Mohit Bhandari

This work provides a systematic review of the literature from January 2003 to April 2014 pertaining to the incidence, pathophysiology, diagnosis, and treatment of osteonecrosis of the jaw (ONJ), and offers recommendations for its management based on multidisciplinary international consensus. ONJ is associated with oncology-dose parenteral antiresorptive therapy of bisphosphonates (BP) and denosumab (Dmab). The incidence of ONJ is greatest in the oncology patient population (1% to 15%), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of ONJ is estimated at 0.001% to 0.01%, marginally higher than the incidence in the general population (<0.001%). New insights into the pathophysiology of ONJ include antiresorptive effects of BPs and Dmab, effects of BPs on gamma delta T-cells and on monocyte and macrophage function, as well as the role of local bacterial infection, inflammation, and necrosis. Advances in imaging include the use of cone beam computerized tomography assessing cortical and cancellous architecture with lower radiation exposure, magnetic resonance imaging, bone scanning, and positron emission tomography, although plain films often suffice. Other risk factors for ONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures, as well as other drugs, including antiangiogenic agents. Prevention strategies for ONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of ONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of ONJ is based on the stage of the disease, size of the lesions, and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Localized surgical debridement is indicated in advanced nonresponsive disease and has been successful. Early data have suggested enhanced osseous wound healing with teriparatide in those without contraindications for its use. Experimental therapy includes bone marrow stem cell intralesional transplantation, low-level laser therapy, local platelet-derived growth factor application, hyperbaric oxygen, and tissue grafting.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

IMPORTANCE: Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). OBJECTIVE: To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. EXPOSURES: Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. MAIN OUTCOMES AND MEASURES: A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. RESULTS: Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom. CONCLUSIONS AND RELEVANCE: Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

BACKGROUND: The optimal choice for the stabilization of displaced femoral neck fractures remains controversial, with alternatives including arthroplasty and internal fixation. Our objective was to determine the effect of arthroplasty (hemiarthroplasty, bipolar arthroplasty, and total hip arthroplasty), compared with that of internal fixation, on rates of mortality, revision, pain, function, operating time, and wound infection in patients with a displaced femoral neck fracture. METHODS: We searched computerized databases for randomized clinical trials published between 1969 and 2002, and we identified additional studies through hand searches of major orthopaedic journals, bibliographies of major orthopaedic textbooks, and personal files. Of 140 citations initially identified, fourteen met all eligibility criteria. Three investigators independently graded study quality and abstracted relevant data, including information on revision and mortality rates. RESULTS: Nine trials, which included a total of 1162 patients, provided detailed information on mortality rates over the first four postoperative months, which ranged from 0% to 20%. We found a trend toward an increase in the relative risk of death in the first four months after arthroplasty compared with the risk in the first four months after internal fixation (relative risk, 1.27). At one year, the relative risk of death was 1.04. The risk of death after arthroplasty appeared to be higher than that after fixation with a compression screw and side-plate but not higher than that after internal fixation with use of screws only (relative risk = 1.75 and 0.86, respectively; p < 0.05). Fourteen trials that included a total of 1901 patients provided data on revision surgery. The relative risk of revision surgery after arthroplasty compared with the risk after internal fixation was 0.23 (p = 0.0003). Pain relief and the attainment of overall good function were similar in patients treated with arthroplasty and those treated with internal fixation (relative risk, 1.12 for pain relief and 0.99 for function). Infection rates ranged from 0% to 18%, and arthroplasty significantly increased the risk of infection (relative risk, 1.81; p = 0.009). In addition, patients who underwent arthroplasty had greater blood loss and longer operative times than those who were treated with internal fixation. CONCLUSIONS: In comparison with internal fixation, arthroplasty for the treatment of a displaced femoral neck fracture significantly reduces the risk of revision surgery, at the cost of greater infection rates, blood loss, and operative time and possibly an increase in early mortality rates. Only larger trials will resolve the critical question of the impact on early mortality.

BACKGROUND: Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings. In this study, we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials. METHODS: We examined a consecutive series of 332 randomized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals. Each eligible study was independently reviewed for methodological quality using a 21-point index with 5 domains: randomization, outcomes, eligibility criteria, interventions and statistical issues. Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant. For studies that did not explicitly identify a primary outcome, we defined a "positive" study as one with at least 1 statistically significant outcome measure. We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results, while controlling for study quality and sample size. RESULTS: Among the 332 randomized trials, there were 158 drug trials, 87 surgical trials and 87 trials of other therapies. In 122 (37%) of the trials, authors declared industry funding. An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.3-3.5). The association remained significant after adjustment for study quality and sample size (adjusted OR 1.8, 95% CI 1.1-3.0). There was a nonsignificant difference between surgical trials (OR 8.0, 95% CI 1.1-53.2) and drug trials (OR 1.6, 95% CI 1.1-2.8), both of which were likely to have a pro-industry result (relative OR 5.0, 95% CI 0.7-37.5, p = 0.14). INTERPRETATION: Industry-funded trials are more likely to be associated with statistically significant pro-industry findings, both in medical trials and surgical interventions.