What Are the Frequency,Related Mortality,and Factors Associated with Bone Cement Implantation Syndrome in Arthroplasty Surgery?

BackgroundBone cement implantation syndrome (BCIS) is characterized by hypoxia, hypotension, and the loss of consciousness during cemented arthroplasty; it may result in death. Its incidence has only been explored for hemiarthroplasty and THA after fracture or cancer. To our knowledge, there are no studies that comprehensively explore and compare the incidence of BCIS in other arthroplasty procedures.Questions/purposes(1) To report the incidence of BCIS in TKA, unicondylar knee arthroplasty, hip hemiarthroplasty, THA, shoulder arthroplasty, TKA, and revision THA and TKA; (2) to determine whether severe BCIS is associated with an increased risk of death within 30 days of surgery; and (3) to identify factors associated with the development of severe BCIS.MethodsAll patients undergoing cemented arthroplasty for any reason (TKA [11% cemented, 766 of 7293], unicondylar knee arthroplasty [100% cemented, 562 procedures], hip hemiarthroplasty for femur fractures [100% cemented, 969 procedures], THA [8% cemented, 683 of 8447], shoulder arthroplasty [84% cemented, 185 of 219], and revision arthroplasty of the hip and knee [36% cemented, 240 of 660]) between January 2008 and August 2019 were considered for inclusion in the current retrospective observational study. Fixation choice was dependent on surgeon preference (THA and TKA), prosthesis design (shoulder arthroplasty), or bone quality (revision arthroplasty). The following procedures were excluded because of insufficient data: < 1% (1 of 766) of TKAs, 1% (4 of 562) of unicondylar knee arthroplasties, 6% (54 of 969) of hip hemiarthroplasties, 1% (6 of 683) of THAs, 6% (12 of 185) of shoulder arthroplasties, and 14% (34 of 240) of revision procedures. This resulted in a final inclusion of 3294 procedures (765 TKAs [23%], 558 unicondylar knee arthroplasties [17%], 915 hip hemiarthroplasties [28%], 677 THA [21%], 173 shoulder arthroplasties [5%], and 206 revision arthroplasties [6%]), of which 28% (930 of 3294) had an emergent indication for surgery. Of the patients, 68% (2240 of 3294) were females, with a mean age of 75 ± 11 years. All anesthetic records were extracted from our hospital’s database, and the severity of BCIS was retrospectively scored (Grade 0 [no BCIS], Grade 1 [O₂% < 94% or fall in systolic blood pressure of 20% to 40%], Grade 2 [O₂% < 88% or fall in systolic blood pressure of > 40%], and Grade 3 [cardiovascular collapse requiring CPR]). Procedures were dichotomized into no or moderate BCIS (Grades 0 and 1) and severe BCIS (Grades 2 and 3). The adjusted 30-day mortality of patients with severe BCIS was assessed with a multivariate Cox regression analysis. A multivariate logistic regression analysis was performed to identify factors associated with the development of severe BCIS.ResultsBCIS occurred in 26% (845 of 3294) of arthoplasty procedures. The incidence was 31% (282 of 915) in hip hemiarthroplasty, 28% (210 of 765) in TKA, 24% (165 of 677) in THA, 23% (47 of 206) in revision arthroplasty, 20% (113 of 558) in unicondylar knee arthroplasty, and 16% (28 of 173) in shoulder arthroplasty. Patients with severe BCIS were more likely (hazard ratio 3.46 [95% confidence interval 2.07 to 5.77]; p < 0.001) to die within 30 days of the index procedure than were patients with less severe or no BCIS. Factors independently associated with the development of severe BCIS were age older than 75 years (odds ratio 1.57 [95% CI 1.09 to 2.27]; p = 0.02), American Society of Anesthesiologists Class III or IV (OR 1.58 [95% CI 1.09 to 2.30]; p = 0.02), and renal impairment (OR 3.32 [95% CI 1.45 to 7.46]; p = 0.004).ConclusionBCIS is common during cemented arthroplasty; severe BCIS is uncommon, but it is associated with an increased risk of death within 30 days of surgery. Medically complex patients undergoing hip hemiarthroplasty may be at particular risk. Patients at high risk for severe BCIS (renal impairment, ASA III/IV, and age older than 75 years) should be identified and preventive measures such as medullary lavage before cementation, femoral venting, and avoidance of excessive pressurization of implants should be taken to reduce the likelihood and consequences of BCIS. Because of the increased risk of periprosthetic fractures in uncemented hip stems, factors associated with the development of BCIS should be weighed against the risk factors for sustaining periprosthetic fractures (poor bone quality, female sex) to balance the risks of fixation method against those of BCIS for each patient.Level of EvidenceLevel III, therapeutic study.     

The Impact of Pre-exposure Prophylaxis on Sexual Well-Being Among Men Who Have Sex with Men

Archives of Sexual Behavior - Pre-exposure prophylaxis (PrEP) is a promising strategy to reduce HIV incidence among men who have sex with men (MSM). How and when PrEP is used could in part be...     

Reimbursement models to tackle market failures for antimicrobials: Approaches taken in France,Germany, Sweden,the United Kingdom,and the United States

IntroductionThe pipeline of new antibacterials remains limited. Reasons include low research investments, limited commercial prospects, and scientific challenges. To complement existing initiatives such as research grants, governments are exploring policy options for providing new market incentives to drug developers.Materials and methodsReimbursement interventions for antibacterials in France, Germany, Sweden, US, and UK were reviewed and analysed by the authors.ResultsIn France, Germany, and the US, implemented interventions centre on providing exceptions in cost-containment mechanisms to allow higher prices for certain antibacterials. In the US, also, certain antibacterials are granted additional years of protection from generic competition (exclusivity) and faster regulatory review. The UK is piloting a model that will negotiate contracts with manufacturers to pay a fixed annual fee for ongoing supply of as many units as needed. Sweden is piloting a model that will offer manufacturers of selected antibacterials contracts that would guarantee a minimum annual revenue. A similar model of guaranteed minimal annual revenues is under consideration in the US (PASTEUR Act).ConclusionsThe UK and Sweden are piloting entirely novel procurement and reimbursement models. Existing interventions in the US, France, and Germany represent important, but relatively minor interventions. More countries should explore the use of novel models and international coordination will be important for ‘pull’ incentives to be effective. If adopted, the PASTEUR legislation in the US would constitute a significant ‘pull’ incentive.     

Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial

BACKGROUND: An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. OBJECTIVE: We studied the effect of coffee consumption on plasma homocysteine in a crossover trial. We used unfiltered coffee so as to include the possible effects of coffee diterpenes, which are removed by filtering. DESIGN: Sixty-four healthy volunteers (31 men and 33 women) with a mean (+/-SD) age of 43 +/- 11 y were randomly assigned to 2 groups. One group (n = 30) drank 1 L unfiltered cafetière (French press) coffee daily for 2 wk. Such coffee is rich in the cholesterol-raising diterpenes kahweol and cafestol. The other group (n = 34) received water, milk, broth, tea, and chocolate drinks instead of coffee. After a washout period of 8 wk, both groups received the alternate intervention for another 2 wk. RESULTS: Consumption of 1 L unfiltered coffee/d for 2 wk significantly raised fasting plasma homocysteine concentrations by 10%, from 12.8 to 14.0 micromol/L. CONCLUSIONS: Unfiltered coffee increases plasma homocysteine concentrations in volunteers with normal initial concentrations. It is unclear whether the effect is caused by the cholesterol-raising diterpenes present exclusively in unfiltered coffee or by factors that are also present in filtered coffee.     

P53 mutation analysis of colorectal liver metastases: relation to actual survival, angiogenic status, and p53 overexpression.

PURPOSE: To correlate TP53 mutations with angiogenic status of the tumor and prognosis after liver surgery in patients with colorectal liver metastases and to correlate immunohistochemical staining of p53 protein with TP53 gene mutations. EXPERIMENTAL DESIGN: Tumors of 44 patients with surgically treated colorectal liver metastases were analyzed for (a) TP53 mutations using denaturing gradient gel electrophoresis followed by sequencing, (b) microvessel density using the hot spot overlap technique, (c) apoptotic rate in tumor cells and endothelial cells of tumor microvessels using double immunostaining for anti-cleaved caspase 3 and anti-CD34, and (d) expression of p53 protein using immunohistochemistry. RESULTS: TP53 mutations were detected in 36% of the metastases and occurred more frequently in liver metastases from left-sided colon tumors than from right-sided colon tumors (P = 0.04). In metastases with TP53 mutations, microvessel density was higher compared with tumors with wild-type p53. Endothelial cell apoptosis was not different in tumor microvessels from TP53-mutated versus nonmutated tumors. The 5-year actual survival was not influenced by TP53 mutational status, microvessel density, or endothelial cell apoptotic rate of the tumors. Based on immunohistochemical p53 overexpression, the positive and negative predictive values of TP53 mutations were 61% and 82%. CONCLUSIONS: In patients with surgically treated colorectal liver metastases, TP53 mutations and angiogenic status did not influence prognosis. Immunohistochemistry is not a reliable technique for detecting TP53 mutations.     

Immunogenicity, including vitiligo, and feasibility of vaccination with autologous GM-CSF-transduced tumor cells in metastatic melanoma patients.

PURPOSE: To determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients. PATIENTS AND METHODS: Sixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays. RESULTS: The high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1- or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1- and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-gamma on specific antigenic stimulation. CONCLUSION: We conclude that vaccination with GM-CSF-transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation.     

Cognitive stimulation by caregivers for people with dementia

Cognitive stimulation (CS) is a psychological intervention for people with dementia aimed at maintaining cognitive functioning. CS provided by caregivers would allow long-term maintenance without greatly increasing demands on health services, but raises questions concerning treatment fidelity and acceptability, which were investigated in this study. Caregivers of home-living people with dementia were trained to provide CS activities to their relative with dementia. Recordings of intervention sessions and analysis of training manuals suggested adequate delivery of the intervention. Dyads continued with the activities after caregiver training had stopped. In addition, presentation of the activities without supervision from a health care professional had no detrimental effect on well-being in the caregiver or the person with dementia. The majority of caregivers indicated that, even though they experienced some burden from doing the activities with their relative, they themselves had also benefited from the intervention and intended to continue with some of the activities.     

Infliximab induces remission in cryptogenic multifocal ulcerous stenosing enteritis:First case

We present the case of a 29-year-old patient with a history of abdominal pain and vomiting.Based on wireless video capsule findings he was previously diagnosed with ileal Crohn’s disease at a different institution,although the clinical and radiological picture was not typical and the response to corticosteroids was poor.We performed a single-balloon enteroscopy showing a short,ulcerous stenosis 50 cm proximal from Bauhin’s valve.The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis(CMUSE).High dose corticosteroids were again started,without effect.The monoclonal tumor necrosis factor-α(TNF-α) antibody infliximab was added to the medical therapy.After induction therapy,both clinical and endoscopic amelioration was obtained.Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.