Technical, Psychological, and Economic Aspects of DIEP Flap Breast Reconstruction

In the Western world the incidence of breast cancer (BC) is high. In the Netherlands the lifetime risk for women to develop BC is around 13%, making it the most common form of cancer among women with approximately 12.000 women being diagnosed annually. Also, increasing numbers of women are being identifi ed to be genetically predisposed to develop BC due to a known mutation (e.g., BRCA 1 or 2) or a strong family history. Continuous progress in early detection, diagnostics and treatment of BC have produced signifi cant improvements in disease-free and breast cancer related survival. Despite these advances, mastectomy remains an important surgical option to either adequately manage the disease locally (therapeutic mastectomy) or reduce the signifi cantly increased risk of developing BC in genetically predisposed women (prophylactic mastectomy). This mutilating procedure is a potentially traumatic event in a woman’s life, and a wide range of lasting psychological adjustment problems has been described. Breast reconstruction (BR) is aimed at restoring the amputated breast and thus improving patients’ quality of life and body image after mastectomy. Psychological, social, emotional and functional benefi ts of BR, including improved psychological health, self-esteem, sexuality, and body image have been documented

6-Minute Push Test in Youth Who Have Spina Bifida and Who Self-Propel a Wheelchair: Reliability and Physiologic Response

Objective. Despite the common occurrence of lower levels of physical activity and physical fitness in youth with spina bifida (SB) who use a wheelchair, there are very few tests available to measure and assess these levels. The purpose of this study was to determine reliability and the physiologic response of the 6-minute push test (6MPT) in youth with SB who self-propel a wheelchair. Methods. In this reliability and observational study, a sample of 53 youth with SB (5-19 years old; mean age = 13 years 7 months; 32 boys and 21 girls) who used a wheelchair performed 2 exercise tests: the 6MPT and shuttle ride test. Heart rate, minute ventilation, respiratory exchange ratio, and oxygen consumption were measured using a calibrated mobile gas analysis system and a heart rate monitor. For reliability, intraclass correlation coefficients (ICCs), SE of measurement, smallest detectable change for total covered distance, minute work, and heart rate were calculated. Physiologic response during the 6MPT was expressed as percentage of maximal values achieved during the shuttle ride test. Results. The ICCs for total distance and minute work were excellent (0.95 and 0.97, respectively), and the ICC for heart rate was good (0.81). The physiologic response during the 6MPT was 85% to 89% of maximal values, except for minute ventilation (70.6%). Conclusions. For most youth with SB who use a wheelchair for mobility or sports participation, the 6MPT is a reliable, functional performance test on a vigorous level of exercise. Impact. This is the first study to investigate physiologic response during the 6MPT in youth (with SB) who are wheelchair using. Clinicians can use the 6MPT to evaluate functional performance and help design effective exercise programs for youth with SB who are wheelchair using

Pediatric Achalasia: Diagnosis, Management and Follow-Up in the Netherlands

Su206

CD5L is a canonical component of circulatory IgM

Immunoglobulin M (IgM) is an evolutionary conserved key component of humoral immunity, and the first antibody isotype to emerge during an immune response. IgM is a large (1 MDa), multimeric protein, for which both hexameric and pentameric structures have been described, the latter additionally containing a joining (J) chain. Using a combination of single-particle mass spectrometry and mass photometry, proteomics, and immunochemical assays, we here demonstrate that circulatory (serum) IgM exclusively exists as a complex of J-chain-containing pentamers covalently bound to the small (36 kDa) protein CD5 antigen-like (CD5L, also called apoptosis inhibitor of macrophage). In sharp contrast, secretory IgM in saliva and milk is principally devoid of CD5L. Unlike IgM itself, CD5L is not produced by B cells, implying that it associates with IgM in the extracellular space. We demonstrate that CD5L integration has functional implications, i.e., it diminishes IgM binding to two of its receptors, the FcαµR and the polymeric Immunoglobulin receptor. On the other hand, binding to FcµR as well as complement activation via C1q seem unaffected by CD5L integration. Taken together, we redefine the composition of circulatory IgM as a J-chain containing pentamer, always in complex with CD5L

Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling

The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (J-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a J-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and J-chain coupled dimeric IgA1. The serum dimeric J-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins; one of these produces dimeric J-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum

CD5L is a canonical component of circulatory IgM

Immunoglobulin M (IgM) is an evolutionary conserved key component of humoral immunity, and the first antibody isotype to emerge during an immune response. IgM is a large (1 MDa), multimeric protein, for which both hexameric and pentameric structures have been described, the latter additionally containing a joining (J) chain. Using a combination of single-particle mass spectrometry and mass photometry, proteomics, and immunochemical assays, we here demonstrate that circulatory (serum) IgM exclusively exists as a complex of J-chain-containing pentamers covalently bound to the small (36 kDa) protein CD5 antigen-like (CD5L, also called apoptosis inhibitor of macrophage). In sharp contrast, secretory IgM in saliva and milk is principally devoid of CD5L. Unlike IgM itself, CD5L is not produced by B cells, implying that it associates with IgM in the extracellular space. We demonstrate that CD5L integration has functional implications, i.e., it diminishes IgM binding to two of its receptors, the FcαµR and the polymeric Immunoglobulin receptor. On the other hand, binding to FcµR as well as complement activation via C1q seem unaffected by CD5L integration. Taken together, we redefine the composition of circulatory IgM as a J-chain containing pentamer, always in complex with CD5L

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management