Evidence for thyroid hormone regulation of amygdala-dependent fear-relevant memory and plasticity.

The amygdala is an established site for fear memory formation, and clinical studies suggest involvement of hormone signaling cascades in development of trauma-related disorders. While an association of thyroid hormone (TH) status and mood disorders is established, the related brain-based mechanisms and the role of TH in anxiety disorders are unknown. Here we examine the role that TH receptor (TR, a nuclear transcriptional repressor when unbound and a transcriptional activator when bound to TH) may have in mediating the initial formation of fear memories in the amygdala. We identified mRNA levels of TR and other TH pathway regulatory genes, including thyrotropin-releasing hormone (Trh), transthyretin (Ttr), thyrotropin-releasing hormone receptor (Trhr), type 2 iodothyronine deiodinase (Dio2), mediator complex subunit 12 (Med12/Trap230) and retinoid X receptor gamma (Rxrg) to be altered in the amygdala following Pavlovian fear conditioning. Using TH agonist and antagonist infusion into the amygdala, we demonstrated that this pathway is both necessary and sufficient for fear memory consolidation. Inhibition of TH signaling with the TR antagonist 1-850 decreased fear memory consolidation; while activation of TR with T3 (triiodothyronine) resulted in increased memory formation. Using a systemic hypothyroid mouse model, we found that intra-amygdala infusions of T3 were sufficient to rescue deficits in fear memory. Finally, we demonstrated that T3 was sufficient to activate TR-specific gene pathways in the amygdala. These findings on the role of activity-dependent TR modulation support a model in which local TH is a critical regulator of fear memory-related plasticity in the amygdala.

AdipoRon reduces TGFß1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFß1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFß1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

Developing Topics.

BACKGROUND: The novel diffusion-based Neurite Orientation and Dispersion Imaging (NODDI) model may provide complementary information to Diffusion Tensor Imaging (DTI) to increase sensitivity in characterizing tissue microarchitecture. We examined if one or a combination of both approaches can improve our understanding of at-risk tissue in and around white matter hyperintensities (WMH). METHOD: From ADNI3, we identified individuals [n = 54, age = 78 ± 7, 46% F) with concurrent measures of multi-shell DTI, 3D FLAIR, and 3D MPRAGE. We segmented WMH from structural data using Lesion Segmentation Toolbox. We derived DTI (FA, MD) and NODDI parameters (NDI, ODI, Fiso) using QSIprep. We dilated up to 5 mm outside the WMH, applied an FA threshold of ≥ 0.2 to exclude gray matter, calculated DTI and NODDI parameters at 1 mm intervals within this region. We performed Pearson correlations between all parameters. Assuming normal white matter at 5 mm, we normalized these parameters with their respective values at 5 mm and plotted the spatial variation of each parameter in and outside the WMH. RESULT: Normalized DTI and NODDI parameters representing spatial variations within the 5 mm region are shown in Fig 1A. Table 1 shows p-values comparing DTI and NODDI parameters between WMH the subsequent regions outside it. Compared to WMH, Fiso was significantly different at all distances. FA showed similar spatial characteristics with NDI and was negatively correlated with ODI. Fiso correlated very strongly with MD. CONCLUSION: In the WMHs and its immediate vicinity, low FA, NDI, ODI suggest lower cell density, while low Fiso and MD suggest low extracellular fluid volume. Together these observations may reflect cytotoxic edema, cell loss, and injury. Normal appearing white matter (3-5 mm) showed high FA, NDI, ODI, and low MD consistent with high cell density and normal extracellular water. In the transition between WMH vicinity and normal white matter, low FA, NDI, ODI, high MD and Fiso suggest cell loss only. This transition region could be at risk of converting to WMH. Future work will include longitudinal evaluation of WMH growth in the at-risk tissue. However, final validation of WMH pathology will need histological confirmation.

Clinical Manifestations.

BACKGROUND: The Hachinski ischemic score (HIS) scale is used to exclude as much as possible, individuals with dominant cerebrovascular pathology from those with dominant AD pathology. White matter hyperintensities (WMH) are the gold-standard for evaluating cerebrovascular pathology and linked to worsening cognitive impairment. HIS ≤ 4 are used to minimize non-AD pathology in ADNI participants. Here we sought to understand whether HIS scores for hypertension (HMHYPERT) in ADNI3 were associated with greater WMH burden (and hence cerebrovascular pathology) even within individuals with HIS ≤ 4. METHOD: We compared HMHYPERT scores between individuals with normal cognition (CN) and with mild cognitive impairment (MCI), and participants and correlated with percent WMH burden. A total of 263 subjects screened for ADNI3 (92 MCI [38 F], age = 73 ± 6; 146 CN [94 F], age = 74 ± 7) who had HIS scores and FLAIR MRI acquisitions within a year of each other. 25 All AD participants were excluded. WMH burden was calculated by segmenting them using the Lesion Segmentation Toolbox and normalizing their volume by total intracranial volume. We used the HMHYPERT as a vascular risk factor, excluding those with any focal neurological symptoms. For analysis, we dichotomized participants into those with HMHYPERT = 0 and HMHYPERT>0. To examine whether a non-zero HMHYPERT score corresponds to greater WMH burden, we examined the prevalence of WMH in between these 2 groups and within the MCI and CN groups. RESULT: Although not significant, HMHYPERT scores were higher in MCI. (Fig. 1A, MCI = 0.48±0.50, CN = 0.39±0.49). We found a greater proportion of MCI subjects had HMHYPERT>0 than CN subjects (Fig. 1B, HMHYPERT = 0: CN = 61.0% and MCI = 52.2%; HMHYPERT > 0: CN = 40.0% and MCI = 48.1%). WMH burden was greater in MCI (0.33±0.53) than CN (0.20±0.32) (Fig. 2A). MCI participants with HMHYPERT>0 had the highest WMH burden followed by MCI participants with HMHYPERT = 0, CN with HMHYPERT >0, and CN with HMHYPERT = 0 had the lowest WMH burden. (Fig. 2B). CONCLUSION: Cerebrovascular pathology increases significantly with diagnosis, but its severity increases further with findings of hypertension even when total HIS ≤ 4.

Engaging youth and parents in clinical pediatric research: A case-based example.

Background: Youth and parent engagement is a key component of clinical research. There are many ways to actively and meaningfully engage youth and parents as integral members of research teams, for example, through ad-hoc committees, advisory councils, or as co-leads on projects. When youth and parents are actively and meaningfully engaged in research projects, they share knowledge from their lived experiences to improve the quality and relevance of research. Methods: We describe a case-based example of engaging youth and parent research partners when co-designing a questionnaire to assess preferences for pediatric headache treatments, from both a researcher and youth/parent perspective. We also summarize best practices in patient and family engagement from the literature and pertinent guidelines to assist researchers with integrating patient and family engagement into their studies. Results: As researchers, we felt that the integration of a youth and parent engagement plan into our study significantly altered and strengthened questionnaire content validity. We encountered challenges throughout the process and detailed these experiences to help educate others about challenge mitigation and best practices in youth and parent engagement. As youth and parent partners, we felt that engaging in the process of questionnaire development was an exciting and empowering opportunity, and that our feedback was valued and integrated. Conclusions: By sharing our experience, we hope to catalyze thought and discussion around the importance of youth and parent engagement in pediatric research, with the goal of stimulating more appropriate, relevant, and high-quality pediatric research and clinical care in the future.

Multiple organ dysfunction after trauma.

BACKGROUND: The nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries to reach critical care. The aim of this study was to characterize contemporary MODS subtypes in trauma critical care at a population level. METHODS: Adult patients admitted to major trauma centre critical care units were enrolled in this 4-week point-prevalence study. MODS was defined by a daily total Sequential Organ Failure Assessment (SOFA) score of more than 5. Hierarchical clustering of SOFA scores over time was used to identify MODS subtypes. RESULTS: Some 440 patients were enrolled, of whom 245 (55·7 per cent) developed MODS. MODS carried a high mortality rate (22·0 per cent versus 0·5 per cent in those without MODS; P < 0·001) and 24·0 per cent of deaths occurred within the first 48 h after injury. Three patterns of MODS were identified, all present on admission. Cluster 1 MODS resolved early with a median time to recovery of 4 days and a mortality rate of 14·4 per cent. Cluster 2 had a delayed recovery (median 13 days) and a mortality rate of 35 per cent. Cluster 3 had a prolonged recovery (median 25 days) and high associated mortality rate of 46 per cent. Multivariable analysis revealed distinct clinical associations for each form of MODS; 24-hour crystalloid administration was associated strongly with cluster 1 (P = 0·009), traumatic brain injury with cluster 2 (P = 0·002) and admission shock severity with cluster 3 (P = 0·003). CONCLUSION: Contemporary MODS has at least three distinct types based on patterns of severity and recovery. Further characterization of MODS subtypes and their underlying pathophysiology may lead to future opportunities for early stratification and targeted interventions.

ANTECEDENTES: La naturaleza del síndrome de disfunción orgánica múltiple (Multiple Organ Dysfunction Syndrome, MODS) resultante de un traumatismo está evolucionando a medida que avanzan las prácticas de reanimación y más pacientes sobrevive a las lesiones y pueden recibir cuidados críticos. El objetivo de este estudio fue caracterizar los subtipos actuales MODS en atención crítica de trauma a nivel poblacional. MÉTODOS: Los pacientes adultos ingresados en unidades de cuidados intensivos de trauma se incluyeron en este estudio de prevalencia puntual de 4 semanas. MODS se definió como una puntuación total diaria de la escala de Evaluación de Fallo Orgánico Secuencial (Sequential Organ Failure Assessment, SOFA) > 5. Se utilizó el agrupamiento jerárquico de las puntuaciones SOFA a lo largo del tiempo para determinar los subtipos MODS. RESULTADOS: Se incluyeron 440 pacientes, de los cuales 245 (56%) presentaron MODS. MODS conllevó una alta mortalidad (22% versus 1%, P < 0,001) y 24% de las muertes fueron precoces, durante las primeras 48 horas tras el traumatismo. Se identificaron tres patrones de MODS, estando todos presentes al ingreso. En el tipo 1, MODS se resolvió de forma temprana, con una mediana de tiempo de recuperación de 4 días y una mortalidad del 14%. El tipo 2 presentaba un tiempo de recuperación retardado (mediana 13 días) y una mortalidad del 35%. El tipo 3 presentaba un tiempo de recuperación prolongado (mediana 25 días) y una mortalidad asociada alta del 46%. El análisis multivariable reveló asociaciones clínicas diferentes para cada tipo de MODS, con la administración de cristaloides durante 24 horas fuertemente asociada al tipo 1 (P < 0,001); el traumatismo craneal al tipo 2 (P < 0,01); y la gravedad del shock al ingreso al tipo 3 (P < 0,01). CONCLUSIÓN: Los MODS actuales presentan al menos tres tipos distintos basados en patrones de gravedad y recuperación. La caracterización de los subtipos de MODS y su fisiopatología subyacente puede contribuir a futuras oportunidades de estratificación temprana e intervenciones dirigidas.

Diurnal variation in the production of vocal information about food supports a model of social adjustment in wild songbirds.

Wintering songbirds have been widely shown to make economic foraging decisions to manage the changing balance of risks from predation and starvation over the course of the day. In this study, we ask whether the communication and use of information about food availability differ throughout the day. First, we assessed temporal variation in food-related vocal information produced in foraging flocks of tits ( Paridae) using audio recordings at radio-frequency identification-equipped feeding stations. Vocal activity was highest in the morning and decreased into the afternoon. This pattern was not explained by there being fewer birds present, as we found that group sizes increased over the course of the day. Next, we experimentally tested the underlying causes for this diurnal calling pattern. We set up bird feeders with or without playback of calls from tits, either in the morning or in the afternoon, and compared latency to feeder discovery, accumulation of flock members, and total number of birds visiting the feeder. Irrespective of time of day, playbacks had a strong effect on all three response measures when compared to silent control trials, demonstrating that tits will readily use vocal information to improve food detection throughout the day. Thus, the diurnal pattern of foraging behaviour did not appear to affect use and production of food-related vocalizations. Instead, we suggest that, as the day progresses and foraging group sizes increase, the costs of producing calls at the food source (e.g. competition and attraction of predators) outweigh the benefits of recruiting group members (i.e. adding individuals to large groups only marginally increases safety in numbers), causing the observed decrease in vocal activity into the afternoon. Our findings imply that individuals make economic social adjustments based on conditions of their social environment when deciding to vocally recruit group members.

Content of First Prenatal Visits.

Objective The purpose of this study was to examine the content of the first prenatal visit within an academic medical center clinic and to compare the topics discussed to 2014 American College of Obstetrics and Gynecologists guidelines for the initial prenatal visit. Methods Clinical interactions were audio recorded and transcribed (n = 30). A content analysis was used to identify topics discussed during the initial prenatal visit. Topics discussed were then compared to the 2014 ACOG guidelines for adherence. Coded data was queried though the qualitative software and reviewed for accuracy and content. Results First prenatal visits included a physician, nurse practitioner, nurse midwife, medical assistant, medical students, or a combination of these providers. In general, topics that were covered in most visits and closely adhered to ACOG guidelines included vitamin supplementation, laboratory testing, flu vaccinations, and cervical cancer screening. Topics discussed less often included many components of the physical examination, education about pregnancy, and screening for an identification of psychosocial risk. Least number of topics covered included prenatal screening. Conclusions for Practice While the ACOG guidelines may include many components that are traditional in addition to those based on evidence, the guidelines were not closely followed in this study. Identifying new ways to disseminate information during the time constrained initial prenatal visit are needed to ensure improved patient outcomes.

Reciprocity to Increase Participation of Compatible Living Donor and Recipient Pairs in Kidney Paired Donation.

Inclusion of compatible living donor and recipient pairs (CPs) in kidney paired donation (KPD) programs could increase living donor transplantation. We introduce the concept of a reciprocity-based strategy in which the recipient of a CP who participates in KPD receives priority for a repeat deceased donor transplant in the event their primary living donor KPD transplant fails, and then we review the practical and ethical considerations of this strategy. The strategy limits prioritization to CPs already committed to living donation, minimizing the risk of unduly influencing donor behavior. The provision of a tangible benefit independent of the CP's actual KPD match avoids many of the practical and ethical challenges with strategies that rely on finding the CP recipient a better-matched kidney that might provide the CP recipient a future benefit to increase KPD participation. Specifically, the strategy avoids the potential to misrepresent the degree of future benefit of a better-matched kidney to the CP recipient and minimizes delays in transplantation related to finding a better-matched kidney. Preliminary estimates suggest the strategy has significant potential to increase the number of living donor transplants. Further evaluation of the acceptance of this strategy by CPs and by waitlisted patients is warranted.

Segmental resection is a safe oncological alternative to total proctocolectomy in elderly patients with ulcerative colitis and malignancy.

AIM: The standard approach for the surgical management of colorectal cancer (CRC) in the setting of ulcerative colitis (UC) involves total proctocolectomy (TPC). However, some patients also undergo a partial resection (PR). This may be an attractive option in older patients with a high risk for surgery. The aim of this study was to compare the risk of metachronous cancer after PR or TPC for CRC in the setting of UC. METHOD: This was a retrospective cohort study conducted through the Nationwide Veterans Affairs Healthcare System (VA). Patients who had UC and underwent a PR or TPC for CRC were followed from the time of their surgery to their most recent clinical follow-up. The primary outcome was development of metachronous cancer in the PR group. Secondary outcomes included surgical and medical outcomes. RESULTS: Fifty-nine patients were included: 24 (40.7%) underwent PR and 35 (59.3%) underwent TPC. The median age at cancer diagnosis was 73.0 and 61.7 years in PR and TPC groups, respectively (P < 0.0005). Amongst patients undergoing PR, 15 (60%) had no active UC at the time of surgery, whereas in patients undergoing TPC, at the time of surgery eight (23.5%) had no active UC (P = 0.005). No patient who underwent a partial colectomy developed a metachronous cancer in the retained colonic segment during the follow-up period (median 7 years). CONCLUSION: Our study suggests that PR for CRC in the setting of UC may be a viable option in a selected cohort of patients, especially among the elderly.

Meta-analysis of prognostic factors for amputation following surgical repair of lower extremity vascular trauma.

BACKGROUND: Lower extremity vascular trauma (LEVT) is a major cause of amputation. A clear understanding of prognostic factors for amputation is important to inform surgical decision-making, patient counselling and risk stratification. The aim was to develop an understanding of prognostic factors for amputation following surgical repair of LEVT. METHODS: A systematic review was conducted to identify potential prognostic factors. Bayesian meta-analysis was used to calculate an absolute (pooled proportion) and relative (pooled odds ratio, OR) measure of the amputation risk for each factor. RESULTS: Forty-five studies, totalling 3187 discrete LEVT repairs, were included. The overall amputation rate was 10·0 (95 per cent credible interval 7·4 to 13·1) per cent. Significant prognostic factors for secondary amputation included: associated major soft tissue injury (26 versus 8 per cent for no soft tissue injury; OR 5·80), compartment syndrome (28 versus 6 per cent; OR 5·11), multiple arterial injuries (18 versus 9 per cent; OR 4·85), duration of ischaemia exceeding 6 h (24 versus 5 per cent; OR 4·40), associated fracture (14 versus 2 per cent; OR 4·30), mechanism of injury (blast 19 per cent, blunt 16 per cent, penetrating 5 per cent), anatomical site of injury (iliac 18 per cent, popliteal 14 per cent, tibial 10 per cent, femoral 4 per cent), age over 55 years (16 versus 9 per cent; OR 3·03) and sex (men 7 per cent versus women 8 per cent; OR 0·64). Shock and nerve or venous injuries were not significant prognostic factors for secondary amputation. CONCLUSION: A significant proportion of patients who undergo lower extremity vascular trauma repair will require secondary amputation. This meta-analysis describes significant prognostic factors needed to inform surgical judgement, risk assessment and patient counselling.

Impact of including regional anaesthesia in enhanced recovery protocols: a scoping review.

Regional anaesthesia (RA) is often included in enhanced recovery protocols (ERPs) as an important component of a bundle of interventions to improve outcomes after surgery. We sought to delineate whether the literature supports the use of RA in this setting with regard to commonly measured outcomes. We further sought to assess whether such improvements would translate into positive impacts on healthcare value as defined by the Institute for Healthcare Improvement Triple Aim. We conducted a scoping review to address our objectives. Studies of ERPs that included RA and reported at least one outcome of interest in comparison to a control group were included. MEDLINE, EMBASE, CENTRAL, CDSR, PROSPERO, and the NHS Economic Evaluation Database were searched up to May 2015. Two reviewers assessed studies and extracted data. Of 695 identified citations, 58 studies were included for analysis. The majority (53%) were in colorectal surgery. Positive impacts of RA on all outcomes were identified; however, value-based outcomes were rarely reported. Where value-based outcomes were reported, RA appears to have a positive impact on global measures of health and function and on economic outcomes. Existing literature supports a positive impact of RA on ERP outcomes, which may be reflected in improved healthcare value. In order to justify the value of RA in ERPs, a future focus on appropriate measures is needed to align research with widely accepted frameworks, such as the Triple Aim.

Oral health of elite athletes and association with performance: a systematic review.

BACKGROUND: We aimed to systematically review the epidemiology of oral disease and trauma in the elite athlete population and to investigate the impact of oral health on sporting performance. METHODS: Authors searched Ovid MEDLINE (1950 to October 2013), Ovid EMBASE (1980 to October 2013), EBSCO SPORTDiscus (up to October 2013) and OpenGrey (http://www.opengrey.eu). No date or language restrictions were applied. Papers were included if they evaluated the oral health of professional athletes. The methodological quality of papers was evaluated using a modification of the Newcastle-Ottawa scale. RESULTS: The literature search led to 9858 potentially relevant citations. Following a set of predefined exclusion criteria, 34 studies remained. Twenty-six studies reported on dental trauma, which ranged in prevalence from 14% to 47% varying by sport and country. Sixteen studies considered the oral health of athletes and reported high prevalence of oral diseases: dental caries 15-75%, dental erosion 36-85%, periodontal disease 15%. In four studies, a range between 5% and 18% of athletes reported negative impact of oral health or trauma on performance. The methodological quality of included studies was generally low. CONCLUSIONS: Within the limits of the review, oral health of athletes is poor. We hypothesise that poor oral health associates with self-reported performance; however, this needs to be tested. Further studies on representative samples of athletes are needed to assess the size of the problem of poor oral health as well as to investigate the possible impact on performance using objective measures of performance.

Hypercalcemia in renal transplant patients: prevalence and management in Canadian transplant practice.

Hypercalcemia, occurring in up to 25% of patients within 12 months following renal transplantation, and persistent hyperparathyroidism were evaluated following renal transplantation, by retrospective chart review of 1000 adult patients transplanted between January 1, 2003 and January 31, 2008 with at least six months follow-up. Serum calcium, parathyroid hormone, and phosphate levels were recorded at 12, 24, 36, and 48 months. Average follow-up was 766 (535) d (mean (SD); median 668 d). Majority were first transplants (85%); deceased donor 57%. Point prevalence of hypercalcemia (serum Ca(2+) > 2.6 mM) was 16.6% at month 12, 13.6% at month 24, 9.5% at month 36, and 10.1% at month 48. Point prevalence of serum parathyroid hormone (PTH) > 10 pM was 47.6% at month 12, 51.1% at month 24, 43.4% at month 36, and 39.3% at month 48. Estimated glomerular filtration rate (GFR) was maintained throughout and was not different between patients with or without hypercalcemia or elevated PTH. Cinacalcet was prescribed in 12% of patients with hypercalcemia and persistent hyperparathyroidism; parathyroidectomy was performed in 112/1000 patients, 15 post-transplant. Persistent hyperparathyroidism, often accompanied by hypercalcemia, is common following successful renal transplantation, but the lack of clear management suggests the need for further study and development of evidence-based guidelines.

Meaning, trust, and belonging: Exploring the factors that foster elite forced migrant athletes' growth.

BACKGROUND AND PURPOSE: Researchers have highlighted elite refugee athletes' acculturation and sport-related challenges upon transitioning into host country sports systems. Using a strength-based approach, we aimed to broaden this view through exploring the internal and external factors that have fostered refugee athletes' abilities to find meaning and growth following their transitions into a national sports system. METHODOLOGY: Data collection began with an arts-based drawing activity which was then discussed in a conversational interview. Fourteen (n = 11 male, 3 female) national and international refugee athletes participated. The interviews were analyzed using a reflexive thematic analysis, a form of qualitative analysis used to derive commonalities that connect athletes' experiences. The data is represented through polyphonic vignettes (narrative featuring multiple perspectives) to safeguard athletes' anonymity whilst showcasing varying perspectives. RESULTS: Athletes were at various phases of growth at the time of the interviews. The primary internal factor that facilitated growth was responsibility to find and pursue meaning. External factors of trust and belonging, actualized through supporting elite athletes' personal differences, were external factors that fostered their abilities to find meaning. CONCLUSION: Elite refugee athletes' growth occurred at the nexus of individual responsibility, trusting relationships, and inclusive sport environments. The findings inform individual and environmental growth-based interventions for current and future elite athletes who face varying adversities within their sports contexts.

3D-Printed Metaphyseal Cones in Revision Total Knee Arthroplasties: Excellent Survivorship of 740 Cones at 5 Years.

BACKGROUND: Porous metaphyseal cones are frequently utilized during revision total knee arthroplasty (TKA) procedures. The purpose of the present study was to evaluate 3D-printed metaphyseal cones used for revision TKA, with specific emphasis on implant survivorship, radiographic appearance, and clinical outcomes after short-term follow-up. METHODS: We identified 740 cones (498 tibial, 242 femoral) that had been inserted during 533 revision TKA procedures that had been performed at a single tertiary care academic institution. Aseptic loosening (n = 199), periprosthetic joint infection (PJI) (n = 183), and instability (n = 84) were the most common reasons for the index revision. Type-2B or 3 bone loss was present in 67% of the knees. The mean age was 66 years, the mean body mass index was 34 kg/m 2 , and 55% of the patients were female. Serial radiographs were reviewed. The mean duration of follow-up was 4 years. RESULTS: The 5-year cumulative incidence of cone revision for aseptic loosening was 1% (95% confidence interval [CI], 0% to 3%). The 5-year cumulative incidence of any cone revision or removal was 6% (95% CI, 4% to 9%). In total, 37 cones (19 femoral, 18 tibial) were revised, with PJI (n = 23; 14 recurrent), periprosthetic femoral fracture (n = 3), arthrofibrosis (n = 3), and aseptic loosening of the femoral component and femoral cone (n = 3) as the most common reasons for cone revision. The 5-year cumulative incidence of any TKA re-revision was 14% (95% CI, 11% to 18%). There were a total of 67 re-revisions, with PJI (n = 38), persistent drainage (n = 6), and extensor mechanism disruption (n = 3) being the most common reasons. Radiographically, 2 unrevised femoral cones and 1 unrevised tibial cone appeared to be possibly loose; all 3 cones were in knees with distal femoral replacements or hinged constructs. CONCLUSIONS: This large series showed that 3D-printed titanium metaphyseal cones were very durable at short-term follow-up, with a 5-year cumulative incidence of cone revision for aseptic loosening of 1%. PJI was the most common reason for cone revision and any revision. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Contemporary Aseptic Revision Total Hip Arthroplasty in Patients ≤50 Years of Age: Results of >500 Cases.

BACKGROUND: There has been a paucity of long-term outcomes data on aseptic revision total hip arthroplasties (THAs) in the young adult population. The purpose of this study was to evaluate implant survivorship, complications, and clinical outcomes in a large cohort of contemporary aseptic revision THAs in patients ≤50 years of age at the time of the surgical procedure. METHODS: We identified 545 aseptic revision THAs performed at a single academic institution from 2000 to 2020 in patients who were 18 to 50 years of age. Patients who underwent conversion THAs and patients with a history of any ipsilateral hip infection were excluded. The mean age was 43 years, the mean body mass index (BMI) was 29 kg/m 2 , and 63% were female. The index indication for revision THA was aseptic loosening in 46% of cases, polyethylene wear or osteolysis in 28% of cases (all revisions of conventional polyethylene), and dislocation in 11% of cases. There were 126 hips (23%) that had undergone at least 1 previous revision (median, 1 revision [range, 1 to 5 revisions]). The mean follow-up was 10 years. RESULTS: In the entire cohort, the 20-year survivorship free of any re-revision was 76% (95% confidence interval [95% CI], 69% to 82%). There were 87 re-revisions, with 31 dislocations, 18 cases of aseptic loosening of the femoral component, and 16 periprosthetic joint infections (PJIs) being the most common reasons for re-revision. Dislocation as the indication for the index revision was associated with an increased risk of re-revision (hazard ratio, 2.9; p < 0.001). The 20-year survivorship free of any reoperation was 73% (95% CI, 66% to 78%). There were 75 nonoperative complications (14%), including 32 dislocations. The mean Harris hip score significantly improved (p < 0.001) from 65 preoperatively to 81 at 10 years postoperatively. CONCLUSIONS: Contemporary aseptic revision THAs in patients ≤50 years of age demonstrated a re-revision risk of approximately 1 in 4 at 20 years. Dislocation, aseptic loosening of the femoral component, and PJI were the most common reasons for re-revision. Index revision THAs for dislocation had a 3 times higher risk of re-revision. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Draft genomes of 12 Bifidobacterium isolates from human IBD fecal samples.

Twelve Bifidobacterium strains were isolated from fecal samples of inflammatory bowel disease patients and matched "household control" individuals. These include the species Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum.

Individual personalities predict social behaviour in wild networks of great tits (Parus major).

Social environments have an important effect on a range of ecological processes, and form a crucial component of selection. However, little is known of the link between personality, social behaviour and population structure. We combine a well-understood personality trait with large-scale social networks in wild songbirds, and show that personality underpins multiple aspects of social organisation. First, we demonstrate a relationship between network centrality and personality with 'proactive' (fast-exploring) individuals associating weakly with greater numbers of conspecifics and moving between flocks. Second, temporal stability of associations relates to personality: 'reactive' (slow-exploring) birds form synergistically stable relationships. Finally, we show that personality influences social structure, with males non-randomly distributed across groups. These results provide strong evidence that songbirds follow alternative social strategies related to personality. This has implications not only for the causes of social network structure but also for the strength and direction of selection on personality in natural populations.

Surgical tracheostomy in a patient with a stuck tracheal tube in situ.

The inability to extubate a patient's trachea due to a mechanical complication is rarely encountered in clinical practice. The risks of attempting to remove a stuck tracheal tube include laryngeal trauma, vocal cord injury and arytenoid dislocation, all of which have significant implications. Here, we report the case of a patient who was admitted to the intensive care unit for mechanical ventilation following liver transplant surgery. Her trachea was initially extubated on the second postoperative day, but she required further mechanical ventilation the following day and her trachea was re-intubated. Five days later, she was deemed suitable for tracheal extubation, but the formation of granulation tissue around the tracheal tube prevented its removal. A multi-disciplinary decision-making approach was taken when deciding to site a surgical tracheostomy. A flexible bronchoscope was used as an aid for safe placement. This facilitated safe extrication of the tracheal tube, which was freed by gentle manipulation both proximally and distally. We suspect that tracheal tube size may have been a factor in the development of the granulation tissue in this case. It is important to consider tracheal tube size in all patients, particularly if they require tracheal re-intubation or are likely to require mechanical ventilation for a prolonged period.