Treatment of non-culprit lesions detected during primary PCI: long-term follow-up of a randomised clinical trial

Background

There are conflicting data regarding optimal treatment of non-culprit lesions detected during primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). We aimed to investigate whether ischaemia-driven early invasive treatment improves the long-term outcome and prevents major adverse cardiac events (MACE).

Methods

121 patients with at least one non-culprit lesion were randomised in a 2:1 manner, 80 were randomised to early fractional flow reserve (FFR)-guided PCI (invasive group), and 41 to medical treatment (conservative group). The primary endpoint was MACE at 3 years.

Results

Three-year follow-up was available in 119 patients (98.3 %). There was no significant difference in all-cause mortality between the invasive and conservative strategy, 4 patients (3.4 %) died, all in the invasive group (P = 0.29). Re-infarction occurred in 14 patients (11.8 %) in the invasive group versus none in the conservative group (p = 0.002). Re-PCI was performed in 7 patients (8.9 %) in the invasive group and in 13 patients (32.5 %) in the conservative group (P = 0.001). There was no difference in MACE between these two strategies (35.4 vs 35.0 %, p = 0.96).

Conclusions

In STEMI patients with MVD, early FFR-guided additional revascularisation of the non-culprit lesion did not reduce MACE at three-year follow-up compared with a more conservative strategy. The rate of MACE in the invasive group was predominantly driven by death and re-infarction, whereas in the conservative group the rate of MACE was only driven by repeat interventions.     

Systematic Testing of Literature Reported Genetic Variation Associated with Coronary Restenosis: Results of the GENDER Study

Background

Coronary restenosis after percutaneous coronary intervention still remains a significant problem, despite all medical advances. Unraveling the mechanisms leading to restenosis development remains challenging. Many studies have identified genetic markers associated with restenosis, but consistent replication of the reported markers is scarce. The aim of the current study was to analyze the joined effect of previously in literature reported candidate genes for restenosis in the GENetic DEterminants of Restenosis (GENDER) databank.

Methodology/Principal Findings

Candidate genes were selected using a MEDLINE search including the terms ‘genetic polymorphism’ and ‘coronary restenosis’. The final set included 36 genes. Subsequently, all single nucleotide polymorphisms (SNPs) in the genomic region of these genes were analyzed in GENDER using set-based analysis in PLINK. The GENDER databank contains genotypic data of 2,571,586 SNPs of 295 cases with restenosis and 571 matched controls. The set, including all 36 literature reported genes, was, indeed, significantly associated with restenosis, p = 0.024 in the GENDER study. Subsequent analyses of the individual genes demonstrated that the observed association of the complete set was determined by 6 of the 36 genes.

Conclusion

Despite overt inconsistencies in literature, with regard to individual candidate gene studies, this is the first study demonstrating that the joint effect of all these genes together, indeed, is associated with restenosis.     

Chromosomal abberations and sister-chromatid exhanges (SCEs) in patients undergoing long-term Imuran therapy

13 patients treated daily for an extended time with Imuran and prednisone and 4 patients treated in the samy way with Imuran only were cytogenetically analysed for the induction of structural chromosomal aberrations and SCEs. There was an increase in the number of aberrations and SCEs in nearly all patients analysed. However, we did not find any dose-dependent cumulative effect on chromosomal damgae, with the exception of 1 patient tested in a small group of 4 patients involved in a prospective cytogenetic study, who showed a significant time-dependent increase in the number of aberrations.     

Risk factors for mortality in end-stage kidney disease patients under online-hemodiafiltration: three-year follow-up study

The aim of this work was to evaluate the predictors of mortality in a group of end-stage kidney disease (ESRD) patients under dialysis, by performing a three-year follow-up study. From the 236 patients included in this study, 54 patients died during the three-year follow-up period. Our data showed that the risk of death was higher in patients presenting lower levels of mean cell hemoglobin concentration, transferrin, and albumin. Our study showed that poor nutritional status and an inflammatory-induced iron depleted erythropoiesis are important factors for mortality in these patients.     

The Absorb bioresorbable vascular scaffold in real-world practice: long-term follow-up of the AMC Single Centre Real World PCI Registry

Background

Bioresorbable scaffolds have been introduced to overcome the shortcomings of drug-eluting stents. Higher rates of device thrombosis, however, have been reported up to 3 years after implantation of the Absorb bioresorbable vascular scaffold (BVS). In the current article, we therefore report long-term clinical outcomes of the AMC Absorb Registry.

Methods and results

In the AMC Absorb Registry, all patients who underwent a percutaneous coronary intervention with Absorb BVS implantation between 30 August 2012 and 5 August 2013?at the Amsterdam University Medical Centre—Academic Medical Centre were included. The composite endpoint of this analysis was target-vessel failure (TVF). The median follow-up of the study cohort of the AMC Absorb Registry was 1534 days. At the time of the cross-sectional data sweep the clinical status at 4 years was known in 124 of 135 patients (91.9%). At long-term follow-up, the composite endpoint of TVF had occurred in 27 patients. The 4?year Kaplan-Meier estimate of TVF was 19.8%. At 4 years cardiac death had occurred in 4 patients (3.2%) and target-vessel myocardial infarction in 9 (6.9%) patients. Definite scaffold thrombosis occurred in 5 (3.8%) patients. We found 1 case of very late scaffold thrombosis that occurred at 911 days after device implantation in a patient who was not on dual anti-platelet therapy.

Conclusion

In a patient population reflecting routine clinical practice, we found that cases of TVF continued to accrue beyond 2 years after Absorb BVS implantation.

     

Monte Carlo study on the secondary cancer risk estimations for patients undergoing prostate radiotherapy: A humanoid phantom study

AimThe aim of this study was to estimate the secondary malignancy risk from the radiation in FFB prostate linac-based radiotherapy for different organs of the patient.BackgroundRadiation therapy is one of the main procedures of cancer treatment. However, the application the radiation may impose dose to organs of the patient which can be the cause of some malignancies.Materials and methodsMonte Carlo (MC) simulation was used to calculate radiation doses to patient organs in 18 MV linear accelerator (linac) based radiotherapy. A humanoid MC phantom was used to calculate the equivalent dose s for different organs and probability of secondary cancer, fatal and nonfatal risk, and other risks and parameters related to megavoltage radiation therapy. In out-of-field radiation calculation, it could be seen that neutrons imparted a higher dose to distant organs, and the dose to surrounding organs was mainly due to absorbed scattered photons and electron contamination.ResultsOur results showed that the bladder and skin with 54.89 × 10⁻³ mSv/Gy and 46.09 × 10⁻³ mSv/Gy, respectively, absorbed the highest equivalent dose s from photoneutrons, while a lower dose was absorbed by the lung at 3.42 × 10⁻³ mSv/Gy. The large intestine and bladder absorbed 55.00 × 10⁻³ mSv/Gy and 49.08 × 10⁻³, respectively, which were the highest equivalent dose s due to photons. The brain absorbed the lowest out-of-field dose, at 1.87 × 10⁻³ mSv/Gy.ConclusionsWe concluded that secondary neutron portion was higher than other radiation. Then, we recommended more attention to neutrons in the radiation protection in linac based high energy radiotherapy.     

Dynamic temporal change of cerebral microbleeds: long-term follow-up MRI study

Background

Cerebral microbleeds (MBs) are understood as an important radiologic marker of intracerebral hemorrhage. We sought to investigate the temporal changes of MBs and clinical factors associated with the changes using long-term follow-up MRI.

Methods/Principal Findings

From October 2002 to July 2006, we prospectively enrolled patients with stroke or transient ischemic attack, and followed-up their brain MRIs with an interval >12 mo. We compared demographic factors, vascular risk factors, laboratory findings, and radiologic factors according to the presence or changes of MBs. A total of 224 patients successfully completed the follow-up examinations (mean, 27 months). Newly developed MBs were noted in 10 patients (6.8%) among those without MBs at baseline (n = 148), and in those with MBs at baseline (n = 76), the MB count had decreased in 11 patients (14.5%), and increased in 41 patients (53.9%). The estimated annual rate of change of MB numbers was 0.80 lesions per year in all patients, a value which became greater in those patients who exhibited MBs at baseline (MBs≥5, 5.43 lesions per year). Strokes due to small vessel occlusion and intracerebral hemorrhage, as well as white matter lesions were independently associated with an increased MB count, whereas the highest quartile of low-density lipoprotein (LDL) cholesterol was associated with a decreased MB count.

Conclusion

During the follow-up period, most of MBs showed dynamic temporal change. Symptomatic or asymptomatic small vessel diseases appear to act as risk factors while in contrast, a high level of LDL cholesterol may act as a protective factor against MB increase.     

The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality

Background

The occurrence of variations in the spectrum of cardiovascular disease between different regions of the world and ethnic groups have been the subject of great interest. This study report the 24-h variation of myocardial infarction (MI) occurrence in patients recruited from CCU located in Argentina and Uruguay.

Methods

A cohort of 1063 patients admitted to the CCU within 24 h of the onset of symptoms of an acute MI was examined. MI incidence along the day was computed in 1 h-intervals.

Results

A minimal MI incidence between 03:00 and 07:00 h and the occurrence of a first maximum between 08:00 and 12:00 h and a second maximum between 15:00 and 22:00 h were verified. The best fit curve was a 24 h cosinor (acrophase ~ 19:00 h, accounting for 63 % of variance) together with a symmetrical gaussian bell (maximum at ~ 10:00 h, accounting for 37 % of variance). A similar picture was observed for MI frequencies among different excluding subgroups (older or younger than 70 years; with or without previous symptoms; diabetics or non diabetics; Q wave- or non-Q wave-type MI; anterior or inferior MI location). Proportion between cosinor and gaussian probabilities was maintained among most subgroups except for older patients who had more MI at the afternoon and patients with previous symptoms who were equally distributed among the morning and afternoon maxima.

Conclusion

The results support the existence of two maxima (at morning and afternoon hours) in MI incidence in the Argentine and Uruguayan population.     

The FOLLOWPACE study: a prospective study on the (cost-)effectiveness of routine follow-up visits in patients with a pacemaker

In the Netherlands, following implantation of a pacemaker (PM) commonly two or three out-patient follow-up visits are scheduled in the first year to check the patient''s health and the PM programme, in order to guarantee optimal patient outcome. Anually, about 200,000 follow-up visits of 20 minutes are performed, in total about 80,000 working hours. The question arises whether and to what extent these regular follow-up checks are truly necessary for the prognosis of the patient and whether they are cost-effective. Yet no information is available on how frequently and extensively a routine PM follow-up visit should be performed. This is probably because it is largely unknown which factors — either documented at PM implantation or at the follow-up visits - predict the occurrence of complications. The FOLLOWPACE study is designed to address these issues. Below we briefly discuss the rationale, objectives and expected results of FOLLOWPACE.     

Changes in the risk of fine-root mortality with age: a case study in peach, Prunus persica (Rosaceae)

Previous studies suggest that younger roots are more vulnerable to mortality than older roots. We analyzed minirhizotron data using a mixed-age, proportional hazards regression approach to determine whether the risk of mortality (or "hazard") was higher for younger roots than for older roots in a West Virginia peach orchard. While root age apparently had a strong effect on the hazard when considered alone, this effect was largely due to different rates of mortality among roots of different orders, diameters, and depths. Roots with dependent laterals (higher order roots) had a lower hazard than first-order roots in 1996 and 1997. Greater root diameter was also associated with a decreased hazard in both 1996 and 1997. In both years, there was a significant decrease in the hazard with depth. When considered alone, age appeared to be a strong predictor of risk: a 1-d increase in initial root age was associated with a 1.26-2.62% decrease in the hazard. However, when diameter, order, and depth were incorporated into the model, the effect of root age disappeared or was greatly reduced. Baseline hazard function plots revealed that the timing of high-risk periods was generally related to seasonal factors rather than individual root age.     

A long-term, single-group follow-up study of biofeedback therapy with chronic medical and psychiatric patients

In a long-term follow-up study, 524 (93%) of 563 consecutive medical and psychiatric patients, who received an average of 8 sessions of biofeedback and relaxation training, provided follow-up evaluations of treatment outcome. Seventy-five percent reported maximum, significant, or moderate improvement. There was a significant positive association between the percent of patients improved and the number of treatment sessions up to 10 sessions, but not thereafter. Symptom frequency decreased by 54% and symptom severity by 30%. About 54% of the medicated patients reported a decrease in medication. No differential therapist effects were found. About twice as many patients rated relaxation training as most helpful compared with the audio/visual signals from biofeedback instruments.     

Determinants of survival in children with congenital abnormalities: a long-term population-based cohort study

BACKGROUND: Today more children with birth defects survive early childhood because of improved medical care; however, little information is available about patterns of long-term mortality and survival in this population. In particular, it is not clear whether other birth characteristics, apart from birth defects, have any role in their mortality. METHODS: Two large cohorts of children with and without birth defects were followed for up to 17 years. More than 45,000 children with birth defects, and 45,000 matched children without birth defects born in Ontario between 1979 and 1986 were followed. Throughout the study period long-term survival rates and the risk of death were compared between the 2 cohorts. Birth characteristics were also examined to determine their effect on the risk of death. RESULTS: During the study the deaths of 3620 and 301 children with and without birth defects, respectively, were recorded, indicating that those with birth defects had a 13 times higher rate of mortality (relative risk [RR], 12.9, 95% confidence interval [CI], 12.1-13.7). Mortality rates in the birth-defects cohort remained higher even after 10-15 years. In both groups children of low gestational age and low birth weight had a higher risk of death. There was a strong dose-response relationship between the number of defects and the risk of death. CONCLUSIONS: Children born with abnormalities face many challenges throughout their lifetimes. If they survive the high mortality risk of the first year of life, they still have to face the considerably higher risk of death in the years to come. In addition to birth defects, other birth characteristics play an independent role in their mortality. These indicators could be used to identify high-risk children.     

A long-term,single-group follow-up study of biofeedback therapy with chronic medical and psychiatric patients

In a long-term follow-up study, 524 (93%) of 563 consecutive medical and psychiatric patients, who received an average of 8 sesisons of biofeedback and relaxation training, provided follow-up evaluations of treatment outcome. Seventy-five percent reported maximum, significant, or moderate improvement. There was a significant positive association between the percent of patients improved and the number of treatment sessions up to 10 sessions, but not thereafter. Symptom frequency decreased by 54% and symptom severity by 30%. About 54% of the medicated patients reported a decrease in medication. No differential therapist effects were found. About twice as many patients rated relaxation training as most helpful compared with the audio/visual signals from biofeedback instruments.This research was funded in part by the Minneapolis Clinic Medical Foundation. The author wishes to thank the biofeedback therapists for their cooperation and excellent service: Jones Adkins, Mike Schwieters, and Suzanne Kroon, especially the latter for her assistance in this program evaluation project. Vital contributions were made by secretarial staff, including Ann Hovde and Linda Bruch. Two undergraduate honors students in psychology from the University of Minnesota also provided important assistance: Steve Ristvedt and Shirley Fors. Computer and statistical consultation was provided by Terri Schultz and Dr. Sanford Weisberg of the St. Paul Computer Center.     

Increased risk of cancer mortality by smoking-induced aryl hydrocarbon receptor repressor DNA hypomethylation in Japanese population: A long-term cohort study

BackgroundSmoking is well known to be a major risk factor for cancer, and to decrease the levels of aryl hydrocarbon receptor repressor (AHRR) DNA methylation. AHRR is a key regulator for AHR signaling, which is involved in chemical metabolism and cancer development. Therefore, smoking-induced AHRR DNA hypomethylation may be associated with cancer development. However, it has not been reported that association between AHHR DNA methylation and cancer mortality in Asian population. Hence, we examined whether AHRR DNA methylation levels were associated with cancer mortality in a Japanese population.MethodsThis study was conducted with 812 participants (aged 38–80 years) who received a health check-up in 1990, and did not have a clinical histories. We followed up the participants until the end of 2019 (median: 27.8 years), and 100 participants died from cancer. The AHRR DNA methylation levels in peripheral blood mononuclear cells (PBMCs) were measured by the pyrosequencing method. We calculated the hazard ratio (HR) and 95% confidence interval (CI) for cancer mortality according to the baseline levels of AHRR DNA methylation.ResultsWe found that AHRR DNA hypomethylation was associated with a higher risk of all cancer mortality, especially smoking related cancers and lung cancer. (all cancer: HR, 1.28, 95% CI, 1.09–1.51; smoking-related cancers: HR, 1.35, 95% CI, 1.12–1.62; lung cancer: HR, 1.68, 95% CI, 1.24–2.26).ConclusionsSmoking-induced AHRR DNA hypomethylation in PBMCs was associated with the risk of cancer mortality in Japanese population; therefore, hypomethylation of AHRR may be a useful biomarker of cancer mortality risk.     

Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden

Context

The treatment for transsexualism is sex reassignment, including hormonal treatment and surgery aimed at making the person''s body as congruent with the opposite sex as possible. There is a dearth of long term, follow-up studies after sex reassignment.

Objective

To estimate mortality, morbidity, and criminal rate after surgical sex reassignment of transsexual persons.

Design

A population-based matched cohort study.

Setting

Sweden, 1973-2003.

Participants

All 324 sex-reassigned persons (191 male-to-females, 133 female-to-males) in Sweden, 1973–2003. Random population controls (10∶1) were matched by birth year and birth sex or reassigned (final) sex, respectively.

Main Outcome Measures

Hazard ratios (HR) with 95% confidence intervals (CI) for mortality and psychiatric morbidity were obtained with Cox regression models, which were adjusted for immigrant status and psychiatric morbidity prior to sex reassignment (adjusted HR [aHR]).

Results

The overall mortality for sex-reassigned persons was higher during follow-up (aHR 2.8; 95% CI 1.8–4.3) than for controls of the same birth sex, particularly death from suicide (aHR 19.1; 95% CI 5.8–62.9). Sex-reassigned persons also had an increased risk for suicide attempts (aHR 4.9; 95% CI 2.9–8.5) and psychiatric inpatient care (aHR 2.8; 95% CI 2.0–3.9). Comparisons with controls matched on reassigned sex yielded similar results. Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls.

Conclusions

Persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population. Our findings suggest that sex reassignment, although alleviating gender dysphoria, may not suffice as treatment for transsexualism, and should inspire improved psychiatric and somatic care after sex reassignment for this patient group.