Quantification of mitochondrial cfDNA reveals new perspectives for early diagnosis of colorectal cancer.

BACKGROUND: To unravel how the integrity of nuclear and mitochondrial circulating cell-free DNA (cfDNA) contributes to its plasma quantity in colorectal cancer (CRC) patients. METHODS: CfDNA from plasma samples of 80 CRC patients stratified by tumour stage and 50 healthy individuals were extracted. Total cfDNA concentration was determined and equal template concentrations (ETC) were analyzed by quantitative real-time PCR (qPCR) resulting in small and long fragments of KRAS, Alu and MTCO3. The obtained data was also examined relative to the total cfDNA concentration (NTC) and diagnostic accuracy was estimated using receiver operating characteristics. RESULTS: Total cfDNA levels were significantly higher in CRC group compared to healthy control and increased with tumour stage. Long nuclear fragment levels were significantly lower in CRC patients in ETC but not NTC condition. The integrity indices of nuclear cfDNA decreased from controls to patients with highly malignant tumor. Mitochondrial cfDNA fragment quantities were strongly reduced in early and late stages of tumor patients and prognostic value was higher in ETC. Predictive models based on either ETC or NTC predictor set showed comparable classification performance. CONCLUSION: Increased blood cfDNA concentration in late UICC stages inversely correlate with nuclear cfDNA integrity index and suggest that necrotic degradation is not a major cause for higher total cfDNA quantity. The diagnostic and prognostic value of MTCO3 is highly significant in early stages of CRC and can be evaluated more comprehensively, using ETC for qPCR analysis. TRIAL REGISTRATION: The study was registered retrospectively on DRKS, the german register for clinical trials (DRKS00030257, 29/09/2022).

Statistical inference in abstracts of three influential clinical pharmacology journals analyzed using a text-mining algorithm.

AIM: To describe the trend in the prevalence of statistical inference in three influential clinical pharmacology journals METHODS: We applied a computer-based algorithm to abstracts of three clinical pharmacology journals published in 1976 to 2016 to identify statistical inference and its subtypes. Furthermore, we manually reviewed a random sample of 300 articles to access algorithm's performance in finding statistical inference in abstracts and as a screening tool for presence and absence of statistical inference in full text. RESULT: The algorithm identified 59% (13,375/22,516 [mid p 95% CI, 59%-60%]) article abstracts with statistical inference. The percentage of abstracts with statistical inference was similar in 1976 and 2016, 48% (179/377 [mid p 95%CI, 42%-52%]) versus 49% (386/791 [mid p 95%CI, 45%-52%]). Statistical reporting pattern varied among journals. Among abstracts containing any statistical inference in the publications from 1976 to 2016 null-hypothesis significance testing was the most prevalent reported statistical inference. The algorithm had high sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for finding statistical inferences in abstract. While PPV for predicting the statistical inference in full text (including abstract, text, tables and figures) was high, NPV was low. CONCLUSION: Despite journal's editorials and statistical associations' guidelines, most authors focused on testing rather than estimation. In future, a better statistical reporting might be ensured by improving the statistical knowledge of authors and an addition of statistical guides to journals' instruction to authors to the extent that editors would like their statistical inference preferences to be incorporated into submitted manuscripts.

[Increasing Mortality from Cardiac Arrhythmia in Germany?] / Ansteigende Sterblichkeit an Herzrhythmusstörungen in Deutschland?

BACKGROUND: The 'Deutscher Herzbericht 2016' [German Heart Report] reported a strongly increasing mortality rate from cardiac arrhythmia in Germany from 1990 to 2014. The increase was higher in women than in men and was rated as 'paradoxical' in light of improved diagnostic and therapeutic procedures. The aim of this paper is to explore the mortality data for cardiac arrhythmias in detail and to generate an explanatory approach. METHODS: We extracted the number of deaths from cardiac arrhythmia (ICD-10 codes I44-I49) for each sex, 5-year-age group and each federal state for 2000-2014 (www.gbe-bund.de). Crude as well as age-specific and age-standardized (standard: Germany census 2011) mortality rates were calculated. RESULTS: While the crude mortality rates increased considerably between 2000 and 2014 (men: 18 to 26, women: 23 to 38 pro 100,000), the age-standardized mortality rates showed only a small increase (men: 31 to 32, women: 22 to 27 per 100,000 person years). This increase was attributable to an increasing mortality rate from atrial fibrillation and flutter (ICD-10: I48) in men and women aged 80 years and older. In younger age groups and in other subgroups of cardiac arrhythmia, no relevant increases were seen. CONCLUSION: The increase of mortality rates from cardiac arrhythmia as reported in 'Deutscher Herzbericht 2016' is largely attributable to the demographic changes in the German population. After age-standardization, there still remains an increase in the mortality rates, but this is smaller. From an epidemiologic perspective, it is a common problem in the interpretation involving crude mortality data. Moreover, the validity of mortality rates for cardiac arrhythmia is limited due to several reasons.

Statistical inference in abstracts of major medical and epidemiology journals 1975-2014: a systematic review.

Since its introduction in the twentieth century, null hypothesis significance testing (NHST), a hybrid of significance testing (ST) advocated by Fisher and null hypothesis testing (NHT) developed by Neyman and Pearson, has become widely adopted but has also been a source of debate. The principal alternative to such testing is estimation with point estimates and confidence intervals (CI). Our aim was to estimate time trends in NHST, ST, NHT and CI reporting in abstracts of major medical and epidemiological journals. We reviewed 89,533 abstracts in five major medical journals and seven major epidemiological journals, 1975-2014, and estimated time trends in the proportions of abstracts containing statistical inference. In those abstracts, we estimated time trends in the proportions relying on NHST and its major variants, ST and NHT, and in the proportions reporting CIs without explicit use of NHST (CI-only approach). The CI-only approach rose monotonically during the study period in the abstracts of all journals. In Epidemiology abstracts, as a result of the journal's editorial policy, the CI-only approach has always been the most common approach. In the other 11 journals, the NHST approach started out more common, but by 2014, this disparity had narrowed, disappeared or reversed in 9 of them. The exceptions were JAMA, New England Journal of Medicine, and Lancet abstracts, where the predominance of the NHST approach prevailed over time. In 2014, the CI-only approach is as popular as the NHST approach in the abstracts of 4 of the epidemiology journals: the American Journal of Epidemiology (48%), the Annals of Epidemiology (55%), Epidemiology (79%) and the International Journal of Epidemiology (52%). The reporting of CIs without explicitly interpreting them as statistical tests is becoming more common in abstracts, particularly in epidemiology journals. Although NHST is becoming less popular in abstracts of most epidemiology journals studied and some widely read medical journals, it is still very common in the abstracts of other widely read medical journals, especially in the hybrid form of ST and NHT in which p values are reported numerically along with declarations of the presence or absence of statistical significance.

Automated determination of 8-OHdG in cells and tissue via immunofluorescence using a specially created antibody.

Despite powerful DNA repair systems, oxidative damage/modification to DNA is an inevitable side effect of metabolism, ionizing radiation, lifestyle habits, inflammatory pathologies such as type-2 diabetes or metabolic syndrome, cancer and natural aging. One of the most common oxidative DNA modifications is 8-OHdG (8­hydroxy-2'-deoxyguanosine), which is the most widely used marker in research and clinical diagnostics. 8-OHdG is easily and specifically detectable in various samples such as urine, plasma, cells and tissues via a large variety of methods like ELISA, HPLC, chromatographic methods, and immunochemistry. Formed by oxidation of guanine and being representative for the degree of DNA damage, 8-OHdG can be also used as biomarker for risk assessment of various cancers as well as degenerative diseases. Here, we present a highly specific, self-developed 8-OHdG antibody in successful comparison to a commercially one, tested in cells (FF95, HCT116, and HT22) and intestinal tissue, focusing on automatized evaluation via fluorescence/confocal microscopy.

Statistical Inference in Abstracts Published in Cardiovascular Journals.

BACKGROUND: In 2016, the American Statistical Association stated that the use of statistical significance leads to distortion of the scientific process. The principal alternative to significance or null hypothesis testing (NHT) is estimation with point estimates and confidence intervals (CIs). OBJECTIVES: The aim of this study was to determine the time trend of statistical inference and statistical reporting style in abstracts in major cardiovascular journals. METHODS: A total of 84,250 abstracts published from 1975 to 2019 in 9 high-ranking cardiovascular journals (Circulation, Circulation Research, European Heart Journal, European Heart Journal: Cardiovascular Imaging, European Journal of Heart Failure, Journal of the American College of Cardiology, JACC: Cardiovascular Imaging, JACC: Cardiovascular Interventions, and JAMA Cardiology) were reviewed; in particular, proportions of abstracts containing statistical inference and its major variants (NHT, significance testing) were compared over time and among journals. RESULTS: Overall, 49,924 abstracts (59%) contained statistical inference. Among these abstracts, NHT was the most frequent reporting style of statistical inference (79% among all journals). Journals differed considerably in the prevalence of CI reporting (1% to 78% in 2017-2019). With the exception of 2 journals, the proportion of abstracts containing CIs was higher in the more recent period. From 2013-2015 to 2017-2019, the proportion of abstracts containing only CIs increased by 5 (95% CI: 0 to 10), 18 (95% CI: 15 to 21), and 9 (95% CI: 3 to 15) percentage points in the European Heart Journal, the Journal of the American College of Cardiology, and JACC: Cardiovascular Imaging, respectively. CONCLUSIONS: NHT is still the prevailing reporting style of statistical inference in major cardiovascular journals. Reporting of CIs in abstracts of major cardiovascular journals appears to be growing more popular.

Retrospective comparison of reinfusion procedures and subsequent leukopenia in autologous stem cell transplantation.

Standard operating procedures for autologous stem cell transplantation (SCT) aim to guarantee best possible engraftment. Three procedures are routinely used for transplant infusion: regular bag infusion (Procedure 1), injection via syringe (Procedure 2), and combination of regular bag infusion and syringe (Procedure 3). We conducted a retrospective analysis of all autologous stem cell transplants done in the hematology department of the Vivantes Clinic Neukoelln in Berlin, Germany, between January 1, 2016 and March 4, 2017. Of the total of 69 patients, 17 underwent Procedure 1, 32 Procedure 2, and 20 Procedure 3. Although speed of transplant reinfusion differed significantly between procedure types, these differences had no effect on duration of leukopenia. However, duration of leukopenia did correlate with need for blood transfusion and use of antibiotics. Our findings contradict the general perception that very rapid reinfusion is necessary. Nevertheless, considering the limitations of this study (retrospective, single center, small sample size) and that longer duration of aplasia is associated with greater need for intervention, efficient transplant reinfusion is advisable. More research is needed regarding timeliness and type of procedure used.

Tracing scientific reasoning in psychiatry: Reporting of statistical inference in abstracts of top journals 1975-2015.

OBJECTIVE: To analyze the reporting of statistical inference in psychiatry. METHOD: We searched 63,928 abstracts, published in 15 leading psychiatric journals (1975-2015). RESULTS: Median abstract length increased from 664 (1975) to 1,323 (2015) characters, and median use of numbers from two to 14/abstract. A total of 3.6% of all abstracts exclusively contained significance terminology in a nonstatistical sense, and 45% showed some form of statistical inference, increasing from 26% to 52%. In those abstracts, statistical inference based on thresholds was dominant. Its proportion decreased from 99% to 66%, but with rising numbers of articles, figures rose from 1,095 to 2,382. Although reporting p values without thresholds did not appear 40 years ago and remains rare, combining precise p values with thresholds is now common. In 2010-2015, 86% of abstracts contained p values or p value thresholds, 22% confidence intervals, and 7% confidence intervals only. Results varied across journals. CONCLUSION: There is a moderate shift from reporting p values along set thresholds, such as p ≤ 0.05, to presenting precise p values and confidence intervals, but not as pronounced as in epidemiology and general medicine. The long debate on estimation over testing has not led to a substantial replacement of p values by confidence intervals. Null hypothesis testing ("p ≤ .05") dominates statistical thinking.