Mortality risk among 5-year survivors of childhood cancer in Germany-Results from the CVSS study (Cardiac and Vascular late Sequelae in long-term Survivors of childhood cancer study).

The growing population of long-term childhood cancer survivors is at increased risk for severe, therapy-related late effects and premature mortality. The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS) study is a cohort of patients from Germany diagnosed with a neoplasia prior to 15 years of age in the time period 1980 to 1990. Late mortality was evaluated in a total of 4505 individuals who survived 5 years or more after the initial diagnosis (5-year survivors). Survivors with a second primary tumor were excluded. Standardized mortality ratios (SMRs) were calculated. By December 2014, 400 patients had died. Available cause of death information from 188 individuals was used to estimate cause-specific mortality for all deceased persons. Compared to the population of (former) West Germany, we observed an excess overall mortality risk (SMR = 9.53, 95% confidence interval [CI] = 8.62-10.51). After correcting for missing cause of death information, an increased cancer mortality (SMR = 43.50, 95% CI = 25.79-73.50) in the 5-year survivors was detected. Cardiac death was ascertained in 14 individuals, resulting in an SMR of 10.85 (95% CI = 2.80-32.02) after correcting for missing values. In conclusion, childhood cancer survivors diagnosed in Germany in 1980 to 1990 have a higher mortality risk overall and an elevated risk of dying from cancer and cardiac causes in particular. The results are consistent with those of international cohort studies. However, the reported results are based on few cases and individuals with secondary cancers were excluded.

Parenting in the face of serious illness: Childhood cancer survivors remember different rearing behavior than the general population.

OBJECTIVE: A child's cancer diagnosis and treatment affect the whole family. While it has been recognized that parents are an important resource for their children, little is known about the specifics of parenting in the face of serious illness. METHODS: We used the Recalled Parental Rearing Behavior Questionnaire in a register-based cohort of adult childhood cancer survivors (CCS) (N = 951) and a representative population sample of the same age range (N = 2042). The questionnaire assesses behavior of mothers and fathers with three scales (emotional warmth, rejection/punishment, and control/overprotection) by querying the (former) child. We compared the two groups using general linear models. With a hierarchical linear regression analysis, we tested associations of recalled rearing behavior with disease- and treatment-related factors. RESULTS: Compared with the general population, CCS remembered both parents as emotionally warmer, more overprotective, and less punishing/rejecting and less ambitious. The regression analysis showed that having received radiotherapy (ß = 0.092; P = .009) and chemotherapy (ß = 0.077; P = .027) was positively related to memories of maternal emotional warmth. CONCLUSIONS: CCS remembered parenting styles which are generally deemed more positive. The extent of recalled control and overprotection deviated from the population in different directions, suggesting that parenting in childhood cancer entails more complex adaptations than being affectionate and giving comfort. The results suggest an adaptation of parental behavior to particularly challenging treatments. They highlight potential vulnerability and resilience factors, some of which were sex-dependent.

Coupling of urban energy balance model with 3-D radiation model to derive human thermal (dis)comfort.

While capabilities in urban climate modeling have substantially increased in recent decades, the interdependency of changes in environmental surface properties and human (dis)comfort have only recently received attention. The open-source solar long-wave environmental irradiance geometry (SOLWEIG) model is one of the state-of-the-art models frequently used for urban (micro-)climatic studies. Here, we present updated calculation schemes for SOLWEIG allowing the improved prediction of surface temperatures (wall and ground). We illustrate that parameterizations based on measurements of global radiation on a south-facing vertical plane obtain better results compared to those based on solar elevation. Due to the limited number of ground surface temperature parameterizations in SOLWEIG, we implement the two-layer force-restore method for calculating ground temperature for various soil conditions. To characterize changes in urban canyon air temperature (Tcan), we couple the calculation method as used in the Town Energy Balance (TEB) model. Comparison of model results and observations (obtained during field campaigns) indicates a good agreement between modeled and measured Tcan, with an explained variance of R2 = 0.99. Finally, we implement an energy balance model for vertically mounted PV modules to contrast different urban surface properties. Specifically, we consider (i) an environment comprising dark asphalt and a glass facade and (ii) an environment comprising bright concrete and a PV facade. The model results show a substantially decreased Tcan (by up to - 1.65°C) for the latter case, indicating the potential of partially reducing/mitigating urban heat island effects.

Thromboembolic Events After Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate: Exploratory Analyses of Two Randomized, Plasma-Controlled Studies.

STUDY OBJECTIVE: We evaluated thromboembolic events after vitamin K antagonist reversal in post hoc analyses of pooled data from 2 randomized trials comparing 4-factor prothrombin complex concentrate (4F-PCC) (Beriplex/Kcentra) with plasma. METHODS: Unblinded investigators identified thromboembolic events, using standardized terms (such as "myocardial infarction," "deep vein thrombosis," "pulmonary embolism," and "ischemic stroke"). A blinded safety adjudication board reviewed serious thromboembolic events, as well as those referred by an independent unblinded data and safety monitoring board. We descriptively compared thromboembolic event and patient characteristics between treatment groups and included detailed patient-level outcome descriptions. We did not power the trials to assess safety. RESULTS: We enrolled 388 patients (4F-PCC: n=191; plasma: n=197) in the trials. Thromboembolic events occurred in 14 of 191 patients (7.3%) in the 4F-PCC group and 14 of 197 (7.1%) in the plasma group (risk difference 0.2%; 95% confidence interval -5.5% to 6.0%). Investigators reported serious thromboembolic events in 16 patients (4F-PCC: n=8; plasma: n=8); the data and safety monitoring board referred 2 additional myocardial ischemia events (plasma group) to the safety adjudication board for review. The safety adjudication board judged serious thromboembolic events in 10 patients (4F-PCC: n=4; plasma: n=6) as possibly treatment related. There were 8 vascular thromboembolic events in the 4F-PCC group versus 4 in the plasma group, and 1 versus 6 cardiac events, respectively. Among patients with thromboembolic events, 3 deaths occurred in each treatment group. All-cause mortality for the pooled population was 13 per group. We observed no relationship between thromboembolic event occurrence and factor levels transiently above the upper limit of normal; there were no notable differences in median factor or proteins C and S levels up to 24 hours postinfusion start in patients with and without thromboembolic events. CONCLUSION: The incidence of thromboembolic events after vitamin K antagonist reversal with 4F-PCC or plasma was similar and independent of coagulation factor levels; small differences in the number of thromboembolic event subtypes were observed between treatment groups.

Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study.

BACKGROUND: Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal. METHODS AND RESULTS: In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8-20.0) for the 4F-PCC group and 3.60 (1.9-38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% [95% confidence interval, -5.8 to 19.9]). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% [95% confidence interval, 39.4 to 65.9]). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (P<0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced ≥1 adverse event. CONCLUSIONS: 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708435.

Rectal cancer: assessment of response to neoadjuvant chemoradiation by dynamic contrast-enhanced MRI.

PURPOSE: To assess pretreatment functional and morphological tumor characteristics with magnetic resonance imaging (MRI) in advanced rectal carcinoma and to identify factors predicting response to neoadjuvant chemoradiation. MATERIALS AND METHODS: In a prospective study, 95 patients with rectal carcinoma underwent dynamic contrast-enhanced MRI before and after chemoradiation. Quantitative parameters were derived from a pharmacokinetic two-compartment model. Tumors were also characterized with regard to mucinous status at pretreatment high-resolution MRI as nonmucinous or mucinous. Response to treatment was defined as a downshift in the local tumor stage. RESULTS: The parameter k21 (contrast medium exchange rate) was higher at pretreatment MRI in nonmucinous compared with mucinous carcinomas (P < 0.001). The effect of chemoradiation on dynamic MR parameters was higher in nonmucinous carcinomas than in the mucinous subtype (P < 0.001). A higher rate of response to treatment was linked with nonmucinous morphology (P < 0.001). Multivariate analysis revealed an association between mucinous tumor morphology and poor response (odds ratio [95% confidence interval]: 0.113 [0.032-0.395], P < 0.001) as well as an association between a high 75th percentile of k21 and a higher response rate (odds ratio: 1.043 [1.001-1.086], P = 0.019). CONCLUSION: Functional and morphological parameters of pretreatment MRI can assess tumor characteristics associated with the effectiveness of chemoradiation before treatment initiation.

Sample size in cluster-randomized trials with time to event as the primary endpoint.

In cluster-randomized trials, groups of individuals (clusters) are randomized to the treatments or interventions to be compared. In many of those trials, the primary objective is to compare the time for an event to occur between randomized groups, and the shared frailty model well fits clustered time-to-event data. Members of the same cluster tend to be more similar than members of different clusters, causing correlations. As correlations affect the power of a trial to detect intervention effects, the clustered design has to be considered in planning the sample size. In this publication, we derive a sample size formula for clustered time-to-event data with constant marginal baseline hazards and correlation within clusters induced by a shared frailty term. The sample size formula is easy to apply and can be interpreted as an extension of the widely used Schoenfeld's formula, accounting for the clustered design of the trial. Simulations confirm the validity of the formula and its use also for non-constant marginal baseline hazards. Findings are illustrated on a cluster-randomized trial investigating methods of disseminating quality improvement to addiction treatment centers in the USA.

Impact of ozone exposure on prostaglandin release in nasal polyps.

A dysregulation of the cyclooxygenases and a leukotriene/prostaglandin imbalance are assumed to be part of the pathogenesis of the aspirin (ASA) intolerance syndrome. Ozone is an air pollutant with known proinflammatory effects on exposed epithelia, however, its impact on the expression of the cyclooxygenases 1 and 2 (cox1/2) and prostaglandin E(2) (PGE(2)) in the nasal mucosa is not well known. Therefore, we analyzed cox expression and PGE(2) levels after ozone exposure in nasal mucosa and in nasal polyps considering ASA intolerance. Isolated epithelial nasal cells from control subjects without chronic rhinosinusitis (CRS), and those from patients with nasal polyps with and without ASA intolerance were cultured and exposed in vitro to ozone. Cox1/2 expression levels were analyzed by immunohistochemistry and PGE(2) release by ELISA. After ozone exposure cox1/2 expression remained unchanged in all the three groups. PGE(2) release was lowered in cell cultures from controls and from polyps of ASA tolerant but not in those of ASA intolerant patients after ozone exposure. In the latter, PGE(2) expression remained unchanged. Our in vitro data suggest that aspirin tolerant patients with polyps might be more affected by ozone compared to aspirin intolerant ones. The potential clinical impact of impaired PGE(2) expression caused by ozone on the functions of respiratory epithelia remains to be clarified.

Long-term functional outcome after unilateral cordectomy.

PURPOSE OF THE STUDY: Our aim was to longitudinally analyze the vocal outcome after endoscopic CO(2) laser resection of early glottic carcinoma. PROCEDURES: Sixteen patients treated with laser surgery for T1 or T2 tumors of the vocal cords received voice therapy and were examined 1, 2, 3, 4.5, 6 and 12 months postoperatively. Besides videolaryngostroboscopy, each examination included history, phonetogram of the speaking and the singing voice, language-specific hoarseness diagram and a questionnaire (Voice Handicap Index 12 in German). RESULTS: Objective parameters demonstrated a broad variability with a slight tendency of improvement over time. For the maximal phonation time a nearly constant improvement was seen. After an initial improvement deterioration for subjective assessment in the Voice Handicap Index was noted in most patients 3-6 months postoperatively. CONCLUSIONS: The functional outcome after cordectomy is variable. MESSAGE OF THE PAPER: Discrepancies between objective findings and patient satisfaction over time have to be considered after cordectomy.

Perioperative pupil size in low-energy femtosecond laser-assisted cataract surgery.

PURPOSE: To assess potential changes in pupil size during femtosecond laser-assisted cataract surgery (FLACS) using a low-energy laser system. METHODS: The pupil sizes of eyes undergoing FLACS were measured using the Ziemer LDV Z8 by extracting images from the laser software after each of the following steps: application of suction, lens fragmentation, and capsulotomy. Furthermore, the pupil diameters were measured based on preoperative surgical microscope images and after releasing the suction. Paired t-test and the two one-sided tests (TOST) procedure were used for statistical analyses. The horizontal and vertical pupil diameters were compared in each of the steps with preoperative values. RESULTS: Data were available for 52 eyes (52 patients, mean age 73.4 years, range 51-87 years). The equivalence between mean preoperative pupil size and status immediately after femtosecond laser treatment was confirmed (p<0.001; 95% confidence interval [-0.0637, 0.0287] for horizontal and p<0.001; 95% CI [-0.0158, 0.0859] for vertical diameter). There was statistically significant horizontal and vertical enlargement of pupil diameters between 0.15 and 0.24 mm during the laser treatment steps as compared with preoperative values (all p values <0.001). CONCLUSIONS: No progressive pupil narrowing was observed using low-energy FLACS. Although a suction-induced, slight increase in pupil area became apparent, this effect was completely reversible after removing the laser interface.

Promotion of Arterial Stiffness by Childhood Cancer and Its Characteristics in Adult Long-Term Survivors.

Background Vascular alterations induced by antineoplastic treatment might be considered as a possible underlying mechanism of increased cardiovascular sequelae in childhood cancer survivors (CCSs). We aimed to evaluate arterial stiffness among long-term CCSs and to compare the data against a population-based sample. Methods and Results Arterial stiffness was assessed by digital photoplethysmography (stiffness index; m/s) among 1002 participants of the CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study, diagnosed with neoplasia (1980-1990) before an age of 15 years. A population-based sample from the GHS (Gutenberg Health Study) (n=5252) was investigated for comparison. All subjects underwent a comprehensive, standardized clinical examination in the same study center. CCSs had higher stiffness index (ß=0.66 m/s; 95% CI, 0.51-0.80 m/s) in multivariable linear regression analysis after adjustment for cardiovascular risk factors compared with the population sample of comparable age range. Stiffer vessels were found among CCSs also in absence of arterial hypertension (ß=0.66; 95% CI, 0.50-0.81) or history of chemotherapy/radiotherapy (ß=0.56; 95% CI, 0.16-0.96) in fully adjusted models. Moreover, stiffness index differed by tumor entity, with highest values in bone and renal tumors. Almost 5.2-fold higher prevalence of stiffness index values exceeding age-specific, population-based reference limits was observed among CCSs compared with GHS participants. Conclusions This is the first study demonstrating increased arterial stiffness among long-term CCSs. The data suggest that vascular compliance might differ in survivors of childhood cancer from the established development concept for arterial stiffness in the population; cancer growth and antineoplastic treatment might be relevant determinants of the pathobiological features. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02181049.

Occurence and clinical predictors of spasticity after ischemic stroke.

BACKGROUND AND PURPOSE: There is currently no consensus on (1) the percentage of patients who develop spasticity after ischemic stroke, (2) the relation between spasticity and initial clinical findings after acute stroke, and (3) the impact of spasticity on activities of daily living and health-related quality of life. METHODS: In a prospective cohort study, 301 consecutive patients with clinical signs of central paresis due to a first-ever ischemic stroke were examined in the acute stage and 6 months later. At both times, the degree and pattern of paresis and muscle tone, the Barthel Index, and the EQ-5D score, a standardized instrument of health-related quality of life, were evaluated. Spasticity was assessed on the Modified Ashworth Scale and defined as Modified Ashworth Scale >1 in any of the examined joints. RESULTS: Two hundred eleven patients (70.1%) were reassessed after 6 months. Of these, 42.6% (n=90) had developed spasticity. A more severe degree of spasticity (Modified Ashworth Scale >or=3) was observed in 15.6% of all patients. The prevalence of spasticity did not differ between upper and lower limbs, but in the upper limb muscles, higher degrees of spasticity (Modified Ashworth Scale >or=3) were more frequently (18.9%) observed than in the lower limbs (5.5%). Regression analysis used to test the differences between upper and lower limbs showed that patients with more severe paresis in the proximal and distal limb muscles had a higher risk for developing spasticity (P

Cisplatin sensitivity of testis tumour cells is due to deficiency in interstrand-crosslink repair and low ERCC1-XPF expression.

BACKGROUND: Cisplatin based chemotherapy cures over 80% of metastatic testicular germ cell tumours (TGCT). In contrast, almost all other solid cancers in adults are incurable once they have spread beyond the primary site. Cell lines derived from TGCTs are hypersensitive to cisplatin reflecting the clinical response. Earlier findings suggested that a reduced repair capacity might contribute to the cisplatin hypersensitivity of testis tumour cells (TTC), but the critical DNA damage has not been defined. This study was aimed at investigating the formation and repair of intrastrand and interstrand crosslinks (ICLs) induced by cisplatin in TTC and their contribution to TTC hypersensitivity. RESULTS: We observed that repair of intrastrand crosslinks is similar in cisplatin sensitive TTC and resistant bladder cancer cells, whereas repair of ICLs was significantly reduced in TTC. γH2AX formation, which serves as a marker of DNA breaks formed in response to ICLs, persisted in cisplatin-treated TTC and correlated with sustained phosphorylation of Chk2 and enhanced PARP-1 cleavage. Expression of the nucleotide excision repair factor ERCC1-XPF, which is implicated in the processing of ICLs, is reduced in TTC. To analyse the causal role of ERCC1-XPF for ICL repair and cisplatin sensitivity, we over-expressed ERCC1-XPF in TTC by transient transfection. Over-expression increased ICL repair and rendered TTC more resistant to cisplatin, which suggests that ERCC1-XPF is rate-limiting for repair of ICLs resulting in the observed cisplatin hypersensitivity of TTC. CONCLUSION: Our data indicate for the first time that the exceptional sensitivity of TTC and, therefore, very likely the curability of TGCT rests on their limited ICL repair due to low level of expression of ERCC1-XPF.

What's past is prologue: Recalled parenting styles are associated with childhood cancer survivors' mental health outcomes more than 25 years after diagnosis.

BACKGROUND: With the increased survival rates of childhood cancer, long-term survivors' well-being over the life span has come into focus. A better understanding of the determinants of childhood cancer survivors' (CCS) mental health outcomes contributes to the identification of vulnerable individuals as well as to the development of evidence-based prevention and intervention efforts. It has been noted that psychosocial factors such as parental rearing behavior shape individual differences in mental health. There is also evidence that parents show altered parenting behavior in the face of childhood cancer, e. g. that they express more emotional support, but also more worries. However, little is known about the relevance of different parenting styles for CCS' mental health decades after diagnosis and treatment. METHODS: We examined the associations of recalled parenting styles and disease-related factors with lifetime diagnoses of depression and anxiety disorders in a German, registry-based sample of adult CCS (N = 948, 44.50% women) with survival times >25 years. We conducted logistic regression analyses of lifetime diagnoses of depression and anxiety disorders, respectively, on dimensions of recalled parental rearing behavior (measured with a validated German short version of the EMBU) controlling for relevant adjustment variables such as the presence of physical illnesses. RESULTS: Recalled parenting styles of both parents had statistically relevant associations with CCS' lifetime depression and anxiety diagnoses. Maternal emotional warmth was related to fewer lifetime diagnoses of depression and fewer lifetime diagnoses of anxiety. Memories of paternal control and overprotection were positively associated with lifetime diagnoses of anxiety. CONCLUSION: The results indicate that mental representations of one's caregivers are associated with psychological long-term outcomes. Thus, medical professionals should involve the parents and support them in accompanying their child through the difficult times of treatment and survivorship. Interventions aimed at fostering survivors' quality of life should consider the sustained relevance of early relationships.

Risk factors for suicidal ideation in a large, registry-based sample of adult long-term childhood cancer survivors.

INTRODUCTION: Long-term childhood cancer survivors (CCS) are at risk for physical and psychosocial late effects. Previous research has attested to increased rates of suicidal ideation (SI) in CCS, an especially dangerous indicator of distress. However, little was known about risk factors of SI among CCS which go beyond illness- and treatment related variables. METHODS: A registry-based sample of 916 adult long-term CCS (Mage=34.58 years [SD=5.53], Mage at diagnosis=6.15 years [SD=4.28]) underwent medical assessments and filled out questionnaires. We conducted a linear regression analysis on SI, testing predictors of different areas: sociodemographic, social, physical health and health behavior, and psychological distress symptoms. RESULTS: SI was reported by 73 (8.0%) CCS and previous suicide attempts were reported by 26 (2.8%) CCS. SI was most closely related to social and psychological factors, i.e. to concurrent distress symptoms (depression, anxiety, social phobia), previous suicide attempts, current loneliness, and the present living situation. LIMITATIONS: SI and previous suicide attempts were assessed using short self-report instruments. The cross-sectional study design does not allow for causal inferences. CONCLUSIONS: Long-term CCS are a previously understudied, vulnerable group. Decades after having survived cancer, a considerable percentage is affected by (recurrent) SI. CCS' risk for SI is likely shaped by individual medical and psychological history, and by the current social environment and psychological comorbidities. There is a need for more interdisciplinary research and for screening efforts which take account of these factors. Interventions reducing CCS' risk of suicide should foster social integration and counteract current stressors.

Assessment of postischemic neurogenesis in rats with cerebral ischemia and propofol anesthesia.

BACKGROUND: Postischemic endogenous neurogenesis can be dose-dependently modulated by volatile anesthetics. The intravenous anesthetic propofol is used during operations with a risk of cerebral ischemia, such as neurosurgery, cardiac surgery, and vascular surgery. The effects of propofol on neurogenesis are unknown and, therefore, the object of this study. METHODS: Eighty male Sprague-Dawley rats were randomly assigned to treatment groups with propofol administration for 3 h: 36 mg x kg(-1) x h(-1) propofol with or without cerebral ischemia and 72 mg x kg(-1) x h(-1) propofol with or without cerebral ischemia. In addition, 7 rats with propofol administration for 6 h and 14 treatment-naive rats were investigated. Forebrain ischemia was induced by bilateral carotid artery occlusion and hemorrhagic hypotension. Animals received 5-bromo-2-deoxyuridine for 7 days. 5-Bromo-2-deoxyuridine-positive neurons were counted in the dentate gyrus after 9 and 28 days. Spatial learning in the Barnes maze and histopathologic damage of the hippocampus were analyzed. RESULTS: Propofol revealed no impact on basal neurogenesis. Cerebral ischemia increased the amount of new neurons. After 28 days, neurogenesis significantly increased in animals with low-dose propofol administered during cerebral ischemia compared with naive animals, whereas no significant difference was observed in animals with high-dose propofol during ischemia. Neuronal damage in the CA3 region was increased at 28 days with high-dose propofol. Postischemic deficits in spatial learning were not affected by propofol. CONCLUSIONS: Independent effects of propofol are difficult to ascertain. Peri-ischemic propofol administration may exert secondary effects on neurogenesis by modulating the severity of histopathologic injury and thereby regenerative capacity of the hippocampus.

Prevalence of mental distress among adult survivors of childhood cancer in Germany-Compared to the general population.

BACKGROUND: Increasing survival rates after childhood cancer have raised the issue of long-term mental health consequences in adulthood. This study determines mental health distress among long-term survivors of pediatric cancer and compares it to control groups. METHODS: Childhood cancer survivors (CCS; N = 951, aged 24-49 years) were compared to three age-matched control groups from the general population collected at three time points. The study compared the prevalence of clinically relevant symptoms of a wide range of common mental disorders (depression, somatic distress, suicidal ideation, generalized anxiety, panic, social anxiety, and sleep disturbances) using identical, validated questionnaires. CCS were identified by the German Childhood Cancer Registry. Controls were approached by a demographic consultation company (USUMA) which assured that the three samples were nationally representative. RESULTS: Childhood cancer survivors reported higher education than controls and were less often married. All forms of common mental distress were increased among survivors. Twenty-four percent of male (N = 526) and 41% of female survivors (N = 425) reported some form of clinically relevant mental health symptoms. Somatic distress as the leading complaint was highly frequent among CCS (OR: 10.98, CI 95%: 7.24-16.64). Complaints by generalized anxiety (OR: 5.04, CI 95%: 2.61-9.70), panic (OR: 3.28, CI 95%: 1.60-6.70), depression (OR: 3.36, CI 95%: 2.22-5.09), and suicidality (OR = 2.22; CI 95%: 1.38-3.57) were also strongly increased. Female sex, low education, low income, and unemployment were associated with increased distress. CONCLUSIONS: Findings indicate a need to integrate psycho-oncological screening and care into long-term aftercare. Somatic distress, as cause and indicator of psychological distress, should receive stronger attention, especially tiredness, low energy, and pain.

Status and predictors of planning ability in adult long-term survivors of CNS tumors and other types of childhood cancer.

Long-term childhood cancer survivors' (CCS) quality of life can be impacted by late effects such as cognitive difficulties. Especially survivors of CNS tumors are assumed to be at risk, but reports of cognitive tests in CCS with survival times >25 years are scarce. We assessed planning ability, a capacity closely related to fluid intelligence, using the Tower of London. We compared 122 CNS tumor survivors, 829 survivors of other cancers (drawn from a register-based sample of adult long-term CCS), and 215 healthy controls (using sex-specific one-way ANOVAs and t-tests). Associations of CCS' planning ability with medical and psychosocial factors were investigated with a hierarchical linear regression analysis. Mean planning ability did not differ between CCS and controls. However, female CNS tumor survivors performed worse than female survivors of other cancers and female controls. CNS tumor survivors of both sexes had a lower socioeconomic status, and fewer of them had achieved high education than other survivors. In the regression analysis, lower status and anxiety symptoms were associated with poor planning, suggesting possible mediators of effects of disease and treatment. The results indicate the necessity to contextualize test results, and to include cognitive and psychological assessments into aftercare.

Cardiovascular risk factors are important determinants of platelet-dependent thrombin generation in adult survivors of childhood cancer.

Cardiovascular disease is the most frequent non-malignant cause of morbidity and mortality in adult survivors of childhood or adolescent cancer. Thrombin generation (TG) analysis gives insight in hypercoagulability as an important mechanism linked to cardiovascular risk factors (CVRFs). In 200 individuals, from the cardiac and vascular late sequelae in long-term survivors of childhood cancer study, TG in platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1pM tissue factor was investigated. Endogenous thrombin potential (ETP) and peak height were the analysed parameters of a TG curve. Sex-specific multivariable linear regression analysis adjusted for age and CVRFs was used to assess the clinical determinants of TG. Females presented with higher ETP and peak height compared to males, both in PRP and PFP. Hypertension (beta estimate, ß: 184.8 [90.7; 278.8]), obesity (ß: 161.9 [63.9; 259.5]), and HbA1c (ß: 715.6 [97.4; 1333.8]) were associated with higher ETP in PRP only. ETP in PRP was positively associated with obesity and HbA1c in both males and females and with dyslipidemia (ß: 253.07 [72.92; 433.22]) and systolic hypertension (ß: 436.7 [119.02; 754.39]) in females only. CVRFs showed no association with TG variables in PFP. In conclusion, this study presents an important relation between traditional CVRFs and TG in the presence of platelets only. Sex-specific differences in TG with females presenting with higher TG, particularly those with dyslipidemia and systolic hypertension, were demonstrated. These results highlight the potential of the platelet-coagulant function in identifying cancer survivors at higher risk for adverse cardiovascular events.

Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample.

Female sex is a risk factor for long-term adverse outcome in cancer survivors, however very little is known for the underlying pathophysiological mechanisms rendering the increased risk. This study investigated sex-specifically the relation between thrombin generation (TG) with and without presence of platelets and vascular function in 200 adult survivors of a childhood cancer compared to 335 population-based control individuals. TG lag time, peak height and endogenous thrombin potential (ETP) measured in presence and absence of platelets were correlated to reflection index (RI) and stiffness index (SI). A sex-specific correlation analysis showed a negative relation in female survivors for platelet-dependent peak height and/or ETP and RI only. An age adjusted linear regression model confirmed the negative association between RI and platelet-dependent ETP (beta estimate: -6.85, 95% confidence interval: -12.19,-1.51) in females. Adjustment for cardiovascular risk factors resulted in loss of the association, whereby arterial hypertension and obesity showed the largest effects on the observed association. No other relevant associations were found in male and female cancer survivors and all population-based controls. This study demonstrates a link between platelet coagulant and vascular function of resistance vessels, found in female cancer survivors, potentially mediated by the presence of arterial hypertension and obesity.