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Unstable ankle fractures are traditionally treated with open reduction and internal fixation. An alternative surgical option is primary tibio-talar-calcaneal fusion. Our aims were to determine the indication, complication rates, and functional outcomes, of tibio-talar-calcaneal nailing when used as the primary treatment of ankle fractures. A multidatabase literature search was performed on December 14, 2019 according to PRISMA guidelines. All studies in the English language reporting complications and outcomes involving tibio-talar-calcaneal nailing for primary treatment of ankle fractures were included. Ten studies with 252 ankle fractures were included. Mean age of patients was 75.5 (32-101) years. Mean follow-up duration was 79 weeks (36-104 weeks). Surgical site infection occurred in 11.2% (95% confidence interval [CI] 6.3%-19%) of patients, implant failure occurred in 8.1% (95% CI 5%-12.8%) of patients, and unplanned return to operating room occurred in 10.1% (95% CI 6.1%-16.2%) of patients. There were no cases of wound dehiscence. All-cause mortality rate at the end of follow-up was 26.6% (95% CI 19.7%-34.9%). Average reduction in Olerud-Molander Ankle Score after surgery was 7.9 points (5.0-11.8). Eighty-one point five percent (95% CI: 67.4%-90.4%) of patients were able to return to similar preoperative mobility aid after surgery. Tibio-talar-calcaneal nailing is an alternative procedure for patients who have sustained fractures unsuitable for nonoperative management, but have low functional demands and at increased risks of complications after open reduction and internal fixation. About 81.5% (95% CI 67.4%-90.4%) of patients were able to return to a similar preinjury mobility status after tibio-talar-calcaneal nailing., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Enterococcus faecalis is a frequent opportunistic pathogen of wounds, whose infections are associated with biofilm formation, persistence, and recalcitrance toward treatment. We have previously shown that E. faecalis wound infection persists for at least 7 days. Here we report that viable E. faecalis are present within both immune and non-immune cells at the wound site up to 5 days after infection, raising the prospect that intracellular persistence contributes to chronic E. faecalis infection. Using in vitro keratinocyte and macrophage infection models, we show that E. faecalis becomes internalized and a subpopulation of bacteria can survive and replicate intracellularly. E. faecalis are internalized into keratinocytes primarily via macropinocytosis into single membrane-bound compartments and can persist in late endosomes up to 24 h after infection in the absence of colocalization with the lysosomal protease Cathepsin D or apparent fusion with the lysosome, suggesting that E. faecalis blocks endosomal maturation. Indeed, intracellular E. faecalis infection results in heterotypic intracellular trafficking with partial or absent labelling of E. faecalis-containing compartments with Rab5 and Rab7, small GTPases required for the endosome-lysosome trafficking. In addition, E. faecalis infection results in marked reduction of Rab5 and Rab7 protein levels which may also contribute to attenuated Rab incorporation into E. faecalis-containing compartments. Finally, we demonstrate that intracellular E. faecalis derived from infected keratinocytes are significantly more efficient in reinfecting new keratinocytes. Together, these data suggest that intracellular proliferation of E. faecalis may contribute to its persistence in the face of a robust immune response, providing a primed reservoir of bacteria for subsequent reinfection., Competing Interests: The authors have declared that no competing interests exist.

Whether due to simplicity or hypocrisy, the question of access to patient data for biomedical research is widely seen in the public discourse only from the angle of patient privacy. At the same time, the desire to live and to live without disability is of much higher value to the patients. This goal can only be achieved by extracting research insight from patient data in addition to working on model organisms, something that is well understood by many patients. Yet, most biomedical researchers working outside of clinics and hospitals are denied access to patient records when, at the same time, clinicians who guard the patient data are not optimally prepared for the data's analysis. Medical data collection is a time- and cost-intensive process that is most of all tedious, with few elements of intellectual and emotional satisfaction on its own. In this process, clinicians and bioinformaticians, each group with their own interests, have to join forces with the goal to generate medical data sets both from clinical trials and from routinely collected electronic health records that are, as much as possible, free from errors and obvious inconsistencies. The data cleansing effort as we have learned during curation of Singaporean clinical trial data is not a trivial task. The introduction of omics and sophisticated imaging modalities into clinical practice that are only partially interpreted in terms of diagnosis and therapy with today's level of knowledge warrant the creation of clinical databases with full patient history. This opens up opportunities for re-analyses and cross-trial studies at future time points with more sophisticated analyses of the same data, the collection of which is very expensive., (© The Author(s) 2019.)

Group A Streptococcus (GAS) is a human pathogen that causes infections ranging from mild to fulminant and life-threatening. Biofilms have been implicated in acute GAS soft-tissue infections such as necrotising fasciitis (NF). However, most in vitro models used to study GAS biofilms have been designed to mimic chronic infections and insufficiently recapitulate in vivo conditions along with the host-pathogen interactions that might influence biofilm formation. Here, we establish and characterise an in vitro model of GAS biofilm development on mammalian cells that simulates microcolony formation observed in a mouse model of human NF. We show that on mammalian cells, GAS forms dense aggregates that display hallmark biofilm characteristics including a 3D architecture and enhanced tolerance to antibiotics. In contrast to abiotic-grown biofilms, host-associated biofilms require the expression of secreted GAS streptolysins O and S (SLO, SLS) that induce endoplasmic reticulum (ER) stress in the host. In an in vivo mouse model, the streptolysin null mutant is attenuated in both microcolony formation and bacterial spread, but pretreatment of soft-tissue with an ER stressor restores the ability of the mutant to form wild-type-like microcolonies that disseminate throughout the soft tissue. Taken together, we have identified a new role of streptolysin-driven ER stress in GAS biofilm formation and NF disease progression., (© 2018 John Wiley & Sons Ltd.)

Enterococcus faecalis is one of the most frequently isolated bacterial species in wounds yet little is known about its pathogenic mechanisms in this setting. Here, we used a mouse wound excisional model to characterize the infection dynamics of E faecalis and show that infected wounds result in 2 different states depending on the initial inoculum. Low-dose inocula were associated with short-term, low-titer colonization whereas high-dose inocula were associated with acute bacterial replication and long-term persistence. High-dose infection and persistence were also associated with immune cell infiltration, despite suppression of some inflammatory cytokines and delayed wound healing. During high-dose infection, the multiple peptide resistance factor, which is involved in resisting immune clearance, contributes to E faecalis fitness. These results comprehensively describe a mouse model for investigating E faecalis wound infection determinants, and suggest that both immune modulation and resistance contribute to persistent, nonhealing wounds., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Physical absorption process is always nullified by the presence of cavitation under low frequency ultrasonic irradiation. In the present study, high frequency ultrasonic of 1.7MHz was used for the physical absorption of CO2 in a water batch system under elevated pressure. The parameters including ultrasonic power and initial feed pressure for the system have been varied from 0 to 18W and 6 to 41bar, respectively. The mass transfer coefficient has been determined via the dynamic pressure-step method. Besides, the actual ultrasonic power that transmitted to the liquid was measured based on calorimetric method prior to the absorption study. Subsequently, desorption study was conducted as a comparison with the absorption process. The mechanism for the ultrasonic assisted absorption has also been discussed. Based on the results, the mass transfer coefficient has increased with the increasing of ultrasonic power. It means that, the presence of streaming effect and the formation of liquid fountain is more favorable under high frequency ultrasonic irradiation for the absorption process. Therefore, high frequency ultrasonic irradiation is suggested to be one of the potential alternatives for the gas separation process with its promising absorption enhancement and compact design., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Enterococcus faecalis is frequently associated with polymicrobial infections of the urinary tract, indwelling catheters, and surgical wound sites. E. faecalis co-exists with Escherichia coli and other pathogens in wound infections, but mechanisms that govern polymicrobial colonization and pathogenesis are poorly defined. During infection, bacteria must overcome multiple host defenses, including nutrient iron limitation, to persist and cause disease. In this study, we investigated the contribution of E. faecalis to mixed-species infection when iron availability is restricted. We show that E. faecalis significantly augments E. coli biofilm growth and survival in vitro and in vivo by exporting L-ornithine. This metabolic cue facilitates E. coli biosynthesis of the enterobactin siderophore, allowing E. coli growth and biofilm formation in iron-limiting conditions that would otherwise restrict its growth. Thus, E. faecalis modulates its local environment by contributing growth-promoting cues that allow co-infecting organisms to overcome iron limitation and promotes polymicrobial infections., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Microbial pathogenesis research has, historically, focused on the study of infections as monomicrobial events. However, the advent of next generation sequencing and culture-independent identification methods has revealed that many, if not most, infections are polymicrobial either in origin or in manifestation. Polymicrobial infections are often associated with increased infection severity and poorer patient outcome. Multiple infecting microbes can interact synergistically to induce virulence traits, alter the infected niche, or modulate the host immune response, all of which can promote polymicrobial infection. Importantly, a polymicrobial environment at the time of inoculation, consisting of multiple pathogens or pathogens in combination with the native microbiota, can contribute to the pathogenic progression of a single predominant organism at the time of diagnosis. Hence, in order to completely understand and elucidate the impact of these polymicrobial interactions on infection outcomes, a thorough examination of the entire microbial community present throughout the pathogenic cascade is required: from the time of inoculation to symptomology to resolution. In this review, we highlight the themes of metabolite exploitation, immune modulation, niche optimization, and virulence induction that contribute to polymicrobial infections. We focus on recent literature about microbe-microbe and microbe-host interactions that promote polymicrobial infections with an emphasis on understanding these interactions to identify better interventions for these sometimes complex infections., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Maintaining the calcaneal length after calcaneal fractures is vital to restoring the normal biomechanics of the foot, because it acts as an important lever arm to the plantarflexors of the foot. However, estimation of the length of the calcaneus to be reconstructed in comminuted calcaneal fractures can be difficult. We propose a new method to reliably estimate the calcaneal length radiographically by defining the calcaneotalar length ratio. A total of 100 ankle radiographs with no fracture in the calcaneus or talus taken in skeletally mature patients were reviewed by 6 observers. The anteroposterior lengths of the calcaneus and talus were measured, and the calcaneotalar length ratio was determined. The ratio was then used to estimate the length of the calcaneus. Interobserver reliability was determined using Cronbach's α coefficient and Pearson's correlation coefficient. The mean length of the calcaneus was 75 ± 0.6 mm, and the mean length of the talus was 59 ± 0.5 mm. The calcaneotalar ratio was 1.3. Using this ratio and multiplying it by the talar length, the mean average estimated length of the calcaneus was within 0.7 mm of the known calcaneal length. Cronbach's α coefficient and Pearson's correlation coefficient showed excellent interobserver reliability. The proposed calcaneotalar ratio is a new and reliable method to radiographically estimate the normal length of the calcaneus when reconstructing the calcaneus., (Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Knowledge about the functional consequences of lower limb long bone fractures is helpful to inform patients, clinicians and employers about their recovery process and prognosis. This study aims to describe the epidemiology and health outcomes of femoral and tibial shaft fractures treated at two level I trauma centres, by comparing the differences between patients with delayed union or nonunion and patients with union., Patients and Methods: An analysis of registry data over two years, supplemented with medical record review, was conducted. Fracture healing was retrospectively assessed by clinical and radiological evidence of union, and the need for surgical intervention. SF-12 scores, and work and pain status were prospectively recorded at six and twelve months post injury., Results: 285 fractures progressed to union and 138 fractures developed delayed union or nonunion. There was a significant difference between the two cohorts with regards to the mechanism of injury, association with multi-trauma, open fractures, grade of Gustilo classification, patient fund source, smoking status and presence of comorbidities. The SF-12 physical component score was less than 50 at both six and twelve months with improvement in the union group, but not in the delayed union or nonunion group. 72% of patients with union had returned to work at one year, but 54% continued to have pain. The difference compared to patients with delayed union or nonunion was significant., Discussion: Even patients whose fractures unite in the expectant time-frame will have residual physical disability. Patients with delayed union or nonunion have still poorer outcomes, including ongoing problems with returning to work and pain. It is important to educate patients about their injury so that they have realistic expectations. This is particularly relevant given that the patients most likely to sustain femoral or tibial shaft fractures are working-age healthy adults, and up to a third of fractures may develop delayed union or nonunion., Conclusion: Despite modern treatment, the patient-reported outcomes of lower limb long bone shaft fractures do not return to normal at one year. Patients with delayed union or nonunion can expect poorer outcomes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)