Quadriceps tendon autograft is becoming increasingly popular in revision ACL reconstruction

© 2021, The Author(s). Purpose: To evaluate trends in revision anterior cruciate ligament reconstruction (ACL-R), with emphasis on intra-articular findings, grafts, and concurrent procedures. It was hypothesized that revision ACL-Rs over time show a trend toward increased complexity with increased use of autografts over allografts. Methods: This was a two-center retrospective study including patients undergoing revision ACL-R between 2010 and 2020. Demographic and surgical data including intra-articular findings and concurrent procedures were collected and compared for the time periods 2010–2014 and 2015–2020. All collected variables were compared between three pre-defined age groups (\u3c 20 years, 20–30 years, \u3e 30 years), right and left knees, and males and females. A time series analysis was performed to assess trends in revision ACL-R. Results: This study included 260 patients with a mean age of 26.2 ± 9.4 years at the time of the most recent revision ACL-R, representing the first, second, third, and fourth revision ACL-R for 214 (82%), 35 (14%), 10 (4%), and 1 (\u3c 1%) patients, respectively. Patients age \u3e 30 years showed a significantly longer mean time from primary ACL-R to most recent revision ACL-R (11.1 years), compared to patients age \u3c 20 years (2.2 years, p \u3c 0.001) and age 20–30 years (5.5 years, p \u3c 0.05). Quadriceps tendon autograft was used significantly more often in 2015–2020 compared to 2010–2014 (49% vs. 18%, p \u3c 0.001). A high rate of concurrently performed procedures including meniscal repairs (45%), lateral extra-articular tenodesis (LET; 31%), osteotomies (13%), and meniscal allograft transplantations (11%) was shown. Concurrent LET was associated with intact cartilage and severely abnormal preoperative knee laxity and showed a statistically significant and linear increase over time (p \u3c 0.05). Intact cartilage (41%, p \u3c 0.05), concurrent medial meniscal repairs (39%, p \u3c 0.05), and LET (35%, non-significant) were most frequently observed in patients aged \u3c 20 years. Conclusion: Quadriceps tendon autograft and concurrent LET are becoming increasingly popular in revision ACL-R. Intact cartilage and severely abnormal preoperative knee laxity represent indications for LET in revision ACL-R. The high rate of concurrent procedures observed demonstrates the high surgical demands of revision ACL-R. Level of evidence: Level III

Closing-Wedge Posterior Tibial Slope-Reducing Osteotomy in Complex Revision ACL Reconstruction

Background: A posterior tibial slope (PTS) >12° has been shown to correlate with failure of anterior cruciate ligament (ACL) reconstruction (ACLR). PTS-reducing osteotomy has been described to correct the PTS in patients with a deficient ACL, mostly after failure of primary ACLR. Purpose: To report radiologic indices, clinical outcomes, and postoperative complications after PTS-reducing osteotomy performed concurrently with revision ACLR (R-ACLR). Study design: Case series; Level of evidence, 4. Methods: A review of medical records at 3 institutions was performed of patients who had undergone PTS-reducing osteotomy concurrently with R-ACLR between August 2010 and October 2020. Radiologic parameters recorded included the PTS, patellar height according to the Caton-Deschamps Index (CDI), and anterior tibial translation (ATT). Patient-reported outcomes (International Knee Documentation Committee [IKDC] and Knee injury and Osteoarthritis Outcome Score [KOOS]), reoperations, and complications were evaluated. Results: Included were 23 patients with a mean follow-up of 26.7 months (range, 6-84 months; median, 22.5 months). Statistically significant differences from preoperative to postoperative values were found in PTS (median [range], 14.0° [12°-18°] vs 4.0° [0°-15°], respectively; P < .001), CDI (median, 1.00 vs 1.10, respectively; P = .04) and ATT (median, 8.5 vs 3.6 mm, respectively; P = .001). At the final follow-up, the IKDC score was 52.4 ± 19.2 and the KOOS subscale scores were 81.5 ± 9.5 (Pain), 74 ± 21.6 (Symptoms), 88.5 ± 8 (Activities of Daily Living); 52.5 ± 21.6 (Sport and Recreation), and 48.8 ± 15.8 (Quality of Life). A traumatic ACL graft failure occurred in 2 patients (8.7%). Reoperations were necessary for 6 patients (26.1%) because of symptomatic hardware, and atraumatic recurrent knee instability was diagnosed in 1 patient (4.3%). Conclusion: Tibial slope-reducing osteotomy resulted in a significant decrease of ATT and can be considered in patients with a preoperative PTS ≥12° and ≥1 ACLR failure. In highly complex patients with multiple prior surgeries, the authors found a reasonably low graft failure rate (8.7%) when utilizing PTS-reducing osteotomy. Surgeons must be aware of potential complications in patients with multiple previous failed ACLRs

The outburst of the changing-look AGN IRAS23226-3843 in 2019

IRAS23226-3843 has previously been classified as a changing-look AGN based on X-ray and optical spectral variations. In 2019, Swift observations revealed a strong rebrightening in X-ray and UV fluxes in comparison to observations in 2017. We took follow-up Swift, XMM-Newton, and NuSTAR observations together with optical spectra (SALT and SAAO 1.9m telescope) from 2019 until 2021. IRAS23226-3843 showed a strong X-ray and optical outburst in 2019. It varied in the X-ray and optical continuum by a factor of 5 and 1.6, respectively, within two months. This corresponds to a factor of 3 in the optical after correction for the host galaxy contribution. The Balmer and FeII emission-line intensities showed comparable variability amplitudes. The Halpha profiles changed from a blue-peaked profile in the years 1997 and 1999 to a broad double-peaked profile in 2017 and 2019. However, there were no major profile variations in the extremely broad double-peaked profiles despite the strong intensity variations in 2019. One year after the outburst, the optical spectral type changed and became a Seyfert type 2 in 2020. Blue outflow components are present in the Balmer lines and in the Fe band in the X-rays. A deep broadband XMM-Newton/NuSTAR spectrum was taken during the maximum state in 2019. This spectrum is qualitatively very similar to a spectrum taken in 2017, but by a factor of 10 higher. The soft X-ray band appears featureless. The soft excess is well modeled with a Comptonization model. A broadband fit with a power-law continuum, Comptonized soft excess, and Galactic absorption gives a good fit to the combined EPIC-pn and NuSTAR spectrum. In addition, we see a complex and broadened Fe K emission-line profile in the X-rays. The changing-look character in IRAS23226-3843 is most probably caused by changes in the accretion rate -- based on the short-term variations on timescales of weeks to months.Comment: 21 pages, 14 figures, Astronomy & Astrophysics in pres

Personalized medicine with IgGAM compared with standard of care for treatment of peritonitis after infectious source control (the PEPPER trial): study protocol for a randomized controlled trial

Background: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum). Methods/design: A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival. Discussion: This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine. Trial registration: EudraCT, 2016–001788-34; ClinicalTrials.gov, NCT03334006. Registered on 17 Nov 2017. Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort)

Glioblastomas with primitive neuronal component harbor a distinct methylation and copy‑number profle with inactivation of TP53, PTEN, and RB1

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.publishedVersio

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Association of Ferredoxin:NADP+ oxidoreductase with the photosynthetic apparatus modulates electron transfer in Chlamydomonas reinhardtii

R.M. acknowledges support from the MEXT (Ministry of Education, Culture, Sports, Science and Technology, 15K21122). T.H. gratefully acknowledges support from the DFG (DIP project cooperation “Nanoengineered optoelectronics with biomaterials and bioinspired assemblies”) and the Volkswagen Foundation (LigH2t). G.K. acknowledges support from CREST, Japan Science and Technology Agency. M.H. acknowledges support from the DFG (Deutsche Forschungsgemeinschaft, HI 739/13-1)

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human osteosarcoma. Finally, the current position of canine osteosarcoma genetic research is discussed and areas for additional work within the canine population are identified

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits