Prophylactic antibiotic regimens in tumor surgery (PARITY) survey

BACKGROUND: Deep infection following endoprosthetic limb reconstruction for sarcoma of the long bones is a devastating complication occurring in 15% of sarcoma patients. Optimizing infection protocols and conducting definitive surgical trials are critical to improving outcomes. In this study, the PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) investigators aimed to examine surgeon preferences in antibiotic prophylaxis and perceptions about current evidence, as well as to ascertain interest in resolving uncertainty in the evidence with clinical trials. METHODS: We used a cross-sectional survey to examine current practice in the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery. The survey was approved by our institution’s Ethics Board and emailed to all Active Members of the Musculoskeletal Tumor Society (MSTS) and Canadian Orthopaedic Oncology Society (CANOOS). Survey answers were collected using an anonymous online survey tool. RESULTS: Of the 96 surgeons who received the questionnaire, 72 responded (75% response rate (% CI: 65.5, 82.5%)). While almost all respondents agreed antibiotic regimens were important in reducing the risk of infection, respondents varied considerably in their choices of antibiotic regimens and dosages. Although 73% (95% CI: 61, 82%) of respondents prescribe a first generation cephalosporin, 25% favor additional coverage with an aminoglycoside and/or Vancomycin. Of those who prescribe a cephalosporin, 33% prescribe a dosage of one gram for all patients and the reminder prescribe up to 2 grams based on body weight. One in three surgeons (95% CI: 25, 48%) believes antibiotics could be discontinued after 24 hours but 40% (95% CI: 30, 53%) continue antibiotics until the suction drain is removed. Given the ongoing uncertainty in evidence to guide best practices, 90% (95% CI: 81, 95%) of respondents agreed that they would change their practice if a large randomized controlled trial showed clear benefit of an antibiotic drug regimen different from what they are currently using. Further support for a clinical trial was observed by an overwhelming surgeon interest (87%; 95% CI: 77, 93%) in participating in a multi-center randomized controlled study. CONCLUSION: The current lack of guidelines for the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery has left Orthopaedic Oncologists with varying opinions and practices. The lack of current evidence and strong surgeon support for participating in a definitive study provides strong rationale for clinical trials

Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study.

IntroductionLimb salvage with endoprosthetic reconstruction is the standard of care for the management of lower-extremity bone tumours in skeletally mature patients. The risk of deep postoperative infection in these procedures is high and the outcomes can be devastating. The most effective prophylactic antibiotic regimen remains unknown, and current clinical practice is highly varied. This trial will evaluate the effect of varying postoperative prophylactic antibiotic regimens on the incidence of deep infection following surgical excision and endoprosthetic reconstruction of lower-extremity bone tumours.Methods and analysisThis is a multicentre, blinded, randomised controlled trial, using a parallel two-arm design. 920 patients 15 years of age or older from 12 tertiary care centres across Canada and the USA who are undergoing surgical excision and endoprosthetic reconstruction of a primary bone tumour will receive either short (24 h) or long (5 days) duration postoperative antibiotics. Exclusion criteria include prior surgery or infection within the planned operative field, known colonisation with methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at enrolment, or allergy to the study antibiotics. The primary outcome will be rates of deep postoperative infections in each arm. Secondary outcomes will include type and frequency of antibiotic-related adverse events, patient functional outcomes and quality-of-life scores, reoperation and mortality. Randomisation will be blocked, with block sizes known only to the methods centre responsible for randomisation, and stratified by location of tumour and study centre. Patients, care givers and a Central Adjudication Committee will be blinded to treatment allocation. The analysis to compare groups will be performed using Cox regression and log-rank tests to compare survival functions at α=0.05.Ethics and disseminationThis study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB# 12-009). Successful completion will significantly impact on clinical practice and enhance patients' lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in Orthopaedic Oncology will follow

Abnormalities in Oxygen Sensing Define Early and Late Onset Preeclampsia as Distinct Pathologies

BACKGROUND: The pathogenesis of preeclampsia, a serious pregnancy disorder, is still elusive and its treatment empirical. Hypoxia Inducible Factor-1 (HIF-1) is crucial for placental development and early detection of aberrant regulatory mechanisms of HIF-1 could impact on the diagnosis and management of preeclampsia. HIF-1α stability is controlled by O(2)-sensing enzymes including prolyl hydroxylases (PHDs), Factor Inhibiting HIF (FIH), and E3 ligases Seven In Absentia Homologues (SIAHs). Here we investigated early- (E-PE) and late-onset (L-PE) human preeclamptic placentae and their ability to sense changes in oxygen tension occurring during normal placental development. METHODS AND FINDINGS: Expression of PHD2, FIH and SIAHs were significantly down-regulated in E-PE compared to control and L-PE placentae, while HIF-1α levels were increased. PHD3 expression was increased due to decreased FIH levels as demonstrated by siRNA FIH knockdown experiments in trophoblastic JEG-3 cells. E-PE tissues had markedly diminished HIF-1α hydroxylation at proline residues 402 and 564 as assessed with monoclonal antibodies raised against hydroxylated HIF-1α P402 or P564, suggesting regulation by PHD2 and not PHD3. Culturing villous explants under varying oxygen tensions revealed that E-PE, but not L-PE, placentae were unable to regulate HIF-1α levels because PHD2, FIH and SIAHs did not sense a hypoxic environment. CONCLUSION: Disruption of oxygen sensing in E-PE vs. L-PE and control placentae is the first molecular evidence of the existence of two distinct preeclamptic diseases and the unique molecular O(2)-sensing signature of E-PE placentae may be of diagnostic value when assessing high risk pregnancies and their severity

The Role and Regulation of Factor Inhibiting HIF (FIH) in Normal and Pathological Human Placentae

Factor inhibiting HIF (FIH) negatively regulates hypoxia inducible factor-1 (HIF-1) transcriptional activity, selectively controlling certain HIF-1 target genes, such as vascular endothelial growth factor (VEGF) and prolyl hydroxylase domain 3 (PHD3), but not others. PHD3 and VEGF are important for placental development and function and are overexpressed in preeclampsia (PE). The purpose of this study was to examine FIH in both normal and pathological human placentae. I hypothesized that FIH regulates VEGF and PHD3 in the placenta and that this rheostat is altered in PE. Results show that FIH suppresses PHD3 and VEGF in JEG-3 cells; this effect was abrogated by FIH gene silencing. Moreover, my data indicate that seven in absentia homologue-1 (Siah-1) targets FIH for degradation in the placenta; this degradation is enhanced in PE and likely contributes to aberrant VEGF and PHD3 expression. Overall, my data suggest an important role for FIH in the pathogenesis of PE.MAS

A Rare Presentation of Systemic Lupus Erythematous with Lymphadenitis

A 26 year old African American female presented with the chief complaint of persistent fever and a single painful axillary lymph node for two weeks. This is a unique case of systemic lupus erythematous (SLE) presenting with painful lymphadenitis. Moreover, the result of her lymph node biopsy was also unusual, showing histiocytic necrotizing lymphadenitis (HNL) presenting in SLE. She presented with a fever of 103 degrees Fahrenheit and a single painful yet mobile axillary lymph node. She had no rash, joint tenderness, or hepatosplenomegaly on physical exam. Initial lab work showed absolute neutropenia and lymphopenia as well as normocytic anemia. There was initial concern for a possible infectious etiology due to the painful lymphadenopathy, thus broad spectrum antibiotics were initiated. Despite three days of antibiotics, the patient continued to have low grade fevers. HIV, CMV, and EBV testing was negative. Concern for malignancy led to an excisional lymph node biopsy. Additional lab testing that was pending prior to lymph node biopsy subsequently came back positive for ANA (antinuclear antibody) with titer \u3e1:1280 in homogeneous pattern, anti-ds DNA antibody, and anti-Smith antibody, thus pointing towards SLE. She was subsequently started on high dose steroids with improvement of symptoms and her fevers resolved. Histiocytic necrotizing lymphadenitis (HNL) is a histologic feature most commonly associated with Kikuchi-Fujimoto Disease; there are few case reports that have shown an association between HNL and SLE [2, 3]. Given the strongly positive ANA, anti-ds DNA and anti-Smith antibodies, Kikuchi-Fujimoto Disease was deemed less likely and more consistent with SLE. Due to the variability of presentations and the vast differential that Lupus can encompass, Lupus can often be a difficult diagnosis to achieve. Four or more out of 11 criteria must be met of the American College of Rheumatology (ACR) criteria for classifying as possible systemic lupus diagnosis [1]. However none of these criteria include lymphadenopathy. In this case, the patient only met 3 criteria. Lymphadenopathy is seen in 12-59% of patient with SLE, however is often generalized and painless [4,5,6], thus making her presentation so rare. Due to the solitary lymph node that was painful, this initially pointed towards a possible infectious etiology. Also, Lupus can often be mistaken for malignancy; malignancy must be ruled out as patients with SLE are at an increased risk of developing non-Hodgkin lymphoma, Hodgkin lymphoma, and leukemia [1,7]. Therefore, even in patients who do not meet ACR criteria, SLE should still be investigated, if suspected, as patients may be presenting early in the disease course or in an atypical presentation.https://scholarlycommons.henryford.com/merf2019caserpt/1107/thumbnail.jp

Prophylactic antibiotic regimens in tumor surgery (PARITY) survey

Abstract Background Deep infection following endoprosthetic limb reconstruction for sarcoma of the long bones is a devastating complication occurring in 15% of sarcoma patients. Optimizing infection protocols and conducting definitive surgical trials are critical to improving outcomes. In this study, the PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) investigators aimed to examine surgeon preferences in antibiotic prophylaxis and perceptions about current evidence, as well as to ascertain interest in resolving uncertainty in the evidence with clinical trials. Methods We used a cross-sectional survey to examine current practice in the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery. The survey was approved by our institution’s Ethics Board and emailed to all Active Members of the Musculoskeletal Tumor Society (MSTS) and Canadian Orthopaedic Oncology Society (CANOOS). Survey answers were collected using an anonymous online survey tool. Results Of the 96 surgeons who received the questionnaire, 72 responded (75% response rate (% CI: 65.5, 82.5%)). While almost all respondents agreed antibiotic regimens were important in reducing the risk of infection, respondents varied considerably in their choices of antibiotic regimens and dosages. Although 73% (95% CI: 61, 82%) of respondents prescribe a first generation cephalosporin, 25% favor additional coverage with an aminoglycoside and/or Vancomycin. Of those who prescribe a cephalosporin, 33% prescribe a dosage of one gram for all patients and the reminder prescribe up to 2 grams based on body weight. One in three surgeons (95% CI: 25, 48%) believes antibiotics could be discontinued after 24 hours but 40% (95% CI: 30, 53%) continue antibiotics until the suction drain is removed. Given the ongoing uncertainty in evidence to guide best practices, 90% (95% CI: 81, 95%) of respondents agreed that they would change their practice if a large randomized controlled trial showed clear benefit of an antibiotic drug regimen different from what they are currently using. Further support for a clinical trial was observed by an overwhelming surgeon interest (87%; 95% CI: 77, 93%) in participating in a multi-center randomized controlled study. Conclusion The current lack of guidelines for the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery has left Orthopaedic Oncologists with varying opinions and practices. The lack of current evidence and strong surgeon support for participating in a definitive study provides strong rationale for clinical trials.</p

Prophylactic antibiotic regimens in tumor surgery (PARITY) survey

Abstract Background Deep infection following endoprosthetic limb reconstruction for sarcoma of the long bones is a devastating complication occurring in 15% of sarcoma patients. Optimizing infection protocols and conducting definitive surgical trials are critical to improving outcomes. In this study, the PARITY (P rophylactic A ntibiotic R egimens i n T umor Surgery) investigators aimed to examine surgeon preferences in antibiotic prophylaxis and perceptions about current evidence, as well as to ascertain interest in resolving uncertainty in the evidence with clinical trials. Methods We used a cross-sectional survey to examine current practice in the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery. The survey was approved by our institution’s Ethics Board and emailed to all Active Members of the Musculoskeletal Tumor Society (MSTS) and Canadian Orthopaedic Oncology Society (CANOOS). Survey answers were collected using an anonymous online survey tool. Results Of the 96 surgeons who received the questionnaire, 72 responded (75% response rate (% CI: 65.5, 82.5%)). While almost all respondents agreed antibiotic regimens were important in reducing the risk of infection, respondents varied considerably in their choices of antibiotic regimens and dosages. Although 73% (95% CI: 61, 82%) of respondents prescribe a first generation cephalosporin, 25% favor additional coverage with an aminoglycoside and/or Vancomycin. Of those who prescribe a cephalosporin, 33% prescribe a dosage of one gram for all patients and the reminder prescribe up to 2 grams based on body weight. One in three surgeons (95% CI: 25, 48%) believes antibiotics could be discontinued after 24 hours but 40% (95% CI: 30, 53%) continue antibiotics until the suction drain is removed. Given the ongoing uncertainty in evidence to guide best practices, 90% (95% CI: 81, 95%) of respondents agreed that they would change their practice if a large randomized controlled trial showed clear benefit of an antibiotic drug regimen different from what they are currently using. Further support for a clinical trial was observed by an overwhelming surgeon interest (87%; 95% CI: 77, 93%) in participating in a multi-center randomized controlled study. Conclusion The current lack of guidelines for the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery has left Orthopaedic Oncologists with varying opinions and practices. The lack of current evidence and strong surgeon support for participating in a definitive study provides strong rationale for clinical trials