Risk-Adjusted Cancer Screening and Prevention (RiskAP): Complementing Screening for Early Disease Detection by a Learning Screening Based on Risk Factors

BackgroundRisk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action.SummaryTherefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept.     

Clinical findings on the use of long-term heavy tamponades (semifluorinated alkanes and their oligomers) in complicated retinal detachment surgery

BACKGROUND: Heavy tamponades for pathologies in the lower part of the retina are a new development, and different tamponades have recently come into clinical use: semifluorinated alkanes (F(6)H(6), F(6)H(8)) and their oligomers (OL62HV). METHOD: Nine patients had been operated on using F(6)H(8) (n=5) and by OL62HV (n=4). In all cases the reasons for using the tamponades were complicated retinal detachments in the lower part. In three cases the use was primary and in six cases tamponades were used after reoperations. In all cases the endotamponade was removed within 6 weeks. Fluorescein angiography (FLA) was performed in the F(6)H(8) group. RESULTS: In the F(6)H(8)group dispersion developed in two of the three aphacic patients. In two out of five cases soft epiretinal membranes and cellular material could be found between the substance and the lower periphery. In two membranes examined by light microscopy, cystic cells and amorphous material could be found. In one case (PDRP, aphacic) cyclophotocoagulation had to be performed because of persistent elevated IOP. FLA was unremarkable. In the OL62HV group, severe recurrent PVR reaction occurred in the lower periphery (2/4) and unusual precipitates were observed (4/4). In one case, after a normal postoperative period (VA 0.05 after 5 days) an extensive cellular reaction on the complete surface of the tamponade occurred. After 5 weeks VA was no light perception. During removal of the oligomer unusual adherent cellular components were found on the surface of the retina. The retina appeared necrotic, showed constricted retinal vessels and there was optic atrophy. Histologically, fluffy epiretinal material and a lens capsule obtained from one eye filled with OL62HV resembled the appearance with F(6)H(8). CONCLUSION: Heavy endotamponades on the basis of semifluorinated alkanes can lead to an unusual biological reaction and need further investigation before clinical use.     

Influence of Xenogeneic and Alloplastic Carriers for Bone Augmentation on Human Unrestricted Somatic Stem Cells

Alloplastic and xenogeneic bone grafting materials are frequently used for bone augmentation. The effect of these materials on precursor cells for bone augmentation is yet to be determined. The aim of this study was to ascertain, in vitro, how augmentation materials influence the growth rates and viability of human unrestricted somatic stem cells. The biocompatibility of two xenogeneic and one alloplastic bone graft was tested using human unrestricted somatic stem cells (USSCs). Proliferation, growth, survival and attachment of unrestricted somatic stem cells were monitored after 24 h, 48 h and 7 days. Furthermore, cell shape and morphology were evaluated by SEM. Scaffolds were assessed for their physical properties by Micro-CT imaging. USSCs showed distinct proliferation on the different carriers. Greatest proliferation was observed on the xenogeneic carriers along with improved viability of the cells. Pore sizes of the scaffolds varied significantly, with the xenogeneic materials providing greater pore sizes than the synthetic inorganic material. Unrestricted somatic stem cells in combination with a bovine collagenous bone block seem to be very compatible. A scaffold’s surface morphology, pore size and bioactive characteristics influence the proliferation, attachment and viability of USSCs.     

Risk assessment in COVID‐19: Prognostic importance of cardiovascular parameters

BackgroundCardiovascular risk factors and comorbidities are highly prevalent among COVID‐19 patients and are associated with worse outcomes.HypothesisWe therefore investigated if established cardiovascular risk assessment models could efficiently predict adverse outcomes in COVID‐19. Furthermore, we aimed to generate novel risk scores including various cardiovascular parameters for prediction of short‐ and midterm outcomes in COVID‐19.MethodsWe included 441 consecutive patients diagnosed with SARS‐CoV‐2 infection. Patients were followed‐up for 30 days after the hospital admission for all‐cause mortality (ACM), venous/arterial thromboembolism, and mechanical ventilation. We further followed up the patients for post‐COVID‐19 syndrome for 6 months and occurrence of myocarditis, heart failure, acute coronary syndrome (ACS), and rhythm events in a 12‐month follow‐up. Discrimination performance of DAPT, GRACE 2.0, PARIS‐CTE, PREDICT‐STABLE, CHA2‐DS2‐VASc, HAS‐BLED, PARIS‐MB, PRECISE‐DAPT scores for selected endpoints was evaluated by ROC‐analysis.ResultsOut of established risk assessment models, GRACE 2.0 score performed best in predicting combined endpoint and ACM. Risk assessment models including age, cardiovascular risk factors, echocardiographic parameters, and biomarkers, were generated and could successfully predict the combined endpoint, ACM, venous/arterial thromboembolism, need for mechanical ventilation, myocarditis, ACS, heart failure, and rhythm events. Prediction of post‐COVID‐19 syndrome was poor.ConclusionRisk assessment models including age, laboratory parameters, cardiovascular risk factors, and echocardiographic parameters showed good discrimination performance for adverse short‐ and midterm outcomes in COVID‐19 and outweighed discrimination performance of established cardiovascular risk assessment models.     

Management of cervical intraepithelial neoplasia 2 in adolescent and young women

STUDY OBJECTIVE: To evaluate regression rates among adolescents (aged < or =21) with cervical intraepithelial neoplasia (CIN) 2 managed expectantly and to determine factors associated with disease regression. DESIGN: Cohort study using a colposcopic database of 2,996 women seen between August 1999 and November 2005. SETTING: Colposcopy clinic in urban, tertiary care medical center. PARTICIPANTS: Adolescents with CIN 2. Routine management consisted of two options: immediate treatment or repeat colposcopic evaluation in 6 months. MAIN OUTCOME MEASURES: For those managed conservatively, regression was defined either as a subsequent normal colposcopy and/or biopsy and at least 2 smears read as negative for epithelial abnormality or at least 3 consecutive negative smears if repeat colposcopy was not performed. Demographic information, including age, was assessed to determine possible associations with disease regression. RESULTS: Of the 93 adolescents, 53 (57%) elected to undergo immediate treatment with a diagnostic excisional procedure, and 40 (43%) chose management with colposcopic follow-up. Of those treated, high-grade disease (CIN 2+) was found in 40 (75%). Of the 36 young women followed conservatively (4 were lost to follow-up), regression after a median follow-up time of 378 days was documented in 14 (39%). Of the 22 adolescents not fulfilling our criteria for regression, only 3 had evidence of CIN 2 or worse during follow-up. The remaining 19 had either CIN 1 or mildly abnormal cytologic results. Kaplan-Meier survival estimates indicated younger age (< or =16 years) tended to be associated with decreased time to regression. CONCLUSION: Based on significant regression of CIN 2 among adolescent women, primary management in this population should consist of cytologic and colposcopic follow-up.     

Uterine artery Doppler in the prediction of adverse pregnancy outcome

PURPOSE OF REVIEW: To review publications, published during the past year, that have examined uterine artery Doppler findings in women with adverse pregnancy outcome. RECENT FINDINGS: Almost two-thirds of stillbirths that occur in the early preterm period (up to 32 weeks) can be predicted by uterine artery Doppler at 23 weeks. First trimester screening studies have shown that an abnormal result increases the risk of subsequent fetal growth restriction, and such women are at particularly high risk when indices remain abnormal in the second trimester. Studies combining uterine artery Doppler with maternal serum markers have demonstrated that measurement of first-trimester maternal serum pregnancy-associated plasma protein A and free beta human chorionic gonadotrophin improve sensitivities of second-trimester Doppler. As these are frequently measured in Down syndrome screening and they lend themselves in screening for pre-eclampsia. Women with abnormal first and second-trimester serum markers constitute a high-risk group. Maternal serum placental protein 13 remains a promising method for early screening, although a recent study suggests lower sensitivities than initially reported. SUMMARY: Uterine artery Doppler screening identifies women at high risk for developing adverse pregnancy outcomes. Detection rates may be increased and false positive rates reduced by combination with maternal characteristics or serum markers.