Safety and Efficacy With Augmented Second-Generation Perforated Pedicle Screws in Treating Degenerative Spine Disease in Elderly Population.

BACKGROUND: Degenerative spine disease is a common cause of low back pain in people age 65 years or older. Nonsurgical treatment is tried first, but if it is unsuccessful, surgery is advocated. This has special connotations for both underlying disease and the biomechanical characteristics of osteoporotic bone. We conducted an observational study to investigate the clinical and radiological outcome in patients in this age group with poor bone quality and degenerative lumbar instability treated with fusion using perforated pedicle screws augmented with polymethylmethacrylate (PMMA). METHODS: We collected prospective data on treatment, outcome, and patient characteristics from our institution's database. The primary outcome was a change in pain and physical function measured by the visual analog scale, the Core Outcome Measures Index, and the Oswestry Disability Index. Control participants were also analyzed for secondary complications such as hardware mobilization, fusion (as apparent on radiographs), and adjacent fractures or adjacent degenerative disc disease. RESULTS: We included 89 patients who underwent surgery between October 2015 and February 2018 at a mean age of 78 years (range, 67-88 years) and were then monitored for at least 12 months (range, 12-40 months). Findings on pain and function questionnaires showed improvement at 6 months after surgery, maintained at the final evaluation; 90% of patients had final score increases of ≥15 points. No patient developed clinical complications secondary to PMMA leakages. One patient had nonunion and screw breakage. No other patient had clinical or radiological nonunion. Of the control participants, 6 had adjacent disc disease, with 2 of them requiring instrumentation extension. Six deep infections required surgical revision without removal of material. CONCLUSION: PMMA-augmented cannulated pedicle screw instrumentation in spine fusion effectively and safely treats degenerative lumbar disease in patients who are age 65 years or older with poor bone quality.

Enhanced cytoplasmic sequestration of the nuclear export receptor CRM1 by NS2 mutations developed in the host regulates parvovirus fitness.

To investigate whether a DNA virus can evade passive immunotherapy with a polyclonal antiserum, we analyzed the protection of a neutralizing capsid antiserum against a lethal infection of the immunosuppressive strain of the parvovirus minute virus of mice (MVMi) in 42 immunodeficient mice over a period of 200 days. A few mice were effectively protected, but most developed a delayed lethal leukopenic syndrome during the treatment or weeks afterwards. Unexpectedly, viruses isolated from treated but also from control leukopenic mice showed no amino acid changes throughout the entire capsid coding region, although the viral populations were genetically heterogeneous, mainly in the second exon of the coding sequence of the NS2 nonstructural protein. The NS2 point amino acid changes (T88A, K96E, L103P, and L153 M) that were consistently selected in several mice clustered within the nuclear exportin CRM1 binding domain, in a reading frame that did not alter the overlapping NS1 coding region. These mutations endowed emerging viruses with an increased fitness that was demonstrable by their relative resistance to the neutralizing capsid antiserum in a postentry plaque-forming assay, the rapid overgrowth of a competing wild-type (wt) population in culture, and a larger yield of infectious particles. Mutant NS2 proteins interacted with a higher affinity and sequestered CRM1 in the perinuclear region of the cytoplasm more efficiently than the wt. Correspondingly this phenomenon, as well as the following timely ordered release of the NS1 nonstructural protein and the empty capsid from the nucleus to the cytoplasm, occurred markedly earlier in the infection cycle of the mutant viruses. We hypothesize that the enhanced cytoplasmic sequestration of CRM1 by the NS2 mutations selected in mice may trigger pleiotropic effects leading to an accelerated MVMi life cycle and thus to increased fitness. These results strengthen our earlier report on the rapid evolutionary capacity of this mammalian-specific DNA virus in vivo and indicate that the NS2-CRM1 interaction is an important determinant of parvovirus virulence that can be modulated in nature, hampering the effectiveness of passive antibody therapies in the long term.

Parvovirus infection suppresses long-term repopulating hematopoietic stem cells.

The functional disturbance of self-renewing and multipotent hematopoietic stem cells (HSCs) in viral diseases is poorly understood. In this report, we have assessed the susceptibility of mouse HSCs to strain i of the autonomous parvovirus minute virus of mice (MVMi) in vitro and during persistent infection of an immunodeficient host. Purified 5FU(r) Lin(-) Sca-1(+) primitive hematopoietic precursors were permissive for MVMi genome replication and the expression of viral gene products. The lymphoid and myeloid repopulating capacity of bone marrow (BM) cells was significantly impaired after in vitro infection, although the degree of functional effect proportionally decreased with the posttransplantation time. This indicated that MVMi targets the heterogeneous compartment of repopulating cells with differential affinity and suggests that the virus may persist in some primitive HSCs in the quiescent stage, killing those eventually recruited for proliferative activity. Immunodeficient SCID mice oronasally infected with MVMi were cured of the characteristic virus-induced lethal leukopenia by transplantation of immunocompetent BM grafts. However, two double-stranded viral DNA species, probably uncommon replicative intermediates, remained in the marrow of every transplanted mouse months after infectious virus clearance. Genetic analysis of the rescued mice showed that the infection ensured a stable engraftment of donor hematopoiesis by markedly depleting the pool of endogenous HSCs. The MVMi-induced suppression of HSC functions illustrates the accessibility of this compartment to infection during a natural viral hematological disease. These results may provide clues to understanding delayed hematopoietic syndromes associated with persistent viral infections and to prospective gene delivery to HSCs in vivo.