Arterial stiffness, as reflected in the cardio‐ankle vascular index (CAVI), is a risk factor for major adverse cardiovascular events (MACEs).Combining CAVI and metabolic syndrome (MetS) may enhance prediction of MACEs in a general adult population.A total of 3807 employees of the Electricity Generating Authority of Thailand were enrolled in a longitudinal health study during 2007‐2008. Baseline characteristics were collected and CAVI determined. Subjects with previous coronary artery disease or stroke were excluded from analysis. MetS was defined using the modified NCEP‐ATP III for Asians. The primary study endpoint was occurrence of a MACE .P = 0.001). During the 12.4 ± 0.6 years follow‐up, 227 participants developed MACEs and 350 died. MetS was more common in patients who developed a MACE  than was non‐MetS, but it was not a significant risk after adjusting covariables. Participants with CAVI > 9 had greater risk for MACEs 1.34  relative to those with CAVI < 9. Participants with both MetS and CAVI > 9 had the worst outcomes, with the highest frequency of MACEs, among the four groups.MetS was present in 39.2% at study baseline. The prevalence of CAVI > 9 was higher in subjects with MetS compared to those without (33.7% vs. 28.5%, Arterial stiffness assessed by CAVI may enhance prediction of future MACEs, adding to the null predictive power of MetS. This index can be used to motivate MetS patients to modify their life‐styles for prevention. To detect MetS, a newly diagnosed risk factor, fasting blood samples for plasma glucose (FPG) and lipid profile  were collected from these subjects. DM was defined as an overnight fasting plasma glucose (FPG) ≥126 mg/dl or taking anti‐diabetic medications. Hypertension was defined as systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg, or taking anti‐hypertensive medication. Dyslipidemia was defined as elevated total cholesterol ≥200 mg/dl or LDL‐C ≥ 130 mg/dl or taking statin medications. For each subject, ankle‐brachial index (ABI) and CAVI were also determined at baseline.A total of 3807 subjects from the EGAT 1/3 and EGAT 2/4 cohorts seen at follow up in 2007 and 2008 were enrolled into this study. Characteristics at this 2007/2008 time point, including age, sex, atherosclerosis risk factors , body mass‐index  criteria,2.4a{(2ρ/ΔP) × ln(Ps/Pd) × haPWV2} + b, where Ps and Pd are the SBP and DBP, respectively; PWV is the pulse wave velocity between the heart and ankle; ρ is blood density; ΔP is Ps–Pd; a and b are scale conversion constants .CAVI was measured using a Vasera VS‐1000 vascular screening system .2.5Subjects were randomly enrolled from the ongoing EGAT study, among EGAT employees in the Bangkok metropolitan area (EGAT 1) and at three different sites in Western and Northern Thailand (EGAT 2). The age range was selected as 35–54 years old, to maximize the probability of CVD events, given that the retirement age in EGAT in 1985 was 55 years. A large variety of people were recruited, from illiterates working as cleaners to truck drivers, security guards, office clerks, administrators, architectures, engineers, field explorers, lecturers, lawyers, health‐care practitioners, and those on executive boards.Inclusion criteria included the presence of atherosclerosis risk factors but absence of related symptoms. Exclusion criteria included a diagnosis CVD at baseline, either coronary artery disease (CAD), myocardial infarction (MI), or stroke. To ensure correct CAVI measurements, participants with any of the following characteristics were also excluded: 1) abnormal ABI <0.9, 2) interference waveform of phonocardiogram and arterial  pulse waves, 3) atrial fibrillation, and 4) outlier CAVI values (≤3 or ≥ 18).2.6Following the baseline assessments in 2007–2008, all participants were resurveyed for possible study outcomes in December 2019. They were contacted by telephone and invitation letters. The primary endpoint was occurrence of a MACE  and the secondary endpoint was ACD. Cardiovascular death was defined as a CAD death or stroke death. CAD was defined as the presence of at least one of the following criteria: angina, acute coronary syndrome, acute MI, a significant (>70% diameter stenosis) lesion on coronary angiography, revascularization (PCI or CABG), and documented myocardial ischemia during exercise testing. Stroke was defined as a history of ischemic or hemorrhagic stroke, or transient ischemic attack (TIA). If a subject had two cardiovascular events , only the first event was counted. If a subject died of a cardiovascular disease, this subject was counted as both a MACE and an ACD. The names of study participants who did not reply to the surveys or who may have died during the follow‐up period, were cross‐checked against death databases maintained by the National Health Security Office  and the Department of Provincial Administration of the Ministry of the Interior (which compiles death certificates) to ascertain vital status. The cause of death was assessed by an independent adjudication committee, comprised of cardiologists and neurologists, and classified into CAD , stroke (including subarachnoid hemorrhage), other vascular death , non‐cardiovascular death , or unknown).2.7t–test or Chi‐square test. Kaplan–Meier (KM) curves of MACEs were constructed according to MetS and CAVI groups, and these KM curves were compared using a log‐rank test. Multiple Cox proportional hazard models were used to determine whether MetS and CAVI were associated with MACEs. A multivariate Cox regression model was applied to assess association effects of MetS and CAVI on MACEs. Atherosclerosis risk factors, including age, sex, BMI, smoking, DM, hypertension, and dyslipidemia, were also used to adjust the multivariate Cox models if their p‐values in the simple Cox model were less than .20. Forward selection was applied to select only significant risk factors in the MACE model that already contained MetS and CAVI. Hazard ratios (HRs) along with 95% confidence intervals (CIs) were then estimated. A p‐value <.05 was considered statistically significant. All statistical analyses were performed using STATA version 16 .Characteristics at enrollment were described using mean ± SD for continuous variables and percentages for categorical variables. These corresponding variables for the MetS groups were compared using a two‐sided Student's 33.12, and 73.2%, respectively. The overall prevalence of MetS was 39.2%. Baseline characteristics, classified by MetS groups, were compared and are shown in Table p = .001). ABI classified as above or below the median (1.12), was found to be independent of the presence of MetS.Out of 3807 participants, 3630 were included in the analysis Figure ; their a3.2p < .001) and had a higher ACD . The percentages of both fatal and non‐fatal MI events were significantly higher in the MetS group , whereas there were no significant differences in fatal or non‐fatal strokes . There was also no significant difference in non‐CVD death between the two groups ; these non‐CVD deaths consisted of malignancy (49.8%), respiratory and gastrointestinal diseases (10.9%), accidents (7.3%), sepsis (11.2%), metabolic (1.8%), and miscellaneous or unknown (18.9%).During the follow‐up (a period which averaged 12.4 ± 0.6 years), 227 participants experienced a MACE and 350 died. Participants with MetS at baseline, compared to those without, developed more MACEs (8.2% vs 5.0%, 3.3Using bivariate analysis, MetS, CAVI, age, sex, ABI, BMI, waist circumference, smoking, FPG, DM, and hypertension were each found to be significantly associated with MACEs, see Table 3.4p < .001, Figure The interaction effect between MetS and CAVI on MACEs was assessed. Participants with both MetS and CAVI ≥ 9 had the worst outcomes, with the highest frequency of MACEs, among the four groups. Kaplan–Meier curves demonstrate these differences: the highest occurrence of MACEs was in the participants with MetS and CAVI ≥ 9, followed by MetS and CAVI < 9, non‐MetS and CAVI ≥ 9, and non‐MetS and CAVI < 9 (4This is the first study to assess the effects of MetS and CAVI on the occurrence of MACEs in a large longitudinally followed cohort. The prevalence of MetS in our population was nearly 40%, compared to 20%–30% in populations previously reported from Asia and worldwide.Arterial stiffness assessed by CAVI has been reported to be a surrogate marker of atherosclerosis and a predictor of future CVEs, independent of conventional risk factors.In this study, we used the CAVI as a categorical rather than a continuous variables. A cut‐off of CAVI ≥ 9 is generally considered high and to represent the presence of atherosclerosis and as a predictor of CV risk.Other risk factors, such as older age, male sex, are also reported to be associated with higher CAVI.In summary, in patients with MetS, CAVI was an additional risk predictor of future MACEs, independent of traditional coronary risk factors. CAVI was a potentially valuable non‐invasive test which identified high‐risk MetS patients who were likely to benefit from intensive therapeutic approaches.Several limitations of the study need to be mentioned. The study population was enrolled only from among EGAT employees and were mostly middle or older age. Thus, the results may not be generalizable to younger populations. The definition of MetS was defined based on the baseline characteristics on the day of enrollment, and there is a possibility that some participants may have switched over during the follow‐up period. Such switches may have influenced the long‐term clinical outcomes. But since developing MetS was more likely than resolving the syndrome, this influence would tend to underestimate the true differences. Finally, even though this was a cross‐sectional, prospective cohort study, it could not prove causality between arterial stiffness and MACEs.5MetS is an important problem that is associated with MACEs and premature death. Arterial stiffness of a person can be assessed non‐invasively and semi‐quantitatively represented by CAVI, and this index can be used as a screening tool. CAVI may improve prediction of future MACEs, and also used to motivate MetS patients to modify their life‐style for CV disease prevention.None of the authors reported any conflicts of interest.


Active surveillance (AS) is the reference standard treatment for the management of low risk prostate cancer (PCa). Accurate assessment of tumor aggressiveness guides recruitment to AS programs to avoid conservative treatment of intermediate and higher risk patients. Nevertheless, underestimating the disease risk may occur in some patients recruited, with biopsy upgrading and the concomitant potential for delayed treatment.To evaluate the accuracy of mpMRI and GPS for the prediction of biopsy upgrading during active surveillance (AS) management of prostate cancer (PCa).A retrospective analysis was performed on 144 patients recruited to AS from October 2013 to December 2020. Median follow was 4.8  years. Upgrading was defined as upgrading to biopsy grade group ≥2 on follow up biopsies. Cox proportional hazard regression was used to investigate the effect of PSA density (PSAD), baseline Prostate Imaging‐Reporting and Data System (PI‐RADS) v2.1 score and GPS on upgrading. Time‐to‐event outcome, defined as upgrading, was estimated using the Kaplan–Meier method with log‐rank test.2, p = .005), while no significant difference was present for median GPS in the overall cohort . On univariable cox proportional hazard regression analysis, the factors associated with increased risk of biopsy upgrading were PSA , PSAD  and higher PI‐RADS score . On multivariable cox proportional hazard regression analysis, only PSAD  and high PI‐RADS score  were associated with upgrading. A cox regression model combining these three clinical features  yielded a concordance index of 0.71 for the prediction of upgrading.Overall rate of upgrading was 31.9% (n = 46). PSAD was higher in the patients who were upgraded (0.12 vs. 0.08 ng/mlIn this study PSAD has higher accuracy over baseline PI‐RADS score and GPS score for the prediction of PCa upgrading during AS. However, combined use of PSAD, GPS and PI‐RADS Score yielded the highest predictive ability with a concordance index of 0.71. Generally, AS programs require serial digital rectal examination (DRE) and prostate specific antigen (PSA) measurement, annual multi‐parametric Magnetic Resonance Imaging (mpMRI) of the prostate and repeat biopsies 2–3 years after diagnosis.A more accurate assessment of tumor aggressiveness can also guide recruitment to AS programs to avoid conservative treatment of intermediate and higher risk patients. There are commercially available genomic tests that predict treatment outcome in prostate cancer.One major concern for AS management lies in underdiagnosis of clinically significant prostate cancer (csPCa), with subsequent underestimation of disease risk.22.1An institutional review board approved retrospective analysis was performed on 144 patients who were diagnosed with National Comprehensive Cancer Network (NCCN) low risk, and low volume intermediate risk PCa and followed by the AS protocol from October 2013 to December 2020  were anonymized and reported by one reader  in random order using the PI‐RADSv2.1The AS protocol included PSA and DRE every 3–6 months and annual mpMRI. Patients received follow up biopsy if they had a new positive DRE finding, rapid increase in PSA as well as a new or a change in dimensions of PI‐RADS >3 lesions. In the absence of these clinical risk factors, every patient underwent 12‐core standard biopsy every 3 years.2.3Baseline clinical and pathological data included age, race, BMI, PSAD, biopsy Gleason score, PI‐RADS Score, GPS and GPS risk group. For PSAD measurement, the volume data were defined by baseline mpMRI measurement. Patients were stratified by PI‐RADS score  and GPS defined as low risk <18, intermediate risk 18–30 or high risk 31–100. Upgrading was defined as upgrading to grade group ≥2 or higher on follow up biopsies. Upgrading was the primary outcome of the study and resulted in patients being offered definitive therapy, via RP or external beam radiation.2.4Univariable analysis was done by Chi‐squared and fisher's exact test for categorical data and Mann Whitney test for continuous data Time‐to‐event outcomes were estimated using the Kaplan–Meier method and log‐rank test according to GPS risk category, mpMRI PI‐RADS scores and PSAD  and STATA v14 were used for all statistical analyses.A 32 vs. 0.12 ng/ml2 in no vs. upgrading, p = .005). Mean GPS was 22.05 in the overall cohort. . Although there were more high genomic risk patients in the upgraded group , this difference did not reach statistical significance in this cohort. The upgrading group had a higher rate of high‐risk MRI lesions, but again this did not reach statistical significance . Radiogenomic analysis did not demonstrate any significant association between PI‐RADS score and GPS (p = .0632). Mean GPS was 22.3  for low risk PI‐RADS lesions, whereas mean GPS was 21.04  for high risk PI‐RADS lesions. Table p = .0632).The overall rate of upgrading was 31.9% (n = 46). Median time to upgrading between diagnostic and upgrade biopsy was 29.6 months . Baseline characteristics are summarized in Table p = <.0001), PSAD  and high PI‐RADS score . In multivariate cox proportional hazard regression analysis, PSAD  and high PI‐RADS score  were the only factors associated with upgrading. (Table p = .7223) stratified by the GPS score, PI‐RADS and PSAD are shown in Figure In univariate cox proportional hazard regression analysis, the factors associated with increased risk of biopsy upgrading were PSA  yielded a Harrell's concordance index of 0.71 for the prediction of pathological progression, whereas the concordance index for PI‐RADS score alone was 0.582, GPS alone 0.50 and for PSAD alone was 0.65. A model with both PSAD and PI‐RADS had a concordance index of 0.692, demonstrating the addition of GPS did improve predictive accuracy.A cox regression model combining these three clinical features . Furthermore, they demonstrated that patients with a visible lesion at confirmatory biopsy had a higher risk of upstaging compared to no lesions . The same analysis was not carried out for comparison in this cohort, as confirmatory biopsy was not done on patients without lesions on mpMRI. Finally, they showed in a sub‐cohort of patients without any mpMRI lesions, performing a biopsy did not change the rate of progression ,Study (ASIST) trial, which was a randomized study comparing systematic biopsy versus MRI and targeted and systematic biopsy in 259 AS patients, showed baseline MRI prior to confirmatory biopsy, reduced subsequent conversion from AS to treatment by 50% after only 2 years follow up.With regards to mpMRI lesion characteristics, a recent analysis by Gallagher et al. demonstrated results supporting those of our study, although their protocol for MRI reporting was different. Gallagher et al. did not use the PI‐RADS system but rather MRIs were classified as having “high risk” or “moderate risk” lesions or “no lesion”. They reported worse progression free survival in patients with high risk lesions compared to patients with no lesions , whereas, for example, in Cedars et al., the mean time between first and second biopsy (which would have been the upgrade biopsy) was only 14 months (IQR 12–23). Also, in this cohort, there were only three patients with Gleason 7, and only 26 patients with PI‐RADS 4 or 5 lesions, which suggests this AS program is conservative in recruitment with a low threshold for offering radical treatment at the time of diagnosis. Given that in the studies discussed above,Despite the limitations of comparing studies with different mpMRI and AS protocols, there is a reasonable consensus that mpMRI does has value in AS, albeit when combined with other parameters such as PSAD and GPS score.This study is a single center study with retrospective design and so inherent selection bias. Also, the AS protocol for this study differs with most studies in that confirmatory biopsy was not done in every patient, and, in the absence of any changes in disease parameters, repeat biopsy is not done until 3 years after diagnosis. All patients diagnosed at this institution were diagnosed with mpMRI fusion biopsy unless their mpMRI was without lesions, and patients received confirmatory biopsy only if they were diagnosed at an outside institution without targeted biopsy and their follow up mpMRI showed lesions suggestive of csPCa. This practice aims to reduce the number of biopsies. Finally, all mpMRI studies were reported prospectively as part of routine clinical workflow at different institutions and only a portion of studies was re‐reported (n = 75) by one reader unaware of PSA, PSAD, GPS and biopsy findings, which means differences in MRI acquisition protocol and MRI scanners were present during the study period. On the other hand, this study has a reasonable size and is a single surgeon series, so treatment decision‐making did not vary within the cohort.5PI‐RADS score of the baseline mpMRI and GPS were shown to behave some potential for predicting upgrading at nearly 5 years follow up in this single center tertiary referral center AS cohort, however their predictive ability was inferior to PSAD. mpMRI and GPS remain useful tools in AS, however, their optimal use is yet to be determined. Moreover, with the development of scoring systems such as “PRECISE”, the utility of MRI in AS may be expanding. Nevertheless, the combined use of PSAD, GPS and mpMRI yields the highest predictive ability for identifying pathologic upgrading at follow up biopsy in patients undergoing AS in this study, and on that basis, the use of all three parameters when recruiting patients with newly diagnosed PCa to AS programs is recommended.This analysis was institutional review board (IRB) approved with appropriate consent obtained for all patients included.Z.D. is Medical Director and stock owner (by shares) of MedTech Holdings Ltd. AKT as of 2020 listed as company type, relationship type and financial. Urethral Catheterless Radical Prostatectomy, Patent, No. DNA Based Bicistronic Vectors with Inducible and Constitutive Promoters ‐ ID#: 16060, Patent, No. High Intensity Focus Ultrasound and CPG‐Brachyurys iRNA for Treatment of Prostate Cancer ‐ ID# 160403, Patent, No. Patent for a Catheterless Device and Approach, Patent, No. *Promaxo, Leadership position, Yes. *Promaxo, Equity Ownership, yes. Global Prostate Cancer Research Foundation, Leadership position, No. Kalyani Prostate Cancer Institute, Leadership Position, No. Prostate Cancer Foundation, Leadership Position, No. Roivant, Consultant, No. Blank Family Foundation, Grant, Yes. Intuitive Surgical, Scientific Study or Trial, Yes. Department of Defense (DOD), Scientific Study or Trial, Yes. AxoGen, Inc., Scientific Study or Trial, Yes. Oncovir, Inc ‐ Poly ICLC, Scientific Study or Trial, Yes. National Institute of Health (NIH/DHHS), Scientific Study or Trial, Yes. National Cancer Institute, Scientific Study or Trial, Yes. National Institute on Drug Abuse, Scientific Study or Trial, Yes. Dr. Ash Tewari  owns equity in the form of stock certificates in Promaxo, for which he serves as an advisor. Promaxo is a privately traded company which develops MRI technology with a focus on prostate cancer. Kite Pharma, Scientific Study or Trial, Yes. Lumicell, Inc, Scientific Study or Trial, Yes. Dendreon, Scientific Study or Trial, Yes. *PROMAXO: Common Stock Certificate VALUE: 51,205% SHARE RELATED PARTY: 0.63; Intuitive – no salary/see referenced COI’s; Promaxo – no salary/investment – see referenced COI’s; Kite Pharma: Serve as PI. Industry funded for research procedures. Site PI performance – no salary; Poly ICLC: serve as site PI. Phase I Study of IN SITU Autologous Vaccination Against Prostate Cancer With Intratumoral and Systemic HILTONOL (POLY‐ICLC) Prior to Radical Prostatectomy. Product provided free of charge – no other funding ‐ no salary.T.B.: Conceptualization; methodology; writing‐original draft; writing‐review & editing. P.R.: Data curation; formal analysis; methodology; writing‐original draft; writing‐review & editing. Z.D.: WritingOriginalDraft; WritingReviewEditing. R.R.: Data curation; formal analysis; investigation; methodology. S.P.: Data curation; formal analysis. S.S.: Formal analysis; investigation; methodology; writing‐review & editing. D.K.: Data curation; formal analysis; investigation; methodology. R.W.: Formal analysis; investigation; methodology. H.B.: Formal analysis; investigation; methodology. I.J.: Formal analysis; investigation; methodology; writing‐review & editing.


Various surgical centers tend to postpone a kidney transplantation (KT) to the following morning than to operate at night‐time.The objective of our study was to assess whether there was any difference between daytime and night‐time renal transplantation in our institution.This study is a retrospective monocentric study including all the KTs that were performed between 2012 and 2013 by transplant expert surgeons in our institution. Clavien‐Dindo (CD) complications were classified according to 7 variables going from 1 to 5. Time before postgraft diuresis and delayed graft function (DGF) were also analyzed. Two groups of patients were formed according to threshold value of incision time (6.30 p.m.). Data comparison were performed using the Kruskal–Wallis nonparametric test.p < .001), but rewarming time was shorter . No statistically significant differences were observed between the two groups using the Kruskal–Wallis method for CD complications . CD complications proportion was similar, with a majority of grade II complications (72.7% daytime group vs. 75.4% night‐time group (p = .735). DGF  and time before postgraft diuresis  were similar between both groups. Multivariate analysis did not show significant predictors of CD complications Grade 3 and more.A total of 179 patients were included. Median follow‐up was 24 months. Cold ischemia time was longer in the night‐time transplantation (1082 vs. 807 min, Night‐time renal transplantation did not induce more postoperative CD complications than diurnal procedures in our cohort, challenging the false preconceptions that allow surgical teams to delay this surgery.  KT is a challenging situation in surgical team organization, because of several features. First of all, this population is exposed to a higher risk for perioperative morbidity and mortality due to the severity of their disease.In 2019, 3641 renal grafts were transplanted in France (+4% increase compared to 2018) , nor a daytime KT (8 a.m. to 6.30 p.m.).22.1We retrospectively reviewed data that were extracted from a prospective record collection, the French National Renal Transplantation database (DIVAT), of all recipients with a single KT from January 2012 to December 2013, in our University Hospital. DIVAT records prospectively and exhaustively the renal transplantation activity either from living or deceased donor, and is in accordance with the Helsinki Declaration of 1975. Patients included in DIVAT gave their informed consent before their inclusion in the database. Recipient's characteristics . Kidneys were either preserved in cold ice or preserved on pump, following French Transplantation guidelines regarding kidney preservation. Main information concerning each procedure was extracted: operating time, CIT and rewarming time (RT), Clavien‐Dindo (CD) complications, acute rejection, DGF and time before postgraft diuresis. CD complications were classified depending on 7 variables from 1 to 5.2.2Surgery was done by several experienced surgeons, in our transplantation reference centre. Pararectal or Jalaguier‐Gibson incision was performed. Anastomoses were made end‐to‐side on external iliac vessels. Uretero‐vesical reimplantation was performed with the Campos Freire‐Lich‐Gregoire technique and a double J stent was left in place for 6 weeks.2.3The cut‐off incision time was chosen according to the night shift time in the emergency ORs, both medical and paramedical teams. 6.30 p.m. was chosen as the threshold for separating daytime and night‐time surgery.The primary study endpoint was the distribution of complications within each group. Secondary endpoints were the overall rate of complications, for each of the 7 CD complication variables, and time before postgraft diuresis.2.4We reported all data regarding surgical and medical complications in the 30 first days, with or without revision, classified as CD complications2.5Our institution evaluation of postgraft diuresis is based on the number of days when recipient's serum creatinine after renal transplantation matches with donor's kidney serum creatinine at time of procurement. DGF was defined as a need for dialysis in the first postoperative week.2.6Donor and recipient's preoperative data were extracted from DIVAT, while consultation, hospitalization, operative reports, biological and imaging results were extracted from the Clinicom software (Intersystems) used in our centre.p value <.05. Results are expressed as percentages for categorical variables, means ± SD for variables with a normal distribution and as medians for variables with a non‐normal distribution.Statistical analysis was performed using Stata software. Statistical significance was defined as a χ2 test, and mean time before diuresis, using student test. Multivariate analysis was done on CD complications grade 3 or more, and DGF.The difference in distribution of complications was assessed by the nonparametric Kruskal–Wallis test. Proportions were compared using We also represented the data by a plot of the CD complication depending on the time of incision, to visually evaluate an eventual tendency, and assess the robustness of our cut‐off time. Only two‐tailed tests were used, with first species risk of 5%.3p = .024), recipient's age  and Charlson score .A total of 179 patients who underwent KT during our inclusion period were retrospectively included for this study. Main characteristics are shown in Table p < .001). RT was not significantly different.Ischemia times of the transplant are shown in Table p = .735). Table p = .7). We then stratified for complications CD >2 depending on the time of incision, showing the highest complication rate for an incision time between 3 and 5 p.m.   Table .Regarding the description of CD complications, daytime group had 10 CD3 complications, with 1 urinary tract infection needing double J stenting, 2 lymphoceles needing interventional radiology for drainage, 5 redo surgeries for hematomas, 1 artery and 1 venous thrombosis. There were also 8 CD4 complications, with 1 acute respiratory failure needing high volume oxygen, 1 resuscitation after cardiac arrest, 4 acute coronary syndrome needing emergency stenting, 1 acute pulmonary oedema, and 1 Hemolytic Uremic Syndrome.Night‐time group had 8 CD3 complications: 2 urinary tracts infections needing double J stenting, 1 redo surgery for hematoma, 1 lymphocele needing interventional radiology for drainage, 2 marsupializations for lymphocele, 1 redo surgery for renal vein thrombosis and 1 fat embolism syndrome. There was also 2 CD4 complications, with 1 renal vein thrombosis needing emergency explantation and 1 Atrial Fibrillation with the need for cardioversion.4p = .15) for night‐time KT. In a meta‐analysis regarding transplantations performed outside regular working hours, a 1.01 mortality Hazard ratio (95% CI: 0.98–1.04) was shown regarding “non‐regular” hour transplantations.Night‐time surgery has often been associated to a higher morbidity or mortality rate, previous studies confirming these hypotheses.n = 4519), which contrast with Fechner's study,p < .1, n = 260) in his night‐time population.Regarding the distribution of CD complications, we did not find any significant differences between the two groups. There was more 3b CD complications in the night‐time group, however, these results were not significant. However, a larger population on this matter could provide a better stratification of the CD complications repartition. An interesting comparison would also be the peroperative complications, such as bleeding or vascular stenosis, between daytime and night‐time surgery. Interestingly, Brunschot et al.We also found a tendency to DGF for the night‐time transplant group on univariate analysis. On multivariate analysis, only patient's age had a real impact on DGF. DGF has a significant clinical and long‐term impact on the survival and functionality of the future graft.Our two groups differed in terms of recipient's age, but in multivariate analysis, only age was at significant risk of DGF. These results complement Guo et al's study, where kidney donors over 60 had higher 1 or 2 CD complications, but no difference in 3 or 4 groups; however, older patients had a significantly lower eGFR at 1 month and 1 year.In our study, 6.30 p.m. was chosen as a threshold for incision time to differentiate daytime and night‐time population. This threshold differs from most of the other studies comparing daytime and night‐time surgery, with a 8 p.m. incision time as a cut‐off. 6.30 p.m. is the switch time between both nurse and anaesthesiologist team in our center. That time is crucial, with a transfer of all the perioperative informations between teams, and can lead to transmission error. Giugale et al.The success of a KT is mostly due to a short cold ischaemia time,However, it is common sense that excessive duty hours and extended work shifts (24 h or more) inevitably leads to sleep deprivation, which is one of the risk factors of burn out.We recognise several limitations in our study. First, we looked at postoperative CD complications, and DGF, not taking into account the clinical follow‐up regarding kidney graft function or mortality. It would be interesting to monitor this population to evaluate long‐term effects of night‐time transplant surgery, regarding renal function and tardive complications. There are no studies comparing day and night transplants regarding recovery of renal function or hypertension occurrence, but it has already been showed that night‐time renal transplantation had an impact on transplant's lifespan.Our short period of inclusion and absence of contemporary data is also a limitation factor, due to a change in the local KT surgical organization, cancelling all night‐time transplantations in our centre after 2013 because of organizational restrictions. Thirdly, our small population sample and our retrospective analysis are understandably a limit to conclude in night‐time KT being as safe as daytime transplantation regarding postoperative complications.Finally, a comparison between weekday and weekend transplants could add to the analysis regarding surgical planning, as various studies have shown both more postoperative complications,5Our study confirms the absence of difference in the CD postoperative complications between night‐time and daytime KT in our cohort, challenging the false preconceptions that allow surgical teams to delay this surgery, furthermore increasing the risk of kidney graft failure or acute rejection as the cold ischemia time increases. Above all, the main goal of reducing the CIT should be considered. Based on evidence‐based medicine, night‐time KT should no longer be avoided for fear of complication. To do so, organizational boundaries of night‐time KT must be addressed by focusing on dedicated surgical teams and easy access to OR.The authors declare that there are no conflict of interests.All human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 2000 Declaration of Helsinki as well as the Declaration of Istanbul 2008.


Many young adults demonstrate insufficient rates of physical activity (PA) to yield health benefits. The study tested the effectiveness of a text messaging intervention targeting key psychological determinants and PA.Participants received either attitude messages, goal priority messages, a combination of these, or generic PA information (control). After confirming that groups were matched at baseline, a 2 (attitude: yes vs. no) by 2  by 2  randomized control trial tested main and interactive effects.Results showed participants that received attitude messages had significantly more positive attitudes, intentions and rates of PA. Mediational analyses showed the influence of attitude messages on PA to be fully mediated through the serial path via attitude and intention. There were no other main or interactive effects.The study provides support for using attitudinal messages delivered via text messaging to influence key psychological determinants and PA. The benefits of PA are well established. For example, regular participation can reduce mortality rates and delay the onset of many chronic diseases such as cancer, diabetes, and heart disease  but not subjective norm (r = .00) and perceived behavioral control (r = .13) to significantly predict PA intentions. Reviews have also demonstrated medium-to-large changes in intention . Health-related behaviors cluster among university populations and need to be taken into account when designing multi-health interventions and policies  attitude messages would have a main effect on attitude, intention, and PA, (2) the influence of attitude messages on PA would be mediated through attitude and intention, (3) goal priority messages would have a main effect on goal priority and PA, (4) the influence of goal priority messages on PA would be mediated through goal priority, and (5) goal priority messages would augment the effects of attitude messages on PA.The study adopted a 2 (attitude message: yes vs. no) x2  x2  factorial design. Contact lists were generated of departmental offices from many disciplines within 104 universities in the United Kingdom. Emails comprising study information and a recruitment poster were sent and they were asked to circulate the latter to their first-year students. Participants then accessed the survey by either clicking the hyperlink on the poster or copying the URL. Once accessed, further information on the study was provided and those willing to participate read and provided consent to the statements given. Participants then completed the baseline questionnaire (T0) and once complete, were informed when the intervention would commence for them. All interventions started on a Tuesday, but the precise date depended on the time of enrollment. A computer-generated random number sequence was used to allocate participants individually to one of four conditions at the point of enrollment; attitude only, goal priority only, attitude and goal priority, and control. Immediately after undertaking the intervention, participants were asked to respond to the first follow-up questionnaire (T1). Participants were then required to respond to the second follow-up questionnaire four weeks later (T2). All assessments were completed online and participants were sent text messages with links to the relevant questionnaires. Participants could either click the link or insert the URL to gain access. To match data across all three time-points, participants provided their mobile phone number and responded to three personal questions to generate a pseudo code. Ethical approval was gained from the University ethics board prior to study recruitment.n = 106 males, 183 females; M = 18.7 years, SD = 1.17). These were randomized into one of the four intervention conditions; attitude only (n = 71), goal priority only (n = 72), attitude and goal priority (n = 73), and control (n = 73)  aged between 18–25 years, (2) a first-year undergraduate student, and (3) owned a mobile phone. Participants were excluded if; (1) they were currently, or had ever, taken medication for a heart condition or (2) had any medical conditions that may have affected their participation in PA. From the 325 enrolled participants, a total of 289 participants from 57 universities were eligible to participate ( 73) see .Figure n = 2); maximum = 9 (n = 3); mode = 6 (n = 82)) and 25 participants stated ‘Don’t know.’Text messages were distributed to participants using an online text messaging service which enabled messages to be scheduled and sent automatically. All intervention conditions received a total of six messages that were sent on various days  and at various times  throughout the two-week intervention period. Regardless of the condition participants were allocated, the timing of receiving a message was the same for each condition. Message content was based on previous attempts to change attitude towards PA . Examples of a messages sent to the control condition include ‘Current guidelines suggest adults should perform physical activity at least 5 days per week for 30 minutes’ and ‘Physical activity is defined as any bodily movement produced by skeletal muscles that require energy expenditure.’Please note that we are defining physical activity as those moderate to vigorous exercise activities such as jogging, running, and cycling. We also include sports within this definition  and anaerobic exercises , but not light exercises . We are referring to such activities being performed in bouts of at least 30 minutes on at least 5 days of the week over the next 2 weeks.Full measures are provided in the supplementary file, but examples are provided below.To ensure the definition of PA was understood and consistent, participants were provided with the following description at each assessment time point;Psychological constructs. Attitude, intention, and goal priority were measured at each of the three time-points. Five items measured attitude  and three items measured intention . Similar to measures used by Conner et al. . Subjective norm and perceived behavioral control were also measured at T0 using three  and four items , respectively. Assessments of TPB items  followed standard procedures .Data were analyzed in IBM SPSS (version 26). When necessary, items were reverse scored, meaning lower scores represented negative perceptions and higher scores represented positive perceptions of PA. Scores for each of the scale items were summed and averaged, giving one score per construct. Responses to the three PA items were standardized, before being summed and averaged into a single z-score.F = 1.18; Wilks’ Λ = .91, p = .25; χ2 = 1.68, p = .64. This indication the randomization was successful.To check adequate randomization between intervention conditions at baseline (T0), a MANOVA was conducted with age, attitude, subjective norm, perceived behavioral control, intention, goal priority and PA at T0 as the dependent variables and condition  as the independent variable. There were no significant differences between conditions, F = 1.8; Wilks’ Λ = .95, p = .07; 2 = .72, p = .59), condition  = 5.21, p = .15), those receiving attitude messages (yes vs. no)  = .59, p = .44), and those receiving goal priority messages (yes vs. no)  = .28, p = .59). Additionally, patterns of missing data were analyzed and were found to be missing at random (p = .17 for Little’s MCAR test). Consequently, multiple imputation was conducted on all missing values using SPSS. Five new datasets were created using regression models including relevant baseline and post-intervention variables. Analyses were computed separately on each of the five imputed datasets. Similarities were apparent on each of the five analyses and generated values were within expected ranges. Rubin’s rules were then used to combine F, p and η2 values from each of the datasets. These again represented similarities with each of the individual datasets and so results are presented from the first imputation.From the 289 participants completing T0 assessments, 179 participants responded at T1 (61.94%), 169 at T2 (58.48%), and 135 participants completed all three assessments (46.71%). To check whether there were differences in demographics, psychological constructs, and PA at T0 between those completing all three assessments and those not, a MANOVA was conducted with T0 age, attitude, subjective norm, perceived behavioral control, intention, goal priority, and PA as the dependent variables and status of participation (completers and non-completers) as the independent variables. There were no significant differences between study participants who completed or did not complete all time points, Impact of attitude and goal priority messages. To examine the impact of the messages on the psychological variables and PA, a 2 (attitude: yes vs. no) by 2  by 2  mixed MANCOVA was conducted with attitude, goal priority, intention, and PA assessed immediately post-intervention (T1) and four weeks post-intervention (T2) as the (repeated-measures) dependent variables and T0 attitude, goal priority, intention, PA, age, and gender as covariates. Results showed a significant main effect for attitude messages  = 5.76, p = .001, η2 = .07). Specifically, attitude messages had a significant main effect on attitude  = 4.12, p = .04, η2 = .01), intention  = 11.54, p = .001, η2 = .04), and PA  = 17.06, p = .001, η2 = .05) (hypothesis 1). Marginal means showed participants receiving attitude messages had more positive attitudes  and intentions , plus greater PA  than those that did not receive attitude messages. Goal priority messages had no main effect on the psychological constructs and PA  = 1.85, p = .11, η2 = .02) (hypothesis 3) and there were no interactions between messages  = 0.53, p = .70, η2 = .00) (hypothesis 4). Pooled imputed means of study variables by condition can be seen in Mediation analyses. Mediation was undertaken to establish whether changes in attitude and intention at T1 mediated the effects of attitude messages on PA at T2. The serial multiple mediator model (model 6) within the SPSS macro PROCESS was used to examine the causal chain linking the mediators , T1 intention (a2) and T2 PA (c). T1 attitude significantly predicted T1 intention (d21) and T1 intention significantly predicted T2 PA (b2). Attitude messages did not significantly predict T2 PA when controlling for T1 attitude and T1 intention (b1). A statistical diagram of the serial multiple mediator model is shown in Results showed attitude messages significantly predicted T1 attitude . The indirect effects of both intention  and attitude and intention  were significantly positive as the 95% bias-corrected bootstrap CI did not straddle zero. Thus, the impact of attitude messages was mediated by the intention (indirect effect 2) and the attitude and intention (indirect effect 3) paths (hypothesis 2). No indirect effect was stronger than any other.The mediation analyses showed the indirect effect of attitude to be nonsignificant as the 95% bias-corrected bootstrap CI straddled zero (The purpose of the study was to examine the effectiveness of a SMS intervention including attitude messages and goal priority messages targeting students’ participation in PA.In line with hypothesis 1, attitude messages had a significant influence on attitude, intention, and PA and in accordance with hypothesis 2, the effects of the messages on PA were mediated by attitude and intention. Although these effects were small, changes in the psychological constructs are not surprising given participants were students undergoing significant lifestyle transitions and adapting to university life. Indeed, this transitional period represents an ideal opportunity for health interventions to intervene as students’ perceptions towards behaviors are yet to be formed and are more amendable to change (Allom et al., Contrary to hypotheses 3–5, the study did not change goal priority and therefore could not test the effects on PA. There are a number of potential explanations for the lack of success for goal priority manipulations. It has been suggested that interventions adopting the text messaging delivery mode are sometimes less effective than other modalities (Fjeldsoe, Neuhaus, Winkler, & Eakin, There are a number of strengths attached to the study. First, the intervention adopted health psychological theory and sought to address both motivation and intention translation. Due to the importance of adopting such theory and recent attention afforded to bridge the intention-behavior gap, the study was thus timely and important. Second, the study utilized a simple, yet novel implemental strategy that has received little attention to date. Third, the intervention was undertaken using a relevant and cost-effective delivery mode that was able to reach a considerable number of participants. Fourth, the intervention targeted an important health behavior within a population where declines are often seen (Bray & Kwan, Despite these strengths, the study was not without limitations. First, although a significant number of universities were targeted for recruitment, the response rate for participation was low. Second, the study had low rates of retention throughout each assessment timepoint. Third, despite assessing SMS delivery, we could not determine whether messages had been read. Fourth, a relatively short follow-up period was used, and changes may not have been maintained over time. Indeed, it has been recently acknowledged that initial behavior change is not synonymous with behavior maintenance (Kwasnicka, Dombrowski, White, & Sniehotta, There are a number of recommendations from the study. First, research promoting PA could adopt similar text messages to the attitude manipulations used here. Second, research is needed into identifying the most effective ways to influence goal priority (Conner et al., The study examined the effectiveness of attitude and goal priority SMS in changing key psychological mechanisms and PA. Attitude messages successfully influenced attitude, intention and behavior, and changes in behavior were mediated by changes in attitude and intention, with attitude influencing intention. The study therefore supports the TPB’s causal mechanisms through which interventions exert influence on behavior and suggests attitude to be a prominent driver of intention and subsequent PA behavior change. The study did not manage to manipulate goal priority. Future research should make use of the SMS delivery method in addressing motivational and implemental issues towards PA whilst also considering different delivery characteristics influencing its effectiveness.Click here for additional data file.


A CV event was experienced by 208 participants (23.1%), 68.3% of them were male (p<.001). High nighttime ambulatory PP predicted independently CV mortality  and all‐cause mortality in the whole population . In males, both 24‐h PP and nighttime PP associated with CV mortality and all‐cause mortality . Accordingly, nighttime PP; HR for CV mortality 3.13; CI 95% 1.14–8.56, p=.026, and for all‐cause mortality HR 2.26; CI 95% 1.29–3.96, p=.004. Cox regression analyses were adjusted by sex, CV risk factors, and appropriate ambulatory mean systolic BP. In our study, high ambulatory nighttime PP was detected as a long‐term risk factor for CV and all‐cause mortality in middle‐aged individuals.Office pulse pressure (PP) is a predictor for cardiovascular (CV) events and mortality. Our aim was to evaluate ambulatory PP as a long‐term risk factor in a random cohort of middle‐aged participants. The Opera study took place in years 1991–1993, with a 24‐h ambulatory blood pressure measurement (ABPM) performed to 900 participants. The end‐points were non‐fatal and fatal CV events, and deaths of all‐causes. Follow‐up period, until the first event or until the end of the year 2014, was 21.1 years (mean). Of 900 participants, 22.6% died (29.6% of men/15.6% of women,  PP increases with ageing, as SBP increases, and DBP decreases.There is evidence that ambulatory PP could be an even better method in predicting the risk of CV events and mortality than office PP,In the present study, our aim was to investigate ambulatory PP  as a predictor for long‐term cardiovascular events and all‐cause mortality in a middle‐aged population as a whole, and also separately in both sexes, because sex differences have been reported earlier.22.1This study is part of the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) project, a prospective, population‐based cohort study designed to evaluate the risk factors of atherosclerotic cardiovascular diseases. The details have been published earlier.2.2The participants of the study underwent a clinical examination, including height and weight measurements. A questionnaire covering the past medical history, medication use, alcohol consumption, and smoking habits was completed by two trained nurses. The laboratory tests, including a 2‐h oral glucose tolerance test, were obtained after an overnight fast, and analyzed in the Central Laboratory of the Oulu University Hospital.2.3The office BP was measured by a specially trained registered nurse, using an appropriately fitted cuff size and automatic oscillometric device ABPM was recorded by a noninvasive fully automatic SpaceLabs90207 oscillometric unit . The measurements were taken every 15 min from 04:00 AM to 12:00 PM and every 20 min between 12:00 PM and 04:00 AM. The British Hypertension Society and the US Association for the Advancement of Medical Instrumentation have previously confirmed the accuracy and reproducibility of the BP readings acquired with this device. The proper positioning of the cuff was ensured in each individual by means of the similarity (difference <5 mmHg) between four SpaceLabs BP measurements and four auscultatory readings using a Y‐connector and the patients were instructed to relax their arm during the measurement. Values were automatically excluded from the analysis if systolic BP (SBP) was less than 70 or more than 250 mmHg, diastolic BP (DBP) less than 40 or more than 150 mmHg, and heart rate less than 40 or more than 150 beats per minute. Less than 3% of the BP readings were rejected as artifacts based on these criteria.2.4Follow‐up time was defined as the time from the date of the baseline examination to the first end‐point event (CV event or death), or, if event free, until December 31, 2014. The mean follow‐up time was 21.1 years .The primary end‐point was CV event—a major coronary heart disease (CHD) event or stroke, non‐fatal or fatal, whichever occurred first. The secondary end‐point was death of all‐causes. Information on events leading to hospitalization was obtained from the Care register for health care of the Finnish institute for health and welfare. Data on fatal outcome and causes of death were obtained from death certificates from the Archive of death certificates of Statistics Finland. Each study participant was identified and followed with a personal social security number. The diagnoses were classified according to the International Classification of Diseases, Ninth Revision (ICD‐9) before 1994 and the Tenth Revision (ICD‐10) thereafter. CHD was based on the following diagnosis: I20, I21, I22 (ICD‐10) / 410, 4110 (ICD‐9) as the main diagnosis, and I21, I22 (ICD‐10) / 410 (ICD‐9) as a first or second side diagnosis or third diagnosis (ICD‐9 only), or coronary artery bypass grafting, or coronary angioplasty. CHD as a cause of death included I20–I25, I46, R96, R98 (ICD‐10) / 410–414, 798 (not 7980A) (ICD‐9) as the underlying or immediate cause of death and I21 or I22 (ICD‐10) / 410 (ICD‐9) as the first to the third contributing cause of death. Stroke as an end‐point included I61, I63 (not I63.6), I64 (ICD‐10), and 431, 4330A, 4331A, 4339A, 4340A, 4341A, 4349A, 436 (ICD‐9) as the main diagnosis or as a side diagnosis, or as a cause of immediate or contributing cause of death.2.5t test or with Mann–Whitney's test, when appropriate. Pearson's Chi‐square test was used to test differences between categorical variables. Log transformation was made for fasting insulin and triglycerides. Hazard curves were estimated by using the Kaplan–Meier method and tested by log‐rank test. We used Cox regression analysis to estimate the pulse pressure tertiles as a predictor for cardiovascular events and all‐cause mortality in multivariate models adjusted by variables with significance in univariate analyses. 24‐h PP range was 32–44 mmHg in the lowest tertile (T1), 45–51 mmHg in the middle (T2), and 52–89 mmHg in the highest tertile (T3). Daytime PP was 24–45 mmHg in T1, 46–52 mmHg in T2, and 53–93 mmHg in T3. Nighttime PP range was 24–42 mmHg (T1), 43–48 mmHg (T2), and 49–88 mmHg (T3). All of the fully‐adjusted regression analyses in this study also included the corresponding ambulatory mean SBP as a cofactor: either 24‐h SBP for models assessing 24‐h PP, or daytime SBP for models with daytime PP, or nighttime SBP for models evaluating nighttime PP. p values <.05 were considered as statistically significant.Data analyses were performed with IBM SPSS Statistics for Windows . Data are expressed as mean ± standard deviation for continuous variables, or median with 25th and 75th quartiles for skewed variables. Continuous variables were tested for difference between the groups with Student's 3Originally 1045 participants attended the OPERA study. All those  who underwent a qualified 24‐h ABPM recording in the baseline study were included in the analyses. Only three recordings were disqualified on the basis of missing nighttime readings.The characteristics of the study population at baseline are presented in Table In laboratory measures, fasting glucose, insulin, and triglyceride levels were higher, and HDL cholesterol was lower among those who died, but there were no differences in total cholesterol or LDL levels.During the follow‐up time of 21 years, 208 (23.1%) CV events  occurred, and the majority  of them in the highest 24‐h PP tertile. Men experienced 68.3 % of the CV events. Total number of deaths was 203 (22.6% of the study population). All‐cause mortality was the highest in the highest 24‐h PP tertile (30.5 % vs the lowest tertile 16.2%). All‐cause mortality among men (29.6%) was almost two‐fold compared with women (15.6%). There were 68  CV deaths, and 75% of those occurred in men.Regarding CV events, those who experienced a CV event in comparison with those who were event‐free, the differences in above mentioned variables were quite similar Table . HoweverThe baseline population was divided into tertiles according to 24‐h mean PP  was added to Cox regression models, the statistical significance of high PP as a risk factor for CV events was lost in the whole study population . When the analyses were performed by sex, PP did not appear as a significant factor either. The result of the analyses is available as a supplemental material.3.3Figures 4In our 21‐year follow‐up study higher nighttime PP in all participants, and higher 24‐h PP in men were associated with the risk of CV and all‐cause mortality in a random cohort of middle‐aged population. The latter associations were evident after extensive adjustments including mean systolic ambulatory BP measurements.independent association between nighttime PP and CV as well as all‐cause mortality was detected.The increasing of PP is a phenomenon usually seen with aging as SBP rises with age, while DBP begins to gradually decline after a plateau phase between 50 and 60 years.Recently, Tadic and coworkersIn the studies by Khattar and StaessenThe reason why nighttime PP is an independent predictor for total mortality remains unknown. Several morbidities, such as hypertension and diabetes, may potentially increase PP and mortality. In our study, both hypertension and diabetes were associated with increased PP but controlling these diseases in the multivariate analysis did not change the results. In the present study the day‐ and nighttimes were fixed to certain hours and no data about participants sleeping habits were acquired. Another major concern is the lacking data on sleep apnoea, as sleep apnoea may affect the nighttime BP values.In conclusion, nighttime ambulatory pulse pressure showed a significant and independent association with CV and all‐cause mortality in a random cohort of middle‐aged normotensive and hypertensive participants in the long‐term follow‐up. Also 24‐h PP was detected as a prognostic factor in male participants. Wide PP, especially nighttime PP, may identify individuals with an increased risk for mortality, and therefore ambulatory BPM should be in use, together with office BP measurements.Supporting InformationClick here for additional data file.


In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger signals and pathogen infection. In manipulating the cleavage of gasdermins (GSDMs), researchers have found that GSDM proteins serve as the real executors and the deterministic players in fate decisions of pyroptotic cells. Whether inflammatory characteristics induced by pyroptosis could cause damage the host or improve immune activity is largely dependent on the context, timing, and response degree. Here, we systematically review current points involved in regulatory mechanisms and the multidimensional roles of pyroptosis in several metabolic diseases and the tumor microenvironment. Targeting pyroptosis may reveal potential therapeutic avenues. Gasdermins are executors of pyroptosis, which cause inflammatory cell death, accompanied with various inflammatory mediators.Pyroptosis plays a dual role in tumor microenvironment, including anti‐tumor and pro‐tumor effects.Pyroptosis can be used as a new target to fight against the tumor. AKTprotein kinase BANSDauditory neuropath spectrum disorderASCapoptosis‐associated speck‐like protein containing a CARDATPadenosine triphosphateCARchimeric antigen receptorCatGCathepsin GCCAextrahepatic cholangiocarcinomacGAScyclic GMP‐AMP synthaseCRCcolorectal cancerCRScytokine‐release syndromeCTC‐terminalDACdecitabineDAGdiacylglycerolDAMPsdamage‐associated molecular patternsDCsdendritic cellsDHAdocosahexaenoic acidDNdiabetic nephropathydsDNAdouble‐stranded DNAECsendothelial cellsELANEneutrophil elastaseERendoplasmic reticulumERKextracellular signal‐regulated kinaseESCRTendosomal sorting complexes required for transportGGAgeranylgeranoic acidGSDMDgasdemin DGSDMEgasdemin EGSDMsgsderminsGZMAgranzyme AGZMBgranzyme BHcyHomocysteineHER2human epidermal growth factor receptor 2HFDhigh‐fat dietHGhigh‐glucoseHMGB1high‐mobility group box 1HUVECshuman umbilical vein endothelial cellsICDinflammatory cell deathICIimmune checkpoint inhibitorIFN‐γinterferon‐gammaIRF2IFN regulatory transcription factor‐2JNKc‐Jun N‐terminal kinaseLOFloss‐of‐functionLPClysophosphatidylcholineLPSlipopolysaccharideLUADlung adenocarcinomaMDMsmonocyte‐derived macrophagesMLZEmelanoma‐derived leucine zipper extranuclear factormtDNAmitochondrial DNANaBsodium butyrateNAFLDnon‐alcoholic fatty liver diseaseNFATc1nuclear factor of activated T‑cells, cytoplasmic 1NF‐κBnuclear factor kappa BNKnatural killerNTN‐terminal domainOAoleic acidox‐LDLoxidized low‐density lipoproteinP2 × 7RP2 × 7 receptorPApalmitic acidPD‐L1programmed death‐ligand 1PGE2prostaglandin E2PRRspattern recognition receptorsRIPK1receptor‐interacting serine/threonine protein kinase 1ROSreactive oxygen speciesS1Psphingosine‐1‐phosphateS1PR2S1P receptor 2SGNsspiral ganglion neuronsSIRT1Sirtuin1SMsphingomyelinSMSssphingomyelin synthasesSScsystemic sclerosisSTAT3signal transducer and activator of transcription 3T1D, T2DType 1 and 2 diabetesT3SStype‐3 secretion systemTcdBClostridium difficile (C. difficile) toxin BTET2tet methylcytosine dioxygenaseTILstumor‐infiltrating lymphocytesTLR4toll‐like receptor 4TMAOtrimethylamine N‐oxideTMEtumor microenvironmentTNF‐αtumor necrosis factor alphaUQCRC1ubiquinol cytochrome c reductase core protein IVSMCsvascular smooth muscle cellsYAPyes‐associated protein1Shigella flexneri, a type of gram‐negative bacterial pathogen.In 1992, the initial phenomenon of pyroptosis was first discovered; this is a novel type of suicide in macrophages infected by 2Cell death is a complex and important regulatory network, which involves the immune system.2.12.1.1+/Ca2+ efflux, mitochondria and lysosome‐related damages and etc.Bacillus anthracis lethal toxin, Toxoplasma gondii, which activates assembly of the NLRP1 inflammasome and induces pyroptosis.Clostridium difficile (C. difficile) toxin B (TcdB), Clostridium botulinum ADP‐ribosylating C3 toxin, and Vibrio parahaemolyticus VopS, some specific mutations like S208A and S242R, as well as the Yersinia pestis GTPase‐activating protein (YopE) and cysteine protease (YopT) can all activate the pyrin inflammasome.The inflammasomes are large multiprotein complexes which usually consist of pattern recognition receptors (PRRs), inflammatory caspases (caspase‐1) and sometimes an adaptor protein, like apoptosis‐associated speck‐like protein containing a CARD (ASC).2.1.2+ efflux, and induce pyroptosis.In contrast, the non‐canonical inflammasome pathway is independent of inflammasomes and directly activated by bacterial lipopolysaccharide (LPS) to cleave precursors of human caspase‐4, caspase‐5, and mouse caspase‐11.2.1.3Yersinia can activate the RIPK1/caspase‐8‐dependent GSDMD cleavage, resulting in pyroptotic cell death.In addition to inflammatory caspases , apoptosis‐related caspases  are also involved in pyroptosis. Caspase‐3 can trigger gasdemin E (GSDME)‐dependent pyroptosis with tumor necrosis factor alpha (TNF‐α) treatment, chemotherapy drugs, and the high‐expression of GSDME.2.1.4Moreover, GSDMs are cleaved beyond different caspases. Granzyme family members including GZMA and GZMB are also proved to activate GSDM B (GSDMB) and GSDME, respectively.2.2GSDMA), GSDM B (GSDMB), GSDMC, GSDMD, GSDME , and DFNB59 . As for mice, they have three Gsdma genes , four Gsdmc genes , one Gsdmd gene, and one Gsdme gene; however, they lack a Gsdmb gene. Their sequences share about 45% homology, with the exception of DFNB59. GSMDs A‐E all have two domains, an NT and a C‐terminal (CT) domain, which are capable of binding with each other by a flexible linker, while DFNB59 only possesses the NT domain.GSDMs have been identified as the executors of pyroptosis, which are protein families encoded by six paralogous genes in humans: GSDM A  is strongly linked with asthma susceptibility and intermediate phenotypes in asthma.GSDMA variant (rs3894194) also modulates systemic sclerosis (SSc) susceptibility in monocyte‐derived macrophages (MDMs).The molecular mechanism of GSDMA is not well known until now. It may play roles in stress responses due to its expression in the suprabasal layer, differentiating cells and the epidermis outside the tumor.Gsdma genes in mice, mutations of Gsdma3 are hotspots, which not only cause alopecia during the formation of hair follicle‐associated sebaceous glands, as well as the transition from catagen to telogen at the final period of hair follicle morphogenesis,Among the three 2.2.2Gsdmb gene has been identified in mice. Human GSDMB has six isoforms . There are differences in the length and sequence of the linkers between the CT and NT domains of isoforms 1–4 and isoform 6, whereas there is no NT domain in isoform 5.GSDMB is found on human chromosome 17q21.1, while no Highly expressed GSDMB is also linked to tumor aggressiveness in several types of cancers, such as gastric, hepatic, colon, and cervical cancer,244 site, leading to pyroptosis in GSDMB‐positive cells.Interferon‐gamma (IFN‐γ) upregulates the expression of GSDMB, lymphocyte‐derived GZMA cleave GSDMB between the CT and NT linkers at the LysGSDMB (rs9303277) in CD4+ T cells is an SSc‐associated susceptibility locus.Genome‐wide sequencing and functional genes indicate that single nucleotide polymorphisms of GSDMB are related to the increased susceptibility of ulcerative colitis and Crohn's disease, as well as asthma exacerbations and antiviral pathways.2.2.3GSDMC in mice is composed of four members, Gsdmc 1, Gsdmc 2, Gsdmc 3, and Gsdmc 4, which are clustered on mouse chromosome 15 (15D1).GSDMC is originally isolated from melanoma cells, so it is known as a melanoma‐derived leucine zipper extranuclear factor (MLZE), whose gene is located on human chromosome 8q24.21. The homolog of Mycoplasma hyopneumoniae (M. hyo) Ab variations in pigs,Ultraviolet irradiation can induce the expression of GSDMC mediated by the calcium/calcineurin/nuclear factor of activated T‐cells, the cytoplasmic 1 (NFATc1) pathway and the extracellular signal‐regulated kinase (ERK)/c‐Jun N‐terminal kinase (JNK)/matrix metalloproteinase 1 pathway in human skin keratinocytes.GSDMC. Experiments in vivo have shown that GSDMC, along with nuclear PD‐L1 and caspase‐8, is required in the tumor necrosis induced by TNF‐α which are derived from macrophages.GSDMC variants at the chromosome 8q24 locus also modulate genetic risk to several cancers, including prostate cancer.GSDMC functions as an oncogene, mediating varieties of progressive processes involving types of tumors. GSDMC may serve as a significant therapeutic target in CRC patients as it promotes tumor cell proliferation in CRC by reducing activation of the transforming growth factor β receptor type II.2.2.4GSDMD is located on human chromosome 8q24.3, while Gsdmd is found on mouse chromosome 15D3‐E1. GSDMD is first identified as the efficient substrate of inflammatory caspases among the GSDM family members.Although GSDMD is the first effector protein to be found in pyroptosis and has been studied the most frequently, the perspicuous regulatory mechanism is not well known. IFN regulatory transcription factor‐2 (IRF2) is found to transcriptionally regulate GSDMD expression.GSDMD is found to be cleaved by inflammasome‐activated caspase‐1 and LPS‐activated caspase‐4/5/11. However, the way in which GSDMD is recognized specifically by these caspases is not clear. Until recently, crystal structural analysis of caspase‐1‐GSDMD‐C complex and caspase‐4/11‐GSDMD‐C complex has revealed the specific recognition mode.The pyroptosis pathway mediated by GSDMD can also be limited in different ways. For example, disulfiram is reported to specifically inhibit pore formation by modification at the Cys191/Cys192 sites of GSDMD in human/mouse, but this does not disturb the processing of IL‐1β and GSDMD, thereby blocking IL‐1β release and GSDMD‐mediated pyroptosis.2.2.5GSDME, also known as DFNA5, is located on human chromosome 7p15.3, while Gsdme, also known as Dfna5, is found on mouse chromosome 6B2.3. GSDME mutation was first identified to cause an autosomal dominant hearing impairment.2.2.6DFNB59, also known as Pejvakin (PJVK), is located on human chromosome 2q31.2 and comprises seven exons,Dfnb59, also known as Pjvk is found on mouse chromosome 2C3. PJVK encoded by DFNB59, is a protein (352 residues) which is distantly related to other GSDM protein family members.DFNB59, the same as its paralog DFNA5, is also reported to be associated with progressive hearing loss. DFNB59 is first identified as the causal gene of autosomal recessive deafness, which also plays key role during the signal transmit of auditory nerve.DFNB59 are linked with non‐syndromic hearing loss.3Pyroptosis is accompanied by inflammasome activation, GSDM and caspase cleavage, and cytokine releases, leading to inflammatory death in cells and expending inflammation in multi‐tissues; all of these processes have impacts on a variety of metabolic disorders in different organs, including the liver, cardiovascular system, allergic and autoimmune diseases, diabetes, obesity, and others. In the case of the most studied NLRP3 inflammasome, which is a critical sensor of nutrient overload, this can be activated by various metabolic danger signals, such as uric acid crystals in gout,−/−Rag2 mice.+ memory T cells, which is responsible for rapid IFN‐γ recall responsesIn response to infective pathogens and dangerous signaling molecules, profound metabolic fluctuation normally appears in immune cells.3.1in vitro and in vivo.Sulfatide is a type of 3‐O‐sulfogalactosylceramide, whose production is dependent on cerebroside sulfotransferase and ceramide galactosyltransferase. As this has a multifunctional role in diverse biological fields, abnormal expression or metabolic changes to sulfatide correlate with many different types of diseases including cancer.3.2Pyroptosis is activated by various pathological conditions, which are known risk factors of atherosclerosis, including oxidative stress, hyperglycemia, dyslipidemia, and inflammation.It is known that pyroptotic cell numbers decrease following pretreatment with colchicine and cholesterol crystals in HUVECs, and the limitation to cholesterol crystals by colchicine can function through AMP‐dependent kinase (AMPK)/ Sirtuin1 (SIRT1) signaling.Apolipoprotein‐M and sphingosine‐1‐phosphate (S1P) can restrain TNF‐α‐induced pyroptosis by binding to S1P receptor 2 (S1PR2), thereby attenuating atherosclerosis.3.3Hyperglycemia is the obvious feature of diabetes, which is a complex metabolic syndrome. Hyperglycemia induces pyroptosis in diabetic cardiomyopathy by upregulating miR‐30d.HG insult causes damage to adipose function. Metformin and resveratrol could suppress dynamin‐related protein 1 activity and prevent activation of the NLRP3 inflammasome by limiting ER stress to reverse the damage process and protect mitochondrial integrity.3.4Nlrp3 under HFD.ob/ob mice and obese humans, as active caspase‐1 is detected in the cytoplasm of some hypertrophic adipocytes. Also, adipose tissue inflammation is linked to the death of hypertrophic adipocytes.Obesity is strongly associated with low‐grade inflammation in whole bodies and adipose tissue, with adipocyte death in both mice and human subjects reported to be at a 30‐fold increased level. This cell death is partly due to the pyroptosis of adipocytes caused by macrophages.3.5Non‐esterified fatty acids are reported to induce pyroptosis and inflammation via the NLRP3 inflammasome and TLR4/NF‐κB pathway, which can be alleviated by N‐acetylcysteine.4Pyroptosis is a double‐edged sword and plays an important role both in tumorigenesis and antitumor immunity at all stages of tumor development, which shows tumor promoting or tumor suppressive effects in this context, mainly relying on types of tumor, host inflammatory status and immunity, and the involved effector molecules.4.14.1.1The inflammatory state of the TME has implications for the response to immune checkpoint inhibitor (ICI) therapy. By triggering pyroptosis, a form of ICD, converting these immune “cold” tumors to “hot” tumors may alter the TME and the influx of tumor‐infiltrating lymphocytes (TILs). Pyroptotic immune response involves a long process which goes from the release of damage‐associated molecular patterns (DAMPs)  and inflammatory cytokines, directly modulating the innate immune response, to enhancing the recruitment of adaptive immune cells along with increased antigen presentation and TLR activation, leading to broader immune activation.+ T cell responses, increase Th1 CD4+ T cell numbers, and inhibit the differentiation of immunosuppressive T regulatory cells.+ T cell‐mediated tumor regression in models of adenocarcinoma, melanoma, and sarcoma.Which features of pyroptotic tumor cells contribute to activating antitumor immunity is not currently clear. Inflammatory cytokines and immunostimulatory alarmins released during pyroptosis, including IL‐1β, IL‐18, ATP, and HMGB1, could be prime suspects. During pyroptosis, IL‐1β is activated and released from the GSDM pores to exert an influence on the TME. IL‐1β signaling could induce DC maturation and monocyte differentiation into DCs and inflammatory macrophages. Then, antigens will be represented to T cells to elicit immune killing. In addition, IL‐1β can directly act on cells in the lymphoid compartment to drive antigen‐specific cytotoxic CD8IL‐18 can strongly induce γ‐IFN when it combines with IL‐12 or IL‐15, which both upregulate the IL‐18 receptor levels. Thus, IL‐18 exerts an important effect on natural killer (NK) cell recruitment and activation, as well as Th‐1 polarization.+ T cell differentiation and decreasing regulatory T cell differentiation.In addition to IL‐1β and IL‐18, other types of cytokines such as IL‐6, are also released from pyroptotic cells. Accumulating evidence shows that IL6 has a profound impact on the adaptive immune response. For instance, IL‐6 signaling can increase T cell immune response to an actively responsive state from a suppressive state, thereby effectively fighting against tumors. Also, IL‐6 is also important for enhancing T cell trafficking to lymph nodes and the tumor sites. Then, they have chances to be activated and further execute their cytotoxic effector functions.+ T‐cell activation and IFN‐γ production.As a type of alarmins, extracellular ATP reinforces pyroptosis by triggering of purinergic P2 × 7R signaling in infiltrating immune cells or cancer cells.4.1.2+ T cells, NK cells, granzymes, and perforin. On the other hand, given that immunotherapeutic strategies often aim to improve T cell responses to cancer, the overexpression of GSDME in cancer cells significantly increases the number and function of infiltrating NK cells and antigen‐specific CD8+ T lymphocytes inside tumors, as well as the expression of effective molecules including GZMB, perforin, IFN‐γ, and TNF‐α in TILs, together with the phagocytosis of tumor‐associated macrophages (TAMs).Pyroptosis is essential for lymphocyte cytotoxicity against tumor cells, and pyroptotic tumor cells induce the TME toward an immunostimulatory state. To some extent, a positive feedback loop is formed in anticancer immunity as for the promotion between pyroptosis and cytotoxic lymphocytes. In the case of GSDME, a tumor suppressor which activates pyroptosis, this enhances antitumor immunity.4.1.3As for GSDMC, it has been shown that the expression of GSDMC under hypoxia is transcriptionally enhanced by p‐STAT3 and is physically correlated with PD‐L1 and its nuclear translocation. Then, after treatment with TNF‐α derived from macrophages, GSDMC is specifically cleaved by caspase‐8, liberating the NT domain to form pores on the plasma membrane, thereby inducing pyroptosis. The high expression of GSDMCs is also associated with poor patient survival.4.1.4244 site, resulting in pyroptotic cell death in GSDMB‐positive cells killed by NK cells and CTLs.In cellular immunity, CTLs and NK cells kill target cells via the delivery of serine protease granzymes by perforin. Notably, lymphocyte‐derived GZMA could cleave GSDMB between CT and NT linker at LysBRAF V600E/K‐mutant melanoma. However, the efficacy of the BRAFi + MEKi approach is correlated with immune responses in the TME. Given that pyroptosis could elicit antitumor immunity in the tumor immune microenvironment, the involvement of pyroptosis in ICI treatment is being investigated in new researches. They have found that the treatment of BRAF‐mutant melanoma cells with BRAFi + MEKi inhibitors promotes the cleavage of GSDME and the release of HMGB1, all of which are markers of pyroptotic cell death. Interestingly, GSDME‐deficient melanoma represents defective HMGB1 release, the reduced infiltration of tumor‐associated T cells and activated DCs in response to BRAFi + MEKi treatment, and the more frequent tumor regrowth after drug removal. Importantly, BRAFi + MEKi‐resistant diseases show the decreased infiltration of intra‐tumoral T cells and the lack of pyroptosis‐related markers but still retain sensitivity to pyroptosis‐induced chemotherapy.KRAS‐, EGFR‐, or ALK‐driven lung cancer, upon treatment of diverse small‐molecule inhibitors, robust pyroptotic cell death, associated with GSDME cleavage, and the mitochondrial intrinsic apoptotic pathway are elicited and spread in lung cancer cells uniformly, making concession under genotype‐specific regimens.Tumor cells undergoing pyroptosis release IL‐1β, IL‐18, and various DAMPs, which are signals used to activate and recruit DCs or macrophages to phagocytose the pyroptotic cells and promote their maturation. Then, mature DCs present tumoral antigens to tumor‐specific CTLs, killing pyroptotic tumor cells.4.1.5+, CD8+, NK cell, and M1 macrophage populations, while decreasing regulatory T cell, M2 macrophage, monocyte, neutrophil, and myeloid‐derived suppressor cell (MDSC) populations. As a new application, the system uncovers the antitumor immune potential of pyroptosis, suggesting that a GSDM agonist may improve the efficacy of cancer immunotherapy.As tumor treatment is obstructive and complex, the effect of immunotherapy is gaining increasing prominence. However, the immune checkpoint blockade often responds ineffectively to some tumor treatments as for the low inflammatory response among the TME. Thus, the development of new approaches to boost antitumor immunity is critical. Recently, the Phe‐BF3 desilylation bio‐orthogonal system applied efficiently has been shown to transport desilylation catalyzed by Phe‐BF3 with the NP‐GSDMA3‐mediated delivery into specific mammary tumor cells in mice. The novel technique leads to T cell‐dependent tumor progression along with increasing numbers and the function of CD4Pyroptosis also functions in patients with extrahepatic cholangiocarcinoma (CCA). Tumor‐cell‐derived microvesicles whose plasma membranes are infused with methotrexate could induce pyroptosis in CCA cells through a GSDME‐dependent pathway. Then, intracellular contents released from pyroptotic CCA cells activate patient‐derived macrophages to produce pro‐inflammatory cytokines, which attract the secondary accumulation of neutrophils to the tumor site. The procedure is relevant to the upregulation of uridine diphosphate glucose and complement C5, leading to degradation of the stromal barrier in the CCA TME. The approach has been proved to relieve biliary obstruction in nearly 25% of CCA patients.Another application of pyroptosis is that of a commonly used tumor‐targeting nanoliposome loaded with cisplatin, which is applied in drug delivery and administration. Combining decitabine (DAC) with chemotherapy nanodrugs to manage drugs to activate and upregulate the caspase‐3/GSDME signal, further triggers pyroptosis in tumor cells, therefore strengthening the immunological effect of chemotherapy with cisplatin in a mouse triple‐negative breast cancer model. Also, DAC can demethylate the GSDME gene in tumor cells with specific tumor‐bearing mice.The chimeric co‐stimulatory converting receptor is designed to disturb the PD‐1 pathway which enhances the activity of chimeric antigen receptor (CAR)‐NK cells to fight solid tumors. Then, the antitumor activity of NK92 cells was enhanced by the neo‐complex PD1‐NKG2D‐41BB receptor, which is mainly dependent on pyroptosis activation.4.2In certain contexts, ICD caused by pyroptosis may also be pro‐tumorigenic. This is consistent with the complicated roles of inflammation in both enhancing and inhibiting tumor growth, thus suggesting that the timing, levels, and components of pyroptosis induction need to be closely controlled. It is MDSCs which are substantial contributors to the immunosuppressive TME and are closely associated with tumor progression.+ and CD8+ T cells.The main alarmin, HMGB1, released by pyroptotic cells, could promote tumor cell survival, which largely suggests that HMGB1 drives the accumulation of MDSCs by inducing autophagy, thereby maintaining MDSC viability.Besides, IL‐18 exerts antitumor activity when it combines with other inflammatory cytokines, paradoxically, IL‐18 can promote Th2 responses and angiogenesis, which leads to increased migration and invasion in tumors in the absence of other cytokines.Moreover, TAMs also contribute to the immunosuppressive microenvironment, which display an upregulated NLRP3 inflammasome activity, thereby significantly promoting the expression of IL‐1β and thus aggravating inflammation and favoring the progression of CRC.5c and activation of apoptosome, augmenting apoptosis,Cell death is a complex regulatory net which decides cell fate. Among the forms of programed cell death, pyroptosis and necroptosis all are ICD, while apoptosis is non‐inflammatory. In some contexts, they all contribute to the homeostasis of the host by different molecular pathways. However, given that (1) caspase‐8 involves both the pyroptosis, necroptosis and apoptosis pathwaysMetabolic nutrients play a central role in monitoring the immune cell fate, and tumors, especially solid tumors, likely produce an immunosuppressive TME which is deprived of metabolic nutrients including glucose and free fatty acids; in contrast, this is rich in metabolic wastes, such as hypoxic and lactic acid.+ T cells, and the therapeutic effect has been shown in some solid tumors such as melanoma and lung cancer.+ T cells and other lymphocytes as well as myeloid cells to the surrounding tumor lesions in the TME.The success of immunotherapy is largely dependent on the high activity of intratumoral CD8However, ICIs, like CAR‐T cell therapy, have also been reported to induce cytokine‐release syndrome (CRS), which may counteract the effectiveness of CAR‐T cell therapy partly as a severe consequence of extensive pyroptosis. It is shown that CAR‐T cells could rapidly activate caspase‐3 in target cells through the release of GZMB. Then, the latter cleaves GSDME, causing extensive pyroptosis. Consequently, other pyroptotic factors are triggered and further activate the caspase‐1/GSDMD pathway in macrophages, which results in the increased release of cytokines and more serious CRS.Fortunately, the research has shown that nanodrugs potentially reduce the side effect of ICIs, as the application of nanoparticles could promote the more appropriate distribution of pyroptosis inducers in target cells other than the adjacent tissues. Thus, the new utilization of pyroptosis will improve therapeutic effects.Although the molecular features of GSDM family members, especially GSDMD, are gradually revealed in pyroptosis, the exact regulatory mechanisms of other GSDMs are not very clear. In addition, large inflammatory factors are found to be released from immune cells but not cancer cells, although they exert an important impact on the latter. Also, they have the opposite impact in different regions and evolving periods of TME. In summary, more in‐depth and innovative exploration into the roles of pyroptosis in metabolism and the TME are required in the future.Lutao Du, Chuanxin Wang, and Juan Li designed the manuscript. Tiantian Du, Jie Gao, and Peilong Li searched the literature and wrote the manuscript. Lutao Du, Chuanxin Wang, Juan Li, Jie Gao, and Peilong Li provided the funding. Xiaoyan Liu, Qiuchen Qi, and Yunshan Wang provided the conception, edited, and polished the manuscript. All authors read and approved the final manuscript.The authors declare that they have no conflict of interest.