Ocular radiation exposure is negligible in normal volume endourological practice.

INTRODUCTION: The annual dose limit for radiation exposure to the eye has been reduced recently; the eye is widely recognised as one of the most radiosensitive tissues in the body. There is minimal good quality research as to the radiation dose that the eye receives during endourological surgery and this study aimed to address this. METHODS: A prospective study was performed over an 8-month period at a single large teaching hospital in the UK. Three index procedures were included: ureteric stent insertion, ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL). Surgeons wore a dosimeter on the glabella with fluoroscopy time (FT) and dose area product (DAP) recorded for each case. RESULTS: A total of 404 procedures were included (247 URSs, 150 ureteric stent insertions and 7 PCNLs). Dosimeters were worn by ten surgeons. Mean FTs (URS 20.56s; ureteric stent 18.96s; PCNL 360.67s) and mean DAP (URS 100.82cGy/m2, ureteric stent 119.82cGy/m2 and PCNL 1121.62cGy/m2) were identified with significant intersurgeon variability. No surgeon had a total dosimeter dose >0.00mSv. CONCLUSIONS: The International Commission on Radiological Protection recently reduced the yearly eye dose limit from 150 to 20mSv. Cataractogenesis is no longer considered a typical deterministic effect, with a threshold level below which no effect occurs. Even in higher volume centres, these annual limits are unlikely to be reached. Lead glasses may be considered for surgeons and radiologists with the highest exposure but, for the majority, ocular radiation exposure is negligible.

Return to Activities of Daily Living after Breast Cancer Surgery: An Observational Prospective Questionnaire-Based Study of Patients Undergoing Mastectomy with or without Immediate Reconstruction.

Background: Patients often ask about the time taken to return to activities of daily living (ADLs) after breast surgery, but there is a lack of data to give accurate guidance. We aimed to assess the feasibility of a study to determine the time taken to return to ADLs after mastectomy with or without breast reconstruction. Materials and Methods: A prospective multicentre, self-reported questionnaire-based feasibility study of women who had undergone mastectomy ± reconstruction was performed, between Jan 2017 and Dec 2019. Women were asked to self-report when they returned to 15 ADLs with a 5-option time scale for "return to activity." Results: The questionnaire was returned by 42 patients (median [range] age: 64 [31-84]). Of these, 22 had simple mastectomy, seven mastectomy and implant reconstruction, seven mastectomy and autologous reconstruction (DIEP), and six did not specify. Overall, over 90% could manage stairs and brush hair by two weeks and 84% could get in and out of the bath by four weeks. By 1-2 months, 92% could do their own shopping and 86% could drive. 68% of women employed returned to work within four months. Compared to simple mastectomy, patients undergoing reconstruction took a longer time to return to getting in/out of bath (<2 vs. 2-4 weeks), vacuuming (2-4 weeks vs. 1-2 months), and fitness (1-2 vs. 3-4 months). There was a slower return to shopping (1-2 months vs. 2-4 weeks), driving and work (both 3-4 vs. 1-2 months), and sports (3-4 vs. 1-2 months) in autologous reconstruction compared to implant reconstruction. Conclusion: This study is feasible. It highlights slower return to specific activities (particularly strength-based) in reconstruction patients, slower in autologous compared with implant reconstruction. The impact on return to ADLs should be discussed as part of the preoperative counselling as it will inform patients and help guide their decision making. A larger study is required to confirm these results.

Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions.

Filopodia are actin-rich membrane protrusions essential for cell morphogenesis, motility, and cancer invasion. How cells control filopodium initiation on the plasma membrane remains elusive. We performed experiments in cellulo, in vitro, and in silico to unravel the mechanism of filopodium initiation driven by the membrane curvature sensor IRSp53 (insulin receptor substrate protein of 53 kDa). We showed that full-length IRSp53 self-assembles into clusters on membranes depending on PIP2. Using well-controlled in vitro reconstitution systems, we demonstrated that IRSp53 clusters recruit the actin polymerase VASP (vasodilator-stimulated phosphoprotein) to assemble actin filaments locally on membranes, leading to the generation of actin-filled membrane protrusions reminiscent of filopodia. By pulling membrane nanotubes from live cells, we observed that IRSp53 can only be enriched and trigger actin assembly in nanotubes at highly dynamic membrane regions. Our work supports a regulation mechanism of IRSp53 in its attributes of curvature sensation and partner recruitment to ensure a precise spatial-temporal control of filopodium initiation.

Hospice Palliative Care (HPC) and Medical Assistance in Dying (MAiD): Results From a Canada-Wide Survey.

BACKGROUND: With the legalization of medical assistance in dying (MAiD) in Canada, physicians and nurse practitioners now have another option within their scope of practice to consider alongside hospice palliative care (HPC) to support the patient and family regardless of their choice toward natural or medically assisted death. To elucidate insights and experiences with MAiD since its inception and to help adjust to this new end-of-life care environment, the membership of the Canadian Hospice Palliative Care Association (CHPCA) was surveyed. METHODS: The CHPCA developed and distributed a 16-item survey to its membership in June 2017, one year following the legalization of MAiD. Data were arranged in Microsoft® Excel and open-ended responses were analyzed thematically using NVivo 12 software. RESULTS: From across Canada, 452 responses were received (response rate: 15%). The majority of individuals worked as nurses (n = 161, 33%), administrators (n = 79, 16%), volunteers (n = 76, 16%) and physicians (n = 56, 11%). Almost 75% (n = 320) of all respondents indicated that they had experienced a patient in their program who had requested MAiD. Participants expressed dissatisfaction with the current psychological and professional support being provided by their health care organization and Ministry of Health - during and after the MAiD procedure. CONCLUSION: The new complexities of MAiD present unique challenges to those working in the health-care field. There needs to be an increased focus on educating/training providers as without proper support, health-care workers will be unable to perform to their full potential/scope of practice while also providing patients with holistic and accessible care.

An online diabetes nutrition education programme for American Indian and Alaska Native adults with type 2 diabetes: perspectives from key stakeholders.

OBJECTIVE: To explore stakeholder perspectives regarding online diabetes nutrition education for American Indians and Alaska Natives (AI/AN) with type 2 diabetes (T2D). DESIGN: Qualitative data were collected through focus groups and interviews. Focus group participants completed a brief demographic and internet use survey. SETTING: Focus groups and community participant interviews were conducted in diverse AI/AN communities. Interviews with nationally recognised content experts were held via teleconference. PARTICIPANTS: Eight focus groups were conducted with AI/AN adults with T2D (n 29) and their family members (n 22). Community participant interviews were conducted with eleven clinicians and healthcare administrators working in Native communities. Interviews with nine content experts included clinicians and researchers serving AI/AN. RESULTS: Qualitative content analysis used constant comparative method for coding and generating themes across transcripts. Descriptive statistics were computed from surveys. AI/AN adults access the internet primarily through smartphones, use the internet for many purposes and identify opportunities for online diabetes nutrition education. CONCLUSIONS: Online diabetes nutrition education may be feasible in Indian Country. These findings will inform the development of an eLearning diabetes nutrition education programme for AI/AN adults with T2D.

Cystoscopy with antibiotic irrigation during pelvic reconstruction and minimally invasive gynecologic surgery: A double-blind randomized controlled trial.

AIMS: After pelvic reconstructive surgery, the risk of postoperative urinary tract infection (UTI) is significant; intraoperative cystoscopy may contribute to this risk. Intravesical antibiotics are used in the ambulatory setting and may be applied to the surgical arena. Our objective was to evaluate the efficacy of antibiotic irrigation during intraoperative cystoscopy to prevent postoperative UTI. METHODS: This double-blind randomized controlled trial enrolled 216 women undergoing cystoscopy with elective surgery for pelvic organ prolapse, stress urinary incontinence, or laparoscopic gynecologic surgery at an academic medical center 2016-2019. Participants were randomized to cystoscopic irrigation fluid type: normal saline (control) or 200,000 U polymyxin B + 40 mg neomycin solution in normal saline (antibiotic). Patients and providers who treated UTIs were blinded. The primary outcome was treatment of UTI within 6 weeks postoperatively, defined as positive culture or treatment for a symptomatic UTI. χ2 and multivariable logistic regression analyses were performed. RESULTS: We enrolled 216 women: 111 control (51.4%) and 105 antibiotic (48.6%). Mean age was 51.6 years. Groups were well matched in medical comorbidities and surgery type. Primary vaginal surgery was most common (n = 127, 58.8%). Overall, 10.7% of patients developed a postoperative UTI with no difference in incidence between groups: 9.9% of control (n = 11, 95% confidence interval [CI]: 4.0%-16.0%) versus 11.4% of antibiotic subjects (n = 12, 95% CI: 5.0%-18.0%), on χ2 (p = .718) and logistic regression analysis (adjusted odds ratio, 1.3; CI: 0.53-3.16; p = .569). CONCLUSION: When cystoscopy is performed during elective pelvic surgery, use of antibiotic irrigation does not impact the rate of postoperative UTI.

Structural Insights into How Protein Environments Tune the Spectroscopic Properties of a Noncanonical Amino Acid Fluorophore.

Genetically encoded fluorescent noncanonical amino acids (fNCAAs) could be used to develop novel fluorescent sensors of protein function. Previous efforts toward this goal have been limited by the lack of extensive physicochemical and structural characterizations of protein-based sensors containing fNCAAs. Here, we report the steady-state spectroscopic properties and first structural analyses of an fNCAA-containing Fab fragment of the 5c8 antibody, which binds human CD40L. A previously reported 5c8 variant in which the light chain residue IleL98 is replaced with the fNCAA l-(7-hydroxycoumarin-4-yl)ethylglycine (7-HCAA) exhibits a 1.7-fold increase in fluorescence upon antigen binding. Determination and comparison of the apparent pKas of 7-HCAA in the unbound and bound forms indicate that the observed increase in fluorescence is not the result of perturbations in pKa. Crystal structures of the fNCAA-containing Fab in the apo and bound forms reveal interactions between the 7-HCAA side chain and surrounding residues that are disrupted upon antigen binding. This structural characterization not only provides insight into the manner in which protein environments can modulate the fluorescence properties of 7-HCAA but also could serve as a starting point for the rational design of new fluorescent protein-based reporters of protein function.

A point prevalence study to determine the inpatient rate of carbapenemase-producing organisms at a large London NHS Trust.

BACKGROUND: There has been an increase in the number of carbapenemase-producing organisms documented across the UK over the past 10 years. From these, the 'big five' carbapenemases (KPC, OXA-48, IMP, VIM, and NDM) are the most common types reported in the order Enterobacterales, identified from a variety of reactive screening, outbreak, inpatient surveillance, and diagnostic samples. AIM: To perform a point prevalence study to determine the inpatient carriage rate of carbapenemase-producing organisms at Barts Health NHS Trust, which encompasses 2.5 million patients across four London boroughs: Tower Hamlets, Newham, Redbridge, and Waltham Forest. METHODS: Rectal swabs were collected from consenting inpatients, alongside details of the ward's medical specialty, patient's country of birth, history of foreign travel, length of hospitalization, and history of prior hospitalization. Swabs were enriched and subcultured on to mSuperCARBA selective medium. All Enterobacterales, Acinetobacter, and Pseudomonas species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy and underwent antibiotic susceptibility testing by disc diffusion, according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. All isolates were screened for the 'big five' carbapenemases using a modified version of a published reverse transcriptase-polymerase chain reaction assay. FINDINGS: Of the 977 inpatients tested, 35 CPOs were isolated from 30 patients. NDM was the most frequently detected carbapenemase, followed by OXA-48, with an overall prevalence of 3.1%. Organisms isolated included Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, and Escherichia coli. Renal and elderly care patients had the highest prevalences of CPOs, whereas the intensive care unit prevalence was low. Statistical analysis found that hospitalization abroad, any previous hospitalization, foreign travel and, specifically, travel to India, Pakistan, and Bangladesh were associated with increased risk of CPO carriage. CONCLUSION: The overall prevalence of CPOs at Barts Health Trust was 3.1%, comprising NDM and OXA-48-type carbapenemases, which is in line with other London-based studies. Renal patients and the elderly had the highest burden of CPOs, whereas previous hospitalization and foreign travel were associated with an increased risk of CPO carriage.

Community prevalence of carbapenemase-producing organisms in East London.

BACKGROUND: Over the last decade there has been a rapid, worldwide increase in carbapenem resistance, which is of growing concern. The main protagonists, the carbapenemases Klebsiella pneumoniae carbapenemase (KPC), oxacillinase ß-lactamase 48 (OXA-48), imipenemase metallo-ß-lactamase (IMP), Verona integron-borne metallo-ß-lactamase (VIM), and New Delhi metallo-ß-lactamase (NDM) have also been reported across the UK. However, these reports are derived from a combination of reactive screening, outbreak control, inpatient surveillance, and diagnostic samples. Therefore, the true community prevalence is unknown. AIM: To determine the community prevalence of carbapenemase-producing organisms (CPOs) in the area served by Barts Health NHS Trust. METHODS: Active screening of 200 non-duplicate community stool samples was performed. Patient demographics and foreign travel history were extracted from the laboratory information management system to identify potential risk factors for carriage of CPOs. FINDINGS: Patients in this study were aged from one to 93 years and were evenly distributed between male and female. Foreign travel in the last year was listed for 46 out of 200 (23%) patients, with the most commonly visited countries including Bangladesh (4%), India (2.5%), Morocco (2%), and Turkey (1.5%). However, only one patient tested positive for a CPO, an NDM-producing Pseudomonas aeruginosa, and this patient had travelled to the Caribbean. CONCLUSION: To date, there have been no studies investigating the prevalence of CPOs in the UK community. Given the high-risk patient population served by Barts Health NHS Trust, it is reassuring that the prevalence observed here was low. However, it should be highlighted that travel to countries not previously categorized as high risk may also pose a threat.

Beyond electrostatics: Antimicrobial peptide selectivity and the influence of cholesterol-mediated fluidity and lipid chain length on protegrin-1 activity.

Antimicrobial peptides (AMPs) are a promising class of innate host defense molecules for next-generation antibiotics, as they uniquely target and permeabilize membranes of pathogens. This selectivity has been explained by the electrostatic attraction between these predominantly cationic peptides and the bacterial membrane, which is heavily populated with anionic lipids. However, AMP-resistant bacteria have non-electrostatic countermeasures that modulate membrane rigidity and thickness. We explore how variations in physical properties affect the membrane affinity and disruption process of protegrin-1 (PG-1) in phosphatidylcholine (PC) membranes with altered lipid packing densities and thicknesses. From isothermal titration calorimetry and atomic force microscopy, our results showed that PG-1 could no longer insert into membranes of increasing cholesterol amounts nor into monounsaturated PC membranes of increasing thicknesses with similar fluidities. Prevention of PG-1's incorporation consequently made the membranes more resistant to peptide-induced structural transformations like pore formation. Our study provides evidence that AMP affinity and activity are strongly correlated with the fluidity and thickness of the membrane. A basic understanding of how physical mechanisms can regulate cell selectivity and resistance towards AMPs will aid in the development of new antimicrobial agents.

Developing a Palliative Care Competency Framework for Health Professionals and Volunteers: The Nova Scotian Experience.

BACKGROUND AND OBJECTIVES: In 2014, Nova Scotia released a provincial palliative care strategy and implementation working groups were established. The Capacity Building and Practice Change Working Group, comprised of health professionals, public advisors, academics, educators, and a volunteer supervisor, was asked to select palliative care education programs for health professionals and volunteers. The first step in achieving this mandate was to establish competencies for health professionals and volunteers caring for patients with life-limiting illness and their families and those specializing in palliative care. METHODS: In 2015, a literature search for palliative care competencies and an environmental scan of related education programs were conducted. The Irish Palliative Care Competence Framework serves as the foundation of the Nova Scotia Palliative Care Competency Framework. Additional disciplines and competencies were added and any competencies not specific to palliative care were removed. To highlight interprofessional practice, the framework illustrates shared and discipline-specific competencies. Stakeholders were asked to validate the framework and map the competencies to educational programs. Numerous rounds of review refined the framework. RESULTS: The framework includes competencies for 22 disciplines, 9 nursing specialties, and 4 physician specialties. CONCLUSIONS: The framework, released in 2017, and the selection and implementation of education programs were a significant undertaking. The framework will support the implementation of the Nova Scotia Integrated Palliative Care Strategy, enhance the interprofessional nature of palliative care, and guide the further implementation of education programs. Other jurisdictions have expressed considerable interest in the framework.

Outcomes of minimally invasive abdominal sacrocolpopexy with resident operative involvement.

INTRODUCTION AND HYPOTHESIS: Resident involvement in complex surgeries is under scrutiny with increasing attention paid to health care efficiency and quality. Outcomes of urogynecological surgery with resident involvement are poorly described. We hypothesized that resident surgical involvement does not influence perioperative outcomes in minimally invasive abdominal sacrocolpopexy (ASC). METHODS: Using the 2006-2012 National Surgical Quality Improvement Program database, we identified 450 cases of laparoscopic or robotic ASC performed with resident involvement. Resident operative participation was stratified by experience (junior [PGY 1-3] vs senior level [PGY ≥4]). The primary outcome was operative time, and multinomial logistic regression was used to determine the effects of resident involvement and experience. Chi-squared analyses were used to assess the relationship between resident participation with length of stay (LOS) and 30-day complications and readmissions. RESULTS: Residents participated in 74% (n = 334) of these surgeries, and these cases were significantly longer (median 220 vs 195 min, p = 0.03). On multivariate analysis, senior level resident involvement was associated with longer operative times across all time intervals compared with <2 h (2 to ≤4 h relative risk reduction [RRR] 4.1, p = 0.007, CI 1.47-11.40; 4 to ≤6 h RRR 6.6, p = 0.001, CI 2.23-19.44; ≥6 h RRR 4.7, p = 0.020, CI 1.28-17.43). Resident participation was not associated with LOS, readmissions, or complications. CONCLUSIONS: Senior level resident involvement in minimally invasive ASC is associated with longer operative times, with no association with LOS or adverse perioperative outcomes. The educational benefit of surgical training does not adversely affect patient outcomes for ASC.

Nucleotide Dependence of Subunit Rearrangements in Short-Form Rubisco Activase from Spinach.

Higher-plant Rubisco activase (Rca) plays a critical role in regulating the activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). In vitro, Rca is known to undergo dynamic assembly-disassembly processes, with several oligomer stoichiometries coexisting over a broad concentration range. Although the hexamer appears to be the active form, changes in quaternary structure could play a role in Rubisco regulation. Therefore, fluorescent labels were attached to the C-termini of spinach ß-Rca, and the rate of subunit mixing was monitored by measuring energy transfer as a function of nucleotide and divalent cation. Only dimeric units appeared to exchange. Poorly hydrolyzable substrate analogues provided locked complexes with high thermal stabilities (apparent Tm = 60 °C) and an estimated t1/2 of at least 7 h, whereas ATP-Mg provided tight assemblies with t1/2 values of 30-40 min and ADP-Mg loose assemblies with t1/2 values of <15 min. Accumulation of ADP to 20% of the total level of adenine nucleotide substantially accelerated equilibration. An initial lag period was observed with ATP·Mg, indicating inhibition of subunit exchange at low ADP concentrations. The ADP Ki value was estimated to exceed the Km for ATP (0.772 ± 96 mM), suggesting that the equilibration rate is a function of the relative contributions of high- and low-affinity states. C-Terminal cross-linking generated covalent dimers, required the N-terminal extension to the AAA+ domain, and provided evidence of different classes of sites. We propose that oligomer reorganization may be stalled during periods of high Rubisco reactivation activity, whereas changes in quaternary structure are stimulated by the accumulation of ADP at low light levels.

Conservative management of mallet injuries: A national survey of current practice in the UK.

INTRODUCTION: Mallet injuries are common and usually treated conservatively. Various systematic reviews have found a lack of evidence regarding the best management, and it is unclear whether this uncertainty is reflected in current UK practice. METHODS: An online survey was developed to determine the current practice for the conservative treatment of mallet injury among specialist hand clinicians in the UK, including physiotherapists, occupational therapists and surgeons. Clinician's views of study outcome selection were also explored to improve future trials. RESULTS: In total, 336 professionals completed the survey. Inconsistency in overall practice was observed in splint type choice, time to discharge to GP, and assessment of adherence. Greater consistency was observed for recommended duration of continuous immobilisation. Bony injuries were most commonly splinted for 6 weeks (n = 228, 78%) and soft tissue injuries for either 8 weeks (n = 172, 56%) or 6 weeks (n = 119, 39%). Post-immobilisation splinting was frequently recommended, but duration varied between 2 and 10 weeks. The outcome rated as most important by all clinicians was patient satisfaction. DISCUSSION: There is overall variation in the current UK conservative management of mallet injuries, and the development of a standardised, evidence-based protocol is required. Clinicians' opinions may be used to develop a core set of outcome measures, which will improve standardisation and comparability of future trials.

National Surgical Trends and Perioperative Outcomes of Midurethral Sling Placement for Stress Urinary Incontinence.

OBJECTIVE: To determine contemporary trends, patient characteristics, and outcomes for midurethral sling placement (MUS) at inpatient and ambulatory facilities from a national database. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified 7767 women who underwent isolated MUS 2006-2012. We stratified patients by hospitalization type (outpatient vs hospitalization). Primary outcomes were 30-day complications, readmissions, and reoperations. Multivariable logistic regression was used to determine patient and surgery factors associated with adverse perioperative outcomes. RESULTS: Among the 7767 women undergoing MUS, 84.3% underwent outpatient surgery (n = 6547), with greater use of outpatient facilities over time (P < .001). Overall, 3.9% of patients (n = 300) experienced one or more postoperative complications. Complications were more likely among inpatients (7.4% vs 3.2%; odds ratio [OR] 0.48, confidence interval [CI] 0.36-0.64, P < .001), with gynecologists as compared to urologists (4.4% vs 3.1%; OR 1.53, CI 1.16-2.02, P = .003), and with resident participation (5.1% vs 3.7%; OR 1.32, CI 1.01-1.73, P = .04). On multivariable analysis, outpatients were less likely to experience readmissions (0.9% vs 2.8%; OR 0.2, CI 0.09-0.56, P = .002) or undergo reoperation (0.3% vs 3.1%; OR 0.10, CI 0.02-0.38, P = .001). CONCLUSION: Use of outpatient surgical centers for MUS is increasing, with lower rates of complications, readmissions, and reoperations compared to inpatient treatment. Although there is a difference in complications by specialty and with resident involvement, overall incidence of complications is low.

Defective Bone Repair in C57Bl6 Mice With Acute Systemic Inflammation.

BACKGROUND: Bone repair is initiated with a local inflammatory response to injury. The presence of systemic inflammation impairs bone healing and often leads to malunion, although the underlying mechanisms remain poorly defined. Our research objective was to use a mouse model of cortical bone repair to determine the effect of systemic inflammation on cells in the bone healing microenvironment. QUESTION/PURPOSES: (1) Does systemic inflammation, induced by lipopolysaccharide (LPS) administration affect the quantity and quality of regenerating bone in primary bone healing? (2) Does systemic inflammation alter vascularization and the number or activity of inflammatory cells, osteoblasts, and osteoclasts in the bone healing microenvironment? METHODS: Cortical defects were drilled in the femoral diaphysis of female and male C57BL/6 mice aged 5 to 9 months that were treated with daily systemic injections of LPS or physiologic saline as control for 7 days. Mice were euthanized at 1 week (Control, n = 7; LPS, n = 8), 2 weeks (Control, n = 7; LPS, n = 8), and 6 weeks (Control, n = 9; LPS, n = 8) after surgery. The quantity (bone volume per tissue volume [BV/TV]) and microarchitecture (trabecular separation and thickness, porosity) of bone in the defect were quantified with time using microCT. The presence or activity of vascular endothelial cells (CD34), macrophages (F4/80), osteoblasts (alkaline phosphatase [ALP]), and osteoclasts (tartrate-resistant acid phosphatase [TRAP]) were evaluated using histochemical analyses. RESULTS: Only one of eight defects was bridged completely 6 weeks after surgery in LPS-injected mouse bones compared with seven of nine defects in the control mouse bones (odds ratio [OR], 0.04; 95% CI, 0.003-0.560; p = 0.007). The decrease in cortical bone in LPS-treated mice was reflected in reduced BV/TV (21% ± 4% vs 39% ± 10%; p < 0.01), increased trabecular separation (240 ± 36 µm vs 171 ± 29 µm; p < 0.01), decreased trabecular thickness (81 ± 18 µm vs 110 ± 22 µm; p = 0.02), and porosity (79% ± 4% vs 60% ± 10%; p < 0.01) at 6 weeks postoperative. Defective healing was accompanied by decreased CD34 (1.1 ± 0.6 vs 3.4 ± 0.9; p < 0.01), ALP (1.9 ± 0.9 vs 6.1 ± 3.2; p = 0.03), and TRAP (3.3 ± 4.7 vs 7.2 ± 4.0; p = 0.01) activity, and increased F4/80 (13 ± 2.6 vs 6.8 ± 1.7; p < 0.01) activity at 2 weeks postoperative. CONCLUSION: The results indicate that LPS-induced systemic inflammation reduced the amount and impaired the quality of bone regenerated in mouse femurs. The effects were associated with impaired revascularization, decreased bone turnover by osteoblasts and osteoclasts, and by increased catabolic activity by macrophages. CLINICAL RELEVANCE: Results from this preclinical study support clinical observations of impaired primary bone healing in patients with systemic inflammation. Based on our data, local administration of VEGF in the callus to stimulate revascularization, or transplantation of stem cells to enhance bone turnover represent potentially feasible approaches to improve outcomes in clinical practice.

Patient and disease factors predictive of adverse perioperative outcomes after nephrectomy.

INTRODUCTION: The aim of this study was to determine the patient and disease factors predictive of adverse perioperative outcomes after nephrectomy using the British Association of Urological Surgeons (BAUS) audit database. METHODS: All nephrectomies entered on the BAUS database for the year 2012 were included and ten patient or disease factors were selected for analysis. Logistic regression was used to calculate the area under the receiver operating characteristic curve (AUC) (0.5 = no better than chance, 1.0 = perfect prediction) for each variable and 500 bootstrap samples were used to determine variable selection. RESULTS: Data were captured for 6,031 nephrectomies in 2012. World Health Organization performance status (WHO-PS) (AUC: 0.733) and anaemia (AUC: 0.696) were the most significant predictors of 30-day mortality in univariate analysis. WHO-PS (AUC: 0.626) and anaemia (AUC: 0.590) also predicted complications classified as Clavien-Dindo grades III-V. Anaemia (AUC: 0.722) and clinical T stage (AUC: 0.713) predicted need for transfusion. CONCLUSIONS: Adverse perioperative outcomes after nephrectomy are predicted by clinical presentation with haematuria, poor WHO-PS and higher TNM (tumour, lymph nodes, metastasis) stage. This study used surgeon collected data as opposed to an administrative database, which may have advantages in terms of accuracy and breadth of data fields. These data form a basis for preoperative patient counselling and informed consent for nephrectomy. They can also be used as a standard against which surgeons and hospitals can compare their own results.