A retrospective cohort study of 27,049 polytraumatized patients age 60 and above: identifying changes over 16 years.

PURPOSE: The number of severely injured patients exceeding the age of 60 has shown a steep increase within the last decades. These patients present with numerous co-morbidities, polypharmacy, and increased frailty requiring an adjusted treatment approach. In this study, we establish an overview of changes we observed in demographics of older severe trauma patients from 2002 to 2017. METHODS: A descriptive analysis of the data from the TraumaRegister DGU® (TR-DGU) was performed. Patients admitted to a level one trauma center in Germany, Austria and Switzerland between 2002 and 2017, aged 60 years or older and with an injury severity score (ISS) over 15 were included. Patients were stratified into subgroups based on the admission: 2002-2005 (1), 2006-2009 (2), 2010-2013 (3) and 2014-2017 (4). Trauma and patient characteristics, diagnostics, treatment and outcome were compared. RESULTS: In total 27,049 patients with an average age of 73.9 years met the inclusion criteria. The majority were males (64%), and the mean ISS was 27.4. The proportion of patients 60 years or older [(23% (1) to 40% (4)] rose considerably over time. Trauma mechanisms changed over time and more specifically low falls (< 3 m) rose from 17.6% (1) to 40.1% (4). Altered injury patterns were also identified. Length-of-stay decreased from 28.9 (1) to 19.5 days (4) and the length-of-stay on ICU decreased from 17.1 (1) to 12.7 days (4). Mortality decreased from 40.5% (1) to 31.8% (4). CONCLUSION: Length of stay and mortality decreased despite an increase in patient age. We ascribe this observation mainly to increased use of diagnostic tools, improved treatment algorithms, and the implementation of specialized trauma centers for older patients allowing interdisciplinary care.

Comparison of serological and DNA PCR-SSP typing results for HLA-A and HLA-B in 421 Black individuals: a Collaborative Transplant Study report.

In a recent study, we observed a discrepancy rate of 8.5% between the results of molecular and serological HLA class I typing in Caucasian kidney donors and recipients. In the present study we addressed the question how often black individuals are mistyped using the serological technique. 421 Blacks whose HLA typing results were reported to the Collaborative Transplant Study (CTS) were typed retrospectively for HLA-A and -B using a PCR-SSP method. 78 of the 421 individuals (18.5%) showed a discrepancy for HLA-A and 107 individuals (25.4%) for HLA-B. 36.3% of all individuals tested showed either an HLA-A or an HLA-B discrepancy. 13.1% of the discrepancies at the HLA-A locus were due to antigen misassignments and 4.8% were due to missed antigens. HLA-B discrepancies were caused in 15.7% by antigen misassignments and in 10.5% by missed antigens. These results demonstrate an impressive advantage of the PCR-SSP method for HLA-A and HLA-B locus typing over serological typing in black individuals. The high typing discrepancy rate observed in Blacks provides a strong argument for replacing serological typing by the DNA method. It is likely that this will improve the HLA matching correlation in clinical transplantation in Blacks.

HLA class I DNA typing of 215 "HLA-A, -B, -DR zero mismatched" kidney transplants.

DNA typing for HLA class II improves the typing quality and this was shown previously to be relevant for kidney graft survival. In this project we addressed the question whether molecular typing for HLA class I also increases the efficacy of HLA matching in kidney transplantation. 215 HLA-A,-B,-DR zero-mismatched donor/recipient pairs as defined by serological typing were selected. Retrospective HLA-A and HLA-B typing was performed both by the PCR-SSP and the PCR-SSOP method. DNA typing for HLA-A revealed discrepant results to serology in 5.7% of the donors and 2.8% of the recipients. HLA-B typing discrepancies were found in 6.6% of the donors and 5.6% of the recipients. 10.4% of the donors and 6.5% of the recipients showed either an HLA-A or an HLA-B discrepancy Nearly one-third of the HLA-A discrepancies affected A19 splits. The most common reason for HLA-A discrepancies was the erroneous assignment of serological blanks, whereas HLA-B errors were caused mainly by the assignment of incorrect specificities. DNA typing allowed the definition of HLA-A and -B split specificities in all 118 "splitable" cases for which only broad specificities were reported based on serological typing. A total of 183 DNA class I compatible transplants had a 15% higher one-year graft survival rate than 32 transplants for which DNA typing revealed a class I incompatibility

Comparison of typing results by serology and polymerase chain reaction with sequence-specific primers for HLA-Cw in 650 individuals.

HLA-Cw typing by standard serological techniques is associated with a high frequency of blanks, and reliable typing reagents for several of the Cw specificities are scarce. We evaluated the PCR-SSP technique for Cw typing in 370 kidney transplant patients and 280 healthy blood donors. Serological typing of all individuals was performed in our laboratory from 1995 to 1997 using commercially available tissue-typing trays. Comparison between serological and PCR-SSP typing revealed a discrepancy rate of 33.6% (n= 94) in blood donors and 32.4%) (n=120) in kidney recipients. Incorrect antigen assignments occurred only rarely (3.6% of the blood donors and 3.2% of the kidney recipients). The vast majority of discrepancies were due to antigens that were not detected serologically. In 26 individuals no Cw antigen was detected by serological typing, whereas PCR-SSP showed 1 allele in 13 and 2 alleles in the other 13 cases. Another 269 individuals were typed serologically with one blank (presumably homozygous). Of these, only 108 were confirmed to be homozygous, whereas an additional Cw allele was found in the remaining 161 cases using the SSP technique. Most of the "missed" specificities (86.5%) were those for which serological reagents were not available (HLA-Cw*12-*17). The most commonly "missed" specificity was HLA-Cw*1203, which occurred in 13.9% of the healthy blood donors. These results indicate that serological HLA-Cw typing is insufficient for examining the clinical importance of HLA-Cw matching in transplantation. Future studies based on molecular typing should allow the proper investigation of HLA-Cw matching in kidney and bone marrow transplantation.

Decreased level of T cell receptor expression by Down syndrome (trisomy 21) thymocytes.

Individuals with Down syndrome (DS) have an enhanced susceptibility to viral and bacterial infections. Previous studies by our laboratory demonstrated alterations in the proportions of peripheral T cell subpopulations and decreased proliferative, interleukin-2, and antibody responses to viral and bacterial antigens in DS. These data suggested that DS lymphocytes have a diminished ability to recognize and respond to specific antigen. It has been proposed that the abnormalities in T cell function in DS may be a result of aberrant T cell maturation within the DS thymus. Therefore, we examined by immunofluorescence and flow cytometry the cell surface expression of the alpha,beta chains of the T cell receptor (TCR alpha,beta) and the associated CD3 molecule on thymocytes from 10 DS and 27 control children. A significantly smaller proportion of cells expressing high levels of TCR alpha,beta was observed in DS thymuses compared to controls (17.0% vs. 34.3%, respectively; P less than 0.01). A similar observation was made for CD3, a molecule responsible for signal transduction through the TCR, where a lower proportion of cells expressing high levels of CD3 was found in DS compared to controls (18.4% vs. 43.3%, respectively; P less than 0.001). These data are evidence for aberrant T cell maturation in DS. In addition, our findings of decreased acquisition of high levels of the molecules which are critical for antigen-specific recognition by T cells suggest a possible mechanism for the decreased T cell function found in individuals with DS.

Overlapping polypeptide induction in human fibroblasts in response to treatment with interferon-alpha, interferon-gamma, interleukin 1 alpha, interleukin 1 beta, and tumor necrosis factor.

Cytokine-induced polypeptides were identified in whole cell lysates of human fibroblasts by computer-based analysis of two-dimensional gels with the use of the PDQuest System. Treatment with interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) enhanced the synthesis of 12 and 28 polypeptides, respectively. Exposure to interleukin 1 alpha (IL-1 alpha) or interleukin 1 beta (IL-1 beta) resulted in the increased synthesis of seven identical polypeptides. Treatment with tumor necrosis factor (TNF) at 100 U/ml led to enhanced expression of seven polypeptides, whereas exposure to TNF at 1000 U/ml increased the levels of these seven plus two additional polypeptides. The antiviral and antiproliferative effects of these cytokines in strain 153 fibroblasts were also assessed. Both IFN-alpha and IFN-gamma exhibited antiviral activity, whereas both IL-1 and TNF stimulated fibroblast growth. IFN-gamma was alone in inhibiting proliferation. Thus, although these cytokines exhibit low degrees of structural homology, they share some common functions, and a number of polypeptides were induced in common by two or more of these agents. The greatest similarities in polypeptide induction occur between IFN-alpha and IFN-gamma and between the IL-1s and TNF. However, polypeptides were also induced in common by IFN-alpha and TNF, IFN-gamma and IL-1, and IFN-gamma and TNF. These similarities in polypeptide induction may reflect the overlapping functions of these cytokines and may be indicative of common biochemical pathways in their mechanisms of action.