The Use of Hindfoot Nails for Elderly Complex Distal Tibial and Ankle Fractures.

Elderly patients who sustain complex ankle or distal tibial fractures are often frail and comorbid and need surgery to contain the talus underneath the tibia in order to protect the soft tissue envelope and allow early unrestricted weightbearing. We performed a retrospective observational review of patients >65 years old who underwent a hindfoot nail fixation of an ankle or distal tibial fracture in our institution. Data collected included: injury sustained, open or closed injury, ASA grade, age at time of surgery, length of stay, postoperative mortality, complications, and further treatment. The primary outcome was reoperation. Secondary outcomes were infection and 1 year mortality. Seventy hind foot nailing procedures were undertaken. Sixty-three out of 70 patients were female. The average age of those who died within 1 year of surgery was 84 years. Forty-five out of 70 were open injuries. Eleven out of 70 patients died with 1 year of surgery (range 1-358 days postsurgery). Five out of 70 (7%) patients developed an infection. Four out of 5 of these injuries were open. Three out of 5 underwent removal of the nail due to infection. Two out of 5 had the infection suppressed with antibiotics. Ten out of 70 (14%) patients underwent locking bolt removal due to it backing out or being prominent and causing wound healing issues. Two out of 70 (3%) patients went on to have below knee amputations. Both were due to ongoing wound problems following open fractures. The hindfoot nail is an important implant when treating complex ankle and distal tibial fractures in an elderly population. It facilitates early mobilization to avoid deconditioning and other medical complications.

Lateral compression type 1 (LC1) pelvic ring injuries: a spectrum of fracture types and treatment algorithms.

Lateral compression type 1 (LC1) fractures are the commonest pelvic ring injury. However, they represent a heterogenous spectrum of injury mechanisms and fracture patterns, resulting in a lack of strong evidence for a universally agreed treatment algorithm. Although consensus exists that LC1 fractures have a preserved posterior ligamentous complex and are vertically stable, controversy persists around defining internal rotational instability. As such, treatment strategies extend from routine non-operative management through to dynamic imaging such as examination under anaesthetic (EUA) or stress radiographs to guide fixation algorithm. Multiple protocols sit between these two, all with slightly different thresholds for advocating surgery or otherwise, exemplifying a broad lack of consensus that is not seen for other, more severe, grades of pelvic ring injury. In the following review we discuss the evolving concepts of pelvic ring instability and management, starting from a historical perspective, through to current trends and controversies in LC1 fracture treatment. Emerging directions for research and emerging pharmacological and surgical treatments/technologies are also considered and expert commentary from 3 leading centres provided. The distinction is made between LC1 fracture arising from high-energy trauma and those following low-energy falls from standing height (so-called fragility fractures of the pelvis-FFP), since these two patient groups have different functional requirements and medical vulnerabilities. Issues pertaining to FFP are considered separately.

Incidence of DVT and PE after surgical reconstruction for pelvic and acetabular fractures: Does routine duplex scanning affect management?

BACKGROUND: Prevention and detection of thromboembolism with pelvic and acetabular fractures remains controversial. The aim of this study was to evaluate a protocol using LMWH prophylaxis and duplex screening both pre-operatively (if there is a delay > 72 h to surgery) and post-operatively at day 5-7. We assessed the incidence of thromboembolism and associated risk factors. METHODS: A total of 255 consecutive patients who underwent pelvic and/or acetabular reconstruction in a major trauma and tertiary referral centre between January 2013 and December 2015 were studied. Forty-three patients were excluded due to non-adherence to protocol leaving 212 patients included in the study. RESULTS: Patients were of mean age 49 years (15-94) and mean ISS 24.5 (4-66). Pre-operative screening detected two patients with asymptomatic above-knee DVT who then underwent pre-operative IVC filter insertion. Post-operative screening detected seven patients (3%) with lower limb DVTs (3 proximal and 4 below knee). The three patients with proximal DVTs were fully anticoagulated and did not develop symptomatic PE. Six patients (2.8%) developed post-operative PE, four of which were symptomatic and confirmed by CT angiography. Seven patients (3%) died in the post-operative period due to non-VTE-related causes. The overall rate of VTE was 6%, including DVT 4% and PE 2.8%. PE was associated with administration of tranexamic acid in ED (p > 0.03) and total amount of blood transfused during admission (p > 0.001). VTE was not associated with age, injury type, ISS, delay to surgery or associated injuries. CONCLUSION: A protocol-based approach to VTE prophylaxis and screening in trauma patients with pelvic and/or acetabular reconstruction resulted in no VTE-related mortality. Pre- and post-operative screening for DVT changed the management in five patients, with none developing PE. Patients requiring more aggressive resuscitation had a higher rate of PE. The VTE rate was lower than previously reported.

Inferring the role of the microbiome on survival in patients treated with immune checkpoint inhibitors: causal modeling, timing, and classes of concomitant medications.

BACKGROUND: The microbiome has been shown to affect the response to Immune Checkpoint Inhibitors (ICIs) in a small number of cancers and in preclinical models. Here, we sought to broadly survey cancers to identify those in which the microbiome may play a prognostic role using retrospective analyses of patients with advanced cancer treated with ICIs. METHODS: We conducted a retrospective analysis of 690 patients who received ICI therapy for advanced cancer. We used a literature review to define a causal model for the relationship between medications, the microbiome, and ICI response to guide the abstraction of electronic health records. Medications with precedent for changes to the microbiome included antibiotics, corticosteroids, proton pump inhibitors, histamine receptor blockers, non-steroid anti-inflammatories and statins. We tested the effect of medication timing on overall survival (OS) and evaluated the robustness of medication effects in each cancer. Finally, we compared the size of the effect observed for different classes of antibiotics to taxa that have been correlated to ICI response using a literature review of culture-based antibiotic susceptibilities. RESULTS: Of the medications assessed, only antibiotics and corticosteroids significantly associated with shorter OS. The hazard ratios (HRs) for antibiotics and corticosteroids were highest near the start of ICI treatment but remained significant when given prior to ICI. Antibiotics and corticosteroids remained significantly associated with OS even when controlling for multiple factors such as Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index score, and stage. When grouping antibiotics by class, ß-lactams showed the strongest association with OS across all tested cancers. CONCLUSIONS: The timing and strength of the correlations with antibiotics and corticosteroids after controlling for confounding factors are consistent with the microbiome involvement with the response to ICIs across several cancers.

Complications resulting from tracker pin-sites in computer navigated knee replacement surgery.

Intra-osseous pin sites used in Computer Navigated knee Arthroplasty are known to cause complications including infection, neurovascular injury, thermal necrosis and peri-prosthetic fracture. Many studies have looked at ways of reducing these risks to improve results in computer-navigated surgery. We present our complication rates and techniques used to reduce complications in a retrospective study of 321 patients performed by a single surgeon in between 2009 and 2013. One patient was identified with a superficial pin site infection. No major complications were recorded during a mean follow up period of 31 months. Attention to detail in every aspect of pin insertion reduces the rates of both minor and major complications. In particular rates of peri-prosthetic fracture were shown to be lower when using a uni-cortical drilling technique compared with the use of bicortical drilling in other studies.

Predicting five-year mortality in soft-tissue sarcoma patients.

Aims: The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients. Methods: Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset. Results: A total of 13,646 patients with STS from the SEER database were included, of whom 35.9% experienced five-year cancer-related mortality. The random forest model performed the best overall and identified tumour size as the most important variable when predicting mortality in patients with STS, followed by M stage, histological subtype, age, and surgical excision. Each variable was significant in logistic regression. External validation yielded an AUC of 0.752. Conclusion: This study identified clinically important variables associated with five-year cancer-related mortality in patients with limb and trunk STS, and developed a predictive model that demonstrated good accuracy and predictability. Orthopaedic oncologists may use these findings to further risk-stratify their patients and recommend an optimal course of treatment.

Mid-term results of the treatment of complex acetabular fractures with combined acute fixation and total hip replacement in the older patient.

INTRODUCTION: The incidence of acetabular fractures in older patients is increasing. The management of these patients is evolving due to the recognition of risks associated with prolonged immobility with conservative treatment. MATERIALS AND METHODS: Consecutive patients undergoing fixation and total hip replacement (THR) for displaced acetabular fractures undergoing single operation with acetabular fixation and THR were identified. Outcomes were assessed using radiographs, clinical notes, Oxford Hip Score and EuroQol-5L. RESULTS: 77 patients were identified with 51 completing outcome scores. Mean age 68 years at time of injury. Mean follow-up 5 (2-12) years, OHS 40, EQ-5D 0.78. Revision surgery performed in 7 patients (9%). DISCUSSION: Acute fixation combined with THR for acetabular fractures in the elderly patient, offers good functional outcomes and a low complication rate in the mid-term.

Prolyl Isomerization-Mediated Conformational Changes Define ATR Subcellular Compartment-Specific Functions.

ATR is a PI3K-like kinase protein, regulating checkpoint responses to DNA damage and replication stress. Apart from its checkpoint function in the nucleus, ATR actively engages in an antiapoptotic role at mitochondria following DNA damage. The different functions of ATR in the nucleus and cytoplasm are carried out by two prolyl isomeric forms of ATR: trans- and cis-ATR, respectively. The isomerization occurs at the Pin1 Ser428-Pro429 motif of ATR. Here, we investigated the structural basis of the subcellular location-specific functions of human ATR. Using a mass spectrometry-based footprinting approach, the surface accessibility of ATR lysine residues to sulfo-NHS-LC-biotin modification was monitored and compared between the cis- and the trans-isomers. We have identified two biotin-modified lysine residues, K459 and K469, within the BH3-like domain of cis-ATR that were not accessible in trans-ATR, indicating a conformational change around the BH3 domain between cis- and trans-ATR. The conformational alteration also involved the N-terminal domain and the middle HEAT domain. Moreover, experimental results from an array of complementary assays show that cis-ATR with the accessible BH3 domain was able to bind to tBid while trans-ATR could not. In addition, both cis- and trans-ATR can directly form homodimers via their C-terminal domains without ATRIP, while nuclear (trans-ATR) in the presence of ATRIP forms dimer-dimer complexes involving both N- and C-termini of ATR and ATRIP after UV. Structural characteristics around the Ser428-Pro429 motif and the BH3 domain region are also analyzed by molecular modeling and dynamics simulation. In support, cis conformation was found to be significantly more energetically favorable than trans at the Ser428-Pro429 bond in a 20-aa wild-type ATR peptide. Taken together, our results suggest that the isomerization-induced structural changes of ATR define both its subcellular location and compartment-specific functions and play an essential role in promoting cell survival and DNA damage responses.

Characterisation of ReNcells CX and VM stimulated with interleukin-1ß and lipopolysaccharide.

Abnormal and dysregulated neuroinflammation has been linked to many neurological disorders and neurodegenerative diseases. Understanding the mechanisms of neuroinflammation, their impact on neurodevelopment and how neuroinflammation might be modulated, are currently considered to be critical to improving neurological treatment. ReNcell CX (originating from the cortical region) and VM (originating from the ventral mesencephalon) are human immortalised neural stem cell lines, that have the potential to be used as experimental models for investigating neuroinflammation in vitro. However, the information on the inflammation response of these cells is limited. This is especially more so for undifferentiated ReNcells. In this report we demonstrate using ELISA that cultured, undifferentiated ReNcell CX and VM produce significant amounts of IL-6 in response to IL-1ß treatment, but not to LPS treatment. Additionally, conventional RT-PCR showed that ReNcell CX cells expressed TNFR1 and NF-κB, whereas ReNcell VM expressed only NF-κB. Our results encourage further investigation into the relationship between 1L-1ß and IL-6 in both ReNcell CX and VM. Moreover, TNF-α treatment might potentially affect neuroinflammation in ReNcell CX, while activation of the NF-κB pathway could also play a critical part in neuroinflammation.

The Efficacy of Medial Patellofemoral Ligament Reconstruction Combined with Tibial Tuberosity Transfer in the Treatment of Patellofemoral Instability.

A systematic review of the literature was undertaken to evaluate the efficacy of medial patellofemoral ligament (MPFL) reconstruction combined with tibial tuberosity transfer (TTT) in the treatment of patellofemoral instability. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic search was carried out to identify and review the published literature pertinent to MFPL reconstruction combined with TTT. Relevant studies were critically appraised with narrative data synthesis. Studies that met the eligibility criteria were suitable for appraisal and consisted of case series and therapeutic series (levels IV & III). All studies had inherent variations in outcomes reporting and limited follow-up. Combined treatment offers restoration of normal anatomy, thus adding clinical value to the currently recommended anatomic approach to MPFL reconstruction. Nevertheless, the current body of evidence does not determine the threshold at which patellofemoral axis requires the need for adjunctive distal realignment as opposed to MPFL reconstruction alone. This review highlighted numerous recurring limitations in the conduct and presentation of the studies, which inadvertently mitigated the interpretation of their results. Future priority should be awarded to larger randomised controlled trials utilising validated patient reported outcome measures.