Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

BRONJ in patients with rheumatoid arthritis: a multicenter case series.

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of various medications (bisphosphonates, anti-resorptive, and anti-angiogenic drugs). ONJ pathogenesis is still unclear although some risk factors have been recognized. Of these, rheumatoid arthritis (RA) has been hypothesized as a potential risk factor for developing ONJ. This observational study will describe a multicenter case series of patients affected with RA and ONJ, and it will attempt to evaluate the association between features of ONJ and pharmacological, systemic, and site variables. METHODS: Demographic, pharmacological, and clinical data from 18 RA patients with ONJ were collected and registered from three Italian centers (i.e., Palermo, Verona, and Padua) from 2004 to 2013. RESULTS: Sixteen (88.9%) patients were in therapy for RA: 9 of 18 (50.0%) with systemic steroids, 3 of 18 (16.7%) with methotrexate, and 4 of 18 (22.2%) with both medications. Two patients were not receiving treatment for RA. All patients took NBPs for secondary osteoporosis (average NBP duration of 69 months, range: 20-130): Fifteen (83.3%) patients were treated with single NBPs, while three (16.7%) with different molecules; one patient was also treated with denosumab. Mandible was affected more frequently (66.7%) than maxilla (33.3%); one patient presented multiple ONJ events. CONCLUSIONS: This is the first multicenter case series in the international literature regarding our topic. Focusing on our data, it could be hypothesized that patients with RA may be more susceptible to ONJ than the majority of osteometabolic patients. In our opinion, it could be important to monitor also denosumab or other biological drug side effects.

Three-dimensional CAD/CAM reconstruction of the iliac bone following DCIA composite flap harvest.

This article reports a new technique to restore iliac bone integrity with a customized titanium device designed by CAD/CAM, in patients undergoing deep circumflex iliac artery (DCIA) composite flap harvest. Eight consecutive patients who underwent the repair of major head and neck defects with DCIA flaps were enrolled retrospectively. Computed tomography scans of the pelvis were obtained preoperatively. Starting from DICOM data, each personalized device was designed using modelling software and was finally made by additive manufacturing using a laser sintering machine. After surgery, the patients were followed up at 3-month intervals to evaluate the incidence of complications and the long-term outcome at the donor site. A subcutaneous seroma developed in one patient and an inguinal skin burn occurred in another. At a median follow-up of 12 months, the patients did not report pain, or any gait or sensory disturbance at the donor site. There was no occurrence of bulging, herniation, or instability or inflammation near the device for the entire follow-up duration. All patients were satisfied with the aesthetic result. In conclusion, reconstruction of the iliac bone with a customized device is safe and well tolerated. We recommend use of this device in patients deemed at high risk of herniation. Further studies are needed to confirm the stability of the device in the long term.

Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature.

OBJECTIVES: To describe clinical characteristics, laboratory tests, radiological data and outcome of pediatric cases with SARS-CoV-2 infection complicated by neurological involvement. STUDY DESIGN: A computerized search was conducted using PubMed. An article was considered eligible if it reported data on pediatric patient(s) with neurological involvement related to SARS-CoV-2 infection. We also described a case of an acute disseminated encephalomyelitis (ADEM) in a 5-year-old girl with SARS-CoV-2 infection: this case was also included in the systematic review. RESULTS: Forty-four articles reporting 59 cases of neurological manifestations in pediatric patients were included in our review. Most (32/59) cases occurred in the course of a multisystem inflammatory syndrome in children (MIS-C). Neurological disorders secondary to cerebrovascular involvement were reported in 10 cases: 4 children with an ischemic stroke, 3 with intracerebral hemorrhage, 1 with a cerebral sinus venous thrombosis, 1 with a subarachnoid hemorrhage, 1 with multiple diffuse microhemorrhages. Reversible splenial lesions were recognized in 9 cases, benign intracranial hypertension in 4 patients, meningoencephalitis in 4 cases, autoimmune encephalitis in 1 girl, cranial nerves impairment in 2 patients and transverse myelitis in 1 case. Five cases had Guillain-Barré syndrome (GBS) and two, including ours, had ADEM. Radiological investigations were performed in almost all cases (45/60): the most recurrent radiological finding was a signal change in the splenium of the corpus callosum. The presence of SARS-CoV-2 viral nucleic acid in the cerebrospinal fluid was proved only in 2 cases. The outcome was favorable in almost all, except in 5 cases. CONCLUSIONS: Our research highlights the large range of neurological manifestations and their presumed pathogenic pathways associated with SARS-CoV-2 infection in children. Nervous system involvement could be isolated, developing during COVID-19 or after its recovery, or arise in the context of a MIS-C. The most reported neurological manifestations are cerebrovascular accidents, reversible splenial lesions, GBS, benign intracranial hypertension, meningoencephalitis; ADEM is also a possible complication, as we observed in our patient. Further studies are required to investigate all the neurological complications of SARS-CoV-2 infection and their underlying pathogenic mechanism.

Fractures of the iliac crest following anterior and posterior bone graft harvesting. Review of the literature and case presentation.

Iliac crest is the most commonly used extra-oral donor site of autologous non-vascularized bone, because of the great amount of bone available and easy access. Bone grafting from the ileum, however, is not without complications. An extensive review of the literature focusing on fractures of the iliac crest and pelvic ring instability due to anterior and posterior bone graft harvesting is reported, and 1 case of anterior stress fracture of the iliac crest is described. Thirty-five of the 37 fractures described up to date in literature were divided in 2 groups depending on the region of bone graft harvesting. Twenty-four fractures - including our case - were related to bone graft harvesting from the anterior region, 12 were due to harvesting from the posterior region. Four out of 24 anterior fractures required further surgical treatment (16.6%). In 8 of the 12 fractures with pelvic ring instability due to posterior bone harvesting, 1 or more additional surgical procedures were performed in order to stabilize multiple fracture sites (66.6%). Anterior iliac crest fractures, even though painful, remain stable and heal spontaneously in most cases without further complications. On the contrary, fractures due to posterior iliac crest harvestings very often require complex surgical treatments and lead to significant disability, which can be permanent.

Intraoral endoscopic enucleation of a solitary bone cyst of the mandibular condyle.

Solitary bone cysts are benign osteolytic lesions rarely involving the mandibular condyle. They are considered pseudocysts due to the absence of epithelium and their pathogenesis is unknown. These lesions are also known with a variety of synonyms, such as traumatic bone cysts, simple bone cysts, haemorrhagic bone cysts and unicameral cysts. The authors report a case of a solitary cyst of the condylar head treated by enucleation and curettage via an intraoral endoscopic-assisted surgical approach, which avoids the risk of facial nerve injury, reduces the patient's hospitalization and speeds up functional recovery.

Vascularized fibula flap reconstruction of the mandible in bisphosphonate-related osteonecrosis.

AIMS: To point out the feasibility of microsurgical reconstruction of the mandible in patients with bisphosphonate-related osteonecrosis (BRONJ). METHODS: Seven patients with extensive mandibular osteonecrosis underwent subtotal mandibulectomy and immediate reconstruction with a free fibula flap. They were six women and one man aged 49-72 years. The mean size of the bone and oral mucosa defects were 18.5 and 22.5 cm(2) respectively. RESULTS: The mean time of surgical intervention was 12 h. All flaps survived and the postoperative course was uneventful. Oral feeding was resumed 14 days after surgery in all cases. The donor legs healed without complications. The pathology report confirmed the diagnosis of BRONJ in all patients. Normal bone was detected at the resection margins in six out of seven patients. Patients were followed-up at intervals of 3 months. After a median follow-up time of 23 months, no clinical and radiographic evidence of recurrent BRONJ were detected in six patients. One patient with osteomyelitis at the resection margins had signs of recurrent BRONJ 6 months after surgery. The overall curative rate of the population was 86%. CONCLUSIONS: Despite the limited number of patients studied so far, our data show that mandible reconstruction with the fibula flap is feasible and does not influence the natural course of the primary disease in BRONJ-resected patients.

[The fluid balance in the critically ill patient]. / Il bilancio idrico nel malato di terapia intensiva.

AIM: In the critically ill patient the hemodynamic management is essential. Usually the hemodynamic status is estimated by the measurement of the intravascular pressure or volume and by computing the fluid balance, while the change in body weight estimates the total body water. The fluid balance is computed by subtracting the fluid output to the input. Although the input (fluids, drugs, infusion.) are well known, the output are difficult to correctly compute, because they depend on several factors such as the body-room temperature, amount of humidity and may change with time. Aim of this study was to prospectively evaluate the accuracy of the fluid balance compared to the body weight measured by a dedicated mattress (Hill-Rom). METHODS: Fifteen critically ill patients were enrolled (mean age of 63.2+/-19.7 years, body mass index of 24.9+/-3.5 kg/m2) and the measurements were computed every 8 hours. The data were analyzed by the Bland-Altman test. RESULTS: Four-hundred and seventy-two measurements for a mean intensive care stay of 12.3.+/-7.3 days were computed. The Bland-Altamn showed a great inaccuracy, because the agreement (the difference between the 2 methods) was poor with a standard deviation of 1 840 L. CONCLUSION: Although the fluid balance was not accurate, the only body weight without any intravascular measurement is not helpful for a correct clinical hemodynamic management of the patient.