The role of Aflibercept in the management of age-related macular degeneration

ABSTRACT

Introduction: During the past decade, significant advances have occurred in the management of neovascular age-related macular degeneration (NV-AMD). The advent of anti-vascular endothelial growth factor (anti-VEGF) therapy has shifted the treatment goal of NV-AMD from merely salvaging vision to improving visual acuity and maintaining a good quality of life. Aflibercept (AFL) is a significant addition to the arsenal of anti-VEGF therapies against the NV-AMD. In the index review, pharmacology and efficacy of AFL has been reviewed.

Areas Covered: An extensive literature search was performed to identify preclinical and clinical studies performed to illustrate the role of AFL in NV-AMD. Randomized clinical trials evaluating other anti-VEGF agents were also included for comparison. Additionally, studies where AFL was employed to treat anti-VEGF-resistant cases agents have been reviewed.

Expert Opinion: AFL is an effective agent in the management of NV-AMD and its efficacy has been found to be comparable to ranibizumab (RBZ). Additionally, AFL is a good alternative agent in patients with NV-AMD resistant to RBZ and bevacizumab (BVZ), and can potentially lessen the treatment burden. As more research is conducted, the role of AFL in varying dosing regimens, as monotherapy and in combination with other agents, will become further defined.     

Inflammatory Response with Osteolysis Related to a Bioabsorbable Anchor in the Finger: a Case Report

Soft tissue fixation of ligaments and tendons in the hand can be achieved by the use of metal or bioabsorbable suture anchors. Advantages of bioabsorbable suture anchors include lack of interference in magnetic resonance imaging, resorption of anchor, replacement by bone, and no need for hardware removal. However, complications of these bioabsorbable implants include inflammatory response to the material use. We present what we believe to be the first case in the hand of a poly(l-lactide-co-d,l-lacitide) suture anchor causing an inflammatory response leading to significant osteolysis 4 months postoperatively after repair of a ring finger flexor digitorum profundus avulsion. Exploration of the distal phalanx revealed an intact implant and repair, no signs of infection, and an extensive bone defect. Pathology showed chronically inflamed tissue. This case has led us to reconsider the use of bioabsorbable anchor sutures in the hand. Further research is necessary to better define the contraindications to bioabsorbable suture anchor use in the hand.     

Tissue transglutaminase interacts with protein kinase A anchor protein 13 in prostate cancer

We have previously described that tissue transglutaminase (tTG) is a high level phenotypic biomarker in prostate cancer, which is down regulated in prostate cancer and surrounding premalignant field compared to benign prostate glands. To understand the function of tTG in prostate cancer, we sought to identify proteins that interact with the transglutaminase moiety of tTG using a human prostate cancer complementary deoxyribonucleic acid library in a Yeast 2-Hybrid system. The Yeast 2-Hybrid experiments identified a strong and novel interaction between the transglutaminase moiety and protein kinase A anchor protein 13 (AKAP13), which was quantified by β-galactosidase assay, confirmed in vitro by immunoprecipitation experiments using PC3 prostate cancer cell lysates, and in vivo colocalization was confirmed by immunofluorescence studies in PC3 cells. Because AKAP plays a major role in protein kinase A and Rho protein mediated signaling, functional studies are underway to elucidate the significance of tTG-AKAP13 interaction in prostate cancer.     

A new device for bone anchor fixation in laparoscopic sacrocolpopexy: The Franciscan laparoscopic bone anchor inserter

Background A laparoscopic modification of the sacrocolpopexy procedure with mesh and bone anchor fixation with the Franciscan laparoscopic bone anchor inserter was developed.Methods We developed a laparoscopic bone anchor inserter for the placement of a titanium bone anchor in sacral segment 3 as fixation for the mesh in laparoscopic sacrocolpopexy procedures performed in women with posthysterectomy vault prolapse.Results Surgery successfully corrected vaginal vault prolapse. Laparoscopic bone anchor insertion with this new and simple device took 2 minutes and provided a firm anchor for mesh fixation. MRI demonstrated an anatomically preferable vaginal axis toward the hollow of the sacrum.Conclusion Application of the newly developed Franciscan laparoscopic bone anchor inserter in laparoscopic sacrocolpopexy is an easy and safe procedure that provides firm fixation and excellent anatomical results.     

Mosaic genes and mosaic chromosomes-genomic variation in Streptococcus pneumoniae

The genome sequences of two strains of Streptococcus pneumoniae, one of the major human pathogens, are currently available: that of the nonencapsulated laboratory strain R6, the origin of which dates back to the early 20th century, and of the serotype 4 TIGR strain isolated recently. The two genomes are not only different in size (2 versus 2.16 Mb) but differ also by approximately 10% of their genes, many of which being organized in large clusters. Their strain-specific genes and gene clusters are described here. The R6 genome contains 69 kb organized in six large regions that are absent from the TIGR strain, which in turn contains an extra 157kb in twelve clusters compared to R6. In addition, the TIGR strain contains 13 clusters of 4 kb and larger that are not shared by a variety of genetically different S. pneumoniae strains. Many regions bear signs of gene transfer events such as the presence of insertion sequences, transposable elements, and putative site-specific integrases/recombinases. Three strain-specific regions are devoted to genes encoding proteins with the cell wall anchor motif LPXTG which are important for the interaction with host cells and appear to be highly variable, similar to cell wall-associated choline-binding proteins.     

Repair of partial patellar ligament avulsion during total knee arthroplasty using the Statak device

 The Statak is a suture anchor device used for attaching soft tissue to bone. This is a report on six knees in which this device was used to repair partial avulsion of the patellar ligament during total knee arthroplasty (TKA). The six patients were all women. The average age of the patients was 69 years. The diagnosis was osteoarthritis in three patients, rheumatoid arthritis in two, and steroid arthropathy in one. Three of the operations were revision arthroplasties. In all six cases, approximately half of the patellar ligaments were accidentally detached from the tibial tubercles during surgery, and were repaired using the Statak devices. The average length of follow-up was 3 years. The Knee Society knee score improved from an average of 15 points preoperatively to 87 points at the latest follow-up. The average total range of motion measured 104° before surgery and 108° at the latest follow-up. Three of the six knees operated on had no extensor lag. The suture anchor simplifies the secure fixation of the ligament to bone. The procedure can be performed easily and quickly. In our opinion, the Statak device has proven itself to be effective for the repair of partial patellar ligament avulsion during TKA. Received: December 14, 2001 / Accepted: March 26, 2002 Correspondence to: K. Yamada     

Novel ultrasound assisted suture anchor system using the BoneWelding® technology yields a comparable primary stability in osteopenic and healthy human humeri as a benchmark anchor

Introduction

The aim of this biomechanical study was to evaluate the primary stability of the SportWelding® Sombrero 3.6 mm suture anchor system in osteopenic and healthy cadaveric humeri.

Fixation Strength of Polyetheretherketone Sheath-and-Bullet Device for Soft Tissue Repair in the Foot and Ankle

Tendon transfers are often performed in the foot and ankle. Recently, interference screws have been a popular choice owing to their ease of use and fixation strength. Considering the benefits, one disadvantage of such devices is laceration of the soft tissues by the implant threads during placement that potentially weaken the structural integrity of the grafts. A shape memory polyetheretherketone bullet-in-sheath tenodesis device uses circumferential compression, eliminating potential damage from thread rotation and maintaining the soft tissue orientation of the graft. The aim of this study was to determine the pullout strength and failure mode for this device in both a synthetic bone analogue and porcine bone models. Thirteen mature bovine extensor tendons were secured into ten 4.0?×?4.0?×?4.0-cm cubes of 15-pound per cubic foot solid rigid polyurethane foam bone analogue models or 3 porcine femoral condyles using the 5?×?20-mm polyetheretherketone soft tissue anchor. The bullet-in-sheath device demonstrated a mean pullout of 280.84 N in the bone analog models and 419.47 N in the porcine bone models. (p?=?.001). The bullet-in-sheath design preserved the integrity of the tendon graft, and none of the implants dislodged from their original position.     

Monitoring humans for somatic mutation in the endogenous PIG-a gene using red blood cells

The endogenous X-linked PIG-A gene is involved in the synthesis of glycosyl phosphatidyl inositol (GPI) anchors that tether specific protein markers to the exterior of mammalian cell cytoplasmic membranes. Earlier studies in rodent models indicate that Pig-a mutant red blood cells (RBCs) can be induced in animals treated with genotoxic agents, and that flow cytometry can be used to identify rare RBCs deficient in the GPI-anchored protein, CD59, as a marker of Pig-a gene mutation. We investigated if a similar approach could be used for detecting gene mutation in humans. We first determined the frequency of spontaneous CD59-deficient RBCs (presumed PIG-A mutants) in 97 self-identified healthy volunteers. For most subjects, the frequency of CD59-deficient RBCs was low (average of 5.1 ± 4.9 × 10(-6) ; median of 3.8 × 10(-6) and mutant frequency less than 8 × 10(-6) for 75% of subjects), with a statistically significant difference in median mutant frequencies between males and females. PIG-A RBC mutant frequency displayed poor correlation with the age and no correlation with the smoking status of the subjects. Also, two individuals had markedly increased CD59-deficient RBC frequencies of ～300 × 10(-6) and ～100 × 10(-6) . We then monitored PIG-A mutation in 10 newly diagnosed cancer patients undergoing chemotherapy with known genotoxic drugs. The frequency of CD59-deficient RBCs in the blood of the patients was measured before the start of chemotherapy and three times over a period of ～6 months while on/after chemotherapy. Responses were generally weak, most observations being less than the median mutant frequency for both males and females; the greatest response was an approximate three-fold increase in the frequency of CD59-deficient RBCs in one patient treated with a combination of cisplatin and etoposide. These results suggest that the RBC PIG-A assay can be adopted to measuring somatic cell mutation in humans. Further research is necessary to determine the assay's sensitivity in detecting mutations induced by genotoxic agents acting via different mechanisms.