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Summary Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. Background Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. Methods Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). Results Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. Conclusion Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.

A wildfire burned through a previously sampled research site, allowing pre- and post-burn measurements of the forest floor, soils, and soil leaching near Lake Tahoe, Nevada. Fire and post-fire erosion caused large and statistically significant (P less than or equal to 0.05) losses of C, N, P, S, Ca, and Mg from the forest floor. There were no statistically significant effects on mineral soils aside from a decrease in total N in the surface (A11) horizon, an increase in pH in the A11 horizon, and increases in water-extractable SO4(2-) in the A11 and A12 horizons. Burning caused consistent but nonsignificant increases in exchangeable Ca(2+) in most horizons, but no consistent or statistically significant effects on exchangeable K(+) or Mg(2+), or on Bray-, bicarbonate-, or water-extractable P concentrations. Before the burn, there were no significant differences in leaching, but during the first winter after the fire, soil solution concentrations of NH4(+), NO3(-), ortho-P, and (especially) SO4(2-) were elevated in the burned area, and resin lysimeters showed significant increases in the leaching of NH4(+) and mineral N. The leaching losses of mineral N were much smaller than the losses from the forest floor and A11 horizons, however. We conclude that the major short-term effects of wildfire were on leaching whereas the major long-term effect was the loss of N from the forest floor and soil during the fire.

The study investigated how the concentration and composition of purified tannin extracts, at various inclusion rates, affect the ruminal in vitro fermentation parameters. Tannin extracts were isolated from four different forage species: birdsfoot trefoil ( Lotus corniculatus) , sulla (Hedysarum coronarium), big trefoil (Lotus pedunculatus), and salad burnet ( Sanguisorba minor ). Plants extracts were purified by Sephadex LH-20 gel chromatography and analyzed by UPLC–ESI–MS/MS. The results showed a large variation among the extracts from different species in terms of tannin composition and structural features. The extracts from salad burnet were dominated by hydrolysable tannins, comprising mainly ellagitannins. The extracts derived from sulla and big trefoil contained predominantly proanthocyanidins (PA), primarily composed of prodelphinidins with high mean degree of polymerisation (mDP). Birdsfoot trefoil extracts comprised procyanidin-rich PAs with low mDP. To determine whether the combined presence of tannins and flavonoid together lead to synergistic or antagonistic effects, the tannin extracts were incubated both with or without rutin at concentrations of 10, 20, and 30 g/kg DM, using a base substrate of perennial ryegrass ( Lolium perenne , control). In general, all the tannin extracts decreased methane (CH 4 ) production compared to the control, while no significant effect of rutin was observed on both gas (GP) and CH 4 production, neither pure, nor in the simultaneous presence of tannins. The highest CH 4 reduction (15%, at 30 g/kg DM) was observed from sulla and big trefoil extracts compared to control, but this was also supplemented with a concomitant reduction in GP (11%) indicating a reduction in feed digestibility. The extracts from birdsfoot trefoil and salad burnet reduced CH 4 by up to 12% without significantly reducing GP, indicating the importance of tannin composition on ruminal fermentation.

Ecosystem susceptibility to invasion by nonnative species is poorly understood, but evidence is increasing that spatial and temporal variability in resources has large-scale effects. We conducted a study in Artemisia tridentata ecosystems at two Great Basin locations examining differences in resource availability and invasibility of Bromus tectorum over elevation gradients and in response to direct and interacting effects of removal of perennial herbaceous vegetation and fire. We monitored environmental conditions, soil variables, and B. tectorum establishment and reproduction over two years. Soil water (measured as the number of days soil matric potential was >-1.5 MPa) and nitrate availability (measured as micromoles of NO3(-) sorbed to resin capsules per day in the ground) decreased with decreasing elevation. Lower-elevation sites had greater annual variability in soil water availability than upper-elevation sites did. Soil nitrate levels were highest at all elevations when soils were wettest; nitrate availability was not more variable at lower elevations. Removal of herbaceous perennials increased soil water and nitrate availability, but burning without removal had only minor effects. Bromus tectorum had low establishment, biomass, and seed production on high-elevation sites and on a mid-elevation site during a cold, short, growing season probably due to ecophysiological limitations resulting from cold temperatures. Establishment, biomass, and seed production were variable at low elevations and best explained by soil characteristics and spatial and temporal variation in soil water. Removal and fire had minor effects on emergence and survival, but biomass and seed production increased two to three times following removal, two to six times after burning, and 10-30 times following removal and burning. Our data indicate that invasibility varies across elevation gradients and appears to be closely related to temperature at higher elevations and soil water availability at lower elevations. High variability in soil water and lower average perennial herbaceous cover may increase invasion potential at lower elevations. Soil water and nitrate availability increase following either fire or removal, but on intact sites native perennials typically increase following fire, limiting B. tectorum growth and reproduction. Following resource fluctuations, invasibility is lowest on sites with relatively high cover of perennial herbaceous species (i.e., sites in high ecological condition).

Background:Psoriatic arthritis (PsA) is an immune-mediated disease associated with skin psoriasis that, if untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA and, in most cases, psoriasis precedes synovio-entheseal inflammation, providing a unique opportunity for early and potentially preventive intervention in a susceptible and readily identifiable population.Objectives:The ongoing Preventing Arthritis in a Multicenter Psoriasis At Risk cohort (PAMPA) study (NCT05004727) aims to evaluate the efficacy of the fully human interleukin (IL)-23p19-subunit inhibitor guselkumab in preventing PsA and reducing musculoskeletal ultrasound (US) abnormalities in a population of patients with psoriasis at increased risk of PsA progression. Interim findings from screening US evaluations to date are reported.Methods:Patients were screened across 5 sites in the US and Canada. PAMPA inclusion required ≥3% body surface area (BSA) affected by psoriasis, no current systemic immunosuppressant therapy at time of screening or prior exposure to biologic/JAK inhibitor, and evidence of musculoskeletal abnormalities on US. The US scanned a set of 36 joints and 34 periarticular structures (including tendons and entheses), each scored by 2 independent central readers using the Rochester Modified (RM)-PsASon scoring system (range 0-614). Participants required a mean score of ≥3.36 to enroll (the maximized Youden’s index based on previous analysis of scores in healthy controls and patients with psoriasis).Results:Among the 49 participants screened to date, 42 met US criteria. The screened population was mostly male (57.1%), white (83.7%), with an average age of 49.2 (SD 14.3) and a body mass index (BMI) of 30.6 (SD 8.6). Participants had mostly plaque psoriasis (95.1%) at the time of enrollment with a mean BSA of 10.4% (SD 11.9). The mean total US score was 13.55 (SD 10.5, range 1-50), composed of inflammatory and structural subscores (Figure 1A-B). The intraclass correlation coefficient (ICC) assessing reader agreement was 0.89 (95% CI 0.80-0.94) and ICCs on joints, tendons, and entheses were all >0.75, indicating excellent reliability (Figure 1C-F). US scores correlated with increasing age (r=0.55, p≤0.001), but did not correlate with BMI, BSA, Functional Assessment of Chronic Illness Therapy-Fatigue score, patient reported pain intensity, or sex (Figure 2).Conclusion:In a biologic-naïve cohort of patients with psoriasis at increased risk for PsA progression, 85.7% of those with US evaluation exceeded a score of 3.36, a previously identified threshold to distinguish those with psoriasis from healthy controls. The interrater reliability of the US scoring was excellent. US scores were moderately correlated with increasing age, but not with other demographic or disease activity measures, and the biological meaning of this finding is unclear. While the ongoing PAMPA study is actively recruiting for a planned enrollment of 350 participants, these preliminary findings suggest that appropriate patients are being enrolled. These data also underscore the need to better characterize clinical and imaging phenotypes of high-risk patients with psoriasis for subclinical soft tissue/structural changes that may foreshadow transition to PsA.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Cinty Gong Employee of Janssen Research & Development, LLC, a wholly owned subsidiary of Johnson & Johnson, and own stocks in Johnson & Johnson, Rebecca H. Haberman Consultant for Janssen, UCB, Sarah Moussavi: None declared, Yan Zhang: None declared, Sydney Catron: None declared, Jonathan Samuels: None declared, Rebecca B. Blank: None declared, Michael Toprover Consultant for ANI Pharmaceuticals, Horizon Therapeutics, Jiyuan Hu: None declared, Vincent Piguet Speaker and/or advisory board member of AbbVie, Almirall, Celgene, Janssen, Kyowa Kirin Co. Ltd, LEO Pharma, Novartis, Pfizer, Sanofi, UCB, and Union Therapeutics; Department Division Director of Dermatology at the University of Toronto, Educational grants from AbbVie, Bausch Health, Celgene, Eli Lilly, Janssen, LEO Pharma, L’Oréal, NAOS, Novartis, Pfizer, Pierre-Fabre, Sandoz and Sanofi, Francisco Tausk: None declared, Jensen Yeung Speaker/consultant/honoraria/trialist for AbbVie, Amgen, Anacor, Arcutis, Astella, Bausch, Baxalta, Boehringer Ingelheim, BMS, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, Janssen, Leo, Medimmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and Xenon, Andrea L. Neimann Consultant for AbbVie, BMS, Janssen, and UCB, Wayne P. Gulliver Consultant/advisory board member/speaker for AbbVie, Actelion, Amgen, Arylide, Bausch Health, Boehringer Ingelheim, Celgene, Cipher, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, PeerVoice, Pfizer, Sanofi-Genzyme, Tribute, UCB, and Valeant, Research grants from AbbVie, Amgen, Eli Lilly, Novartis, and Pfizer; Clinical trial study fees from AbbVie, Asana Biosciences, Astellas, Boerhinger Ingleheim, Celgene, Corrona/National Psoriasis Foundation, Devonian, Eli Lilly, Galapagos, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, and UCB, Joseph F. Merola Pharma Consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB, Alexis Ogdie Consultant for AbbVie, Amgen, BMS, Celgene, CorEvitas, Eli Lilly, Gilead, Happify Health, Janssen, Novartis, Pfizer, and UCB, Research grants to the University of Pennsylvania from AbbVie, Janssen, Pfizer and Novartis and to Forward from Amgen, Proton Rahman Consultant for AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Research grants from Janssen and Novartis, Soumya D. Chakravarty Employee of Janssen Research & Development, LLC, a wholly owned subsidiary of Johnson & Johnson, and own stocks in Johnson & Johnson, Ralf G. Thiele Consultant for Bioclinica and Novartis, Research grants from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, and UCB, Lihi Eder Consultant for AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Research grants from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, and UCB, Christopher T. Ritchlin Consultant for AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Research grants from AbbVie, Amgen, and UCB, Jose U. Scher Consultant for AbbVie, Janssen, Kaleido, Novartis, Pfizer, Sanofi, and UCB, Research grants from Janssen, Novartis, and Pfizer.

Feed production is the main contributor to a subset of environmental impacts of pork production. In this context, this study is concerned with the substitution of soy products in pig diets in order to reduce these impacts. The aim of this study was to assess three alternative diets in gestating and lactating sows as well as growing and finishing pigs in order to reduce the amount of soy products used as ingredients. In the three alternative scenarios soy proteins were compensated for by either using a combination of different feedstuffs (e.g. rapeseed meal, fava beans, and synthetic amino acids) (LOW), maximising the use of legumes (mainly fava beans) (LEG) and increasing the amount of synthetic amino acids (AA). These alternative scenarios were compared with standard diets (ST) and formulated in order to reduce the crude-protein content of the diet while maintaining the same performance of the pigs. Each of the resulting 16 diets was then assessed with respect to global warming, eutrophication, acidification, and land use, both when accounting and not accounting for emissions due to land use change. The analysis per kilogram of feed showed that the ST diets performed best with regard to global warming, eutrophication, and acidification. When emissions from land use and land use change were added, ST and AA diets appeared to have the least impact. In contrast, the assessment of scenarios per kilogram of pork highlighted that the AA scenario contributed the least in all impact categories. In conclusion, it is possible to partly replace soybean products by using synthetic amino acids in order to minimise the environmental impacts of the pork supply chain.

Background Symptomatic iron deficiency (ID) is a disorder affecting 10–20% of menstruating women. ID is diagnosed by measuring serum ferritin, a protein helping to store iron in the body. A deeper understanding of the association between ID and its societal and economic burden is relevant for patients, physicians, health care decision makers. Methods An online household survey was carried out among Swiss women aged 18–50 years suffering from debilitating symptoms due to ID. The data was population-weighted for age and region. The costs of misdiagnosis and the ID-related economic burden (i.e. days of sick leave) from productivity losses on the labor market were determined and extrapolated to the Swiss population. Furthermore, the patient burden was assessed based on quality of life daily measurements. Results The total sample included 1010 women who received an ID diagnosis with a blood test in the last 2 years (mean age: 33.5 years). Most named symptoms were “being tired or exhausted” (96.4%) and reduced physical energy level (41.0%). In total, 354 (35.0% of the total sample) patients received an initial diagnosis other than ID. Of those, 46.8% were treated prior to the ID diagnosis with a pharmacological medical therapy or psychotherapy. Extrapolating these numbers to the Swiss female population aged 18–50 years, the direct medical costs would be CHF 78 million (assuming an annual ID incidence of ID diagnosis of 9.5%). On average, 28.5% of participants in the work-force had to take sick leave due to ID symptoms within a period of 2 years (mean: 5.2 days, i.e. 2.6 days/year). The estimated annual indirect costs in Switzerland would be CHF 33 million (human capital approach) or CHF 26 million (friction cost method), respectively. Being exhausted and impaired concentration appear to be the most important factors negatively impacting daily living and hence quality of life. Conclusion The societal and economic burden among women due to debilitating symptoms of ID in Switzerland is substantial. Timely, correct diagnosis and treatment of ID may contribute to reducing this burden. Further studies are needed in this area to validate our results.

Appropriate preoperative blood typing and cross-matching is an important quality improvement target to minimise costs and rationalise the use of blood bank resources. This can be facilitated using a maximum surgical blood ordering schedule (MSBOS) for specific operations. It is recommended that individual hospitals develop a site-specific MSBOS based on institutional data, but this is challenging in non-tertiary centres without electronic databases. Our aim was to audit our perioperative blood transfusions to develop a site-specific MSBOS. A retrospective audit of blood transfusions in surgical patients in our regional referral hospital was conducted using five years' coded administrative data. Procedures with higher transfusion rates warranting preoperative testing (type and screen with or without subsequent cross-matching) were identified. There were about 15,000 eligible surgical procedures performed in our institution over the audit period. The need for preoperative testing was identified for only a few procedures, namely laparotomy, bowel resection, major amputation, joint arthroplasty, hip/femur fracture and humerus surgery, and procedures for obstetric complications. We observed a reduction in transfusion rates over time for total joint arthroplasty. The use of coding data represents an efficient method by which centres without electronic anaesthesia information management systems can conduct large-scale audits to develop a site-specific MSBOS. This would represent a significant improvement for hospitals that currently base preoperative testing recommendations on expert opinion alone. As many procedures in regional centres have very low transfusion rates, hospitals with a similar case mix to ours could consider selectively auditing higher-risk operations where local data is most likely to alter testing recommendations.

Background Acute generalized exanthematous pustulosis (AGEP) is a rare and severe cutaneous drug eruption. Hydroxychloroquine (HCQ) is one of the known culprit drugs with less than 60 cases reported in the literature, and may have a more severe clinical presentation compared to AGEP induced by other drugs. There are no standardized management strategies for HCQ‐induced AGEP outside of drug discontinuation. Objectives Characterize the clinical presentation of HCQ‐induced AGEP and management strategies. Methods Retrospective chart review of nine patients clinically diagnosed with HCQ‐induced AGEP using the EuroSCAR score from 2017 to 2022 at four academic medical centres in the United States. Results All patients in our series were female and the median age was 52. Four patients initially presented with fever, and eight patients had neutrophilia. Median time to rash was 15 days. Biopsies obtained in six patients showed typical characteristics of AGEP. In most patients, rash morphology consisted of generalized pinpoint pustules atop atypical targetoid lesions and annular plaques. Five patients were hospitalized for AGEP. All patients were treated with methylprednisolone and/or prednisone, and the average days treated with systemic corticosteroids was 35. Conclusions Our case series is the largest to date describing HCQ‐induced AGEP. Clinicians should be wary that HCQ‐induced AGEP may present with a longer latency period after drug initiation and with atypical targetoid and annular lesions. Early initiation of systemic corticosteroids should be considered due to the severity of this drug reaction with addition of cyclosporine in refractory cases. Hydroxychloroquine (HCQ) can trigger acute generalized exanthematous pustulosis (AGEP), a rare and severe drug eruption. Retrospective chart review of nine patients diagnosed with HCQ‐induced AGEP was performed to characterize HCQ‐induced AGEP and management. Rash morphology consisted of pinpoint pustules atop targetoid lesions and annular plaques, and all patients were treated with systemic corticosteroids. Clinicians should know that HCQ‐induced AGEP may present with a longer latency period and atypical targetoid lesions. Treatment with systemic corticosteroids should be considered, given the severity.