Up to 5-year retention of abatacept in Belgian patients with moderate-to-severe rheumatoid arthritis: a sub-analysis of the international, observational ACTION study.

Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23-45%) per protocol, and 51% (95% confidence interval, 40-61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept.

Performance comparison of 159 Thoroughbred racehorses and matched cohorts before and after desmotomy of the interspinous ligament.

Racehorses may perform poorly because of impinging dorsal spinous processes (DSPs) of the thoracolumbar vertebrae. No study has looked objectively at the long-term outcome of racehorses undergoing desmotomy of the interspinous ligament as a treatment for horses with poor performance caused by impinging DSPs. The aim of this study was to examine objectively, by using pre-operative and post-operative racing records, the effectiveness of desmotomy of the interspinous ligament (DISL) in improving the performance of racehorses with impinging DSPs. Medical records of all horses undergoing desmotomy of one or more interspinous ligaments at a referral equine hospital, between February 2015 and September 2016, were reviewed. The study was confined to Thoroughbred racehorses with sufficient historical information and racetrack data to allow their racing performances be compared to that of matched controls. Matched controls were of the same age, sex, and racing type and were trained at the same time by the same trainer as those undergoing desmotomy. The time to follow-up was at least 12 months. Of the 6545 horses presented for poor performance or lameness during the study period, 236 horses (3.6%) underwent desmotomy of one or more interspinous ligaments, and of these, 159 met the inclusion criteria. Horses undergoing desmotomy had significantly better improvement in racing performance than did matched controls. Eight horses developed unilateral neurogenic atrophy of epaxial musculature. DISL between impinging DSPs can improve the performance of racehorses experiencing from poor performance caused by pain resulting from the impinging processes.

Cutting edge: the spirochetemia of murine relapsing fever is cleared by complement-independent bactericidal antibodies.

Abs are the major effectors of host defense against infections with BORRELIA: Bactericidal murine mAbs and their Fabs destroy B. burgdorferi, the agent of Lyme disease, and relapsing fever Borrelia in the absence of complement. These in vitro observations led to the expansion of a search for functionally similar Abs in vivo. In this study, we demonstrate that functionally unique IgM Abs develop in vivo and are responsible for the elimination of spirochetemia in murine models of relapsing fever, without the assistance of complement. Mice deficient in the fifth or third component of complement can clear the spirochetemia, whereas B cell-deficient mice cannot. The B cell-deficient mice developed spirochetemia that was an order of magnitude higher and persisted for a longer period of time in comparison to the wild-type mice. Additionally, B cell-deficient mice passively immunized with immune IgM and with immune serum were protected from challenge.

Labeled Schwann cell transplants versus sural nerve grafts in nerve repair.

This study evaluated the ability of Schwann cell transplants to enhance the recovery of function in injured nerves and compared the results to those produced by sural nerve grafts. Schwann cells were isolated from sciatic nerves, prelabeled with gold fluorescent dye admixed with collagen gel, and placed in resorbable collagen tubes. Twenty-four adult rats underwent severing of the bilateral sciatic nerves, with a 10-mm gap between the nerve stumps. The rats were then divided into two groups. A collagen tube with implanted Schwann cells was implanted in one leg of the Group I rats, and the contralateral leg served as a control and was repaired with a collagen tube filled with collagen gel only. The Group II animals received conduits packed with labeled Schwann cells in one leg to bridge the 10-mm gap; the contralateral leg was repaired with an autogenous sural nerve graft. Recovery of function was assessed physiologically and morphologically. Nerve conduction velocity and nerve action potential amplitude measurements showed that the Schwann cell implants induced return of function comparable to that of the sural nerve grafts. Morphological assessments of myelination suggested a tendency toward greater numbers of myelinated axons in Schwann cell implants than in sural nerve grafts. Anatomical analyses of gold fluorescent dye showed both high viability of prelabeled Schwann cells at 120 days after transplantation and migration as far as 30 mm away from the implant site.

Salvage of vision after hypotension-induced ischemic optic neuropathy.

No effective treatment has been established for nonarteritic anterior ischemic optic neuropathy. Although most cases occur spontaneously, acute hypotension plays a clear role in a subset of patients. We examined three patients with severe visual loss from ischemic optic neuropathy induced by hypotension. The first patient developed anterior ischemic optic neuropathy after excessively rapid correction of malignant hypertension. In the second patient, anterior ischemic optic neuropathy occurred after an episode of orthostatic hypotension from systemic hypovolemia. The third patient developed anterior ischemic optic neuropathy after becoming hypotensive during a routine hemodialysis session. Measures were undertaken immediately to reverse the hypotension in all three patients. This intervention resulted in partial recovery of vision in each patient.

Comparison of macropore, semipermeable, and nonpermeable collagen conduits in nerve repair.

Twelve rabbits were used to study functional nerve regeneration through macropore, semipermeable, and nonpermeable collagen conduits. Each animal underwent a 10-mm bilateral resection of posterior tibial nerve. Lesions were repaired with a macropore collagen tube in one leg, and with a semipermeable or a nonpermeable collagen tube contralaterally. Functional nerve regeneration was evaluated at 6 and 12 weeks post-repair periods. Functional recovery was assessed by electrophysiologic analysis of nerve conduction velocity, amplitude of nerve action potential, amplitude and area of muscle action potential, and by quantitative and qualitative histologic analysis of myelinated nerve fibers from the distal nerve stumps. The macropore-collagen-tube group showed significantly greater functional recoveries than semipermeable or nonpermeable collagen-tube groups, based on electrophysiologic and histologic analyses.

Immunohistochemical localization of basic fibroblast growth factor in mature and developing retinas of normal and RCS rats.

Basic fibroblast growth factor (bFGF) delays photoreceptor degeneration when injected intraocularly in Royal College of Surgeons (RCS) rats with inherited retinal dystrophy. In the present study, we have determined the localization of endogenous bFGF in retinas of normal and RCS rats during the normal developmental period (postnatal days 0-20) and the period of photoreceptor degeneration in RCS rats (days 20-90). bFGF was localized immunohistochemically by indirect immunoperoxidase using two different polyclonal antibodies and one monoclonal antibody against bFGF. bFGF was present in retinas as early as birth, and remained through adult age. Controls using either PBS, non-immune IgG or antibody preabsorbed with bFGF peptide were devoid of label. In normal rats between the ages of birth and postnatal day (P) 4, bFGF was found in developing ganglion cells, superficial blood vessels, some of the innermost cells in the neuroblastic layer, developing horizontal cells, and retinal pigment epithelial (RPE) cells. Between P0 and P4, the intensity of staining increased significantly in horizontal cells. From P6-P10, some cells in the inner nuclear layer remained positive, but horizontal cell staining became less intense in the central retina. The superficial vessels, ganglion cells and RPE cells also remained positive for bFGF. At P20-25, when the retina was essentially mature, bFGF was found in RPE cells, most cells of the ganglion cell layer, and many cells of the inner nuclear layer, but horizontal cells and blood vessels showed a lower concentration of bFGF than they did at younger ages. At P45 and older, blood vessels no longer showed bFGF immunoreactivity. The staining pattern in RCS rats was indistinguishable from that for normal rats at all ages examined. These results show that bFGF is present in the developing and adult rat retina in some neural cells, in addition to vessels and RPE cells. The transient elevated expression of bFGF immunoreactivity in developing horizontal cells and blood vessels suggests a possible role for this growth factor in retinal development. In addition, if RCS retinas possess any difference in bFGF localization or concentration compared to normal retinas, it must be too small to detect by immunohistochemical means, or at least with the reagents used.

Electrophysiological studies of various graft lengths and lesion lengths in repair of nerve gaps in primates.

Electrophysiological studies were used to evaluate neurological recovery in 14 rhesus monkeys with different nerve lesion lengths and graft lengths. After exposure of both sciatic nerves in each animal, baseline evoked nerve action potentials, muscle action potentials, and muscle strength values were determined for the posterior tibial nerves. Each nerve was then crushed over a measured distance. Three weeks later, the crushed segments were resected and the defects repaired with sural nerve grafts. In seven animals, 20-mm resection sites were repaired by 4 x 20-mm grafts in one leg and by 4 x 40-mm grafts contralaterally. In the other seven animals, the lengths of resection sites were 10 mm in one leg and 30 mm contralaterally; both nerve defects in these animals were repaired by 4 x 30-mm grafts. Electrophysiological studies were repeated at one interval of either 4, 7, or 12 months after repair. Postoperative electrophysiological values were compared to baseline values and described by the mean values and by percent recovery. Muscle strength recovery was significantly better in limbs with short lesions. In animals with identical lesion lengths, lesions repaired with shorter grafts (the same length as the defect) did significantly worse than did lesions repaired with longer grafts. This may suggest that any degree of tension at the graft repair site has a deleterious effect on functional nerve regeneration. Nevertheless, it was generally found that nerve lesion length had the greatest negative effect on functional nerve regeneration.

Initial evaluation of variable graft lengths and lesion lengths in the repair of nerve gaps.

This experiment evaluated the electrical and histologic differences between two groups of rats, one of which underwent same-length bilateral resection of posterior tibial nerves prior to being repaired with grafts of different lengths, while the other group underwent different-length resections with same-length graft repair. In this rat model, 18 animals were used and divided into two groups. The first group of animals underwent bilateral resection of 8-mm segments of posterior tibial nerve. To repair these nerves, one leg received two 8-mm sural nerve grafts (Group A), while the other leg received two 16-mm sural nerve grafts (Group B). The second group of rats underwent posterior tibial nerve resections of 8 mm and 16 mm, respectively. The leg with the 8 mm of posterior tibial nerve resected, received two side-by-side 16-mm sural nerve grafts (Group C); the other leg with 16 mm resected, received two 16-mm sural nerve grafts (Group D). Electrophysiologic comparison of nerve conduction velocity for Groups A and B showed a significant difference (p less than 0.05), as did the same comparison for Groups C and D (p less than 0.05). Histologic studies showed that Groups A and D had marked extrafascicular escape of the regenerating nerve axons, disorganizational growth of minifascicles, and loss of integrity of the donor fascicles, while Groups B and C had very minimal extrafascicular escape of regenerating axons.(ABSTRACT TRUNCATED AT 250 WORDS)

A prototype retractor system designed to minimize ischemic brain retractor injury: initial observations.

The authors have developed and patented a neurosurgical retractor system incorporating an infrared emitter and detector that allows detection of cerebral pulsations. Gentle contact with the surface of cat brains shows cerebral pulsations that correlate with arterial pulse as well as mechanical ventilation. The amplitude of cerebral pulsations decreases with higher retraction pressure and disappears at approximately 20 mmHg. The pressure on the surface of the brain decreased 50% in 5 minutes even though the position of the retractor was maintained constant. The authors postulate that monitoring cerebral pulsation may prove useful in clinical neurosurgery with respect to avoiding excessive retraction, which causes brain damage.

Characterization of vascular development in the mouse retina.

The murine retina provides an ideal model for the study of vascular development. In this investigation we have examined the development of blood vessels in flat-mounted whole retinas from C57B6 mice ranging from birth to 4 months of age. Basement membrane components of blood vessels were visualized by indirect immunofluorescence with antibodies against type IV collagen and laminin. Endothelial cells (EC) were labeled with a plant lectin, Ricinus communis agglutinin I (RCA), and antibodies against angiotensin converting enzyme. Results show three stages of vascular differentiation. During the first stage (postnatal days P0-P10), vessels develop radially from optic disc to ora serrata within the presumptive nerve fiber layer. In the second stage beginning P4, vessels form within deeper retinal layers. In the third stage beginning P7, a capillary network develops as branches of radial vessels in the nerve fiber layer. The entire vascular system begins as a polygonal network of capillary-like vessels. Selective regression of various segments of these polygons leads to the ultimate arborous pattern of arteries, arterioles, veins, venules, and capillaries seen in the adult. Some individual EC appear to be left behind during this retraction process and pericytes may have a role in determining which vessel segments regress. This combination of flat-mounted whole retinas and probes specific for vascular elements provides an ideal system for the study of retinal vascularization and the characterization of vasculogenesis in general.