the potential to regulate axonal regeneration after SCI . In an eOne of the secondary characteristics of SCI is the aggregation of a considerable number of reactive astrocytes, which always results in localized scarring . SpatialN6-methyladenosine modification can regulate the physiological functions of astrocytes . In a stin vitro, lack of Mettl14 was shown to reduce the apoptosis of C8-D1A murine astrocytes after simulation of SCI-induced apoptosis with H2O2 (Recently, several studies have shown that changes in m6A modification affect the aggregation of astrocytes following SCI . Lingyanith H2O2 . This imWhile astrocytes are involved in scarring postinjury, the role of pericytes in SCI cannot be ignored . PericytIn addition to the pathological processes mentioned above, the effects of local inflammation and myelination dysfunction on prognosis after SCI should not be ignored , and m6AFurthermore, oligodendrocytes, whose primary function is to form the myelin sheath of axons and contribute to the efficient and rapid transmission of information, are inextricably linked to myelin regeneration during the process of nerve repair after SCI . In receThis review discusses in detail the current status of research on m6A modification and the relationship between m6A modification and pathophysiological processes after SCI, including cell death, axonal regeneration, and scarring. Although there has been research on the role of m6A modification in some neurological diseases, such as Alzheimer’s disease and stroke, research on the role of this posttranslational modification in SCI is still in its infancy. Research on this topic is limited to bioinformatics analysis of gene expression and differential expression at the tissue and cell levels, and studies on the specific mechanism of m6A modification after SCI are extremely rare. Simultaneously, the only m6A modification-regulating molecules that have been studied after SCI are “writers,” and more research on the impact of demethylases and binding proteins after SCI is needed. The importance of m6A modification in neurological diseases cannot be overstated. This dynamic modification could be a possible target for influencing the pathological process of SCI and promoting recovery of spinal cord function. Clearly, the role of m6A modification in SCI needs to be explored further.DL, BF, and JL contributed the central idea and wrote the manuscript. JM and TS collected the related data. XZ and SF participated in key revisions of the manuscript and finalized the final version. All authors contributed to the revision of the manuscript and approved the submitted version.


Background: The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab in psoriatic arthritis, but it did not include a pharmacoeconomic analysis. The objective of this study was to compare the cost per responder of secukinumab versus adalimumab in patients with psoriatic disease. Methods: The cost per responder was calculated by multiplying the cost of treatment by the number needed to treat for each therapy. The 52-week primary endpoint was the American College of Rheumatology response rate (ACR) 20; secondary endpoints were ACR 50, Psoriasis Area and Severity Index (PASI) 90, and minimal disease activity (MDA). Results: The cost per responder for ACR 20 was €19,846 versus €19,766 for secukinumab and adalimumab, respectively, whereas the costs per responder for ACR 50 and PASI 90 were €27,820 versus €27,384 and €22,102 versus €32,375 for secukinumab and adalimumab, respectively. The cost per MDA responder was €34,072 and €38,906 for secukinumab versus adalimumab. Conclusions: The costs per responder associated with the psoriatic arthritis end points were similar for adalimumab and secukinumab; conversely, the costs for psoriasis and composite end points were lower for secukinumab. Psoriasis is a common chronic immune-mediated disease that affects 1–4% of the population worldwide, and about 14 million people in Europe  and are A cost per responder analysis of secukinumab versus adalimumab was developed based on the efficacy data from the EXCEED study  13,14].,14.13,14The cost per responder model was based on the perspective of the Italian National Health System. Regarding the costs of biologic drugs, ex-factory wholesale purchase prices were used, including the mandatory discounts according to the national legislation   16,17].,17.16,17®, Novartis Farma S.p.A, Largo U. Boccioni 1—21040 Origgio (VA), Italy) includes two syringes; each package of adalimumab , Italy) includes two syringes. Each package of secukinumab , the cost per responder was lower for secukinumab. Given the chronic nature of psoriatic disease and its long-term therapy, it is important to investigate the economic value of the different biologic agents, as even small differences in costs can be meaningful. With regard to PsA, biologic agents were shown to be cost effective compared to csDMARDs because, despite their higher costs, they are more effective in reducing the symptoms and signs of PsA, improving quality of life, and inhibiting structural radiological damage . Among bThe present study failed to detect the higher cost effectiveness of secukinumab over adalimumab in PsA that was found in previous studies. However, this may be explained by methodological differences: this study used a cost per responder model based on efficacy data from a phase 3 trial with a 1-year time horizon, whereas previous studies employed cost effectiveness analyses over much longer time horizons. Indeed, short-term cost calculations tend to penalize drugs with a more expensive induction phase , such asn = 274) and adalimumab (n = 87) were unbalanced [Conversely, regarding plaque psoriasis, the findings of the present study are in line with previous studies. In particular, a German 52-week cost per responder model that compared secukinumab with other biologics for the treatment of plaque psoriasis found that secukinumab had the lowest cost per sustained PASI 90 responder  compared with adalimumab, etanercept, infliximab, and ustekinumab . Of notebalanced . FurtherOf note, secukinumab also presents further advantages over adalimumab other than its cost effectiveness. First, its higher efficacy allows a higher percentage of patients to reach PASI 90 or PASI 100 ,33. ThisThere are limitations to this study that should be noted. First, ex-factory wholesale purchase prices with the mandatory discounts  were used in the cost responder model, yet retail discounts may vary widely (from 20% to 80%) and could change the economic evaluation. Furthermore, adalimumab originator was considered for the model because it was the one tested in the EXCEED study. However, adalimumab biosimilars are available and have shown a comparable efficacy to the originator, while their cost is significantly lower than that of the originator ,39,40. AThe costs per responder associated with the ACR 20 and ACR 50 end points were similar for adalimumab compared to secukinumab; conversely, for the psoriasis and composite end points, they were lower for secukinumab.


Small for gestational age (SGA) infants are at a higher risk of neurodevelopmental delay than infants appropriate for gestational age (AGA). Previous studies have confirmed that gut microbiota in early life influences subsequent neurodevelopment. However, few studies have reported corresponding data in SGA populations.We aimed to evaluate the characteristics of the gut microbiota of term SGA infants and the associations between the gut microbiota in SGA infants and neurodevelopmental outcomes at 6 months of age.Fecal samples were collected on days 1, 3, 5, and 7 from term SGA and AGA infants born between June 2020 and June 2021 at the Peking University First Hospital. 16S ribosomal deoxyribonucleic acid amplicon sequencing was used to analyze the fecal microbiota. We followed up for 6 months and used the Ages and Stages Questionnaires-3 (ASQ-3) to evaluate the neurodevelopmental outcomes among SGA infants.Ralstonia  and Clostridium (3 and 7 days). The dominant microorganisms of the SGA group were Ralstonia on day 1, Escherichia_Shigella on days 3 and 7, and Clostridia on day 5. We found that the gut microbial diversity of SGA infants with poor communication scores was higher than that of SGA infants with good communication scores on day 3. Fine motor scores were negatively correlated with the relative abundance of Bacteroides_fragilis on day 1. A negative correlation was observed between gross motor scores and relative abundance of Clostridium_saccharobutylicum on day 7. Bacteroidota, Bacteroidia, Bacteroides, and Bacteroides_fragilis were the dominant microorganisms in the good communication score group on day 7. Communication scores were positively correlated with the relative abundance of Bacteroidota, Bacteroides, and Bacteroides_fragilis on day 7.A total of 162 neonates were enrolled, with 41 SGA infants (25.3%) in the study group and 121 AGA infants (74.7%) in the control group. The gut microbial diversity in the SGA group was lower than that in the AGA group on days 1, 3, 5, and 7. Non-metric multidimensional scaling and analysis of similarities showed significant differences between the two groups. The SGA group had increased relative abundances of Escherichia_Shigella, Ralstonia and Clostridium increased or formed the dominant microbiota in SGA infants. Alpha diversity, Bacteroidota, Bacteroides, Bacteroides_fragilis, and Clostridium_saccharobutylicum found in SGA infants may be associated with neurodevelopmental outcomes at 6 months of age, indicating possible therapeutic targets for clinical intervention.The gut microbial diversity of term SGA infants was significantly lower in the first week of life than that of term AGA infants. Certain pathogenic and conditional pathogenic bacteria, such as  Small for gestational age (SGA) infants, defined as having a birth weight less than the 10th percentile of the birth weight of the same sex at the same gestational age, comprise a heterogeneous group . The incIn recent years, gut microbiota has become a research hotspot in the fields of biology and medicine. Researchers have realized that the gut microbiota plays an important role in digestion, immune response, nutrient absorption, growth, and metabolism. The gut microbiota is involved in the regulation of many diseases such as inflammatory bowel disease, metabolic syndrome, and diabetes . StudiesThe so-called “gut–brain axis” represents a two-way communication network between the gut microbiota and the brain. The gut–brain axis theory proposes that the gut microbiota participates in the regulation of brain development and maturation, thus impacting brain functions, including anxiety-like behavior, locomotor behavior, social cognition, learning, and working memory . CompareBacteroidetes in late infancy and subsequent cognitive and language performance  neonates in the study group needed to meet the diagnostic criteria of SGA infants: newborns whose birthweight was less than the 10th percentile of the birth weight of the same sex at the same gestational age (1); (b) gestational age was defined as ≥ 37 and < 42 weeks; (c) neonates without asphyxia, neonatal hypoxic-ischemic encephalopathy, severe intracranial hemorrhage, cerebral infarction, cytomegalovirus infection, recurrent hypoglycemia, bilirubin encephalopathy, and genetic metabolic diseases were enrolled; (d) informed consent was provided by the legal guardian(s); and (e) neonates were only enrolled with the agreement of cooperation with the follow-up by the legal guardian(s).The following exclusion criteria were used: (1) critical clinical conditions, such as sepsis and multiple organ failure; (2) gastrointestinal malformation, abdominal distension, vomiting, diarrhea, bloody stool, necrotizing enterocolitis, and other gastrointestinal diseases within 1 week; and (3) the presence of diseases that might affect neurological development during the follow-up period, such as severe brain trauma, epilepsy, meningitis, and genetic metabolic diseases.Clinical data, including sex, gestational age, birth weight, mode of delivery, and antibiotic application within 1 week after birth, were collected. Feces produced on postnatal days 1, 3, 5, and 7 were collected. Fecal samples were stored in sterile freezing tubes  at −20°C and subjected to microbiota analysis within 1 week.§ DNA PCR-Free Sample Preparation Kit. Quality was evaluated with the assistance of the Qubit@ 2.0 and Agilent Bioanalyzer 2100 system. High-throughput sequencing was performed using an Illumina NovaSeq 6000 platform.A biological information database was built using an Illumina TruSeqThe effective data were obtained by filtering the original data. The sequences were then clustered into operational taxonomic units (OTUs) with 97% identity, and the OTUs sequences were compared with the silva138 database for species annotation to obtain the basic analysis results of the OTUs and taxonomic pedigree for each sample. Finally, the analysis of OTUs, including alpha and beta diversity, was completed according to species annotation.•Alpha diversity analysis: The richness and diversity of microbiota can be indicated by alpha diversity, wherein Observed species, Chao1, abundance-based coverage estimator (ACE), Shannon, Simpson, and goods coverage are major evaluation indices of alpha diversity. Observed species represents the actual number of OTUs in the sample. The Chao1 and ACE indices use different calculation methods to estimate the number of OTUs in a sample; the higher the number of OTUs, the higher the diversity of the sample. The abundance and uniformity of the gut microbiota can be expressed using the Shannon and Simpson indices. If all the OTUs contained in the sample were the same, the diversity was the lowest; if they were different, the diversity was the highest. The larger the values of the Shannon and Simpson indices, the higher the diversity of the samples. Good coverage index indicates the sequencing depth; the higher the value, the better the sequencing. The closer the value is to 1, the closer the sequencing depth is to cover all bacteria in the test sample. Rarefaction and rank variance curves are common curves that describe the diversity of the samples in the group. The rarefaction curve directly reflects the rationality of the sequencing data and indirectly reflects the richness of species in the sample, whereas the rank variance curve intuitively reflects the richness and uniformity of species in the sample.•P-value < 0.05 indicates statistical significance.Beta diversity analysis: Beta diversity analysis focuses on the differences in the microbial community composition of different samples, which is used for the analysis of differences between groups. Principal coordinate analysis (PCoA) and non-metric multidimensional scaling (NMDS) directly reflects the differences in community composition between groups based on the distance between samples. Each point in the figure represents a sample; points of the same color belong to the same group, and the distance between points represents the degree of difference. The distance is directly proportional to the difference between points. A stress score < 0.2 indicates that NMDS can accurately reflect the degree of difference between groups. Analysis of similarities (Anoism) is a non-parametric test used to test the significance of differences. An R-value > 0 indicates significant differences between groups, an R-value < 0 indicates that the differences within groups were greater than those between groups, and a •Differential analysis of gut microbiota: (1) Differential relative abundance: We compared the differences in microbial distribution between groups according to the relative abundance of communities at different levels of phylum, class, order, family, genus, and species. In this study, we used the Metastat method to analyze microbial differences between the two groups at the phylum, family, and genus levels. (2) Differentially dominant microorganisms: We found microbial differences between groups using linear discriminant analysis effect size (LEfSe) analysis. The LEfSe calculation method not only has statistical significance, but also focuses on biological correlation by using linear discriminant analysis (LDA) to reduce the dimension and evaluate the impact of species with significant differences . The default LDA score was 2, which can be increased according to the characteristics of the community distribution to obtain more accurate data.We followed up with the SGA infants until 6 months after birth and assessed their neurodevelopmental outcomes using the Age and Staging Questionnaire-3 (ASQ-3). The same neurodevelopmental professional evaluation doctor, proficient in ASQ-3 scoring criteria, conducted the evaluation. ASQ-3 mainly includes five parts, namely communication, gross motor, fine motor, problem-solving, and personal–social, with each part containing six specific assessment questions.x ± s). Student’s t-test was used to compare two groups, while analysis of variance (ANOVA) was used to compare three or more groups. The measurement data that were not in line with the normal distribution were expressed as median (IQR) or median . The Wilcoxon Mann–Whitney U test was used for the comparison between two groups, while the Kruskal–Wallis H test was used for the comparison of three groups and above. The enumeration data were expressed as the number of cases and percentages, and comparisons between groups were performed using the χ2 test. If the total number n was < 40 or at least one actual frequency, t < 1, Fisher’s exact test method was applied. For the correlation analysis of two quantitative datasets, Pearson correlation analysis was adopted if it conformed to the bivariate normal distribution; otherwise, Spearman correlation analysis was adopted. Statistical significance was set at P < 0.05.Statistical software (SPSS 25.0) was used to analyze the data. Measurement data consistent with a normal distribution are expressed as the mean ± standard deviation  and 33 neonates (27.5%) delivered via cesarean section. All neonates were born at a gestational age of 37–42 weeks and fed a mixed feed (breast milk + formula). The clinical characteristics of the enrolled neonates are presented in A total of 41 SGA neonates were enrolled in the SGA group, including 19 males (46.3%) and 24 neonates (58.5%) delivered In this study, an average of 76,816 tags were measured per sample, and an average of 75,108 valid data points was obtained after quality control. The sequence was clustered into OTUs with 97% identity and 13,747 OTUs were obtained.After obtaining all the OTUs, a rarefaction curve was drawn to evaluate whether the current sequencing depth of each sample could fully reflect the microbial diversity in the community samples. When the dilution curve tended to be flat , the seqA comparison of the alpha diversity of fecal microbiota in the SGA group on different days in the first week of life revealed no statistical difference in the Chao1, ACE, Observed species, Simpson, and Shannon indices, indicating that there was no significant difference in the richness and diversity of gut microbiota within the SGA group at postnatal days 1, 3, 5, and 7 .P < 0.05), whereas there was no significant difference in the Simpson and Shannon indices . On days 3, 5, and 7, the Chao1, ACE, and Observed species indices of fecal microbiota of the SGA group remained significantly lower than the AGA group ( indices .P < 0.05)  . The NMD < 0.05)  indicate < 0.05) .Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes . On day 7, the communication scores were positively correlated with the relative abundances of g-Bacteroides  and s-Bacteroides_fragilis , whereas a negative correlation was observed between gross motor scores and the relative abundance of s-Clostridium_saccharobutylicum  infants completed the follow-up and three infants were lost to follow-up (7.3%). The fine motor scores of ASQ-3 were negatively correlated with the relative abundance of We followed SGA infants until 6 months of age, and 38 of them completed the follow-up. A communication score ≥ 40 was considered normal. There were 31 (81.6%) infants with normal communication scores and 7 (18.4%) infants with poor communication scores in the SGA group. The two subgroups showed no significant differences in sex, gestational age, birth weight, mode of delivery, feeding pattern, or antibiotic application within 1 week after birth .P < 0.05), whereas there was no significant difference in the Simpson and Shannon indices . There were no significant differences in gut microbiota on days 3 and 5 in the good and poor communication score groups; the R-value was < 0, but the statistical analysis within groups showed no significant difference (P > 0.05)  . However > 0.05) .Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes at the phylum level . There were no dominant microorganisms in the good communication score group on days 1, 3, and 5  delivered by cesarean section and 17 neonates (41.5%) through vaginal delivery. The two subgroups showed no significant differences in sex, gestational age, birth weight, feeding patterns, or antibiotic application within 1 week after birth .A comparison of alpha diversity of fecal microbiota between the cesarean birth and vaginal delivery groups revealed no statistical difference in the Chao1, ACE, Observed species, Simpson, and Shannon indices on days 1, 3, and 5 .P > 0.05; PCoA and Anosim showed no significant differences in gut microbiota between the cesarean birth and vaginal delivery groups; the R-value was > 0, but the statistical analysis between the groups showed no significant difference  treated with antibiotics and 10 neonates (24.4%) treated without antibiotics, according to their condition. The two subgroups showed no significant differences in sex, gestational age, birth weight, feeding patterns, or delivery mode .A comparison of the alpha diversity of fecal microbiota between the group with antibiotics and the group without antibiotics revealed no statistical difference in the Chao1, ACE, Observed species, Simpson, and Shannon indices on days 1, 3, and 5 .P-values were > 0.05 on days 1 and 5, indicating that there was no statistical difference between the two groups on days 1 and 5. On day 3, R-value < 0 and P > 0.05 3, indicating that there was no statistical difference between the two groups  and Cyanobacteria  were significantly lower in the SGA group. Furthermore, another study found that pigs with intrauterine growth restriction had a lower relative abundance of Actinobacteria  and Parkinson’s disease (PD), and its mechanism may involve neuroinflammation and immune activation (F-Enterobacteriaceae (7 days), g-Escherichia_Shigella , and g-Helicobacter (7 days) were the dominant microorganisms in the SGA group. Escherichia_Shigella is well-known as a pathogenic enterobacterium; some strains of Helicobacter are recognized as important pathogens in gastrointestinal diseases, such as peptic ulcers and gastric cancer, and some strains are associated with bacteremia in immunocompromised and immunocompetent human hosts  , Streptococcus , Bifidobacterium, and Lactococcus (3 days). Some strains of these four genera are considered probiotics , suggesting that increased Akkermansia in MS may be a compensatory beneficial response  . The SGAobiotics  because obiotics . Ileibaccharides . An incrisorders . Akkermacrobiota , with elresponse .Escherichia_Shigella, Ralstonia, and Clostridium.In summary, large differences were observed in the gut microbiota between the SGA and AGA groups in the first week of life, which can be summarized as follows: (1) compared with AGA infants, the alpha diversity of term SGA infants was significantly lower; (2) certain pathogenic and conditional pathogenic bacteria increased or formed the dominant microorganisms in SGA infants, such as After a 6 month follow-up, we found an association between higher alpha diversity on day 3 and communication problems in SGA infants. This finding was surprising because a more mature gut microbial community in infancy usually has a high level of biological diversity , and decg-Allobaculum was the dominant microbiota in the SGA group with a poor communication score on day 1. Allobaculum may provide good anti-inflammatory functions by producing free long-chain fatty acids and short-chain fatty acids (SCFAs) which are related to glucose and lipid metabolism , identified as a common opportunistic pathogen in clinical infections, mainly causes colitis and systemic inflammation with the stimulation of toxins or lipopolysaccharides. The second subtype, non-toxigenic B. fragilis (NTBF), has been suggested as a potential probiotic in recent studies because of its ability to produce immunomodulatory substances such as polysaccharide A (PSA) and SCFAs  higher alpha diversity on day 3 was associated with poor communication performance in SGA infants at 6 months of age; (2) Bacteroides, Bifidobacterium, and Lactobacillus  This was a single-center study; there may be differences in the gut microbiota of SGA infants from other hospitals. The results need to be further confirmed by multicenter and large-exponent investigations. (2) We only studied the gut microbiota of term SGA infants within 1 week after birth and the neurological prognosis at 6 months of age; we will follow up with SGA infants and discuss the relationship between neonatal gut microbiota and neurological development by comprehensively considering various factors, such as education mode and society. (3) The ASQ-3 is a screening scale, and because of the prevalence of the novel coronavirus, it was difficult to use diagnostic scales such as the Bayley scale to evaluate the prognosis of neurodevelopment.Escherichia_Shigella, Ralstonia, and Clostridium. This study suggests that there may be associations between alpha diversity, certain gut microbiota, and neurodevelopmental outcomes in SGA infants. The results showed that higher alpha diversity on day 3 was associated with poor communication performance in SGA infants at 6 months of age, and the gut microbiota factors affecting the prognosis of SGA infants included Bacteroidota, Bacteroides, Bacteroides_fragilis, and Clostridium_saccharobutylicum. SGA infants are at a higher risk for adverse neurodevelopmental outcomes; however, current methods for the clinical treatment of neurodevelopmental delay in SGA infants are limited. With further studies of the gut microbiota of SGA infants, we hope to provide further insights into the early treatment of SGA infants.Compared to AGA infants, the gut microbial diversity of term SGA infants was significantly lower in the first week of life. Certain pathogenic and conditional pathogenic bacteria increased or formed the dominant microbiota in SGA infants, such as The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of Peking University First Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.All authors listed have made great contributions to this work and have read and agreed to the published version of the manuscript.


Succinylation modification of the lysine site plays an important role in tumorigenesis and development, but it is rarely reported in prostate cancer (PCa), so this study aims to elucidate its expression in and clinical correlation with PCa.A total of 95 tumor, 3 normal and 52 paired adjacent tissue of PCa were involved for succinylation stanning. 498 PCa samples with 20 succinylation modification-related genes from TCGA were downloaded for model construction. Statistical methods were employed to analyze the data, including Non-Negative Matrix Factorization (NMF) algorithm, t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm and Cox regression analysis.The pan-succinyllysine antibody stanning indicated that tumor tissues showed higher succinyllysine level than adjacent tissues (p<0.001). Gleason grade and PDL1 expression levels were significantly different (p<0.001) among the high, medium and low succinylation staining scores. The types of PCa tissue were divided into four clusters using RNA-seq data of 20 succinylation-related genes in TCGA database. Clinical characterize of age, PSA level, and pathological stage showed differences among four clusters. The expression of succinylation-related genes  and PCa related genes  were significantly different in 52 matched tumor and adjacent tissues (p<0.001). GLYATL1 and AR gene expression was significantly related to the pathological stage of PCa.Succinylation was significantly increased in PCa tissues and was closely related to Gleason grade and PD-L1 expression. Model construction of 20 genes related to succinylation modification showed that the later the pathological stage of PCa, the higher the level of succinylation modification. The GLOBOCAN database of the International Center for Research on Cancer (IARC) showed that 1,414,259 new cases of prostate cancer (PCa) emerged in 2020, in which 375,304 were dead, marking the cancer as the fourth most common in the world and the second most common among men  is ubiquitous in various prokaryotes and eukaryotes, participating in various life activities . Common 95 cases of PCa, 52 cases of adjacent tissues, and 3 cases of normal prostate paraffin-embedded tissues were collected from the Second Affiliated Hospital of the Army Military Medical University from January 2018 to March 2022. All patients with PCa underwent radical prostatectomy treatment in our hospital; none received radiotherapy, chemotherapy, or anti-androgen before surgery. All tissues were diagnosed by more than 2 pathologists after routine HE staining. The age of the 95 PCa patients ranged from 51 to 84 years, with a mean age of (70.7 ± 5.43) years. The patient’s age, PSA, Gleason grade, PDL1 expression and other clinical data were collected for analysis. Patient inclusion criteria: (1) PCa diagnosed by pathological examination according to EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer ; (2) TheA rabbit polyclonal antibody (pAb) specific for succinyllysine (PTM-401) was purchased from PTM Bio ; and immunohistochemical detection kits and DAB chromogenic reagent were purchased from Xinchao Company . The simple methods for IHC were as follows: the paraffin-embedded tissue paraffin block 3 μm thick serial sections were taken and routinely deparaffinized to water. The Multimer marker two-step assay was performed step-by-step by a fully automated multi-function pathology detection system . The basic conditions were: antigen retrieval for 30 min, washing with buffer, adding UV DAB inhibitor , 37°C for 4 min. Wash with buffer, add primary antibodies (PTM-401), and incubate at 37°C for 30 min. The buffer was washed, and UV HRP multimer  was added, and the temperature was 37°C for 8 min. The buffer was washed, and an equal volume of DAB and DAB H2O2  was added, at 37°C for 8 min. Rinse with buffer, add Bluing Reagent, keep at 37°C for 4 min, rinse with buffer, and mount. Use PBS instead of the primary antibody as a negative control.Tissue sections were repeatedly observed by 2 pathologists, and 5 high-power fields were randomly selected. According to the percentage of positive cells, the fields were scored as: 0 points for no positive cells, 1 point for the number of positive cells ≤ 10%, 2 points for 11% to 25%; 3 points for 26% to 50%; and 4 points for 51% to 100%. According to the intensity of positive staining, the fields were scored as: 0 points for no positive staining, 1 point for light yellow, 2 points for tan, and tan 3 points. The two scores are multiplied for the final score: high IHC scores ≥10, 10>medium IHC scores>6 and low IHC scores ≤6.https://www.cancer.gov/tcga). The samples with data annotation were removed in the original data process, and the average gene expression is lower than 1. According to the database information, the sequencing data were divided into the adjacent and PCa groups. After filtering and normalizing the data, a differential analysis was performed and RNA-seq data of 20 genes were associated with succinylation. Genes related to succinate metabolism include succinate dehydrogenase , succinyl-CoA ligase , protein post-translational modification related enzymes, erasure enzymes  and synthetases .Transcriptome data and corresponding clinical data of 498 PCa patients were downloaded from the TCGA public database  was used to analyze the data, and the correlation between the expression of anti-succinyllysine and the clinicopathological characteristics of the patients was analyzed by χ2 test or Fisher exact test. COX proportional hazards regression model was used to analyze the independent prognostic factors affecting pathological stage patients with PCa. P<0.05 denoted a statistically significant difference.R software , medium (10>IHC scores>6) and low level (IHC scores ≤6) groups. Age distribution showed no significant difference among the three groups. However, the Gleason grades of III and IV are more enriched in the group of high IHC scores . TherefoWe hypothesized some gene expressions are associated with succinylation modification, and these genes dominate the progress of PCa. Therefore, RNA-seq data of 20 succinylation-related genes from the TCGA database were chosen for risk model construction. 498 PCa samples were clustered into four subtypes based on the RNA-seq data of 20 succinylation-related genes Figure 4In summary, we found high levels of succinylation modification enriched in PCa patients compared with adjacent and normal prostate tissues. We provided evidence that succinylation modification-related genes contribute to the PCa pathological stage and may associate with the heterogeneity of PCa. We even found succinylation-related two genes (GLYATL1 and AR) that were also associated with higher pathology in PCa. However, the mechanism behind high levels of succinylation modification and the development of PCa remains to be explained.Immunohistochemistry utilizes specific antibodies to detect and localize specific antigens in cells and tissues, which is an essential technique for tissue-based diagnostics and biomarker detection . It is uProgrammed cell death receptor (PD-1) is an important immunosuppressive molecule, which can down-regulate the immune system response to avoid autoimmune diseases , 21. PD-Using public published big data, we found that the expression of succinylation-related gene Glycine-N-acyltransferase-like 1 (GLYATL1) and prostate cancer-related gene (AR) in 498 PCa tissues were significantly higher than that in non-cancer tissues. In addition, the expression levels of AR and GLYATL1 were correlated with the pathological stage. These findings suggest that AR and GLYATL1 were involved in the development of PCa. AR is the intersection of signal transduction systems in the growth, differentiation and malignant transformation of prostate epithelial cells, which is closely related to the occurrence and development of PCa –26. At pThere is currently no report about the important role played by GLYATL1 and succinylation. GLYAT in the detoxification of endogenous and exogenous acyl-CoA. GLYATL1 and GLYATL2 are members of the GLYAT family , 28, andDespite the numerous findings of this study, it has limitations. First of all, the number of samples involved in this study is small. In the future, a greater amount of sample is needed to further confirm the research results. Second, this study did not elaborate the molecular mechanism in depth, and the role of success in prostate cancer needs to be further elaborated in the future. Third, part of the data in this study comes from biological information analysis, and the analysis itself has bias limitations. Fourth, because of differences in race, age and disease progression, the research results are not representative enough.This study found that the level of succinylation in PCa tissue was significantly increased, and high level of succinylation was associated with high Gleason grade and high PDL1 expression in PCa. The model construction of 20 succinylation related genes showed that the succinylation related gene GLYATL1 might be closely related to the late pathological stage of PCa.urologyzhaoj@sohu.com.The data analyzed in this study is subject to the following licenses/restrictions: The datasets generated and analyzed during the current study are not publicly available due to health privacy concerns, but are available from the corresponding author on reasonable request. Requests to access these datasets should be directed to This study was approved by the Committee of the Army Military Medical University of China . The patients/participants provided their written informed consent to participate in this study.ZZ, JZ, SD: Conceptualization, methodology, investigation, writing - original draft. YC, LF: Investigation, software. ZZ, JZ, SD: Investigation, validation, resources. ZZ, JZ, SD: Formal analysis, data curation, visualization, writing - review and editing, funding acquisition, supervision. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China (NSFC81974101).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Congenital heart diseases represent one of the hallmarks of 22q11.2 deletion syndrome. In particular, conotruncal heart defects are the most frequent cardiac malformations and are often associated with other specific additional cardiovascular anomalies. These findings, together with extracardiac manifestations, may affect perioperative management and influence clinical and surgical outcome. Over the past decades, advances in genetic and clinical diagnosis and surgical treatment have led to increased survival of these patients and to progressive improvements in postoperative outcome. Several studies have investigated long-term follow-up and results of cardiac surgery in this syndrome. The aim of our review is to examine the current literature data regarding cardiac outcome and surgical prognosis of patients with 22q11.2 deletion syndrome. We thoroughly evaluate the most frequent conotruncal heart defects associated with this syndrome, such as tetralogy of Fallot, pulmonary atresia with major aortopulmonary collateral arteries, aortic arch interruption, and truncus arteriosus, highlighting the impact of genetic aspects, comorbidities, and anatomical features on cardiac surgical treatment. In the last 30 years, the continuous progress in fetal diagnosis, cardiac surgery and perioperative management allowed a significant reduction in mortality and morbidity, even for the most complex congenital heart diseases (CHDs) ,2. DespiThe 22q11.2 deletion syndrome (22q11.2DS) (OMIM 188400/192430), also known as DiGeorge syndrome or velocardiofacial syndrome, is the most frequent chromosomal microdeletion disorder in humans, with an estimated prevalence ranging from 1:3000 to 1:6000 live births . The cliOver time, the in-depth knowledge of the cardiac anatomy’s features, more commonly found in this genetic syndrome, led to improved cardiac surgical outcomes with a consequent increased survival during pediatric age and achievement of adulthood . NeverthMoreover, the little data available on the adult population with 22q11.2DS report that the leading cause of mortality in this genetic syndrome are cardiovascular ones, such as sudden death and heart failure, not only in patients with major CHD but also in those without it ,14.As in other genetic syndromes, such as Down syndrome , Ellis-vSeveral previous studies analyzed data on cardiac surgical outcome of patients with CTDs, including those with 22q11.2DS, showing that, over the years, with advances in medical and surgical treatment, the mortality rate after cardiac surgery has been reduced and the postsurgical outcome has been significantly improved ,21,22,23Indeed, in some subgroups of patients, the presence of 22q11.2DS appears to be related to a longer duration of postsurgical intensive care, increased mechanical ventilation and prolonged hemodynamic support ,30,31,32It remains unclear whether cardiac surgery for CHDs in patients with 22q11.2DS is responsible for a worse neurological outcome. Some studies have demonstrated that patients with 22q11.2DS and CHDs have an unfavorable neurodevelopmental outcome than the non-syndromic counterparts, which appears to be more related to the presence of the chromosomal abnormality rather than to the underlying cardiac defect or surgical treatment ,36. MahaThis review is an update of the literature of the last decades on the impact of 22q11.2DS on cardiac treatment for each of the most frequently associated CHDs, highlighting how the extensive knowledge of specific cardiac phenotypes and related extracardiac anomalies are critical, in order to provide the most suitable surgical approach and the most appropriate perioperative management to improve outcome and prognosis of these patients.CHDs represent one of the most recurring features of 22q11.2DS, with a prevalence of 75–80% ,8,9,38. Several prevalence studies of CTDs in persons with 22q11.2DS reported that ToF is the most frequent cardiac defect, occurring in about 20–45% of patients, followed by PA-VSD that is present in about 10–25%. Approximately 5–20% of patients with 22q11.2 have IAA, 5–10% TA and 10–50% VSD. In addition, AAA may also be associated with this syndrome with a prevalence of 10% ,8,9,38 .Over the years, studies on cardiac phenotype allowed the identification of specific forms and subtypes of heart defects associated with this genetic syndrome ,18,19. ISpecifically, in individuals with 22q11.2DS, ToF may occur in association with hypoplasia or absent infundibular septum, absent pulmonary valve, discontinuity, diffuse hypoplasia or crossing of the pulmonary arteries (PAs) and AAA (such as RAA and CAA) with or without aberrant left subclavian artery ,44,45,46A possible feature of TA in patients with 22q11.2DS is the discontinuity of PAs and AAAs (as IAA type B with RAA or DAA), and severe dysplasia with truncal valve stenosis ,48. MoreThe aortic root dilation (ARD) is another cardiac finding reported among children and young adults with 22q11.2DS, isolated or associated with minor cardiovascular anomalies ,52. NowaCurrently, the clinical significance and the long-term implications of the isolated ARD in patients with 22q11.2DS are still unknown. Considering that, to date, there is no evidence of aortic dissection in the 22q11.2DS population and there are no surgical data on this aspect, it remains unclear whether the progression of dilatation may become significant over time.The genotype–phenotype correlation between the microdeletion and the presence of CHDs is now well known, but the pathogenetic mechanisms leading to this strong association are still not fully understood. An increased risk of having a CHD in 22q11.2DS has been attributed primarily to the presence of the hemizygous deletion, and several authors have focused on the role of protein encoding genes within the critical deletion region. Multiple mouse model approaches have demonstrated that, within this region, TBX1 is the major transcription factor, mainly responsible for the clinical phenotype, including the cardiac ones ,57,58,59Zhao and colleagues have in fact recently provided compelling findings on genetic modifiers of CHDs in 22q11.2DS . The autA miRNA-related mechanism was also observed in 22q11.2DS. Indeed, another gene that appears to be implicated in the cardiac phenotype of this syndrome is DGCR8, which encodes an RNA binding protein that is involved in miRNA biogenesis. In mouse models, inactivation of both DGCR8 alleles in neural crest cells has been proven to cause heart defects .Understanding in more detail the pathogenic process leading to the presence of CHDs in those patients, may also allow to better comprehending the cause of coexisting comorbidities that could influence clinical and surgical outcome.It is known that a significant percentage of patients with 22q11.2DS and CHD may require repeated cardiac operations, cardiac catheterization, and interventional procedures . To dateAbout 20–40% of children with 22q11.2DS suffer from ToF ,8,9. Of In about 50% of patients with 22q11.2DS, ToF recurs in association with particular cardiac anomalies: absent or hypoplastic infundibular septum, absent pulmonary valve, hypoplastic pulmonary arteries, and AAA  with or without aberrant subclavian arteries ,44,45,46The appropriate choice of surgical techniques tailored on syndromic patients led to the accomplishment that 22q11.2DS is not a surgical risk factor in children with ToF . MichielThe following study by Michielon et al.  confirmeMcDonald and colleagues  demonstrHowever, early operative outcomes in a particular ToF subset can be affected by genotype, as demonstrated by Mercer Rosa et al. . In factImpact of genetics on perioperative outcomes has also been investigated by a recent study of the same group  who demoMoreover, interestingly, the authors did not find any significant difference in feeding status upon discharge, even though it is well known that patients with 22q11.2DS may have more feeding difficulties and can be discharged more commonly on gastric feeding.PA-VSD+/−MAPCAs is found in 10–25% of individuals with 22q11.2DS , represeThe impact of genetics on perioperative and postoperative courses of patients with PA-VSD/MAPCAs has been the topic of numerous investigations.In contrast to ToF in the context of 22q11.2DS, several studies demonstrated an increased mortality risk for patients with PA-VSD/MAPCAs and 22q11.2DS, underlying that the risk of mortality for PA-VSD was higher, particularly if associated with MAPCAs, probably due to a less favorable pulmonary vascular anatomy ,33,69.Carotti et al.  found a Mahle et al.  showed tGenotype affecting adverse perioperative outcome was also demonstrated by Kyburz and colleagues , who perA higher rate of postsurgical complications in 22q11.2DS patients was also reported by Ziolkowska and colleagues . The autA recent study by Koth and colleagues  confirmeTA can be associated with 22q11.2DS in up to 35% of cases ,71,72. AThe reported data needed to be analyzed mindfully, as most of the studies were carried out over a prolonged period and therefore, some techniques could have updated, impacting their results over the study.In terms of surgical timing, the current literature reports a younger age at correction in children with 22q11.2DS with TA, especially in the TA type 1, with the majority of interventions performed during the neonatal period .In addition, some studies have pointed out the association between genetic syndromes and the need of unforeseen cardiac reoperations, without a definite explanation yet . More spWhen compared to the control groups, some authors also reported a more common need of gastrostomy postoperatively, which could be related to the known feeding issues characterizing the syndrome itself. The time spent in the hospital prior to surgery was not influenced by the presence of the syndrome, but postoperatively, it was longer in 22q11DS subjects in most studies .Consistently with a required longer total LOS, the 22q11DS population showed a greater use of resources, as a need for longer mechanical ventilation (twice as long as the control group), prolonged time of intensive care, and a more frequent use of consultation and medical treatment at discharge.p < 0.001 and OR = 1.39; 95% CI: 0.95–2.03; p = 0.087, respectively. In neonates with 22q11.2DS undergoing TA repair, the operative course was longer and more complex, in relation to non-cardiac features related to the syndrome.The incidence of non-cardiac complications was also greater. Hamzah and colleagues reported a postsurgical mortality rate from 6.9 to 11% ,77,78. PIAA occurs in about 5–20% of children with 22q11.2DS ,9 Table. In partThe typical intracardiac phenotype of the IAA in 22q11.2DS includes a hypoplastic and posteriorly deviated infundibular septum, particularly visible in type B anatomy ,50. A biSome studies have previously shown that, although 22q11.2DS was not clearly acknowledged as an additional risk factor per se, many of its anatomical features could impact the surgical technique, contributing to increased mortality ,79. AnacIn addition, a report by Kyburz and colleagues found a high risk of mortality and morbidity, mainly as the consequence of the severity of the CHD, but also influenced by the concomitant extracardiac anomalies, indicating a mortality rate of 30% for IAA .These results have not been confirmed by a more recent retrospective study on a larger cohort of children undergoing neonatal repair for TA or IAA, comparing perioperative outcomes between individuals with 22q11DS and those without deletion. Indeed, the authors demonstrated that there were no significant differences in terms of immediate postsurgical mortality between syndromic and non-syndromic patients . The lonIn particular, the association between the presence of 22q11.2DS and prolonged total LOS, longer time of mechanical ventilation and intensive care, and higher frequency of cardiac events was statistically significant in the subgroup of patients with IAA. Furthermore, the duration of cardiopulmonary bypass and deep hypothermic circulatory arrest was longer in patients with IAA than those with TA. Finally, the authors demonstrated that, compared to non-syndromic individuals with IAA, patients with 22q11.2DS and IAA required a greater number of subspecialty consultations and more medical treatments at discharge, while feeding problems did not affect the length of hospitalization .McDonald and colleagues also reported that postsurgical intensive care unit hospitalization was longer in patients with 22q11.2DS undergoing surgery for IAA than in a non-syndromic group .A very recent article demonstrated that the co-occurrence of simple and complex CHDs in patients with 22q11.2DS and IAA resulted in a higher risk of hospital complications (such as increased risk of gastrostomy tube placement and sepsis) compared with the non-syndromic counterpart .Various authors highlighted a significant risk of mortality and morbidity in patients with 22q11.2DS when analyzing the postsurgical outcome and the possibility of a tailored pre-surgical management. This risk has been subsequently stratified for different eras of cardiac surgery, confirming a significant decrease during the recent years when compared to what was previously reported .Nonetheless, patients with 22q11.2DS undergo surgical palliation more frequently than the complete surgical treatment  . Severe An additional extracardiac surgery (more than 40% of cases reported) was often a complication of the clinical outcome .Different causes of death have been described in these patients. Even though mortality for cardiac illness remains most frequently reported (more than 54% of cases), immunological disorders sometimes worsen the outcome, particularly in patients younger than 2 years who still experience a worse postoperative outcome .The patients with 22q11DS frequently need a prolonged time of mechanical ventilation postoperatively, with a consequent increased risk of lung infections. The same high risk is corroborated by a significant percentage of reintubation over the following day post operation. A dramatic risk of bacterial  or fungaMoreover, the role of hypocalcemia has been suggested, by some authors, for its impact on postsurgical outcomes. 22q11.2DS patients are well known to be prone to severe hypocalcemia, particularly in the neonatal period. In persons with 22q11.2DS, the high susceptibility to hypocalcemia, whether related to a preexisting condition of hypoparathyroidism and/or surgery-induced stress, is responsible for an increased risk of postoperative complications and mortality . Yeoh anp = 0.020), pneumonia (p < 0.001), sepsis (p = 0.001), respiratory failure (p = 0.028), prolonged intubation/tracheostomy (p = 0.014), laryngeal stridor (p < 0.001), and hypocalcemia (p = 0.015) [Ziolkowska and colleagues compared patients with CTDs, with and without 22q11.2DS, and underlined, in the syndrome, a greater risk for heart failure (= 0.015) .Despite that the postsurgical outcome in these patients has vastly improved in the recent period ,22, all Atallah et al. followed-up patients at 18–24 months and reported a lower neurodevelopmental outcome, and a higher motor and mental delay with lower IQ scores . TherefoConversely, some other authors suggested the importance of a preoperative immunological evaluation of the T cell function. This information could indeed lead consultants and surgeons to a more specific postoperative antimicrobic management, in order to reduce complications  Table 2Table 2.Due to the tendency of 22q11.2DS patients to manifest thrombocytopenia and prolonged time of bleeding, a complete blood and platelet count should be perioperatively performed ,82 Tabl.The use of previously filtered or irradiated red cells should be carefully considered to reduce graft versus hosting disease in the time of transfusion or for aortic cross-clamping .Furthermore, a careful imaging study of some anatomical features, often found in 22q11.2DS , can allow to reducing the risk of complications during surgery ,60,83,84Finally, targeted therapies  may be required due to an increased risk of hypotension, related to vasomotor instability, and airway over-reactivity ,86 Tabl.Over the years, the deep knowledge of the anatomic cardiac phenotype allowed the adaptation of routine surgical techniques and has greatly improved surgical results in patients with 22q11.2DS.To date, although 22q11.2DS does not represent an independent risk factor for mortality after cardiac surgery, the short-term surgical outcome may vary for subgroups of patients with specific cardiac phenotypes, especially in patients with PA-VSD and MAPCAs due to unfavorable pulmonary vascular anatomy. Different surgical outcomes have been reported by different centers in the last decades. Certainly, the reason is multifactorial depending on variables such as the sample size of population of patients, age and weight of patients at the moment of the operation, primary or staged surgical approach, metabolic abnormalities, and undetected infections. Considering that the presence of this genetic syndrome and related comorbidities may adversely affect the postoperative course, results of cardiac surgery of the more recent studies are extremely relevant to preoperative counseling, to guide surgical decisions, and for tailored perioperative management.With a deeper understanding of cardiac phenotypes, perioperative management and genotype–phenotype correlations of patients with 22q11.2DS, it will be possible to offer to families, even in the prenatal period, appropriate counseling in terms of prognosis, to plan surgical procedures, and to define postoperative management strategies in order to improve outcomes and resource management when taking care of this highly complex population of patients.