High rate of reoperation and conversion to total hip arthroplasty after internal fixation of young femoral neck fractures: a population-based study of 796 patients.

Background and purpose - Most often, the goal of non-geriatric femoral neck fracture surgery is to preserve the native hip joint. However, reoperations for painful implants, osteonecrosis, and nonunion are common. We determined the reoperation rate and time-to-reoperation following internal fixation of these fractures in a large population cohort. Patients and methods - This retrospective cohort study included patients between the ages of 18 and 50 years old who underwent internal fixation for a femoral neck fracture during 1997-2013. Patients were followed until December 2013. Primary outcomes were reoperation rate and time-to-reoperation. Time-to-event analysis was performed to estimate the rate of any reoperation and for THA specifically, while testing the dependency of time-to-reoperation on secondary variables. Results - 796 young femoral neck fracture patients were treated with internal fixation during the study period (median age 43 years, 39% women). Median follow-up was 8 years (IQR 4-13). One-third underwent at least 1 reoperation at a median 16 months after the index surgery (IQR 8-31). Half of reoperations were for implant removal, followed by conversion to total hip arthroplasty. 14% of the cohort were converted to THA. The median time to conversion was 2 years (IQR 1-4). Neither female sex nor older age had a statistically significant effect on time-to-reoperation or time-to-THA conversion. Interpretation - Following internal fixation of young femoral neck fracture, 1 in 3 patients required a reoperation, and 1 in 7 were converted to THA. These data should be considered by patients and surgeons during treatment decision-making.

Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes.

Methotrexate (MTX) is a folic acid antagonist that is widely used to treat a variety of diseases. One of the most serious side effects of MTX therapy is hepatotoxicity. The potential molecular cytotoxic mechanisms of MTX toward isolated rat hepatocytes were investigated using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques. A concentration and time dependent increase in cytotoxicity and reactive oxygen species (ROS) formation and a decrease in mitochondrial membrane potential (MMP) were observed with MTX. Furthermore, a significant increase in MTX (300 µM)-induced cytotoxicity and ROS formation were observed when glutathione (GSH)-depleted hepatocytes were used whereas addition of N-acetylcysteine (a GSH precursor) decreased cytotoxicity. Catalase inactivation also increased MTX-induced cytotoxicity, while the direct addition of catalase to the hepatocytes decreased cytotoxicity. MTX treatment in isolated rat mitochondria caused swelling and significantly decreased adenosine triphosphate (ATP) and GSH content, and cytochrome c release. Potent antioxidants such as mesna, resveratrol and Trolox decreased MTX-induced cytotoxicity and ROS formation and increased MMP. This study suggests that MTX-induced cytotoxicity caused by ROS formation and GSH oxidation leads to oxidative stress and mitochondrial injury in rat hepatocytes.

When Surgical Resources are Severely Constrained, Who Receives Care? Determinants of Access to Orthopaedic Trauma Surgery in Uganda.

BACKGROUND: In low- and middle-income countries, the volume of traumatic injuries requiring orthopaedic intervention routinely exceeds the capacity of available surgical resources. The objective of this study was to identify predictors of surgical care for lower extremity fracture patients at a high-demand, resource-limited public hospital in Uganda. METHODS: Skeletally mature patients admitted with the intention of definitive surgical treatment of an isolated tibia or femur fractures to the national referral hospital in Uganda were recruited to participate in this study. Demographic, socioeconomic, and clinical data were collected through participant interviews at the time of injury and 6 months post-injury. Social capital (use of social networks to gain access to surgery), financial leveraging, and ethnicity were also included as variables in this analysis. A probit estimation model was used to identify independent and interactive predictors of surgical treatment. RESULTS: Of the 64 patients included in the final analysis, the majority of participants were male (83%), with a mean age of 40.6, and were injured in a motor vehicle accident (77%). Due to resource constraints, only 58% of participants received surgical care. The use of social capital and femur fractures were identified as significant predictors of receiving surgical treatment, with social capital emerging as the strongest predictor of access to surgery (p < 0.05). CONCLUSION: Limited infrastructure, trained personnel, and surgical supplies rations access to surgical care. In this environment, participants with advantageous social connections were able to self-advocate for surgery where demand for these services greatly exceeded available resources.

Risk factors for colorectal cancer in man induce aberrant crypt foci in rats: Preliminary findings.

Epidemiological studies have demonstrated clear associations between specific dietary and environmental risk factors and incidence of colorectal cancer, but the mechanisms responsible for these associations are not known. An animal model could facilitate such an understanding. Both genotoxic and nongenotoxic carcinogens induce aberrant crypt foci (ACF) in the colons of F344 rats. F344 rats were provided with diets that contained putative risk factors for CRC: low calcium and low vitamin D, high iron, high fructose, and decreased light (UV) exposure or a control diet for 14 wk. The rats were then assessed with biochemical measures and by topological examination for evidence of colon abnormalities. Circulating ionized calcium was decreased from 2.85 to 1.69 mmol/L, and ACF were increased from 0.7 to 13.6 lesions/colon (both P < 0.001). Rats exposed to the multiple environmental conditions associated with colon cancer, developed ACF similar to the heterogeneous or ill-defined ACF in the human colon. Heterogeneous ACF are the most frequently seen in humans and are also seen in rats shortly after exposure to the non-genotoxic colon carcinogen, dextransulfate sodium. The rodent model could be used to assess the pathways from diet and environment to colon cancer and to provide guidance for clinical studies.

Risk factors for acute compartment syndrome of the leg associated with tibial diaphyseal fractures in adults.

BACKGROUND: We sought to examine the occurrence of acute compartment syndrome (ACS) in the cohort of patients with tibial diaphyseal fractures and to detect associated risk factors that could predict this occurrence. MATERIALS AND METHODS: A total of 1,125 patients with tibial diaphyseal fractures that were treated in our centre were included into this retrospective cohort study. All patients were treated with surgical fixation. Among them some were complicated by ACS of the leg. Age, gender, year and mechanism of injury, injury severity score (ISS), fracture characteristics and classifications and the type of fixation, as well as ACS characteristics in affected patients were studied. RESULTS: Of the cohort of patients 772 (69 %) were male (mean age 39.60 ± 15.97 years) and the rest were women (mean age 45.08 ± 19.04 years). ACS of the leg occurred in 87 (7.73 %) of all tibial diaphyseal fractures. The mean age of those patients that developed ACS (33.08 ± 12.8) was significantly lower than those who did not develop it (42.01 ± 17.3, P < 0.001). No significant difference in incidence of ACS was found in open versus closed fractures, between anatomic sites and following IM nailing (P = 0.67). Increasing pain was the most common symptom in 71 % of cases with ACS. CONCLUSIONS: We found that younger patients are definitely at a significantly higher risk of ACS following acute tibial diaphyseal fractures. Male gender, open fracture and IM nailing were not risk factors for ACS of the leg associated with tibial diaphyseal fractures in adults. LEVEL OF EVIDENCE: Level IV.

Bonding-induced thermal conductance enhancement at inorganic heterointerfaces using nanomolecular monolayers.

Manipulating interfacial thermal transport is important for many technologies including nanoelectronics, solid-state lighting, energy generation and nanocomposites. Here, we demonstrate the use of a strongly bonding organic nanomolecular monolayer (NML) at model metal/dielectric interfaces to obtain up to a fourfold increase in the interfacial thermal conductance, to values as high as 430 MW m(-2) K(-1) in the copper-silica system. We also show that the approach of using an NML can be implemented to tune the interfacial thermal conductance in other materials systems. Molecular dynamics simulations indicate that the remarkable enhancement we observe is due to strong NML-dielectric and NML-metal bonds that facilitate efficient heat transfer through the NML. Our results underscore the importance of interfacial bond strength as a means to describe and control interfacial thermal transport in a variety of materials systems.

Evaluation of the cytotoxicity of organic dust components on THP1 monocytes-derived macrophages using high content analysis.

Organic dust contains pathogen-associated molecular patterns (PAMPs) which can induce significant airway diseases following chronic exposure. Mononuclear phagocytes are key protecting cells of the respiratory tract. Several studies have investigated the effects of PAMPs and mainly endotoxins, on cytokine production. However the sublethal cytotoxicity of organic dust components on macrophages has not been tested yet. The novel technology of high content analysis (HCA) is already used to assess subclinical drug-induced toxicity. It combines the capabilities of flow cytometry, intracellular fluorescence probes, and image analysis and enables rapid multiple analyses in large numbers of samples. In this study, HCA was used to investigate the cytotoxicity of the three major PAMPs contained in organic dust, i.e., endotoxin (LPS), peptidoglycan (PGN) and ß-glucans (zymosan) on THP-1 monocyte-derived macrophages. LPS was used at concentrations of 0.005, 0.01, 0.02, 0.05, 0.1, and 1 µg/mL; PGN and zymosan were used at concentrations of 1, 5, 10, 50, 100, and 500 µg/mL. Cells were exposed to PAMPs for 24 h. In addition, the oxidative burst and the phagocytic capabilities of the cells were tested. An overlap between PGN intrinsic fluorescence and red/far-red fluorescent dyes occurred, rendering the evaluation of some parameters impossible for PGN. LPS induced sublethal cytotoxicity at the lowest dose (from 50 ng/mL). However, the greatest cytotoxic changes occurred with zymosan. In addition, zymosan, but not LPS, induced phagosome maturation and oxidative burst. Given the fact that ß-glucans can be up to 100-fold more concentrated in organic dust than LPS, these results suggest that ß-glucans could play a major role in macrophage impairment following heavy dust exposure and will merit further investigation in the near future.

Toward 'omic scale metabolite profiling: a dual separation-mass spectrometry approach for coverage of lipid and central carbon metabolism.

Although the objective of any 'omic science is broad measurement of its constituents, such coverage has been challenging in metabolomics because the metabolome is comprised of a chemically diverse set of small molecules with variable physical properties. While extensive studies have been performed to identify metabolite isolation and separation methods, these strategies introduce bias toward lipophilic or water-soluble metabolites depending on whether reversed-phase (RP) or hydrophilic interaction liquid chromatography (HILIC) is used, respectively. Here we extend our consideration of metabolome isolation and separation procedures to integrate RPLC/MS and HILIC/MS profiling. An aminopropyl-based HILIC/MS method was optimized on the basis of mobile-phase additives and pH, followed by evaluation of reproducibility. When applied to the untargeted study of perturbed bacterial metabolomes, the HILIC method enabled the accurate assessment of key, dysregulated metabolites in central carbon pathways (e.g., amino acids, organic acids, phosphorylated sugars, energy currency metabolites), which could not be retained by RPLC. To demonstrate the value of the integrative approach, bacterial cells, human plasma, and cancer cells were analyzed by combined RPLC/HILIC separation coupled to ESI positive/negative MS detection. The combined approach resulted in the observation of metabolites associated with lipid and central carbon metabolism from a single biological extract, using 80% organic solvent (ACN:MeOH:H2O 2:2:1). It enabled the detection of more than 30,000 features from each sample type, with the highest number of uniquely detected features by RPLC in ESI positive mode and by HILIC in ESI negative mode. Therefore, we conclude that when time and sample are limited, the maximum amount of biological information related to lipid and central carbon metabolism can be acquired by combining RPLC ESI positive and HILIC ESI negative mode analysis.

Molecular cytotoxic mechanisms of chlorpromazine in isolated rat hepatocytes.

Chlorpromazine (CPZ), a member of the largest class of first-generation antipsychotic agents, is known to cause hepatotoxicity in the form of cholestasis and hepatocellular necrosis in some patients. The mechanism of CPZ hepatotoxicity is unclear, but is thought to result from reactive metabolite formation. The goal of this research was to assess potential cytotoxic mechanisms of CPZ using the accelerated cytotoxicity mechanism screening (ACMS) technique with freshly isolated rat hepatocytes. This study identified CPZ cytotoxicity and inhibition of mitochondrial membrane potential (MMP) to be concentration-dependent. Furthermore, inhibition of cytochrome P450s (CYPs), including CYP2D1 and 1A2, delayed CPZ cytotoxicity, suggesting a role for CYP activation of CPZ to a toxic metabolite(s) in this model. Metabolism studies also demonstrated glucuronide and glutathione (GSH) requirement for CPZ detoxification in hepatocytes. Inactivating the 2-electron reduction pathway, NAD(P)H quinone oxidoreductase (NQO1), caused a significant increase in hepatocyte susceptibility to CPZ, indicating quinoneimine contribution to CPZ cytotoxicity. Nontoxic concentrations of peroxidase/H(2)O(2) (inflammatory model) increased cytotoxicity in CPZ-treated hepatocytes and caused additional mitochondrial toxicity. Inflammation further depleted GSH and increased oxidized glutathione (GSSG) levels. Results suggest activation of CPZ to reactive metabolites by 2 pathways in hepatocytes: (i) a CYP-catalyzed quinoneimine pathway, and (ii) a peroxidase-catalyzed oxidation of CPZ to CPZ radicals.

Malignant melanoma in a grey horse: case presentation and review of equine melanoma treatment options.

A 15 year-old grey Thoroughbred gelding presented for investigation of chronic weight loss and recent onset of respiratory difficulty. Clinical examination confirmed tachypnoea with increased respiratory effort. Thoracic ultrasound examination detected pleural effusion. The dyspnoea was related to the large volume of pleural effusion and, following post-mortem examination, to the presence of a large mediastinal mass. Multiple pigmented masses, likely melanomas, were detected peri-anally. Thoracic radiography, cytological examination of the pleural fluid and a fine needle aspirate of a thoracic mass led to a presumptive diagnosis of malignant melanoma and this was confirmed at post mortem examination. Further metastatic spread to the central nervous system and right guttural pouch was also identified. In conclusion this case manifests the potential malignant behaviour of equine melanomas, and a review of proposed therapies for melanoma treatment highlights the therapeutic options and current areas of research.

Assessing the Change in Operative Treatment Rates for Acute Midshaft Clavicle Fractures: Incorporation of Evidence-Based Surgery Results in Orthopaedic Practice.

In 2007, a randomized controlled trial (RCT) by the Canadian Orthopaedic Trauma Society (COTS) demonstrated better functional outcomes and a lower proportion of patients who developed malunion or nonunion following operative, compared with nonoperative, treatment of midshaft clavicle fractures. The primary aim of the present study was to compare the proportion of midshaft clavicle fractures treated operatively prior to and following the publication of the COTS RCT. An additional exploratory aim was to assess whether the proportion of midshaft clavicle fractures that were treated with surgery for malunion or nonunion decreased. Methods: This retrospective cohort analysis used population-level administrative health data on the residents of British Columbia, Canada. Cases were identified by International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes and procedure fee codes. Adult patients (≥18 years) with closed middle-third clavicle fractures between 1997 and 2018 were included. Multivariable logistic regression modeling compared the proportion of clavicle fractures treated operatively before and after January 1, 2007, controlling for patient factors. The Pearson chi-square test compared the proportion of fractures treated operatively for malunion or nonunion in the cohorts. Results: A total of 52,916 patients were included (mean age, 47.5 years; 65.6% male). More clavicle fractures were treated operatively from 2007 onward: 6.9% compared with 2.2% prior to 2007 (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 3.03 to 3.70, p < 0.001). Male sex, moderate-to-high income, and younger age were associated with a greater proportion of operative fixation. The rate of surgery for clavicle malunion or nonunion also increased over this time period (to 4.1% from 3.4%, OR = 1.26, 95% CI = 1.15 to 1.38, p < 0.001). Conclusions: We found a significant change in surgeon practice regarding operative management of clavicle fractures following the publication of a Level-I RCT. With limited high-quality trials comparing operative and nonoperative management, it is important that clinicians, health-care institutions, and health-authority administrations determine what steps can be taken to increase responsiveness to new clinical studies and evidence-based guidelines. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Metastatic disease of the long bones: a review of the health care burden in a major trauma centre.

BACKGROUND: More than 140,000 new cases of cancer are diagnosed annually in Canada, nearly half of which metastasize to bone. The implications for orthopedic oncology services are potentially huge. We reviewed the experience in a major Canadian orthopedic trauma centre treating long bone metastases. The primary aim was to quantify the caseload, and the secondary aim was to report on the methods of fixation. METHODS: We conducted a retrospective review of all patients treated for pathologic lesions or fracture secondary to metastatic disease over a 20-year period from July 1987 to March 2007. RESULTS: The mean number of cases treated annually was 13. Most patients came from the local oncology centre. The median length of stay in hospital was 11 days. In-hospital mortality was 14%. The fatal pulmonary embolus rate was 5% for femoral lesions. The revision rate for the operative intervention was 3%. CONCLUSION: The caseload was much lower than anticipated, likely owing to under-referring from oncology services. The high mortality rate may reflect delay in seeking orthopedic opinion, but overall the fixation methods appeared durable.

Bacterial cholangiohepatitis in a dog.

A 9-year-old female Yorkshire terrier was presented for vomiting and diarrhea. Blood chemistry tests revealed hepatic dysfunction, cholestasis, and inflammation. Liver ultrasonography and liver biopsy were consistent with cholangiohepatitis. Fine-needle aspiration of the gallbladder revealed the presence of bacteria later identified as Clostridium spp. The cholangiohepatitis was successfully treated.

Quantifying Urinary and Sexual Dysfunction After Pelvic Fracture.

OBJECTIVES: To quantify the severity of urinary and sexual dysfunction and to evaluate the relationship between urinary and sexual dysfunction, injury, and treatment factors in patients with pelvic fracture. DESIGN: Prospective cohort study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: One hundred thirteen patients with surgically treated pelvic fracture (65.5% OTA/AO 61B fractures; 7 open fractures; 74 men). INTERVENTIONS: Surgical pelvic stabilization. MAIN OUTCOME MEASURES: The 36-Item Short Form Health Survey and International Consultation Incontinence Questionnaire responses were collected at baseline, 6 months, and 1, 2, and 5 years. Patients were scored on symptoms of voiding and incontinence, and filling (for women), to derive urinary function. Sexual function was scored as a single domain. Both genders reported urinary and sexual bothersome symptoms. Regression analysis was used to isolate the importance of predictive factors on urinary and sexual function, urinary and sexual bother, and their impact on quality of life. RESULTS: Patients with pelvic fracture have significant urinary and sexual dysfunction, which is sustained or worsens over time. Male urinary function was predicted by Injury Severity Score (P = 0.03) and 61C fracture (odds ratio: 3.23, P = 0.04). Female urinary function was predicted by urinary tract injury at admission (odds ratio: 7.57, P = 0.03). Neurologic injury and anterior fixation were identified as significant predictors for male sexual function and sexual bother, whereas urological injuries were important in predicting female urinary and sexual bother (P < 0.01). Sexual function (P = 0.02) and sexual bother (P < 0.001) were important predictors of overall mental well-being in men. CONCLUSIONS: Urinary and sexual dysfunction are prevalent and sustained in men and women and do not follow the prolonged slow recovery trajectory seen in physical function. Male urinary and sexual dysfunction was closely tied to neurologic injury, whereas female urinary and sexual dysfunction was predicted by the presence of a urinary tract injury. Urinary and sexual dysfunction were important to overall mental well-being in men. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Use of intraoperative impression smear cytology to guide successful treatment of a large renal cyst in a dog: a case report.

A 13-yr-old Shih tzu was referred for surgical management of right-sided cranial abdominal mass, which corresponded to large, cavitated renal mass on ultrasonography, and was suspected to represent neoplasia. Intraoperative impression smear cytology (ISC) of the renal mass wall was consistent with benign renal cyst (RC), without evidence of neoplasia or infection. Deroofing and omentalisation were performed and histopathology was consistent with benign RC. Chronic kidney disease was diagnosed 4 mon postoperatively, however, the dog was asymptomatic, without cyst reoccurrence. Intraoperative ISC is an expedient and inexpensive diagnostic technique that can guide most appropriate treatment in dogs with large RCs.

Unreamed Intramedullary Nailing Versus External Fixation for the Treatment of Open Tibial Shaft Fractures in Uganda: A Randomized Clinical Trial.

OBJECTIVE: To compare unreamed intramedullary nailing versus external fixation for the treatment of Gustilo-Anderson type II and IIIA open tibial fractures admitted to a hospital in rural Uganda. DESIGN: Randomized clinical trial. SETTING: Regional referral hospital in Uganda. PATIENTS: Fifty-five skeletally mature patients with a Gustilo-Anderson type II or IIIA open tibia shaft fracture treated within 24 hours of injury between May 2016 and December 2019. INTERVENTION: Unreamed intramedullary nailing (n = 31) versus external fixation (n = 24). MAIN OUTCOME MEASUREMENTS: The primary outcome was function within 12 months of injury, measured using the Function IndeX for Trauma (FIX-IT) score. Secondary outcomes included health-related quality of life (HRQoL) using the 3-level version of the 5-dimension EuroQol instrument (EQ-5D-3L), radiographic healing using the Radiographic Union Scale for Tibia (RUST) fractures score, and clinical complications. RESULTS: Treatment with an intramedullary nail resulted in a 1.0-point higher [95% credible intervals (CrI), 0.1 to 1.9] FIX-IT score compared with external fixation. Results were similar for the secondary patient-reported outcomes, EQ-5D-3L and the visual analog scale component of the EuroQol instrument (EQ-VAS). RUST scores were not different between groups at any time point. Treatment with an intramedullary nail was associated with a 22.1% (95% CrI, -42.6% to 1.7%) lower rate of malunion and a 20.8% (95% CrI, -44.0% to 2.9%) lower rate of superficial infection. CONCLUSION: In rural Uganda, treatment of open tibial shaft fractures with an unreamed intramedullary nail results in marginal clinically important improvements in functional outcomes, although there is likely an important reduction in malunion and superficial infection. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Responsiveness of the PROMIS physical function measure in orthopaedic trauma patients.

OBJECTIVES: To compare the responsiveness of the Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) to the 36-Item Short Form Survey Physical Component Score (SF36-PCS) in orthopaedic trauma patients from pre-injury to one year recovery. DESIGN AND SETTING: Prospective cohort study at a Level 1 trauma centre. PARTICIPANTS: Patients over the age of 18 with orthopaedic trauma injuries to the pelvis, lower extremity or upper extremity between 2017 and 2018. MAIN OUTCOMES MEASUREMENTS: The PROMIS-PF and SF36-PCS assessments were conducted at baseline, 3 months, 6 months and 12 months. Responsiveness of each measure was assessed between time points by calculating the standardized response mean (SRM), the proportions of patients exceeding minimal clinically important difference (MCID), and the floor and ceiling effects. RESULTS: Sixty-eight patients with completed assessments at every timepoint were included: mean age 44.7 years, 39 were male and mean Injury Severity Score (ISS) was 7.4 (range: 4-16). Mean time of completion for the SF-36 at all the time points was 5.6 min vs 1.7 min for the PROMIS-PF (p<0.01). The SRM was comparable between measures at all the time points. Although a greater proportion of patients achieved MCID for SF36-PCS between all the time points, this only approached statistical significance between the 6- and 12-month assessments (47.1% vs 33.8%; p = 0.15). There was a significant ceiling effect demonstrated with the PROMIS-PF at baseline and 12-month assessments, with 34 (50.0%) patients and 7 (10.3%) patients achieving the maximum scores at each time point, respectively. DISCUSSION AND CONCLUSIONS: PROMIS-PF has a more favourable responder burden based on lower time to completion and comparable responsiveness to the SF-36 PCS. However, there are limitations in responsiveness with the PROMIS-PF in patients who are higher functioning as demonstrated by the ceiling effects in patients at baseline pre-injury and at 12 months post-injury timepoints.

Long-Term Trajectory of Recovery Following Pilon Fracture Fixation.

OBJECTIVES: To describe the trajectory of recovery following fixation of pilon fractures from baseline to 5-year follow-up. DESIGN: Prospective cohort study. SETTING: Level-1 trauma center. PATIENTS/PARTICIPANTS: Patients with pilon fractures (OTA/AO 43.C) treated with open reduction and internal fixation. INTERVENTION: None. MAIN OUTCOMES MEASURES: Patient-reported outcome measures were measured at baseline, 6 months, 1 year, and 5 years using the Short-Form 36 Health Survey (SF-36) Physical Component Score and Mental Component Score, Short Musculoskeletal Functional Assessment, and the Foot and Ankle Outcome Score. RESULTS: One hundred two patients were enrolled: mean age was 42.6 years; 69% were males; 88% had an injury severity score of 9; 74 patients (73%) completed 1-year follow-up; 40 patients (39%) completed 5-year follow-up. Trajectory of recovery of physical function showed a significant decline between baseline and 6 months, with significant improvement between 6 months and 1 year and then ongoing but slower improvement between 1 year and 5 years. Sixty-four patients returned to baseline SF-36 Physical Component Score at 5 years. Pain was a persistent issue and remained significantly worse at 5 years when compared with baseline. Psychological well-being (SF-36 Mental Component Score) did not significantly change from baseline at 5 years. CONCLUSION: Functional recovery following open reduction and internal fixation for pilon fractures was characterized by an initial decrease in function from baseline, followed by an increase between 6 months and 1 year, and then slower but continued increases from 1 year to 5 years. Function did not return to baseline levels, pain was a persistent issue, and mental well-being showed no change from baseline at 5 years. This information may be useful when counselling patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Biomarkers of exposure to endogenous oxidative and aldehyde stress.

We observed an unexpectedly strong association of three different endogenous aldehydes and noted that the association could be explained by multiple reactions in which oxidative stress increased the formation of endogenous aldehydes and endogenous aldehydes increased oxidative stress. These interactions make it reasonable to assess multiple exposures to endogenous oxidative and aldehyde stress with less specific measures such as advanced glycation end-products or protein carbonyls.

100 most cited articles in orthopaedic surgery.

BACKGROUND: Citation analysis reflects the recognition a work has received in the scientific community by its peers, and is a common method to determine 'classic' works in medical specialties. QUESTIONS/PURPOSES: We determined which published articles in orthopaedic journals have been most cited by other authors by ranking the 100 top-cited works. By analyzing characteristics of these articles, we intended to determine what qualities make an orthopaedic article important to the specialty. Finally, we determined if there was a change in level of evidence of studies on this list with time. METHODS: Science Citation Index Expanded was searched for citations to articles published in any of the 49 journals in the subject category "ORTHOPEDICS." Each of the 49 journals was searched separately using the "cited reference search" to determine the 100 most often cited articles. Each article was reviewed for basic information including year of publication, country of origin, source journal of the article, article type, and level of evidence. We categorized the journal article by field of research where possible. RESULTS: The number of citations ranged from 1748 to 353. The 100 most often cited articles in orthopaedic surgery were published in 11 of the 49 journals, spanning from general to more specific subspecialty journals. The majority of the papers (76) were clinical, with the remaining representing some type of basic science research. The most common level of evidence was IV (42 of the 76 studies). Of the 76 clinical articles, 27 introduced or tested classification systems or outcome measurement tools. CONCLUSIONS: Authors aiming to write a highly cited article in an orthopaedic surgery journal will be favored by language of publication, source journal, country of origin, and introduction of a classification scheme or outcome tool.