Bone tissue concentrations of ciprofloxacin released from biodegradable screws implanted in rabbits skull

Previously, ciprofloxacin-releasing polylactide/polyglycolide 80/20 (SR-PLGA) screws have proven to be biocompatible with sufficient strength. However, there has been no information about the local concentrations of ciprofloxacin in bone tissue after their implantation. To measure bone concentrations of ciprofloxacin, two screws were implanted in each rabbit, one on either side of the sagittal suture (n = 28 rabbits). Follow-up periods were 2, 4, 8, 16, 24, 52 and 78 weeks. From each rabbit, bone blocks containing one screw were retrieved and used to measure drug concentration. Ciprofloxacin concentration at 2 weeks follow-up was 4.4 ± 4.2 μg/g, 14.1 ± 2.7 μg/g at 4 weeks and 7.6 ± 4.5 μg/g at 8 weeks. Measured concentrations were very low at 16 weeks (mean 0.09 ± 0.04 μg/g) and 24 weeks (mean 0.04 ± 0.02 μg/g). Surprisingly, the concentration was higher again at 1 year (mean 1.3 ± 1.0 μg/g). At 1.5 years, concentration had decreased again (mean 0.8 ± 0.6 μg/g). The drug concentration in bone tissue was higher than minimal inhibitory concentration of ciprofloxacin (Staphylococcus aureus 0.1–1.0 μg/g) at 2, 4, and 8 weeks. Ciprofloxacin-releasing SR-PLGA 80/20 screws could be used clinically for osteofixation and infection treatment in cranial bone.     

Bisphosphonate treatment in craniofacial fibrous dysplasia—a case report and review of the literature

Fibrous dysplasia (FD) is a benign skeletal disorder which may affect one or multiple bones. Lesions often involve long bones, ribs, and craniofacial bones and cause pain, fractures, and disfigurement. We describe an adolescent girl with mandibular FD who was successfully treated with bisphosphonates. She presented with a tumor-like lesion of the mandible. During the 2-year follow-up, the lesion expanded and caused significant disfigurement and pain necessitating psychiatric support. Treatment with bisphosphonate administered intravenously resulted in rapid pain relief, normalization of bone turnover, and cosmetic improvement. Management of FD has previously consisted of either conservative follow-up or surgery depending on disease activity and localization. Based on published reports and our experience, bisphosphonates should be considered in the treatment of symptomatic cases. This line of treatment may be suitable especially for craniofacial FD in which surgical treatment is particularly challenging.     

Prevalence and natural course of craniocervical junction anomalies during growth in patients with osteogenesis imperfecta

Pathology in the craniocervical junction is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze the prevalence and natural course of craniocervical junction anomalies in patients with OI during growth. In a one-center retrospective study, we analyzed lateral skull radiographs and midsagittal magnetic resonance images of 76 patients with either type I, III, or IV OI. The material included longitudinal series of 31 patients. In total, 150 patient images taken at ages 0 to 39 years were analyzed and compared with age-matched control data. Craniocervical anomalies were observed in 37% of patients and in all OI types studied. Of the three types of anomalies, basilar invagination was seen in 13%, basilar impression in 15%, and platybasia in 29% of the patients. From those with an abnormal finding, 44% displayed more than one type of anomaly. At a group level, we found no evidence of progression of craniocervical junction pathology with age. We provide longitudinal and cross-sectional data on craniocervical junction dimensions in growing patients with OI and, based on those, suggest a radiological management strategy for diagnosis of cranial base pathology. A higher risk of having any of the pathological conditions was associated with a lower height Z-score. Careful follow-up of cranial base anomalies particularly in subjects with OI and severe growth failure is warranted.     

Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

Introduction

Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis.

Methods

We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis.

Results

Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI.

Conclusions

The findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis.     

Current trends in paediatric and neonatal ventilatory care – a nationwide survey

Aim: To assess daily practices in paediatric and neonatal ventilatory care in Finland. Methods: All neonatal and paediatric intensive care units in Finland were sent a questionnaire on ventilatory strategies and were offered a 3‐month prospective survey. Results: A total of 96% of units returned the questionnaire, and clinicians agreed on most of the principles of lung‐protective ventilation. Seventeen hospitals (94%) joined the prospective survey. On average, 2.3 new ventilation episodes were started daily, and totally 211 episodes were monitored. Pulmonary problems (64%) were the main cause of treatment in neonates and postoperative care (68%) in older children. Synchronized intermittent mandatory ventilation with pressure support was the primary mode in 42% of episodes. Hypocapnia was observed repeatedly in all units. In adult intensive care units, children often received high oxygen fraction, leading to hyperoxia, and they were frequently sedated with propofol, which is not licensed for that purpose. A large proportion of children had only light sedation or no sedation at all. Despite the different strategies and practices, most episodes resulted in a favourable outcome. Conclusion: Most of the principles of lung‐protective ventilation have been well accepted by clinicians. More attention should be paid to achieving normocapnia and normoxia and to the correct use of sedatives, especially in units that only occasionally provide paediatric ventilation.