Patterns of follow-up care in adult blood cancer survivors-Prospective evaluation of health-related outcomes, resource use, and quality of life.

BACKGROUND: Information about follow-up care in blood cancer survivors is limited. The questionnaire-based "Aftercare in Blood Cancer Survivors" (ABC) study aimed to identify patterns of follow-up care in Germany and compare different types of follow-up institutions. METHODS: The study's 18-month prospective part compared the follow-up institutions identified in the preceding retrospective part (academic oncologists, community oncologists, primary care physicians). The questionnaires were completed by the follow-up physicians. RESULTS: Of 1070 physicians named by 1479 blood-cancer survivors, 478 (44.7%) consented to participate. For provision of care, most oncologists relied on published guidelines, while most primary care physicians depended on information from other physicians. Survivors with a history of allogeneic transplantation or indolent lymphoma were mainly seen by academic oncologists, whereas survivors with monoclonal gammopathy, multiple myeloma, or myeloproliferative disorders were often seen by community oncologists, and survivors with a history of aggressive lymphoma or acute leukemia by primary care physicians. Detection of relapse and secondary diseases was consistently viewed as the most important follow-up goal. Follow-up visits were most extensively documented by academic oncologists (574 of 1045 survivors cared for, 54.9%), followed by community oncologists (90/231, 39.0%) and primary care physicians (51/203, 25.1%). Relapse and secondary disease detection rates and the patients' quality of life were similar at the three institutions. Laboratory tests were most often ordered by academic oncologists, and imaging by primary care physicians. Psychosocial issues and preventive care were more often addressed by primary care physicians than by oncologists. CONCLUSIONS: Patients at high risk of relapse or late complications were preferentially treated by academic oncologists, while patients in stable condition requiring continuous monitoring were also seen by community oncologists, and patients with curable diseases in long-term remission by primary care physicians. For the latter, transfer of follow-up care from oncologists to well-informed primary care providers appears feasible.

Health-Related Complications during Follow-Up and Their Impact on Blood Cancer Survivors: Results from the "Aftercare in Blood Cancer Survivors" (ABC) Study.

INTRODUCTION: Blood cancer survivors are at increased risk for medical complications. METHODS: Our questionnaire-based study involved 1,551 blood cancer survivors with a ≥3-year interval since the last intense treatment. Its goal was to quantify health-related complications during follow-up and assess their impact on the patients' lives. RESULTS: A total of 20.4% of the responding survivors reported a disease relapse, most often in indolent lymphomas. Second primary malignancies occurred in 14.1%, primarily in lymphoma and allogeneic transplantation survivors. The most frequent malignancy was basal cell carcinoma of the skin, but myeloid malignancies, melanoma, bladder, head-and-neck, and thyroid cancer also appeared disproportionately frequent. An increased infection rate was reported by 43.7%, most often after allogeneic transplantation. New cardiovascular diseases were reported by 30.2%, with a high rate of thromboembolic events in multiple myeloma (MM) and myeloproliferative diseases. Polyneuropathies were reported by 39.1%, most often by survivors with a history of MM or aggressive lymphoma. Disease relapse was perceived as the highest burden, followed by second primary malignancy, increased infection frequency, and polyneuropathy. In each area investigated, the range of perceived severities was wide. CONCLUSIONS: Health-related complications are frequent during blood cancer follow-up, with significant repercussions on the patients' lives.

Impairment of vocational activities and financial problems are frequent among German blood cancer survivors.

Little is known about changes in the personal living conditions of long-term blood cancer survivors in Germany. To gather information about social relationships, work life, overall well-being, and religion, we performed a questionnaire-based retrospective study on 1551 survivors who had been on follow-up for ≥ 3 years (median, 9 years). Most survivors reported that marital status and relationships with relatives and friends remained constant before and after blood cancer. Vocational activities were temporarily impaired for 47.5%, with a median time of 11 months to return to work. More than a third of the patients (35.6%) discontinued work permanently, with disability and retirement pension rates of 7.9% and 38.1%, respectively, at the time of the survey. Financial problems due to reduced income were reported by 26.2%, in particular after relapse or allogeneic transplantation. Patient reports addressing their quality of life showed large variations. It was best in acute leukemia survivors without a history of allogeneic transplantation and worst in patients with myeloproliferative disorders. Religion tended to become more important after blood cancer. In conclusion, vocational impairment and financial problems are frequent among German blood cancer survivors. Efforts should be made at an early stage to reestablish the patients' ability to work.

Preventive health care in blood cancer survivors: results from the ABC study.

BACKGROUND: Blood cancer survivors are at increased risk for second primary malignancies, cardiovascular diseases, and infections. Little is known about preventive care in blood cancer survivors. METHODS: Our questionnaire-based study included blood cancer patients diagnosed at the University Hospital of Essen before 2010, with a ≥ 3-year interval from the last intense treatment. One section of the retrospective study covered preventive care (cancer screening, cardiovascular screening, vaccination). RESULTS: Preventive care was delivered by a general practitioner for 1100 of 1504 responding survivors (73.1%), by an oncologist for 125 (8.3%), by a general practitioner together with an oncologist for 156 (10.4%), and by other disciplines for 123 (8.2%). Cancer screening was more consistently performed by general practitioners than by oncologists. The converse was true for vaccination, with particularly high vaccination rates in allogeneic transplant recipients. Cardiovascular screening did not differ between care providers. Cancer and cardiovascular screening rates in survivors eligible for statutory prevention programs were higher than in the general population (skin cancer screening 71.1%; fecal occult blood testing 70.4%; colonoscopy 64.6%; clinical breast examination 92.1%; mammography 86.8%; cervical smear 86.0%; digital rectal examination 61.9%; blood pressure test 69.4%; urine glucose test 54.4%; blood lipid test 76.7%; information about overweight 71.0%). The Streptococcus pneumoniae vaccination rate was higher (37.0%) and the influenza vaccination rate was lower (57.0%) than in the general population. CONCLUSIONS: Utilization of preventive care is high among German blood cancer survivors. To ensure widespread delivery and avoid redundancy, communication between oncologists and preventive care providers is essential.

Improving 10-year cardiovascular risk prediction in apparently healthy people: flexible addition of risk modifiers on top of SCORE2.

AIMS: In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics. METHODS AND RESULTS: Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736-0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732-0.741)]. CONCLUSION: The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers.

Heart disease is a major health concern worldwide, and predicting an individual's risk for developing heart disease is an important tool for prevention. Current risk prediction models often use factors such as age, gender, smoking, and blood pressure, but other factors like education level, albuminuria (protein in the urine), and coronary artery calcium (CAC) may also affect an individual's risk. The aim of this study was to develop a new method for using these additional risk factors for predicting risk even more accurately. The researchers used data from several large studies that included over 400 000 apparently healthy individuals who were followed for 10 years. They examined the effect of various risk factors on cardiovascular disease (CVD) risk using a statistical model. They found that adding coronary scan ('CAC score'); NT-proBNP, a biomarker of heart strain; and hs-Troponin-T, a marker of heart damage, to the existing risk prediction model (SCORE2) improved the accuracy of predicted CVD risk. The key findings are: The methods presented in the current study can help to add additional risk factors to predictions of existing models, such as SCORE2. This flexible method may help identify individuals who are at higher risk for CVD and guide prevention strategies.

Patient-reported patterns of follow-up care in the 'Aftercare in Blood Cancer Survivors' (ABC) study.

BACKGROUND: Follow-up care provides long-term support for cancer survivors. Little is known about follow-up care in hematologic malignancies. METHODS: Our questionnaire-based study included blood cancer survivors diagnosed at the University Hospital of Essen before 2010, with a ≥ 3-year interval since the last intense treatment. The primary goal of the retrospective study was the identification and characterization of follow-up institutions. RESULTS: Of 2386 survivors meeting the inclusion criteria, 1551 (65.0%) consented to participate, with a follow-up duration > 10 years in 731. The university hospital provided care for 1045 participants (67.4%), non-university oncologists for 231 (14.9%), and non-oncological internists or general practitioners for 203 (13.1%). Seventy-two participants (4.6%) abstained from follow-up care. The disease spectrum differed among follow-up institutions (p < 0.0001). While allogeneic transplant recipients clustered at the university hospital, survivors with monoclonal gammopathy, multiple myeloma, myeloproliferative disorders, or indolent lymphomas were often seen by non-university oncologists, and survivors with a history of aggressive lymphoma or acute leukemia by non-oncological internists or general practitioners. Follow-up intervals mirrored published recommendations. Follow-up visits were dominated by conversations, physical examination, and blood tests. Imaging was more often performed outside than inside the university hospital. Satisfaction with follow-up care was high, and quality of life was similar in all follow-up institutions. A need for improvement was reported in psychosocial support and information about late effects. CONCLUSIONS: The naturally evolved patterns identified in the study resemble published care models: Follow-up clinics for complex needs, specialist-led care for unstable disease states, and general practitioner-led care for stable conditions.

Coronary Artery Calcium Score to Refine the Use of PCSK9i in Asymptomatic Individuals: A Multicohort Study.

Background The value of coronary artery calcium (CAC) in the allocation of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors) among individuals without clinically evident atherosclerotic cardiovascular disease (ASCVD) is unknown for indications that do not require confirmed familial hypercholesterolemia. We aimed to assess the ability of CAC to stratify ASCVD risk under 3 non-familial hypercholesterolemia PCSK9i allocation paradigms. Methods and Results We included participants without clinically evident ASCVD from MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults) study, DHS (Dallas Heart Study), and HNR (Heinz Nixdorf Recall) study. Three PCSK9i eligibility scenarios were defined: a broad scenario informed only by high low-density lipoprotein cholesterol levels (N=567), a restrictive one combining higher low-density lipoprotein cholesterol levels and presence of ≥2 additional risk factors (N=127), and a high-risk scenario where individuals with subclinical organ damage or high estimated risk would be treated to achieve low-density lipoprotein cholesterol <55 mg/dL (N=471). The high-risk scenario had the highest ASCVD event rates (27.8% at 10 years). CAC=0 was observed in 35% participants in the broad scenario, 25% in the restrictive scenario, and 16% in the high-risk scenario. In all, CAC=0 was associated with the lowest incident ASCVD rates at 5 and 10 years, and CAC burden was independently associated with ASCVD events adjusting for traditional risk factors. Conclusions CAC may be used to refine the allocation of PCSK9i, potentially leading to a more conservative use if CAC=0. The value of CAC testing is greater in scenarios that use low-density lipoprotein cholesterol levels and/or traditional risk factors to define PCSK9i eligibility (CAC=0 present in 1 of 3-4 patients), whereas its prevalence is lower when allocation is informed by presence of noncoronary subclinical organ damage.

Dynamics, outcomes and prerequisites of the first SARS-CoV-2 superspreading event in Germany in February 2020: a cross-sectional epidemiological study.

OBJECTIVES: The first German SARS-CoV-2 outbreak was a superspreading event in Gangelt, North Rhine-Westphalia, during indoor carnival festivities called 'Kappensitzung' (15 February 2020). We determined SARS-CoV-2 RT-PCR positivity rate, SARS-CoV-2-specific antibodies, and analysed the conditions and dynamics of superspreading, including ventilation, setting dimensions, distance from infected persons and behavioural patterns. DESIGN: In a cross-sectional epidemiological study (51 days postevent), participants were asked to give blood, pharyngeal swabs and complete self-administered questionnaires. SETTING: The SARS-CoV-2 superspreading event took place during festivities in the small community of Gangelt in February 2020. This 5-hour event included 450 people (6-79 years of age) in a building of 27 m × 13.20 m × 4.20 m. PARTICIPANTS: Out of 450 event participants, 411 volunteered to participate in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: infection status (determined by IgG ELISA). SECONDARY OUTCOME: symptoms (determined by questionnaire). RESULTS: Overall, 46% (n=186/404) of participants had been infected, and their spatial distribution was associated with proximity to the ventilation system (OR 1.39, 95% CI 0.86 to 2.25). Risk of infection was highly associated with age: children (OR 0.33, 95% CI 0.267 to 0.414) and young adults (age 18-25 years) had a lower risk of infection than older participants (average risk increase of 28% per 10 years). Behavioural differences were also risk associated including time spent outside (OR 0.55, (95% CI 0.33 to 0.91) or smoking (OR 0.32, 95% CI 0.124 to 0.81). CONCLUSIONS: Our findings underline the importance of proper indoor ventilation for future events. Lower susceptibility of children/young adults indicates their limited involvement in superspreading.

Fertility preservation and fulfillment of parenthood after treatment of hematological malignancies: results from the 'Aftercare in Blood Cancer Survivors' (ABC) study.

PURPOSE: Treatment of hematological malignancies carries the risk of lasting sterility. We aimed to identify fertility-related unmet needs. METHODS: The 'Aftercare in Blood Cancer Survivors' study is a cohort study of hematological patients who were in treatment-free remission for ≥ 3 years or stable under continuous oral medication. Female patients age 18-45 years and male patients age 18-65 years without a history of pre-treatment infertility were asked to answer a structured questionnaire including questions addressing fertility issues. Multivariable analyses were performed to detect risk factors. RESULTS: Of 1562 study participants, 1031 met the inclusion criteria for the fertility sub-study. A high proportion of patients (72.4%) received information about the risk of losing fertility, but only a minority (15%) took steps to preserve it. Female and older patients were less likely to be informed. A post-treatment wish for parenthood was expressed by 19.3% of patients. It was strongly associated with childlessness at time of diagnosis and could be fulfilled by 29.4%. Fulfillment of desired parenthood increased with increasing time from diagnosis and was low after allogeneic transplantation. CONCLUSIONS: Female and older hematological patients are less likely to be informed about fertility-related issues than other patients. With societal changes towards first parenthood at higher age, the proportion of patients desiring a child after treatment is likely to increase. Fulfillment of desired parenthood remains challenging, especially after allogeneic transplantation. IMPLICATIONS FOR CANCER SURVIVORS: In patients likely to express a wish for post-treatment parenthood, fertility-related issues should routinely be addressed before gonadotoxic treatment is started.

Association of social relationships with incident cardiovascular events and all-cause mortality.

OBJECTIVE: To examine how different aspects of social relationships are associated with incident cardiovascular events and all-cause mortality. METHODS: In 4139 participants from the population-based Heinz Nixdorf Recall study without previous cardiovascular disease (mean (SD) age 59.1 (7.7) years, 46.7% men), the association of self-reported instrumental, emotional and financial support and social integration at baseline with incident fatal and non-fatal cardiovascular events and all-cause mortality during 13.4-year follow-up was assessed in five different multivariable Cox proportional hazards regression models: minimally adjusted model (adjusting for age, sex, social integration or social support, respectively); biological model (minimally adjusted+systolic blood pressure, low-density and high-density lipoprotein cholesterol, glycated haemoglobin, body mass index, antihypertensive medication, lipid-lowering medication and antidiabetic medication); health behaviour model (minimally adjusted+alcohol consumption, smoking and physical activity); socioeconomic model (minimally adjusted+income, education and employment); and depression model (minimally adjusted+depression, antidepressants and anxiolytics). RESULTS: 339 cardiovascular events and 530 deaths occurred during follow-up. Lack of financial support was associated with an increased cardiovascular event risk (minimally adjusted HR=1.30(95% CI 1.01 to 1.67)). Lack of social integration (social isolation) was associated with increased mortality (minimally adjusted HR=1.47 (95% CI 1.09 to 1.97)). Effect estimates did not decrease to a relevant extent in any regression model. CONCLUSIONS: Perceiving a lack of financial support is associated with a higher cardiovascular event incidence, and being socially isolated is associated with increased all-cause mortality. Future studies should investigate how persons with deficient social relationships could benefit from targeted interventions.

Prediction of individualized lifetime benefit from cholesterol lowering, blood pressure lowering, antithrombotic therapy, and smoking cessation in apparently healthy people.

AIMS: The benefit an individual can expect from preventive therapy varies based on risk-factor burden, competing risks, and treatment duration. We developed and validated the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model for the estimation of individual-level 10 years and lifetime treatment-effects of cholesterol lowering, blood pressure lowering, antithrombotic therapy, and smoking cessation in apparently healthy people. METHODS AND RESULTS: Model development was conducted in the Multi-Ethnic Study of Atherosclerosis (n = 6715) using clinical predictors. The model consists of two complementary Fine and Gray competing-risk adjusted left-truncated subdistribution hazard functions: one for hard cardiovascular disease (CVD)-events, and one for non-CVD mortality. Therapy-effects were estimated by combining the functions with hazard ratios from preventive therapy trials. External validation was performed in the Atherosclerosis Risk in Communities (n = 9250), Heinz Nixdorf Recall (n = 4177), and the European Prospective Investigation into Cancer and Nutrition-Netherlands (n = 25 833), and Norfolk (n = 23 548) studies. Calibration of the LIFE-CVD model was good and c-statistics were 0.67-0.76. The output enables the comparison of short-term vs. long-term therapy-benefit. In two people aged 45 and 70 with otherwise identical risk-factors, the older patient has a greater 10-year absolute risk reduction (11.3% vs. 1.0%) but a smaller gain in life-years free of CVD (3.4 vs. 4.5 years) from the same therapy. The model was developed into an interactive online calculator available via www.U-Prevent.com. CONCLUSION: The model can accurately estimate individual-level prognosis and treatment-effects in terms of improved 10-year risk, lifetime risk, and life-expectancy free of CVD. The model is easily accessible and can be used to facilitate personalized-medicine and doctor-patient communication.

Chromosome 3 is a valid marker for prognostic testing of biopsy material from uveal melanoma later treated by brachytherapy.

PURPOSE: Monosomy 3 (M3) in uveal melanoma (UM) obtained after enucleation is significantly associated with metastatic death. With improved biopsy techniques, samples from patients treated with eye-preserving methods have become available. As the choice of treatment depends on tumour size, patients treated with eye-preserving brachytherapy tend to have smaller tumours. It has to be determined if M3 is a valid marker for prognosis of these patients. METHODS: Follow-up and clinical data were collected from a total of 451 UM patients: 291 patients were treated by brachytherapy. Tumour tissue was sampled by transretinal biopsy using the 23-gauge Essen biopsy forceps prior to therapy in 114 of them. Chromosome 3 status was determined by microsatellite analysis. Data were compared to those from 160 patients treated by enucleation. RESULTS: Chromosome 3 status correlates significantly with disease-related survival in both patient groups. The proportion of tumours with M3 is lower in the brachytherapy group compared to patients treated with enucleation (25/77 32% and 102/144 71%, respectively). CONCLUSIONS: M3 is a valid marker for poor prognosis in uveal melanoma later treated by brachytherapy. The higher proportion of D3 tumours might explain, at least in part, the more favourable prognosis of patients treated by brachytherapy.

Pseudophakic retinal detachment in young-aged patients.

OBJECTIVE: To investigate the incidence and risk factors for retinal detachment (RD) after cataract surgery or refractive lens exchange (RLE) in patients aged below 61 years. METHODS: Retrospective medical chart review of 7,886 patients (13,925 eyes) who underwent cataract surgery or RLE. Patients aged below 61 years were selected. Age, gender, axial length, follow-up times, and the occurrence of RD were recorded. Additional characteristics documented for RD cases were: history of RD, preexisting retinal findings, laser capsulotomy, status of macula at RD, date and details of RD. RESULTS: From a total of 421 patients (677 eyes) aged below 61 years 24 cases of RD were identified, resulting in an overall cumulative incidence per eyes of 3.55%. The mean follow-up time was 45 ± 32.8 months. Ninety-two % of all RDs occurred within 3.6 years from surgery. Axial length had a significant effect on the risk of RD after cataract/ RLE surgery (HR = 1.42, P = 0.0001, 95% CI 1.19-1.69). The highest incidence of RD occurred in the subgroup of 25 to 28.9 mm axial length (10.2%). With an increase in age of ten years, the hazard of postoperative RD was not significantly increased by a factor of 1.50 (P = 0.286, 95% CI 0.71-3.15). The highest incidence of RD occurred in patients aged 50-54 years (5.39%). Compared to females, males had an almost twofold not significant risk of postoperative RD (HR = 1.96, P = 0.123, 95% CI 0.83-4.63). None of the RD cases had a history of RD. CONCLUSIONS: Axial length is a significant risk factor for pseudophakic RD. The need for cataract surgery or RLE should be carefully considered in patients with axial lengths between 25 and 29 mm, aged 50-54 years, in males, and in case of preexisting retinal findings.

Aortic Calcification Onset and Progression: Association With the Development of Coronary Atherosclerosis.

BACKGROUND: Thoracic aortic calcification (TAC) and coronary artery calcification (CAC) are markers of subclinical atherosclerosis and are associated with incident major cardiovascular events. We investigated major determinants for incidence and progression of TAC and the association between TAC and CAC incidence and progression. METHODS AND RESULTS: In a population-based cohort study, 3270 participants (aged 45-74 years, 53.1% women) received cardiac computed tomography at baseline and after a mean follow-up of 5.1±0.3 years for quantification of calcification of the ascending (ATAC) and descending thoracic aorta (DTAC) and CAC. Multivariable relative risk regression analysis was used to investigate associations of cardiovascular risk factors with incident TAC, of baseline TAC with incident CAC, and of baseline CAC with incident TAC. Of 1243 participants with baseline TAC of 0, 517 (41.6%) revealed incident TAC after 5 years. Incidence of descending TAC was higher (34.5%) than ascending TAC (23.3%). Incident TAC after 5 years was associated with age (relative risk 1.26 [95% CI 1.21-1.33], per 5 years), blood pressure (relative risk 1.06 [95% CI 1.03-1.10], per 10 mm Hg), low-density lipoprotein cholesterol (relative risk 1.08 [95% CI 1.04-1.12], per 20 mg/dL), and smoking (relative risk 1.28 [95% CI 1.07-1.53]). Among the 1185 participants without CAC at baseline, the risk of developing CAC was 28.3% when baseline TAC was present compared with 22.2% among those without baseline TAC (excess risk 6.1% [95% CI 1.2-11.0%]). The point estimate of excess risk for incident CAC was higher for ascending TAC (10.8% [95% CI 4.8-16.7%]) and low for descending TAC (1.8% [95% CI -3.2% to 6.7%]). Excess risk for developing ascending and descending TAC with present baseline CAC was 16.4% (95% CI 12.7-20.0%) and 15.6% (95% CI 10.8-20.4%), respectively. CONCLUSION: TAC and CAC share similar major determinants for incident calcification. Participants with TAC, especially ascending TAC, are at elevated risk for development of CAC.

Serum Chromogranin A as a Complementary Marker for the Prediction of Prostate Cancer-Specific Survival.

Better prognostication of clinically localized prostate cancer (PCA) is urgently needed. Former studies using different study end-points provided controversial results regarding the prognostic value of serum chromogranin A (CGA) in clinically localized PCA. However, serum CGA was not tested for correlation with the most significant study end-point of long-term disease-specific survival (DSS). CGA and matrix metalloproteinase-7 (MMP7) levels were measured by the BRAHMS KRYPTOR in two independent patient groups with 127 serum and 110 plasma samples. CGA and MMP7 concentrations were correlated with clinicopathological and survival data. In addition, we tested the combinations of CGA with PSA and with a currently identified prognostic factor, MMP7, for their prognostic value. CGA concentrations were significantly elevated in advanced compared to clinically localized cases both in serum and plasma samples (45 vs. 23 ng/ml, p < 0.001 and; 41 vs. 22 ng/ml; p = 0.002 respectively). In accordance, high CGA levels were correlated with poor DSS. In clinically localized cases, CGA levels alone were not prognostic, but its dichotomized combinations with PSA or MMP7 were independently associated with DSS (HR: 4.88, 95% CI: 1.35-17.71, p = 0.016, HR: 7.46, 1.65-33.63, p = 0.009, respectively). Elevated serum CGA levels in progressed PCA and its prognostic value suggest a potential for CGA in disease monitoring. Our results revealed no independent prognostic value for CGA as a single serum marker in clinically localized cases. However, when combining with PSA or MMP7, CGA may improve both marker's performance in distinguishing between clinically significant and indolent PCAs.

Liver steatosis in pre-transplant liver biopsies can be quantified rapidly and accurately by nuclear magnetic resonance analysis.

Donor livers marginally acceptable or acceptable according to extended criteria are more frequently transplanted due to the growing discrepancy between demand and availability of donor organs. One type of marginally acceptable graft is a steatotic donor liver, because it is more sensitive to ischemia-reperfusion injury. Thus, quantitative assessment of steatosis is crucial prior to liver transplantation. Extent of steatosis of 49 pre-reperfusion liver biopsies from patients who received orthotopic liver transplantation was assessed by three techniques: semi-quantitative histological evaluation, computerized histomorphometry, and NMR-based estimation of fat content. The findings were correlated to clinical data and to histological examination of corresponding post-reperfusion biopsies for quantification of ischemia-reperfusion injury. We found that values obtained through all three assessment methods were positively correlated. None of the values obtained by the three applied methods correlated with clinical outcome or extent of ischemia-reperfusion injury. Quantitative evaluation of steatosis by NMR yields results comparable to histological and morphometrical assessment. This technique is rapid (<5 min), accurately quantifies fat in donor livers, and provides results that can be used when evaluation by a pathologist is not available.

Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk Women: A Meta-analysis.

Importance: The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear. Objective: To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women. Design, Setting, and Participants: Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies. Exposures: CAC score by computed tomography. Main Outcomes and Measures: Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated. Results: Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC >0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 [95% CI, 2.02-3.83]; multivariable-adjusted hazard ratio, 2.04 [95% CI, 1.44-2.90]). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction. Conclusions and Relevance: Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy.

Accelerated progression of coronary artery calcification in hypertension but also prehypertension.

OBJECTIVE: To determine the role of hypertension for coronary artery calcification (CAC) progression. METHODS: The population-based Heinz Nixdorf Recall study recruited 4814 participants from a German urban population in 2000-2003. CAC was measured using electron-beam computed tomography at baseline and after 5 years. The present analyses refer to 3481 participants with repeat scan (coronary heart disease until 5 years excluded, age at baseline 45-74 years, and 53.1% women). Blood pressure (BP), Framingham risk factors, and antihypertensive medication were recorded at baseline. BP was staged according to Joint National Committee 7 guidelines. Participants under antihypertensive medication were classified as stage 2. CAC at 5 years was predicted from baseline using our dedicated, publicly available algorithm. CAC progression was accordingly classified as slow, expected, or rapid. RESULTS: Normotension was found in 20.5%, prehypertension in 27.2%, stage 1 hypertension in 15.8%, and stage 2 (ST2) in 36.5%. The frequency of rapid progression increases with BP stage (normotension: 16.7% to ST2: 21.1%, P = 0.004). Risk factor adjusted relative risk [RR (95% confidence interval), reference: normotension] of rapid progression was for prehypertension: 1.22 (0.98;1.51), stage 1: 1.29 (1.01;1.65), and ST2: 1.45 (1.17;1.79). Risk factor adjusted measures of CAC progression per 10 mmHg SBP were already elevated in women with BP below 140/90 mmHg: CAC onset, RR = 1.22 (1.07;1.40), rapid progression, RR = 1.17 (1.05;1.31), 5-year CAC progression, 6.7% (0.5;13.4). In men below 140/90 mmHg, only RR of rapid progression was considerably increased [RR = 1.11 (0.96;1.29)]. CONCLUSION: CAC progression, a sign of ongoing target organ damage, is already accelerated in prehypertensive patients, a substantial proportion of our urban population.

Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE).

PURPOSE: Concurrent chemoradiotherapy with or without surgery are options for stage IIIA(N2) non-small-cell lung cancer. Our previous phase II study had shown the efficacy of induction chemotherapy followed by chemoradiotherapy and surgery in patients with IIIA(N2) disease and with selected IIIB disease. Here, we compared surgery with definitive chemoradiotherapy in resectable stage III disease after induction. PATIENTS AND METHODS: Patients with pathologically proven IIIA(N2) and selected patients with IIIB disease that had medical/functional operability received induction chemotherapy, which consisted of three cycles of cisplatin 50 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days, as well as concurrent chemoradiotherapy to 45 Gy given as 1.5 Gy twice daily, concurrent cisplatin 50 mg/m(2) on days 2 and 9, and concurrent vinorelbine 20 mg/m(2) on days 2 and 9. Those patients whose tumors were reevaluated and deemed resectable in the last week of radiotherapy were randomly assigned to receive a chemoradiotherapy boost that was risk adapted to between 65 and 71 Gy in arm A or to undergo surgery (arm B). The primary end point was overall survival (OS). RESULTS: After 246 of 500 planned patients were enrolled, the trial was closed after the second scheduled interim analysis because of slow accrual and the end of funding, which left the study underpowered relative to its primary study end point. Seventy-five patients had stage IIIA disease and 171 had stage IIIB disease according to the Union for International Cancer Control TNM classification, sixth edition. The median age was 59 years (range, 33 to 74 years). After induction, 161 (65.4%) of 246 patients with resectable tumors were randomly assigned; strata were tumor-node group, prophylactic cranial irradiation policy, and region. Patient characteristics were balanced between arms, in which 81 were assigned to surgery and 80 were assigned to a chemoradiotherapy boost. In arm B, 81% underwent R0 resection. With a median follow-up after random assignment of 78 months, 5-year OS and progression-free survival (PFS) did not differ between arms. Results were OS rates of 44% for arm B and 40% for arm A (log-rank P = .34) and PFS rates of 32% for arm B and 35% for arm A (log-rank P = .75). OS at 5 years was 34.1% (95% CI, 27.6% to 40.8%) in all 246 patients, and 216 patients (87.8%) received definitive local treatment. CONCLUSION: The 5-year OS and PFS rates in randomly assigned patients with resectable stage III non-small-cell lung cancer were excellent with both treatments. Both are acceptable strategies for this good-prognosis group.

10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study).

BACKGROUND: Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed. OBJECTIVES: The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. METHODS: Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). RESULTS: Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell's C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate. CONCLUSIONS: An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.