Pica caused by emetic drugs in laboratory rats with kaolin, gypsum, and lime as test substances.

Pica refers to eating nonfood substances. The pica behavior has been the focus of attention in physiological and pharmacological studies, because its consumption is a good marker of nausea in laboratory rats, which cannot vomit due to neuroanatomical reasons. Almost all pica studies with rats have used kaolin clay pellets as nonfood substances. The present study primarily aimed to explore an alternative (or more suitable) substance to kaolin for detection of nausea induced by emetic drugs. Two calcium compounds, gypsum and lime, were evaluated in this study. An injection of lithium chloride (LiCl) increased pica behavior not only in the rats given kaolin but also in the rats given gypsum, suggesting that gypsum consumption could be used as an indicator of nausea. However, its sensitivity was no greater than that of kaolin consumption. In addition, lime is not a useful marker for nausea because the size of pica was small in the LiCl-injected rats, and did not differ from the control in the cisplatin-injected rats. In short, the superiority of kaolin as a test substance for nausea could not be overturned. However, the fact that nauseous rats displayed pica behavior with gypsum and lime refutes the claim that aluminosilicate, the main component of kaolin, is the critical determinant of emetic-caused pica in laboratory rats.

Efficacy and safety of vancomycin-loaded calcium sulfate versus conventional surgical debridement for pediatric acute osteomyelitis: a retrospective study.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of vancomycin-loaded calcium sulfate beads and negative-pressure wound therapy (NPWT) in treating children with acute hematogenous osteomyelitis (AHOM). METHODS: A retrospective cohort study was conducted from January 2017 to January 2020 examining children (n = 60) with AHOM who were treated with surgical debridement followed by vancomycin-loaded calcium sulfate beads and NPWT (n = 32) and compared to treatment by conventional surgical debridement (n = 28) followed by NPWT. Conventional surgical treatment consisted of fenestration of necrotic infected bone, debridement of surrounding soft tissue, and washing of the medullary canal before the application of NPWT. In the vancomycin group, the antibiotic-loaded beads were implanted after washing the medullary canal and before the application of NPWT. Epidemiological factors, complications during the procedure, outcomes at last follow-up (30.0 ± 11.7 months, range 13-58 months), and laboratory parameters were documented and compared between the two groups. RESULTS: Good outcomes were achieved at last follow-up in 71.4% of the conventional treatment group and 75% of the vancomycin group. In the vancomycin group, it took a mean of 4.8 ± 2.5 days for CRP levels to decrease to 50% of initial inflammatory levels compared to 13 ± 9.6 days for the conventional treatment group (p = 0.001, t-test). The conventional group also had seven patients who underwent four or more surgeries whereas no patients in the vancomycin group underwent more than three surgeries (p = 0.013, chi-square test). CONCLUSION: Localized vancomycin delivery with NPWT effective for treating cases of AHOM that required. No perioperative adverse reactions or complications occurred from this treatment method. Based on the shortened recovery period of CRP levels, prolonged administration of post-operational parenteral antibiotics can possibly be reduced with this treatment method.

Hypercalcaemia caused by calcium sulfate beads.

Hypercalcaemia is a relatively common metabolic disturbance seen in hospitalised patients; however, given the complicated systems of calcium regulation, it can take a significant amount of time and testing to pinpoint the aetiology. This case discusses a patient who developed acute hypercalcaemia from calcium sulfate-containing antibiotic beads placed during an orthopaedic procedure. These beads are used in surgical procedures to fill gaps/voids in bony structures and for local delivery of antibiotics. The case highlights the importance of careful review of a patient's hospital course, including the administration of medical products that may not be clearly documented on a patient's medicine administration record when working up an unexplained finding.

Symptomatic hypercalcaemia following the use of calcium sulfate beads in periprosthetic joint infections.

Calcium sulfate beads (CSBs) are used as a method of delivery of antibiotics in periprosthetic joint infections, non-union and chronic osteomyelitis.[[1-3]] Symptomatic hypercalcaemia can occur as a complication following the insertion of CSBs however it is rare and few cases have been reported.[[4-7]] The cause of hypercalcaemia is poorly understood.

Respiratory Symptoms of Exposure to Substances in the Workplace among Bulgarian Dental Students: a Self-report Questionnaire Survey.

BACKGROUND: Dental students are at high risk of developing adverse respiratory reactions as a result of their practical work during their dentistry degree program when they come into contact with multiple airborne irritants and allergens. AIM: To estimate the prevalence of respiratory symptoms of exposure to substances in the workplace and associated risk factors in Bulgarian dental students. RESULTS: The prevalence of self-reported respiratory symptoms related to the pre-clinical and clinical training courses of the dentistry program was 12.4%. According to logistic regression analysis, the most important risk factors for work-related respiratory symptoms were a personal history of allergic rhinoconjunctivitis (odds ratio (OR) 6.34, 95% confidence interval (CI): 3.14-12.78), atopic dermatitis (OR 2.81, 95%CI: 1.26-6.26), and exposure to chemicals from dental environment for more than 6 hours a day (OR 3.60, 95%CI: 1.21-10.70). CONCLUSION: The results of this study suggest that work-related respiratory symptoms are frequent among dental students and indicate the need for efforts to establish effective primary preventive programs for occupational respiratory disorders at national level.

Pharmacokinetics of platinum and safety evaluation of carboplatin-impregnated calcium sulfate hemihydrate beads after implantation in healthy cats.

OBJECTIVE: To evaluate the pharmacokinetics (PK) of platinum (Pt) and safety of carboplatin-impregnated calcium sulfate hemihydrate (C-I CSH) beads after implantation in healthy cats. STUDY DESIGN: In vivo experimental study. ANIMALS: Six healthy adult cats. METHODS: Three C-I CSH beads were implanted in muscle pockets over the right and left hemithoraces of each cat (~3.9 mg/kg of Pt; 60.4 mg/m2 of calculated carboplatin). Hematology and blood chemistry were tested at baseline and 3, 7, 14, and 21 days postimplantation. Serum was analyzed for Pt at specific times from 1 hour to 21 days. Tissue was obtained for histopathology and analysis of Pt at 3, 7, 14, and 21 days at standardized distances from implantation sites. RESULTS: Platinum was detected in tissues at all times and distances (range, 0.1-4.19 µg/g). Serum Pt increased up to 2.6 hours (3.25 µg/mL) then decreased sharply. Samples containing muscle had higher Pt compared with samples without muscle (P = .004). Mild hypercalcemia was noted in four cats, and mild inflammatory reaction was noted on histopathology of all samples. CONCLUSION: Platinum was released from C-I CSH beads differentially into surrounding tissues over 21 days. Systemic absorption of Pt was minimal, but mild hypercalcemia occurred. CLINICAL SIGNIFICANCE: Implantation was well tolerated by healthy adult cats. Securing beads within muscle may limit Pt diffusion to targeted tissue. Although Pt concentrations did not achieve levels reported to be cytotoxic for feline sarcoma cells in culture, results provide evidence to support evaluation of efficacy in the tumor microenvironment of cats with locally invasive cancers.

[The analysis of health effects of exposure to occupational hazards on works in gypsum mining enterprise].

Objective: To investigate the health of gypsum miners in Hubei province and analyze the health effects of occupational disease hazards exposure on gypsum miners. Methods: In April 2017, occupational disease hazard factors were tested on the site of a gypsum mine, and 500 workers were selected by random sampling to conduct questionnaires, relevant data such as occupational health examination was collected, and descriptive statistical analysis was performed. Results: The main occupational hazards of gypsum miners were gypsum dust and noise. The time-weighted average concentration of 8 h in the workplace was 4.32 to 9.34 mg/m(3), and the post pass rate was 69.2% (9/13) ; Respiratory dust 0.13-5.15 mg/m(3), post pass rate 75.0% (3/4). Gypsum miners had finger dysfunction and muscle numbness, joint pain (29.2%, 88/301) and chest pain and breathing difficulties (17.6%, 53/301). Followed by tinnitus, auricle pus, running water (4.7%, 14/301), abnormal muscle tension (2.7%, 8/301). The exposure of occupational disease hazards was associated with respiratory, auditory and neurological symptoms of gypsum miners. Conclusion: The long-term exposure of gypsum workers to gypsum dust, noise and other harmful factors may result in obvious symptoms of respiratory system and other health damage.

Is Hypercalcemia a Frequent Complication following Local Use of Calcium Sulfate with Antibiotics for the Treatment of Extremity Posttraumatic Osteomyelitis? A Preliminary Study.

BACKGROUND: Previous study had reported hypercalcemia as a frequent complication (20%) following local use of antibiotic-eluting calcium sulfate (CS) during treatment of periprosthetic joint infections (PJIs). However, whether this complication may occur in patients who receive local CS implantation for management of posttraumatic osteomyelitis (OM) remains unclear. METHODS: Between April 2016 and May 2017, we included 55 patients with extremity posttraumatic OM who received local antibiotic-loaded CS therapy. Serum calcium levels were detected preoperatively and on the 1st, 3rd, and 7th postoperative days (PODs). Comparisons were performed regarding serum calcium levels among the four time points and between two different CS volume groups (≤ 20 cc group and > 20 cc group). Additionally, potential associations were examined regarding CS volume and preoperative calcium level with postoperative calcium levels, respectively. RESULTS: Altogether 46 males and 9 females were included, with a median CS volume of 20 cc. Outcomes showed that prevalence of asymptomatic hypocalcemia was more frequent, with 16.4% before surgery and 60%, 53.8%, and 25% on the 1st, 3rd, and 7th PODs, respectively. Hypercalcemia was not found in any patients, at any time point. In addition, significant differences were identified regarding serum calcium levels among different time points, suggesting significantly decreased calcium levels on the 1st (P < 0.001) and 3rd PODs (P < 0.001) and back to near preoperative level on the 7th POD (P = 0.334). However, no statistical differences were observed regarding serum calcium levels between the two CS volume groups at any time points (P > 0.05). Moreover, no significant links were identified between CS volume and postoperative calcium levels (P > 0.05). Serum calcium levels on the 3rd (P = 0.019) and 7th PODs (P = 0.036) were significantly associated with the preoperative calcium level. CONCLUSIONS: In contrast to what had occurred in PJI patients, asymptomatic hypocalcemia appeared to be more frequent in this cohort with posttraumatic OM. Hypercalcemia may be an infrequent complication before and after local CS use for the treatment of extremity posttraumatic OM.

Hip osteonecroses treated with calcium sulfate-calcium phosphate bone graft substitute have different results according to the cause of osteonecrosis: alcohol abuse or corticosteroid-induced.

INTRODUCTION: The aim of the study was to assess the factors influencing the final results of treatment of the femoral head osteonecrosis (ONFH) with core decompression and bone substitute grafting. The special interest was focused on comparison between alcohol- and steroid-induced ONFHs. MATERIAL AND METHODS: In this prospective study, a total of 53 patients (58 hips) in the mean age of 35.5 years were included: 29 had a history of alcohol use (32 hips) and 24 of steroid use (26 hips). The mean follow-up was 4.2 years (minimum 3 years). RESULTS: At last follow-up, significant improvements were noted in the Harris Hip Score (HHS) (mean 44.0 vs 55.9 points, p < 0.00002) and VAS scores (mean 7.0 vs 5.8 points, p < 0.0002) for the whole ONFH cohort, comparing to pre-operative status. The degree of improvement did not differ between Ficat and Arlet grade II and grade III (mean 14.9 vs 6.2 points, respectively, p = 0.1). No change was found between the final and initial results in this group in the steroid group (HHS mean 42.2 vs 45.5 points, p = 0.5 and VAS mean 6.8 vs 6.5 points, p = 0.5), but the improvement was noted in the alcohol group (HHS mean 45.5 vs 64.4 points, p < 0.0001; VAS mean 7.1 vs 5.2 points, p < 0.0001) comparing to pre-operative status. CONCLUSIONS: Presented treatment of ONFH significantly improves hip function, offers pain reduction, and gives similar functional improvement for hips scoring grade II and III on the Ficat and Arlet scale. A good response to operative treatment is seen in patients with alcohol-induced ONFH, but not in those with steroid-induced ONFH.

Modifications to advanced Core decompression for treatment of Avascular necrosis of the femoral head.

BACKGROUND: "Advanced Core Decompression" (ACD) is a new technique for treatment of osteonecrosis of the femoral head (ONFH) that includes removal of the necrotic tissue using a percutaneous expandable reamer followed by refilling of the drill hole and the defect with an injectable, hard-setting, composite calcium sulphate (CaSO4)-calcium phosphate (CaPO4) bone graft substitute. As autologous bone has been shown to be superior to all other types of bone grafts, the aim of the study is to present and evaluate a modified technique of ACD with impaction of autologous bone derived from the femoral neck into the necrotic defect. METHODS: A cohort of patients with an average follow-up of 30.06 months (minimum 12 months) was evaluated for potential collapse of the femoral head and any reasons that led to replacement of the operated hip. Only patients in stages 2a to 2c according to the Steinberg classification were included in the study. RESULTS: In 75.9% the treatment was successful with no collapse of the femoral head or conversion to a total hip replacement. Analysis of the results of the different subgroups showed that the success rate was 100% for stage 2a lesions and 84.6% respectively 61.5% for stages 2b and 2c lesions. CONCLUSIONS: Previous studies with a comparable follow-up reported less favourable results for ACD without autologous bone. Especially in stages 2b and 2c the additional use of autologous bone has a positive effect. In comparison to other hip-preserving techniques, the modified ACD technique is a very promising and minimally invasive method for treatment of ONFH. TRIAL REGISTRATION: German clinical trials register ( DRKS00011269 , retrospectively registered).

Combination therapy with vancomycin-loaded calcium sulfate and vancomycin-loaded PMMA in the treatment of chronic osteomyelitis.

BACKGROUND: Chronic post-traumatic and postoperative osteomyelitis is a refractory disease which results in significant morbidity and mortality. The effect of combination therapy with vancomycin-loaded calcium sulfate and vancomycin-loaded polymethyl methacrylate (PMMA) was unknown. METHODS: Fifty-one patients suffering from chronic post-traumatic or postoperative osteomyelitis of the lower extremities were included in the retrospective investigation. The patients were assigned to the study group of the combination therapy with antibiotic-loaded calcium sulfate and antibiotic-loaded PMMA or the control group of the antibiotic-loaded PMMA. Hematological parameters, eradication of infection, rate of infection recurrence and reoperation rate were evaluated during the follow-up. RESULTS: The cases were followed up for an average of 24 months (range, 15-48 months) after the first-stage surgical operation. In the study group, all the patients revealed complete calcium sulfate resorption at an average of 6 weeks (range, 30-60 days). In the study group, infection was primarily eradicated in 92.31% (24 of 26) of patients and re-operation rate of 7.69% (2 of 26) after the first-stage surgery. Two patients underwent further surgical operation in the study group. One case achieved infection eradication in the recurrent two cases, with a secondary infection eradication rate of 96.15% (25 of 26). There was no persistent infection in the study group. In the control group, infection was eradicated in 64.00% (16 of 25) of patients and re-operation rate was 36.00% (9 of 25) after the first-stage surgery. Nine patients in the control group underwent further surgical operation. Two case achieved infection eradication in these cases who suffered from persistent or recurrent infection, with a secondary infection eradication rate of 72.00% (18 of 25). There was more re-operation rate in the control group (PMMA group, 9 vs combination therapy group, 2; P = 0.034). CONCLUSION: The combination therapy with vancomycin-loaded calcium sulfate and vancomycin-loaded PMMA possibly achieved more effective control of infection in the treatment of osteomyelitis through synergistic effect. The immediate structural stabilization and higher concentration of antibiotic at the local site of infection may be achieved through the combination of biodegradable and non-biodegradable devices in the treatment of chronic post-traumatic and postoperative osteomyelitis. The study was retrospectively registered at 11/16/2016 (TRN: NCT02968693).

Biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites.

The aim of this study was to evaluate the in vitro and in vivo biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites. In vitro cytotoxicity tests by cholecystokinin octapeptide (CCK-8) assay showed that the 5%Van-MSN-CaSO4 and Van-CaSO4 bone cements were cytocompatible for mouse osteoblastic cell line MC3T3-E1. The microscopic observation confirmed that MC3T3-E1cells incubated with Van-CaSO4 group and 5%Van-MSN-CaSO4 group exhibited clear spindle-shaped changes, volume increase and maturation, showing that these cements supported adhesion of osteoblastic cells on their surfaces. In addition, the measurement of alkaline phosphatase activity revealed the osteoconductive property of these biomaterials. In order to assess in vivo biocompatibility, synthesized cements were implanted into the distal femur of twelve adult male and female New Zealand rabbits. After implantation in artificial defects of the distal femur, 5%Van-MSN-CaSO4 and Van-CaSO4 bone cements did not damage the function of main organs of rabbits. In addition, the Van-MSN-CaSO4 composite allowed complete repair of bone defects with new bone formation 3 months after implantation. These results show potential application of Van-MSN-CaSO4 composites as bone graft materials for the treatment of open fracture in human due to its mechanical, osteoconductive and potential sustained drug release characteristics and the absence of adverse effects on the body.

Hypercalcaemia following the use of antibiotic-eluting absorbable calcium sulphate beads in revision arthroplasty for infection.

Periprosthetic joint infection (PJI) is a devastating complication for patients and results in greatly increased costs of care for both healthcare providers and patients. More than 15 500 revision hip and knee procedures were recorded in England, Wales and Northern Ireland in 2013, with infection accounting for 13% of revision hip and 23% of revision knee procedures. We report our experience of using antibiotic eluting absorbable calcium sulphate beads in 15 patients (eight men and seven women with a mean age of 64.8 years; 41 to 83) as part of a treatment protocol for PJI in revision arthroplasty. The mean follow-up was 16 months (12 to 22). We report the outcomes and complications, highlighting the risk of hypercalcaemia which occurred in three patients. We recommend that serum levels of calcium be routinely sought following the implantation of absorbable calcium sulphate beads in orthopaedic surgery.

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures.

BACKGROUND: Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). METHODS/DESIGN: CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. DISCUSSION: CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01828905.

Adverse reactions of artificial bone graft substitutes: lessons learned from using tricalcium phosphate geneX®.

BACKGROUND: Artificial bone graft substitutes are widely used to fill bony defects after curettage of benign tumors. We sought to evaluate the efficacy of one such bone graft substitute, geneX®, which contains tricalcium phosphate and calcium sulphate; however, during the course of this study we observed a high number of complications. QUESTIONS/PURPOSES: The primary aim of this prospective series was assessment of the effectiveness of geneX® concerning resorption profile and bone healing and remodeling after surgery. We present the types and frequencies of complications observed in patients treated for bone tumors by curettage and filling the defect using geneX®. METHODS: We planned to study 40 patients; however, after enrollment of the first 31 patients, the study was stopped as a result of serious complications. There were 20 female and 11 male patients with a mean age at surgery of 40 years (range, 6­71 years). Plain radiographs were obtained at different intervals during followup and CT scans were obtained 6 and 12 months postoperatively. Complications were assessed using a 5-point scale according to Goslings and Gouma. RESULTS: Five of the 31 patients (16%) had complications develop after surgery. In three cases, a sterile inflammation adjacent to the geneX® occurred, with delayed wound healing in two patients and local pain. In the third patient, geneX® produced moderate to severe skin damage in the area of the scar, needing revision surgery. In two other patients, inflammatory cystic formations developed in the soft tissues with sizes up to 15 cm, which gradually reduced in size with time. Overall, there were four Grade 1 complications and one Grade 2 according to Goslings and Gouma. CONCLUSIONS: We concluded from this series of patients that geneX® causes soft tissue inflammation and pain with its use. Based on this experience we believe that this type of bone substitute should not be used in the treatment of bony defects. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.