Long-acting lenacapavir acts as an effective preexposure prophylaxis in a rectal SHIV challenge macaque model.

Long-acting antiretroviral agents for preexposure prophylaxis (PrEP) represent a promising new alternative to daily oral regimens for HIV prevention. Lenacapavir (LEN) is a first-in-class long-acting capsid inhibitor approved for the treatment of HIV-1 infection. Here, we assessed the efficacy of LEN for PrEP using a single high-dose simian-human immunodeficiency virus (SHIV) rectal challenge macaque model. In vitro, LEN showed potent antiviral activity against SHIV, as it did for HIV-1. In macaques, a single subcutaneous administration of LEN demonstrated dose proportional increases in and durability of drug plasma levels. A high-dose SHIV inoculum for the PrEP efficacy evaluation was identified via virus titration in untreated macaques. LEN-treated macaques were challenged with high-dose SHIV 7 weeks after drug administration, and the majority remained protected from infection, as confirmed by plasma PCR, cell-associated proviral DNA, and serology testing. Complete protection and superiority to the untreated group was observed among animals whose LEN plasma exposure exceeded its model-adjusted clinical efficacy target at the time of challenge. All infected animals had subprotective LEN concentrations and showed no emergent resistance. These data demonstrate effective SHIV prophylaxis in a stringent macaque model at clinically relevant LEN exposures and support the clinical evaluation of LEN for HIV PrEP in humans.

3D-Printed Guides in Bone Tumor Resection: Studying Their Error and Determining a Safety Margin for Surgery.

3D-printed guides, which have recently been introduced in orthopedic oncology, improve resection accuracy compared with traditional bone resection methods, but there are inaccuracies associated with them. These inaccuracies could lead to disastrous outcomes such as positive tumor resection margins. In this Sawbone study, we sought to quantitatively investigate the margin of error for various jig types and to determine a "safety margin" that could serve as a guide for surgeons and jig engineers in creating 3D-printed jigs that would reduce the risk of potential disastrous results such as positive margins. Various 3D-printed jigs were used to simulate wide resection of a distal femoral bone sarcoma on Sawbone specimens by 10 individuals with no specific prior expertise in cutting guides. We developed a mathematical model using kinematic theory. We defined a safety margin as the amount of change in the osteotomy lines that must be incorporated into the jig design to ensure that the surgeon is at least 98% likely not to have a positive tumor margin. Experiments were conducted to determine the mean deviation experienced in placing cutting guides on the bones. The mean deviation for the four types of cutting guides ranged from 2.86 mm to 6.54 mm. We determined that a jig design should have a safety margin of 4.8 mm for standard guides and 8.65 mm for gusset guides to minimize the possibility of cutting into the tumor as a result of human error in guide placement. Further studies involving cadavers and patients are warranted. [Orthopedics. 2022;45(3):169-173.].

Long-acting capsid inhibitor protects macaques from repeat SHIV challenges.

Because no currently available vaccine can prevent HIV infection, pre-exposure prophylaxis (PrEP) with antiretrovirals (ARVs) is an important tool for combating the HIV pandemic1,2. Long-acting ARVs promise to build on the success of current PrEP strategies, which must be taken daily, by reducing the frequency of administration3. GS-CA1 is a small-molecule HIV capsid inhibitor with picomolar antiviral potency against a broad array of HIV strains, including variants resistant to existing ARVs, and has shown long-acting therapeutic potential in a mouse model of HIV infection4. Here we show that a single subcutaneous administration of GS-CA1 provides long-term protection against repeated rectal simian-human immunodeficiency virus (SHIV) challenges in rhesus macaques. Whereas all control animals became infected after 15 weekly challenges, a single 300 mg kg-1 dose of GS-CA1 provided per-exposure infection risk reduction of 97% for 24 weeks. Pharmacokinetic analysis showed a correlation between GS-CA1 plasma concentration and protection from SHIV challenges. GS-CA1 levels greater than twice the rhesus plasma protein-adjusted 95% effective concentration conferred 100% protection in this model. These proof-of-concept data support the development of capsid inhibitors as a novel long-acting PrEP strategy in humans.

Computer-Assisted Surgical Navigation for Primary and Metastatic Bone Malignancy of the Pelvis: Current Evidence and Future Directions.

Computer-assisted navigation and robotic surgery have gained popularity in the treatment of pelvic bone malignancies, given the complexity of the bony pelvis, the proximity of numerous vital structures, and the historical challenges of pelvic bone tumor surgery. Initial interest was on enhancing the accuracy in sarcoma resection by improving the quality of surgical margins and decreasing the incidence of local recurrences. Several studies have shown an association between intraoperative navigation and increased incidence of negative margin bone resection, but long-term outcomes of navigation in pelvic bone tumor resection have yet to be established. Historically, mechanical stabilization of pelvic bone metastases has been limited to Harrington-type total hip arthroplasty for disabling periacetabular disease, but more recently, computer-assisted surgery has been employed for minimally invasive percutaneous fixation and stabilization; although still in its incipient stages, this procedure is potentially appealing for treating patients with bone metastases to the pelvis. The authors review the literature on navigation for the treatment of primary and metastatic tumors of the pelvic bone and discuss the best practices and limitations of these techniques.

Minimally Invasive Fixation of Pelvic Metastases by CT-Assisted Surgical Navigation.

The treatment of patients with painful metastases and pathologic fracture of the pelvis is challenging and based on multidisciplinary approach. Although radiation and disease-specific systemic therapy are the mainstay of treatment, the goal of surgery is to maintain functional independence. Harrington-type total hip arthroplasty has proven invaluable to address periacetabular cancer. However, data on how to best treat patients with disabling pain due to metastases outside the periacetabular region or involving the entire hemipelvis are scant, heterogeneous, and hardly comparable. Minimally invasive strategies in this setting are appealing and conceivably preferable to open surgery because of lower risk of complications and expedited recovery.

Clinical targeting of HIV capsid protein with a long-acting small molecule.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1-5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment-which contributes to virologic failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7-9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and additionally can improve adherence10. Here we describe GS-6207, a small molecule that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the subcutaneous injection site. Drawing on X-ray crystallographic information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clinical studies, monotherapy with a single subcutaneous dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 months. These results provide clinical validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV.

A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model.

People living with HIV (PLWH) have expressed concern about the life-long burden and stigma associated with taking pills daily and can experience medication fatigue that might lead to suboptimal treatment adherence and the emergence of drug-resistant viral variants, thereby limiting future treatment options1-3. As such, there is strong interest in long-acting antiretroviral (ARV) agents that can be administered less frequently4. Herein, we report GS-CA1, a new archetypal small-molecule HIV capsid inhibitor with exceptional potency against HIV-2 and all major HIV-1 types, including viral variants resistant to the ARVs currently in clinical use. Mechanism-of-action studies indicate that GS-CA1 binds directly to the HIV-1 capsid and interferes with capsid-mediated nuclear import of viral DNA, HIV particle production and ordered capsid assembly. GS-CA1 selects in vitro for unfit GS-CA1-resistant capsid variants that remain fully susceptible to other classes of ARVs. Its high metabolic stability and low solubility enabled sustained drug release in mice following a single subcutaneous dosing. GS-CA1 showed high antiviral efficacy as a long-acting injectable monotherapy in a humanized mouse model of HIV-1 infection, outperforming long-acting rilpivirine. Collectively, these results demonstrate the potential of ultrapotent capsid inhibitors as new long-acting agents for the treatment of HIV-1 infection.

TLR7 Agonist GS-9620 Is a Potent Inhibitor of Acute HIV-1 Infection in Human Peripheral Blood Mononuclear Cells.

GS-9620 is a potent and selective oral Toll-like receptor 7 (TLR7) agonist that directly activates plasmacytoid dendritic cells (pDCs). GS-9620 suppressed hepatitis B virus (HBV) in animal models of chronic infection and transiently activated HIV expression ex vivo in latently infected peripheral blood mononuclear cells (PBMCs) from virally suppressed patients. Currently, GS-9620 is under clinical evaluation for treating chronic HBV infection and for reducing latent reservoirs in virally suppressed HIV-infected patients. Here, we investigated the in vitro anti-HIV-1 activity of GS-9620. GS-9620 potently inhibited viral replication in PBMCs, particularly when it was added 24 to 48 h prior to HIV infection (50% effective concentration = 27 nM). Depletion of pDCs but not other immune cell subsets from PBMC cultures suppressed GS-9620 antiviral activity. Although GS-9620 was inactive against HIV in purified CD4+ T cells and macrophages, HIV replication was potently inhibited by conditioned medium derived from GS-9620-treated pDC cultures when added to CD4+ T cells prior to infection. This suggests that GS-9620-mediated stimulation of PBMCs induced the production of a soluble factor(s) inhibiting HIV replication in trans GS-9620-treated PBMCs primarily showed increased production of interferon alpha (IFN-α), and cotreatment with IFN-α-blocking antibodies reversed the HIV-1-inhibitory effect of GS-9620. Additional studies demonstrated that GS-9620 inhibited a postentry event in HIV replication at a step coincident with or prior to reverse transcription. The simultaneous activation of HIV-1 expression and inhibition of HIV-1 replication are important considerations for the clinical evaluation of GS-9620 since these antiviral effects may help restrict potential local HIV spread upon in vivo latency reversal.

Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile.

Bictegravir (BIC; GS-9883), a novel, potent, once-daily, unboosted inhibitor of HIV-1 integrase (IN), specifically targets IN strand transfer activity (50% inhibitory concentration [IC50] of 7.5 ± 0.3 nM) and HIV-1 integration in cells. BIC exhibits potent and selective in vitro antiretroviral activity in both T-cell lines and primary human T lymphocytes, with 50% effective concentrations ranging from 1.5 to 2.4 nM and selectivity indices up to 8,700 relative to cytotoxicity. BIC exhibits synergistic in vitro antiviral effects in pairwise combinations with tenofovir alafenamide, emtricitabine, or darunavir and maintains potent antiviral activity against HIV-1 variants resistant to other classes of antiretrovirals. BIC displayed an in vitro resistance profile that was markedly improved compared to the integrase strand transfer inhibitors (INSTIs) raltegravir (RAL) and elvitegravir (EVG), and comparable to that of dolutegravir (DTG), against nine INSTI-resistant site-directed HIV-1 mutants. BIC displayed statistically improved antiviral activity relative to EVG, RAL, and DTG against a panel of 47 patient-derived HIV-1 isolates with high-level INSTI resistance; 13 of 47 tested isolates exhibited >2-fold lower resistance to BIC than DTG. In dose-escalation experiments conducted in vitro, BIC and DTG exhibited higher barriers to resistance than EVG, selecting for HIV-1 variants with reduced phenotypic susceptibility at days 71, 87, and 20, respectively. A recombinant virus with the BIC-selected M50I/R263K dual mutations in IN exhibited only 2.8-fold reduced susceptibility to BIC compared to wild-type virus. All BIC-selected variants exhibited low to intermediate levels of cross-resistance to RAL, DTG, and EVG (<8-fold) but remained susceptible to other classes of antiretrovirals. A high barrier to in vitro resistance emergence for both BIC and DTG was also observed in viral breakthrough studies in the presence of constant clinically relevant drug concentrations. The overall virologic profile of BIC supports its ongoing clinical investigation in combination with other antiretroviral agents for both treatment-naive and -experienced HIV-infected patients.

Rapid In Vitro Evaluation of Antiretroviral Barrier to Resistance at Therapeutic Drug Levels.

Failure of combination antiretroviral (ARV) therapy in HIV-infected patients is often associated with the emergence of drug resistance-associated mutations (RAMs). To facilitate analysis of the barrier to resistance at therapeutically relevant ARV concentrations, we performed fixed-dose in vitro HIV-1 drug resistance selection assays using the immortalized MT-2 T-cell line and primary human CD4+ T cells with a panel of FDA-approved ARVs, each at their respective cell culture equivalent clinical trough concentration (CCE Cmin). At high multiples of its CCE Cmin, emtricitabine (FTC) selected for the rapid emergence of M184I/V, a result consistent with resistance emergence in vivo. While the rate of viral breakthrough in the presence of rilpivirine or efavirenz was delayed relative to FTC, both inhibitors selected for virus with known clinically relevant RAMs. No viral breakthrough was observed for the protease inhibitor atazanavir even at subtherapeutic drug concentrations, which is consistent with its previously characterized high in vivo barrier to resistance. Depending on assay conditions, treatment with integrase inhibitors elvitegravir and raltegravir resulted in breakthrough of both resistant and wild-type virus. The RAMs observed in drug selections were not detected above a 2% threshold by deep sequencing in the in vitro virus inoculum, and only rarely in isolates from treatment-naive HIV+ patients. These new viral breakthrough assays facilitate the analysis of multiple experimental replicates and conditions in parallel and provide a rapid quantitative means to evaluate drug resistance emergence at therapeutically relevant drug concentrations, which should facilitate the identification of new ARVs with a high barrier to resistance.

Stigma's Effect on Social Interaction and Social Media Activity.

Stigmatized topics, such as HIV/STD, likely constrain related information sharing in ways that should be apparent in social interactions both on and off the Internet. Specifically, the authors predicted that the more people perceive an issue as stigmatized, the less likely they are to talk about the issue both privately (with sexual partners and peers) and publicly (on Twitter). Study 1 tested the effect of stigma on conversations at the individual level: The authors asked a group of participants (N = 138) about perceived STD-testing stigma, interactions with a sexual partner, and conversations with peers about STD testing. Study 2 assessed whether health conditions, in the aggregate, were less likely to generate social media activity as a function of current stigmatization. Using 259,758 archived Twitter posts mentioning 13 medical conditions, the authors tested whether level of stigma predicted the volume of relevant social media conversation, controlling for each condition's amount of advocacy and Google search popularity from a user's perspective. Findings supported our hypotheses. Individuals who reported perceiving a given health conditions in more stigmatic ways also reported interacting less with others about that topic; Twitter results showed a similar pattern. Results also suggest a more complex story of influence, as funding from the National Institutes of Health (i.e., each conditions amount of advocacy) associated with the examined health conditions also predicted Twitter activity. Overall, these results indicated that stigma had a similar, dampening effect on face-to-face and Twitter interactions. Findings hold theoretical and practical implications, which are discussed.

Improving the accuracy of wide resection of bone tumors and enhancing implant fit: A cadaveric study.

BACKGROUND/AIMS: Customized three-dimensional (3-D) jigs have been shown to increase the accuracy of skeletal tumor resection in comparison to freehand techniques. However, the utility of these jigs in subsequently enhancing the fit of endoprosthetic implants has yet to be determined. We hypothesized that custom jigs would improve implant fit compared to freehand resection. METHODS: Nine matched pairs of cadaveric femurs were scanned by CT. The images then had 'virtual' tumors positioned on the distal medial femoral condyle and preoperative resection plans were generated. Custom implants were designed to fit into the resected spaces and 3-D printed. Similarly, customized 3-D jigs were designed and printed for half of the femurs. Resections were then performed using the jigs or freehand. The implants were positioned in the resected femurs and the accuracy-of-fit was quantitatively assessed by re-scanning the resected femurs and calculating the deviation from the implant (in degrees) for each of the 3 cutting planes. The results were then compared between jig and freehand resections. RESULTS: For the first plane, the jig resulted in less deviation than the freehand cut, but it did not achieve statistical significance. However, for the 2nd and 3rd planes, the jigs deviated 1.78° and 2.20° from the implants compared to 4.41° and 7.96° for the freehand cuts, both of which were statistically significant improvements (p = 0.038 and p = 0.003). CONCLUSION: In summary, customized 3-D jigs were shown to improve the accuracy-of-fit between implants and host bone, moving this technology closer to clinical implementation.

Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

Controlled mechanical ventilation (CMV) is associated with the development of diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is thought to contribute significantly to delayed weaning of patients. Therefore, therapeutic strategies for preventing these processes may have clinical benefit. The aim of the current study was to investigate the role of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in CMV-mediated diaphragm wasting and weakness in rats. CMV-induced diaphragm atrophy and contractile dysfunction coincided with marked increases in STAT3 phosphorylation on both tyrosine 705 (Tyr705) and serine 727 (Ser727). STAT3 activation was accompanied by its translocation into mitochondria within diaphragm muscle and mitochondrial dysfunction. Inhibition of JAK signaling during CMV prevented phosphorylation of both target sites on STAT3, eliminated the accumulation of phosphorylated STAT3 within the mitochondria, and reversed the pathologic alterations in mitochondrial function, reduced oxidative stress in the diaphragm, and maintained normal diaphragm contractility. In addition, JAK inhibition during CMV blunted the activation of key proteolytic pathways in the diaphragm, as well as diaphragm atrophy. These findings implicate JAK/STAT3 signaling in the development of diaphragm muscle atrophy and dysfunction during CMV and suggest that the delayed extubation times associated with CMV can be prevented by inhibition of Janus kinase signaling.-Smith, I. J., Godinez, G. L., Singh, B. K., McCaughey, K. M., Alcantara, R. R., Gururaja, T., Ho, M. S., Nguyen, H. N., Friera, A. M., White, K. A., McLaughlin, J. R., Hansen, D., Romero, J. M., Baltgalvis, K. A., Claypool, M. D., Li, W., Lang, W., Yam, G. C., Gelman, M. S., Ding, R., Yung, S. L., Creger, D. P., Chen, Y., Singh, R., Smuder, A. J., Wiggs, M. P., Kwon, O.-S., Sollanek, K. J., Powers, S. K., Masuda, E. S., Taylor, V. C., Payan, D. G., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

Exercise performance and peripheral vascular insufficiency improve with AMPK activation in high-fat diet-fed mice.

Intermittent claudication is a form of exercise intolerance characterized by muscle pain during walking in patients with peripheral artery disease (PAD). Endothelial cell and muscle dysfunction are thought to be important contributors to the etiology of this disease, but a lack of preclinical models that incorporate these elements and measure exercise performance as a primary end point has slowed progress in finding new treatment options for these patients. We sought to develop an animal model of peripheral vascular insufficiency in which microvascular dysfunction and exercise intolerance were defining features. We further set out to determine if pharmacological activation of 5'-AMP-activated protein kinase (AMPK) might counteract any of these functional deficits. Mice aged on a high-fat diet demonstrate many functional and molecular characteristics of PAD, including the sequential development of peripheral vascular insufficiency, increased muscle fatigability, and progressive exercise intolerance. These changes occur gradually and are associated with alterations in nitric oxide bioavailability. Treatment of animals with an AMPK activator, R118, increased voluntary wheel running activity, decreased muscle fatigability, and prevented the progressive decrease in treadmill exercise capacity. These functional performance benefits were accompanied by improved mitochondrial function, the normalization of perfusion in exercising muscle, increased nitric oxide bioavailability, and decreased circulating levels of the endogenous endothelial nitric oxide synthase inhibitor asymmetric dimethylarginine. These data suggest that aged, obese mice represent a novel model for studying exercise intolerance associated with peripheral vascular insufficiency, and pharmacological activation of AMPK may be a suitable treatment for intermittent claudication associated with PAD.

1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists.

A novel series of CCR1 antagonists based on the 1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanone scaffold was identified by screening a compound library utilizing CCR1-expressing human THP-1 cells. SAR studies led to the discovery of the highly potent and selective CCR1 antagonist 14 (CCR1 binding IC(50)=4 nM using [(125)I]-CCL3 as the chemokine ligand). Compound 14 displayed promising pharmacokinetic and toxicological profiles in preclinical species.

The positive effects of different platelet-rich plasma methods on human muscle, bone, and tendon cells.

BACKGROUND: Clinical application of platelet-rich plasma (PRP) in the realm of orthopaedic sports medicine has yielded variable results. Differences in separation methods and variability of the individual may contribute to these variable results. PURPOSE: To compare the effects of different PRP separation methods on human bone, muscle, and tendon cells in an in vitro model. STUDY DESIGN: Controlled laboratory study. METHODS: Blood collected from 8 participants (mean ± SD age 31.6 ± 10.9 years) was used to obtain PRP preparations. Three different PRP separation methods were used: a single-spin process yielding a lower platelet concentration (PRP(LP)), a single-spin process yielding high platelet and white blood cell concentrations (PRP(HP)), and a double-spin that produces a higher platelet concentration and lower white blood cell concentration (PRP(DS)). Human bone, muscle, and tendon cells obtained from discarded tissue samples during shoulder surgery were placed into culture and treated with the 3 PRP preparations, control media (2% fetal bovine serum [FBS] and 10% FBS), and native blood. Radioactive thymidine assays were obtained to examine cell proliferation, and testing with enzyme-linked immunosorbent assay was used to determine growth factor concentrations. RESULTS: Addition of PRP(LP) to osteocytes, myocytes, and tenocytes significantly increased cell proliferation (P ≤ .05) compared with the controls. Adding PRP(DS) to osteoblasts and tenocytes increased cell proliferation significantly (P ≤ .05), but no significance was shown for its addition to myocytes. The addition of PRP(HP) significantly increased cell proliferation compared with the controls only when added to tenocytes (P ≤ .05). Osteoblasts: Proliferation was significantly increased by addition of PRP(LP) compared with all controls (2% FBS, 10% FBS, native blood) (P ≤ .05). Addition of PRP(DS) led to significantly increased proliferation compared with all controls, native blood, and PRP(HP) (P ≤ .05). Proliferation was significantly less when PRP(HP) was added compared with PRP(DS) (P ≤ .05). Myocytes: Proliferation was significantly increased by addition of PRP(LP) compared with native blood (P ≤ .05). Adding PRP(HP) or PRP(DS) to myocytes showed no significant increase in proliferation compared with the controls or the other separations. Tenocytes: Proliferation was significantly increased by addition of PRP(LP) compared with all controls (2% FBS, 10% FBS, native blood) (P ≤ .05). Addition of PRP(DS) showed a significant increase compared with the controls and native blood. For tenocytes, there was a significant increase (P ≤ .05) seen when PRP(HP) was added compared with the controls and native blood but not compared with the other separations. CONCLUSION: The primary findings of this study suggest the application of different PRP separations may result in a potential beneficial effect on the clinically relevant target cells in vitro. However, it is unclear which platelet concentration or PRP preparation may be optimal for the treatment of various cell types. In addition, a "more is better" theory for the use of higher platelet concentrations cannot be supported. This study was not intended to prove efficacy but to provide a platform for future research to be built upon. CLINICAL RELEVANCE: The utilization of different PRP separations may result in a potentially beneficial effect on the clinically relevant target cells in vitro, but it is unclear which platelet concentration or PRP preparation may be optimal for the treatment of various cell types.

Material properties and composition of soft-tissue fixation.

Surgical interference screws and suture anchors for attaching soft tissue, such as ligaments and tendons, to bone are routinely used in arthroscopic surgery and sports medicine. Interference screw fixation provides a press fit between bone, graft/tendon, and screw and is frequently used to attach replacement ligaments in tunnels drilled for anterior and posterior cruciate ligament reconstruction. Suture anchors are used in surgical procedures wherein it is necessary for a surgeon to attach (tie) tissue to the surface of the bone, for example, during joint reconstruction and ligament repair or replacement. The composition of these implants ranges from metals to polymers and composites. Typically, because of the relatively large amount of torque that must be applied during insertion, these screws are constructed from metal. However, interference screws and suture anchors have also been constructed from bioabsorbable polymers and composites. The ideal material would (1) provide adequate mechanical fixation, (2) completely degrade once no longer needed, and (3) be completely replaced by bone. Because no material has been shown to be superior for all applications, the surgeon must weigh the advantages and disadvantages of each to evaluate the optimum material for a given application and patient. The purpose of this article is to present a comprehensive review of the commercially available interference screws and suture anchors, with an emphasis on implant composition, interaction, and design. This article provides the orthopaedic surgeon with a background on biomaterials, specifically those used in interference screws and suture anchors. Because there is no material that is perfect for all surgical situations, this review can be used to make educated decisions on a case-by-case basis.

Social Participation in Health 2.0.

Computer scientists are working with biomedical researchers, policy specialists, and medical practitioners to usher in a new era in healthcare. A recently convened panel of experts considered various research opportunities for technology-mediated social participation in Health 2.0.