Monomeric C reactive protein (mCRP) presents important proinflammatory effects in endothelial cells, leukocytes, or chondrocytes. However, CRP in its pentameric form exhibits weak anti-inflammatory activity. It is used as a biomarker to follow severity and progression in infectious or inflammatory diseases, such as intervertebral disc degeneration (IVDD). This work assesses for the first time the mCRP effects in human intervertebral disc cells, trying to verify the pathophysiological relevance and mechanism of action of mCRP in the etiology and progression of IVD degeneration.

We demonstrated that mCRP induces the expression of multiple proinflammatory and catabolic factors, like nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and lipocalin 2 (LCN2), in human annulus fibrosus (AF) and nucleus pulposus (NP) cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signaling of mCRP.

Our results indicate that the effect of mCRP is persistent and sustained, regardless of the proinflammatory environment, as it was similar in healthy and degenerative human primary AF cells. This is the first article that demonstrates the localization of mCRP in intravertebral disc cells of the AF and NP and that provides evidence for the functional activity of mCRP in healthy and degenerative human AF and NP disc cells.

Aims

CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

Although modern operative intervention for calcaneal fractures has improved the outcome in many patients, there still is no real consensus on treatment, operative technique, or postoperative management. Vira® is a system for reconstruction-arthrodesis of severe calcaneal fractures, consisting in minimally invasive surgery using cannulation technique.

The aim of our study was to elaborate a CPG to assist physiotherapists in decision making and to improve the efficacy and uniformity of care for patients with severe calcaneal fractures.

The CPG was developed according to international methods of guideline development. To identify “best evidence” a structured search was performed. When no evidence was available, consensus between experts (physiotherapist and orthopaedic surgeons) was achieved to develop the guideline. To identify “best clinical experience” and “physiopathology reasoning” focus group of practicing physiotherapists was used. They reviewed the clinical applicability and feasibility of the guideline, and their comments were used to improve it.

CPG include three phases determined from the physiopathology and biomechanical reasoning of surgical system (weeks after the surgery: 2^a–5^a, 5^a–14^a, 14^a–+/−24^a). Unfortunately, evidence related to the treatment of severe calcaneal fracture was sparse and often of poor methodologic quality. The recommendations that were included: early onset (2^a week after the surgery) with early mobility and loading, program of home exercises, manual therapy (articular and miofascial techniques), walking in swimming pool, continuous electromagnetic fields of 99Hz with an intensity of 99 Gaussian during 30 min/day; electrotherapy of the intrinsic muscles of the feet (80Hz; 8:12, 20 mi), a program of active exercises of the feet (dorsiflexion and plantarflexion, not supination and pronation) and resistive exercises of triceps surae muscle (7^a week), criotherapy and anti-inflammatory positions.