Despite the beneficial therapeutic effects of intravenous immunoglobulin (IVIg) in inflammatory diseases, consistent therapeutic efficacy and potency remain major limitations for patients and ...physicians using IVIg. These limitations have stimulated a desire to generate therapeutic alternatives that could leverage the broad mechanisms of action of IVIg while improving therapeutic consistency and potency. The identification of the important anti-inflammatory role of fragment crystallizable domain (Fc) sialylation has presented an opportunity to develop more potent Ig therapies. However, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for clinical use. Therefore, we set out to develop the first, to our knowledge, robust and scalable process for generating a well-qualified sialylated IVIg drug candidate with maximum Fc sialylation devoid of unwanted alterations to the IVIg mixture. Here, we describe a controlled enzymatic, scalable process to produce a tetra-Fc–sialylated (s4-IVIg) IVIg drug candidate and its qualification across a wide panel of analytic assays, including physicochemical, pharmacokinetic, biodistribution, and in vivo animal models of inflammation. Our in vivo characterization of this drug candidate revealed consistent, enhanced anti-inflammatory activity up to 10-fold higher than IVIg across different animal models. To our knowledge, this candidate represents the first s4-IVIg suitable for clinical use; it is also a valuable therapeutic alternative with more consistent and potent anti-inflammatory activity.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
BACKGROUND:Patients undergoing total hip or knee arthroplasty frequently receive blood transfusions. The relationship between transfusion and the risk of infection following total joint arthroplasty ...is unclear. In this study, we sought to examine the impact of allogeneic and autologous transfusion on the risk of acute infection following total hip and total knee arthroplasty.
METHODS:We performed a retrospective study of consecutive primary total knee arthroplasties and total hip arthroplasties. Patients who had a reoperation for suspected infection within three months after the arthroplasty were identified. Differences in risk factors were assessed across transfusion groupsno transfusion, autologous only, and allogeneic exposure (allogeneic with or without additional autologous transfusion). Backward-stepwise logistic regression analysis was used to compare reoperations (as outcomes) between cases with and those without allogeneic exposure. Prespecified covariates were body mass index, diabetes, an American Society of Anesthesiologists (ASA) score of >2, preoperative hematocrit, and total number of units transfused perioperatively.
RESULTS:We identified 3352 patients treated with a total hip or knee arthroplasty (1730 total knee arthroplasties and 1622 total hip arthroplasties) for inclusion in the study. Transfusion was given in 1746 cases836 of them had allogeneic exposure, and 910 had autologous-only transfusion. There were thirty-two reoperations (0.95%) for suspected infection. Between-group risk-factor differences were observed. The mean age and the rates of diabetes, immunosuppression, ASA scores of >2, and bilateral surgery were highest in the allogeneic group, as were estimated blood loss, surgery duration, and total number of units transfused (p < 0.001). In the unadjusted analyses, the rate of reoperations for suspected infection was higher in the cases with allogeneic exposure (1.67%) than in those without allogeneic exposure (0.72%) (p = 0.013). Autologous-only transfusion was not associated with a higher reoperation rate. However, multivariable logistic regression demonstrated that the total number of units transfused (p = 0.011) and an ASA score of >2 (p = 0.008)—but not allogeneic exposure—were significantly predictive of a reoperation.
CONCLUSIONS:Perioperative allogeneic transfusion was associated with a higher rate of reoperations for suspected acute infection. However, patients with allogeneic exposure had increased infection risk factors. After adjustment for the total number of units transfused and an ASA score of >2, allogeneic exposure was not significantly predictive of a reoperation for infection.
LEVEL OF EVIDENCE:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Dual-mobility hip components provide for an additional articular surface, with the goal of improving range of motion, jump distance (ie, vertical or inferior head displacement required for ...dislocation), and stability of the total hip arthroplasty. A large polyethylene head articulates with a polished metal acetabular component, and an additional smaller metal head is snap-fit within the polyethylene. New components have recently been released for use in North America. Although these devices are routinely used in some European centers for primary hip arthroplasty, their greatest utility may be to manage recurrent dislocation in the setting of revision hip arthroplasty. Several small retrospective series have shown satisfactory results for this indication at short- to midterm follow-up. Polyethylene wear and intraprosthetic dislocation are concerns, as is the lack of long-term data. Caution is thus advised in the routine use of dual-mobility components in primary and revision total hip arthroplasty.
Managing impounded river systems is a recurring challenge for aquatic resource professionals because reservoirs serve multiple functions with different ecological and socioeconomic outcomes. However, ...research on fishes in reservoirs has disproportionally focused on recreationally and economically important species, with less attention directed toward fish assemblages despite the potential for management at the assemblage level. As such, evaluation of relationships between reservoir fish assemblages and biotic and abiotic factors and testing whether assemblage structure is affected by changing environmental conditions may deepen ecological understanding and provide insights for reservoir fisheries management. Our overall objective was to assess these relationships in 11 reservoirs from North Carolina, USA. We sampled fish assemblages in the reservoirs, which spanned five river basins representing a range of habitat conditions, using experimental gillnets and pulsed DC nighttime electrofishing. Multivariate statistical analyses indicated that taxonomic differences in fish assemblage composition among river basins followed a gradient of productivity. The top contributing species to reservoir dissimilarity were bluegill (Lepomis macrochirus), gizzard shad (Dorosoma cepedianum), black crappie (Pomoxis nigromaculatus), and white perch (Morone americana). These four species were positively associated with factors that reflect increasing eutrophic conditions in the 11 reservoirs and could, therefore, serve as indicators of reservoir productivity, anthropogenic influence, and fish assemblage structure, in addition to their key role in reservoir fisheries management. Whereas fisheries research has historically focused on assessing fish populations, our results illustrate the ecological and management insights derived from simultaneously collecting assemblage- and population-level data. Research on reservoir fish assemblages in relation to biotic and abiotic conditions may help advance fish ecology and management alike.
Reservoir research has disproportionally focused on individual species of recreational and socioeconomic importance, rather than fish assemblages.
Simultaneous collection of assemblage- and population-level fisheries data may generate both ecological and management insights that species-specific sampling cannot.
As anthropogenic influences on reservoirs continue to increase, integrating environmental (biotic and abiotic conditions) and fish-assemblage data may be helpful for advancing our understanding of fish ecology and management alike.
Within the context of global change, seed dispersal research often focuses on changes in disperser communities (i.e., seed dispersers, such as birds, in an area) resulting from habitat fragmentation. ...This approach may not be completely illustrative due to certain seed disperser communities being more robust to fragmentation. Additionally, this top‐down approach overlooks how changing food resources on landscapes impacts resource tracking and, subsequently, seed dispersal. We hypothesized resource tracking may promote diffuse plant–animal dispersal mutualisms if resource richness is positively linked to disperser and seed rain richness. We predicted increasing food resource richness attracts more visits and species of avian dispersers, resulting in higher counts and greater species richness of seeds deposited at sites (i.e., seed rain). We tested this mechanism in two replicated field experiments using a model system with bird feeders positioned above seed traps. In the first experiment, we demonstrated resource presence skews seed rain. In the second experiment, we explored how species richness of food resources (0, 4, 8, or 12 species) affected the species richness and visitation of avian seed dispersers at feeders and in subsequent seed rain. Collectively, we observed a positive relationship between available food resources and seed rain, likely mediated by resource tracking behavior of avian dispersers. Our findings underscore a potential key mechanism that may facilitate ecological diversity, whereby accumulating species richness in the plant community attracts a more diverse seed disperser community and indirectly promotes more species in seed rain. Importantly, the resource tracking mechanism driving this potential positive feedback loop may also result in negative ecosystem effects if global change diminishes resource availability through homogenization processes, such as invasive species colonization. Future research should explore the bottom‐up effects of global change on food resources and seed disperser behavior to complement the literature on changing disperser communities.
Historically, studies on seed network connectivity and health use a top‐down approach, examining the abundance and distribution of seed dispersers on a landscape. In this study, we used a bottom‐up approach to examine how food resource richness at sites impacted the richness of the seed disperser community visiting each site and the richness of the seed community deposited at sites by dispersers.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
BACKGROUND:Unicompartmental knee arthroplasty is a less-invasive alternative to total knee arthroplasty for patients with arthritis affecting only the medial or lateral compartment. However, little ...is known about recent trends in the use of these procedures and the associated outcomes among older patients.
METHODS:With use of a nationally representative 5% sample of Medicare beneficiaries who were sixty-five years of age or older and who had undergone either unilateral unicompartmental knee arthroplasty or unilateral total knee arthroplasty from 2000 to 2009, we assessed trends in the use of unicompartmental and total knee arthroplasty, associated durations of hospital stay, and postoperative outcomes. The outcome measures were the rates of implant revision or removal within five years and the rates of periprosthetic infection, thromboembolic events, myocardial infarction, and all-cause mortality within one year. We conducted Kaplan-Meier analyses to assess the cumulative incidence of unadjusted outcomes and used Cox proportional-hazards regression to understand the relative risks of the outcomes for each procedure.
RESULTS:A total of 68,603 patients underwent unilateral total knee arthroplasty (n = 65,505) or unilateral unicompartmental knee arthroplasty (n = 3098) from 2000 to 2009. The mean age was seventy-five years; 34% of the patients were men, and 92% were white. The procedure rate was twenty-one times higher for total knee arthroplasty (597 per 100,000 person-years) than unicompartmental knee arthroplasty (twenty-nine per 100,000 person-years). The use of total knee arthroplasty increased 1.7-fold, and the use of unicompartmental knee arthroplasty increased 6.2-fold. The mean length of stay (and standard deviation SD) was 3.9 ± 2.1 days for total knee arthroplasty and 2.4 ± 1.7 days for unicompartmental knee arthroplasty. The five-year revision rate was 3.7% for total knee arthroplasty and 8.0% for unicompartmental knee arthroplasty. After multivariable adjustment, the risk of revision remained 2.4 times higher for unicompartmental knee arthroplasty than for total knee arthroplasty (95% confidence interval CI = 2.03 to 2.83). After multivariable adjustment, patients who underwent unicompartmental knee arthroplasty had no significant differential one-year risk of infection (adjusted hazard ratio HR = 0.74; 95% CI = 0.55 to 1.01), thromboembolic events (adjusted HR =0.86; 95% CI = 0.57 to 1.29), or mortality (adjusted HR = 0.75; 95% CI = 0.50 to 1.11).
CONCLUSIONS:Although unicompartmental knee arthroplasty accounted for only 4.5% of the unilateral knee replacements among Medicare beneficiaries, the use of this procedure has increased dramatically. Compared with those who had total knee arthroplasty, patients who underwent unicompartmental knee arthroplasty had higher revision rates but shorter durations of stay and tended to have lower rates of perioperative complications. These findings need to be confirmed by studies that incorporate detailed clinical information.
LEVEL OF EVIDENCE:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Anthropogenic alterations of the environment have increased, highlighting the need for human-wildlife coexistence and conflict mitigation. Spatial ecology, and the use of passive satellite movement ...technology in particular, has been used to identify patterns in human-wildlife conflict as a function of shared resources that present potential for dangerous situations. Here, we aim to remotely identify patterns indicative of human-crocodile conflict in Guanacaste, Costa Rica by exploring site fidelity and diverse modes of movement (i.e., land and water) across space between nuisance (relocated) and non-nuisance (wild) crocodiles. Advanced satellite remote sensing technology provided near-constant movement data on individuals at the regional scale. Telonics Iridium SeaTrkr-4370-4 transmitters were used with modified crocodilian fitting. Results indicate that relocated crocodiles exhibited large-scale movements relative to wild crocodiles. Nuisance relocated crocodiles either returned to the area of nuisance or potentially attempted to in short time frames. The results presented here highlight the need for alternative management strategies that facilitate relocation efficacy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Clinical outcomes were retrospectively reviewed for 76 primary total hip (THA) and total knee arthroplasties (TKA) performed after kidney, liver, cardiac, and lung transplantation with ...follow-up of 30.2 and 41.2 months, respectively. For the THA and TKA cohorts, there were a high rate of medical complications (29% and 33%), increased hospital length of stay (4.2 and 3.7 days), and more reoperations (7.2% and 9.1%). Only 1 (1.8%) periprosthetic infection was documented for THAs but 3 (14.2%) TKAs required two-stage revisions for infection. All transplant cohorts demonstrated significant increases ( P < 0.05) in HHS and KSS scores with majority of patients reporting overall good or excellent outcomes (82%–100%). These results suggest that various organ transplant patients may accept higher surgical risks for rewarding outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Simultaneous bilateral total knee arthroplasty (TKA) reportedly has higher postoperative complication rates than staged procedures, but little is known about recent trends and outcomes among ...Medicare patients. In a 5% national sample of Medicare beneficiaries older than 65 years, we identified 83,441 patients who underwent elective TKA between 2000 and 2009 and compared patients undergoing simultaneous bilateral TKA ( n = 4519) to staged TKA ( n = 3788). Use of simultaneous TKA did not change over time (3 in 10,000), but use of staged TKA increased three-fold from 1.4 to 4.4 in 10,000 person-years. We assessed length of stay; 5-year risk of revision; periprocedural (i.e., 90-day) risk of infection; hospitalization for venous thromboembolism (VTE) and myocardial infarction (MI); and death using Kaplan–Meier methods. Simultaneous TKA had higher 90-day risk of death (0.7% vs. 0.3%, P = 0.02), VTE (0.9% vs. 0.5%, P = 0.07), and MI (0.5% vs. 0.2%, P = 0.02). Infection and revision rates were similar between the two groups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Lung transplantation is increasingly common with improving survival rates. Post-transplant patients can be expected to seek total hip (THA) and knee arthroplasty (TKA) to improve their ...quality of life. Outcomes of 20 primary total joint arthroplasties (15 THA, 5 TKA) in 14 patients with lung transplantation were reviewed. Clinical follow-up time averaged 27.5 and 42.8 months for THA and TKA respectively. Arthroplasty indications included osteonecrosis, osteoarthritis, and fracture. All patients subjectively reported good or excellent outcomes with a final average Harris Hip Score of 88.7, Knee Society objective and functional score of 92.0. There were 4 minor and 1 major acute perioperative complications. 1 late TKA infection was successfully treated with two-stage revision. The mortality rate was 28.5% (4/14 patients) at an average 20.6 months following but unrelated to arthroplasty. Overall, total joint arthroplasty can be safely performed and provide good functional outcomes in lung transplant recipients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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