Mads H. Rasmussen

BACKGROUND: Using potentially out-of-group blood components, like low titer A plasma and O whole blood, in the resuscitation of trauma patients is becoming increasingly popular. However, very little is known whether the donors' anti-A and/or anti-B titers change over time and whether repeated titer measurements on the same donor are required to ensure that each donation produces a low titer product. METHODS: The anti-A and/or anti-B titers were measured on 56 healthy adult volunteers (47 blood donors; nine blood center personnel) every 3 months for 12 consecutive months using an automated solid phase analyzer. The results were expressed as log2 titer steps (e.g., titer 32 = 5 titer steps). RESULTS: Minor variations in the average anti-A and/or anti-B titers were seen over time; the maximum individual SD in each group was 1.50 (IgG anti-A) or 1.00 (IgM anti-A, IgM, and IgG anti-B). When the SDs for the four titer measurements from all 56 volunteers were combined as appropriate, the highest overall combined SD was 0.47 titer steps for IgG anti-A. This value corresponds to a 95% confidence interval for intraindividual variation in this antibody's titer over 12 months of 0.96 titer steps. Thus, based on one measurement, an IgG anti-A with a titer step of, for example, 6 would be expected to be in the range of titer step 5 to titer step 7 over the course of 1 year with 95% probability. CONCLUSION: The titers of anti-A and/or anti-B among healthy adults are stable over at least 1 year. This suggests that repeated titer measurements within a year on the same donor are not necessary if donations are made at 3 months or longer intervals. LEVEL OF EVIDENCE: Diagnostic study, level V.

OBJECTIVE: To investigate the impact of obesity, fat distribution and weight loss on collagen turnover using serum concentrations of the carboxyterminal propeptide of type I procollagen (S-PICP) and the aminoterminal propeptide of type III pro-collagen (S-PIIINP) as markers for collagen turnover. DESIGN: Blood samples were obtained once at baseline, and after 8 and 16 weeks of dietary treatment (5.0 MJ/day diet). SETTING: Outpatient clinic of Hvidovre University Hospital. MAIN OUTCOME MEASURES: S-PICP, S-PIIINP, fat distribution and weight loss. RESULTS: S-PIIINP was associated with body weight (r = 0.37; P = 0.004), height (r = 0.27; P = 0.04), waist circumference (r = 0.35; P = 0.007), as well as with WHR (r = 0.33; P = 0.01) and was inversely correlated to age (r = -0.40; P = 0.002). Compared with randomly selected controls from a large pool of healthy volunteers, the obese patients had elevated S-PIIINP values before as well as during weight loss, whereas S-PICP levels were within the normal range and did not correlate with any anthropometric measures. The average weight loss after 16 weeks dietary treatment was 8.1 kg (s.d. = 0.8). S-PIIINP decreased during the 16 weeks of energy restriction (P < 0.05) and changes in S-PIIINP was correlated to body weight loss (r = 0.32; P < 0.05) and to changes in waist circumference (r = 0.34; P < 0.05) as well as changes in WHR (r = 0.30; P < 0.05). CONCLUSION: S-PIIINP is elevated in obesity and associated with body fat distribution, suggesting an increased turnover of type III collagen related to obesity in general and to abdominal obesity in particular. S-PIIINP levels decreases during weight loss in obese subjects, whereas S-PICP levels seems un-related to obesity and weight loss.

INTRODUCTION: Circulating tumor (ctDNA) can be used to detect residual disease after cancer treatment. Detecting low-level ctDNA is challenging, due to the limited number of recoverable ctDNA fragments at any target loci. In response, we applied tumor-informed whole-genome sequencing (WGS), leveraging thousands of mutations for ctDNA detection. METHODS: Performance was evaluated in serial plasma samples (n = 1283) from 144 stage III colorectal cancer patients. Tumor/normal WGS was used to establish a patient-specific mutational fingerprint, which was searched for in 20x WGS plasma profiles. For reproducibility, paired aliquots of 172 plasma samples were analyzed in two independent laboratories. De novo variant calling was performed for serial plasma samples with a ctDNA level > 10 % (n = 17) to explore genomic evolution. RESULTS: WGS-based ctDNA detection was prognostic of recurrence: post-operation (Hazard ratio [HR] 6.75, 95 %CI 3.18-14.3, p < 0.001), post-adjuvant chemotherapy (HR 28.9, 95 %CI 10.1-82.8; p < 0.001), and during surveillance (HR 22.8, 95 %CI 13.7-37.9, p < 0.0001). The 3-year cumulative incidence of ctDNA detection in recurrence patients was 95 %. ctDNA was detected a median of 8.7 months before radiological recurrence. The independently analyzed plasma aliquots showed excellent agreement (Cohens Kappa=0.9, r = 0.99). Genomic characterization of serial plasma revealed significant evolution in mutations and copy number alterations, and the timing of mutational processes, such as 5-fluorouracil-induced mutations. CONCLUSION: Our study supports the use of WGS for sensitive ctDNA detection and demonstrates that post-treatment ctDNA detection is highly prognostic of recurrence. Furthermore, plasma WGS can identify genomic differences distinguishing the primary tumor and relapsing metastasis, and monitor treatment-induced genomic changes.

A mother and her daughter with a novel type of familial partial lipodystrophy were studied. Both had atrophy of fat in the face, chest, and upper and lower limbs and abdominal obesity caused by intraabdominal fat accumulation. The mother had severe insulin resistance and impaired glucose tolerance, whereas the daughter had normal glucose tolerance and normal insulin sensitivity. Both had metabolic rates about 30% above normal levels, but normal thyroid function and plasma lipids.

Abstract Background Reliability of ABO‐antibody measurement is important in the context of supplying low‐titer ABO incompatible plasma‐containing blood products. This study investigated the correlation of anti‐A measurements between three different titer methodologies. Methods Thirty‐four blood group O individuals were included. IgM and IgG anti‐A was measured by three different methods: (1) manual method (Bio‐Rad ID‐gel card), (2) automated method (Immucor NEO), (3) flow cytometry (FC) with calibration in molecules of equivalent fluorochrome (MEF). Data were log2 transformed to titer steps (TS) and log2 MEF, respectively. All three methods were benchmarked against the 14/300 WHO anti‐A/anti‐B standard reagent. Results The correlation between the manual and automated methods was statistically significant for both IgM (Spearman's r s = 0.89, p &lt; .0001) and IgG ( r s = 0.95, p &lt; .0001). The mean TS difference between the manual and automated methods was 0.61 for IgM ( p = .0033) and 2.1 for IgG ( p &lt; .0001). The manual method yielded IgM titer results that were generally 1 titer step higher than the automated method, whereas for the IgG titrations the difference was generally a median of 2 TS higher. The FC median log2 MEF level was significantly correlated with TS of IgG and IgM for both manual and automated agglutination‐based titer methods (0.69 ≤ r 2 ≤ 0.91). With the WHO standard reagent, the manual method produced the expected results while the automated method's results were 1 TS lower for both IgM and IgG at all dilutions tested. Conclusion These results indicate that all three methods are suitable for measuring anti‐A in group O whole blood.