Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair.

We hypothesized that ZA treatment would bolster fracture repair. In a rat model for closed fracture healing, a single dose of ZA at 0, 1, or 2 wk after fracture significantly increased BMC and strength of the healed fracture. Delaying the dose (1 or 2 wk after fracture) displayed superior results compared with dosing at the time of fracture. INTRODUCTION: Bisphosphonates are known to increase bone strength and thus the resistance to fracture by decreasing osteoclastic bone resorption. These properties may enable bisphosphonates to also increase the strength of fracture repair. Zoledronic acid (ZA) is a potent bisphosphonate with a high affinity for bone mineral, allowing bolus intravenous dosing in a range of indications. In this study, we examined the application of bolus dose ZA in endochondral fracture repair. MATERIALS AND METHODS: Carbon-14 labeled ZA was used in a closed rat fracture model. Rats were divided into five treatment groups (n = 25 per group): saline control, local ZA (0.01 mg/kg), and three systemic bolus ZA groups (0.1 mg/kg) with different administration times: at fracture, 1 wk after fracture, and 2 wk after fracture. Rats were killed 6 wk postoperatively. Postmortem analyses included radiography, QCT, microCT, biomechanical testing, scintillation counting, autoradiography, and histology. RESULTS: Single-dose systemic ZA administration significantly increased callus volume, callus BMC, and mechanical strength. Perioperative treatment increased mechanical strength by 30% compared with controls (p < 0.05). Administering the systemic dose at 1 or 2 wk after fracture further increased mechanical strength compared with controls by 44% and 50%, respectively (p < 0.05). No significant differences in mechanical parameters were seen with local injection at the dose studied. Autoradiographic analysis indicated that ZA binds significantly to bone that is present at the time of administration. ZA quantification indicated that delayed administration significantly increased the uptake efficiency in the callus. Histological and microCT analysis showed that ZA treated calluses had a distinctive internal structure consisting of an intricate network of retained trabecular bone. CONCLUSIONS: The timing of a single systemic dose of ZA plays an important role in the modulation of callus properties in this rat fracture model; delaying the single dose produces a larger and stronger callus.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Catastrophic paradoxical embolus after hemodialysis access thrombectomy in a patient with a patent foramen ovale

We present the first case of documented clot in-transit through a patent foramen ovale (PFO), caused by mechanical thrombectomy of a clotted AV fistula. Embolus after access thrombectomy is a rare, but known complication of the procedure. Paradoxical embolus is likewise a rare consequence of a right-sided clot, embolising to the left-sided circulation in a patient with a PFO. Suspected embolus through a PFO after dialysis access thrombectomy has been reported, but no case has ever documented the clot in-transit through the PFO.     

Effectiveness of arginine-containing toothpastes in treating dentine hypersensitivity: A systematic review

Objectives

To evaluate by way of a systematic review the effectiveness of arginine-containing desensitising toothpastes in comparison to control agents in reducing dentine hypersensitivity.

Data sources

Electronic databases were searched including: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS (30/03/2012). Reference lists of eligible studies and systematic reviews were cross-checked in an attempt to identify additional studies. Strategies to identify grey literature were employed.

Study selection inclusion criteria

Controlled Clinical Trials (CCTs) and Randomised Controlled Trials (RCTs) comparing arginine-containing desensitising toothpastes to non-arginine-containing control toothpastes.Two review authors independently screened the titles and abstracts of studies identified. Data collection forms were completed for included studies.

Outcomes

Changes in sensitivity to tactile and air-blast stimuli. A subjective assessment of sensitivity was also sought.

Conclusion

Data identified indicates a potential role for arginine-containing toothpastes in managing dentine hypersensitivity. However, this conclusion is based on small sample sizes and the studies identified did not follow patients up in the medium to long term. The authors recommend that there is a need for well-designed RCTs to be conducted prior to any definitive recommendations being made.

Clinical significance

Dentine hypersensitivity is a common condition. Its multi-factorial aetiology has led to several treatment modalities being advocated. The continued introduction of new desensitising agents suggests that no product has yet proven ultimately successful. Arginine-containing toothpastes have recently been introduced, this article systematically reviews the evidence relating to their effectiveness.     

Intervention for Infants at Risk of Developing Autism: A Case Series

Theory and evidence suggest the potential value of prodromal intervention for infants at risk of developing autism. We report an initial case series (n = 8) of a parent-mediated, video-aided and interaction-focused intervention with infant siblings of autistic probands, beginning at 8–10 months of age. We outline the theory and evidence base behind this model and present data on feasibility, acceptability and measures ranging from parent-infant social interaction, to infant atypical behaviors, attention and cognition. The intervention proves to be both feasible and acceptable to families. Measurement across domains was successful and on larger samples promise to be an effective test of whether such an intervention in infancy will modify emergent atypical developmental trajectories in infants at risk for autism.     

Radiological and clinical features of screening-detected pulmonary invasive mucinous adenocarcinoma

 Open in a separate windowOBJECTIVESThe current understanding of pulmonary invasive mucinous adenocarcinoma is largely based on studies of advanced stage patients and data about early-stage invasive mucinous adenocarcinoma are sparse. We evaluated the radiological and clinical features of screening-detected early-stage invasive mucinous adenocarcinoma (SD-IMA).METHODSData from 91 patients who underwent surgical treatment for SD-IMA (≤3 cm) from 2013 to 2019 were reviewed retrospectively. Data on radiological characteristics, clinicopathological findings, recurrence and survival were obtained. Disease-free survival rate was analysed.RESULTSRadiologically, SD-IMAs presented as a pure ground-glass nodule (6.6%), part-solid nodule (38.5%) or solid (54.9%). Dominant locations were both lower lobes (74.7%) and peripheral area (93.4%). The sensitivity of percutaneous needle biopsy was 78.1% (25/32). Lobectomy was performed in 70 (76.9%) patients, and sublobar resection in 21 (23.1%) patients. Seventy-three (80.2%), 15 (16.5%) and 3 (3.3%) patients had pathological stage IA, IB and IIB or above, respectively. Seven patients developed recurrence, and 3 died due to disease progression. Pleural seeding developed exclusively in 2 patients who underwent needle biopsy. The 5-year disease-free survival rate was 89.4%. The disease-free survival rates at 5 years were 86.3% in the lobectomy group and 100% in the sublobar resection group.CONCLUSIONSSD-IMAs were mostly radiologically invasive nodules. SD-IMAs showed favourable prognosis after surgical treatment.