Patient-based decision for resuming activity after ACL reconstruction: a single-centre experience

Purpose

The purpose of the study was to report the functional outcome following anterior cruciate ligament (ACL) reconstruction in patients who decide when to resume work and normal sporting activity post-operatively. The hypothesis tested was that patient-based decision to return to work and sport was possible without compromising functional outcome and increased the rate of repeat rupture in comparison with the existing literature.

Methods

This was a monocentric, retrospective study. Seventy-two patients requiring primary ACL reconstruction were included. All patients were followed up for a mean period of 4.3 years. Return to work and to sporting activity was allowed based on patient’s decision. No restriction was suggested by the physician. Delays to return to work and sports and occurrence of graft failure were documented.

Results

Sixty-six patients (92 %) returned to any sporting activity. The mean delay was 4.1 months for running, 6.1 months for pivoting sports, and 6.6 months for contact sports. Return to competitive sport was possible in 82 % of patients after a mean delay of 7.1 months. Return to work was possible for 96 % of patients after a mean delay of 2.3 months. Index Tegner score normalized in 71 % of patients. Four repeat ruptures (6 %) were observed, all of them following a significant knee injury.

Conclusions

Patient-based decision to return to work and sport was possible without compromising functional outcome. The post-operative restrictions implemented by orthopaedic surgeons following ACL reconstructions may be relaxed and more patient based.

     

Expression and detection strategies for an scFv fragment retaining the same high affinity than Fab and whole antibody: Implications for therapeutic use in prion diseases

Since antibodies currently constitute the most rapidly growing class of human therapeutics, the high-yield production of recombinant antibodies and antibody fragments is a real challenge. Using as model a monoclonal antibody directed against the human prion protein that we prepared previously and tested for its therapeutic value, we describe here experimental conditions allowing the production of large quantities (up to 35 mg/l of bacterial culture) of correctly refolded and totally functional single chain fragment variable (scFv). These quantities were sufficient to characterize the binding properties of this small recombinant fragment through in vitro and ex vivo approaches. Interestingly, this scFv retains full binding capacity for its antigen, i.e. the human prion protein, when compared with the corresponding Fab or whole antibody, and recognizes soluble, solid-phase-adsorbed, and membrane-bound prion protein. This strongly suggests that from the mAb cloning step to the refolding of the recombinant fragment, each stage is well controlled, leading to almost 100% functional scFv. These results are of interest not only in view of possible immunotherapy for prion diseases, but also more generally in emphasizing the great promise of these small recombinant molecules in the context of targeted therapies.     

Carbonic anhydrase enzymes for regulating mast cell hematopoiesis and type-2 inflammation: a patent evaluation (WO2017/058370)

Introduction: Activity modulators of carbonic anhydrases hold great potential for several therapeutic applications against ophthalmologic and neurological disease, cancer, and infectious diseases. The involvement of carbonic anhydrase in the regulation of mast cell response opens new ways for the treatment of mastocytosis, allergic inflammation, and parasite infection.

Areas covered: The application claims the use of carbonic anhydrase activity modulators (inhibitors or activators) for treating allergic disease, bacterial infection, fungal infection, viral infection, mastocytosis, or mast cell–mediated inflammation.

Expert opinion: Although there is a lack of essential biological data, this patent proposes a new type of applications for carbonic anhydrase inhibitors and deserves further studies. This may lead to new advances in the field of carbonic anhydrase with potential therapeutic implications in the management of type-2 inflammation.     

Transbilayer mobility and distribution of red cell phospholipids during storage.

We studied phospholipid topology and transbilayer mobility in red cells during blood storage. The distribution of phospholipids was determined by measuring the reactivity of phosphatidylethanolamine with fluorescamine and the degradation of phospholipids by phospholipase A2 and sphingomyelinase C. Phospholipid mobility was measured by determining transbilayer movements of spin-labeled phospholipids. We were unable to detect a change in the distribution of endogenous membrane phospholipids in stored red cells even after 2-mo storage. The rate of inward movement of spin-labeled phosphatidylethanolamine and phosphatidylserine was progressively reduced, whereas that for phosphatidylcholine was increased. These changes in phospholipid translocation correlated with a fall in cellular ATP. However, following restoration of ATP, neither the rate of aminophospholipid translocation nor the transbilayer movement of phosphatidylcholine were completely corrected. Taken together, our findings demonstrate that red cell storage alters the kinetics of transbilayer mobility of phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine, the activity of the aminophospholipid translocase, but not the asymmetric distribution of endogenous membrane phospholipids, at least at a level detectable with phospholipases. Thus, if phosphatidylserine appearance on the outer monolayer is a signal for red cell elimination, the amount that triggers macrophage recognition is below the level of detection upon using the phospholipase technique.     

The quantified patient: a patient participatory culture

The Quantified Self Movement, which aims to improve various aspects of life and health through recording and reviewing daily activities and biometrics, is a new and upcoming practice of self monitoring that holds much promise. Now, the most underutilized resource in ambulatory health care, the patient, can participate like never before, and the patient’s Quantified Self can be directly monitored and remotely accessed by health care professionals.     

Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling

The CXCR4 chemokine receptor is a G(i) protein-coupled receptor that triggers multiple intracellular signals in response to stromal cell-derived factor 1 (SDF-1), including calcium mobilization and p44/42 extracellular signal-regulated kinases (ERK1/2). Transduced signals lead to cell chemotaxis and are terminated through receptor internalization depending on phosphorylation of the C terminus part of CXCR4. Receptor endocytosis is also required for some receptors to stimulate ERK1/2 and to migrate through a chemokine gradient. In this study, we explored the role played by the 3 intracellular loops (ICL1-3) and the C terminus domain of CXCR4 in SDF-1-mediated signaling by using human embryonic kidney (HEK)-293 cells stably expressing wild-type or mutated forms of CXCR4. ICL3 of CXCR4 is specifically involved in G(i)-dependent signals such as calcium mobilization and ERK activation, but does not trigger CXCR4 internalization after SDF-1 binding, indicating that ERK phosphorylation is independent of CXCR4 endocytosis. Surprisingly, ICL2, with or without the aspartic acid, arginine, and tyrosine (DRY) motif, is dispensable for G(i) signaling. However, ICL2 and ICL3, as well as the C terminus part of CXCR4, are needed to transduce SDF-1-mediated chemotaxis, suggesting that this event involves multiple activation pathways and/or cooperation of several cytoplasmic domains of CXCR4.