Innovative Approach to Isolate and Characterize Glioblastoma Circulating Tumor Cells and Correlation with Tumor Mutational Status.

Circulating tumor cells (CTCs) are one of the most important causes of tumor recurrence and distant metastases. Glioblastoma (GBM) has been considered restricted to the brain for many years. Nevertheless, in the past years, several pieces of evidence indicate that hematogenous dissemination is a reality, and this is also in the caseof GBM. Our aim was to optimize CTCs' detection in GBM and define the genetic background of single CTCs compared to the primary GBM tumor and its recurrence to demonstrate that CTCs are indeed derived from the parental tumor. We collected blood samples from a recurrent IDH wt GBM patient. We genotyped the parental recurrent tumor tissue and the respective primary GBM tissue. CTCs were analyzed using the DEPArray system. CTCs Copy Number Alterations (CNAs) and sequencing analyses were performed to compare CTCs' genetic background with the same patient's primary and recurrent GBM tissues. We identified 210 common mutations in the primary and recurrent tumors. Among these, three somatic high-frequency mutations (in PRKCB, TBX1, and COG5 genes) were selected to investigate their presence in CTCs. Almost all sorted CTCs (9/13) had at least one of the mutations tested. The presence of TERT promoter mutations was also investigated and C228T variation was found in parental tumors and CTCs (C228T heterozygous and homozygous, respectively). We were able to isolate and genotype CTCs from a patient with GBM. We found common mutations but also exclusive molecular characteristics.

A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET).

PURPOSE: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. METHODS: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured. RESULTS: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. CONCLUSIONS: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Pulmonary Circulation on the Crossroads Between the Left and Right Heart in Systemic Sclerosis: A Clinical Challenge for Cardiologists and Rheumatologists.

Involvement of the right heart-pulmonary circulation system in systemic sclerosis is a typical feature, with critical prognostic implications. Pulmonary hypertension may occur in association with interstitial lung disease or as a result of an isolated pulmonary vascular disease that may affect both the precapillary arterioles and the postcapillary venules, as well as a consequence of left heart involvement. These apparently different phenotypes often underlie a significant pathophysiologic overlap, which makes the diagnosis and management of these patients highly complex and uncertain.

The Right Heart International Network (RIGHT-NET): Rationale, Objectives, Methodology, and Clinical Implications.

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response.

The Role of Double Interatrial Septum in Cryptogenic Stroke.

In this work, the case of a 70-year-old Caucasian woman affected by cryptogenic stroke is reported. After discarding other sources of embolism, a transesophageal echocardiogram was performed, which revealed the presence of a double interatrial septum associated with a left-sided atrial pouch. The persistent interatrial space was identified as the most probable source of thrombus.

Exploring Regorafenib Responsiveness and Uncovering Molecular Mechanisms in Recurrent Glioblastoma Tumors through Longitudinal In Vitro Sampling.

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like temozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by Regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glioblastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. Three-dimensional glioblastoma organoids (GB-EXPs) obtained from 18 patients' resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NRs). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n = 9) and 77% (n = 20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp being REGO-NRs. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO compared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal exploration of the molecular changes induced by treatment, unveiling promising biomarkers indicative of drug response.

Clinical and echocardiographic correlations of exercise-induced pulmonary hypertension in systemic sclerosis: a multicenter study.

BACKGROUND: Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation. AIM: The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc. METHODS: We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (<40 mm Hg) who underwent a comprehensive 2-dimensional and Doppler echocardiography and graded bicycle semisupine exercise Doppler echocardiography. Pulmonary artery systolic pressure, cardiac output, and pulmonary vascular resistance (PVR) were estimated noninvasively. Cutoff values of PASP ≥50 mm Hg and PVR ≥3.0 Wood Units at peak exercise were considered a significant exercise-induced increase in PASP and PVR, respectively. RESULTS: Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ≥3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ≥50 mm Hg, but none of these parameters predict elevated peak PVR. CONCLUSIONS: Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc.

O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET as a potential selection tool for second surgery in glioblastoma patients.

BACKGROUND: Treatment-related changes still represent a diagnostic challenge in the management of patients with suspect of recurrent glioblastoma. The specificity of conventional MRI in detecting recurrence remains limited. Brain PET imaging provides information on tumor metabolism and can contribute to improving the diagnostic accuracy of cerebral neoplasms. We performed a retrospective analysis to evaluate the clinical value of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET in the diagnosis of glioblastoma recurrence. METHODS: A retrospective analysis on patients considered suitable for salvage surgery for recurrence glioblastoma was performed. 18F-FET-PET was performed to investigate gadolinium enhancement suspected for recurrence. Static and kinetic 18F-FET parameters were analyzed and related to O-6-methylguanine-DNA methyltransferase (MGMT) status. RESULTS: Forty-two of the 51 patients who underwent 18F-FET-PET were re-operated. In each case, neuropathological diagnosis of tumor recurrence was confirmed. pMGMT hypermethylation was detected in 21 patients. Mean tumor-to-brain ratios (TBR) max was 3.87 (range 2.6-6.0). Static and kinetic 18F-FET parameters were similar according to MGMT status. CONCLUSIONS: 18FET-PET can be a reliable tool to improve the selection of patients suitable for salvage surgery for glioblastoma recurrence.

Use of antidepressant serotoninergic medications and cardiac valvulopathy: a nested case-control study in the health improvement network (THIN) database.

AIMS: To quantify the risk of cardiac valvulopathy (CV) associated with the use of antidepressant serotoninergic medications (SMs). METHODS: We conducted a case-control study nested in a cohort of users of antidepressant SMs selected from The Health Improvement Network database. Patients who experienced a CV event during follow-up were cases. Cases were ascertained in a random sample of them. Up to 10 controls were matched to each case by sex, age, month and year of the study entry. Use of antidepressant SMs during follow-up was defined as current (the last prescription for antidepressant SMs occurred in the 2 months before the CV event), recent (in the 2-12 months before the CV event) and past (>12 months before the CV event). We fitted a conditional regression model to estimate the association between use of antidepressant SMs and the risk of CV by means of odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Sensitivity analyses were conducted to test the robustness of our results. RESULTS: The study cohort included 752,945 subjects aged 18-89 years. Throughout follow-up, 1663 cases (incidence rate: 3.4 per 10,000 person-years) of CV were detected and were matched to 16,566 controls. The adjusted OR (95% CI) for current and recent users compared with past users of antidepressant SMs were 1.16 (0.96-1.40) and 1.06 (0.93-1.22), respectively. Consistent effect estimates were obtained when considering cumulative exposure to antidepressant SMs during follow-up. CONCLUSIONS: These results would suggest that exposure to antidepressant SMs is not associated with an increased risk of CV.

Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background.

BACKGROUND: Glioblastoma (GB) is a devastating primary brain malignancy. The recurrence of GB is inevitable despite the standard treatment of surgery, chemotherapy, and radiation, and the median survival is limited to around 15 months. The barriers to treatment include the complex interactions among the different cellular components inhabiting the tumor microenvironment. The complex heterogeneous nature of GB cells is helped by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance. METHODS: By using fluorescent multiple labeling and a DEPArray cell separator, we recovered several single cells or groups of single cells from populations of different origins from IDH-WT GB samples. From each GB sample, we collected astrocytes-like (GFAP+), microglia-like (IBA1+), stem-like cells (CD133+), and endothelial-like cells (CD105+) and performed Copy Number Aberration (CNA) analysis with a low sequencing depth. The same tumors were subjected to a bulk CNA analysis. RESULTS: The tumor partition in its single components allowed single-cell molecular subtyping which revealed new aspects of the GB altered genetic background. CONCLUSIONS: Nowadays, single-cell approaches are leading to a new understanding of GB physiology and disease. Moreover, single-cell CNAs resource will permit new insights into genome heterogeneity, mutational processes, and clonal evolution in malignant tissues.

Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early.

Background: Glioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients. Methods: GB organoids were grown for a short period of time to prevent any genetic and morphological evolution and divergence from the tumor of origin. We chose metabolic imaging by NAD(P)H fluorescence lifetime imaging microscopy (FLIM) to predict early and non-invasively ex-vivo anti-cancer treatment responses of GB organoids. TMZ was used as the benchmark drug to validate the approach. Whole-transcriptome and whole-exome analyses were performed to characterize tumor cases stratification. Results: Our functional precision medicine approach was completed within one week after surgery and two groups of TMZ Responder and Non-Responder tumors were identified. FLIM-based metabolic tumor stratification was well reflected at the molecular level, confirming the validity of our approach, highlighting also new target genes associated with TMZ treatment and identifying a new 17-gene molecular signature associated with survival. The number of MGMT gene promoter methylated tumors was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ, suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker. Conclusions: For the first time, FLIM-based metabolic imaging was used on live glioblastoma organoids. Unlike other approaches, ex-vivo patient-tailored drug response is performed at an early stage of tumor culturing with no animal involvement and with minimal tampering with the original tumor cytoarchitecture. This functional precision medicine approach can be exploited in a range of clinical and laboratory settings to improve the clinical management of GB patients and implemented on other cancers as well.

Influence of implant-abutment interface design on bone and soft tissue levels around immediately placed and restored single-tooth implants: a randomized controlled clinical trial.

PURPOSE: The purpose of the present study was to compare the clinical and radiographic outcomes of single implants immediately placed and restored with two different implant-abutment connections. MATERIALS AND METHODS: Forty subjects requiring single maxillary premolar replacement were consecutively included in this study and prospectively followed for 12 months. One implant was placed at the time of tooth extraction and immediately restored in each patient. Subjects were randomly selected to receive either prosthetic abutments with a Morse taper connection and a platform switch (test group) or conventional abutments with an internal connection and a matching diameter (control group). A provisional screw-retained crown was positioned and adjusted for nonfunctional loading within 24 hours. Four months later, the definitive crowns were delivered. Periodontal parameters and clinical and radiographic measurements of soft and hard tissue levels were recorded at the moment of prosthesis placement and at 4 and 12 months afterward. Means of the two groups were compared using paired and independent-sample t tests (P = .05). RESULTS: Of the 40 patients recruited, 38 (24 women and 14 men) completed the study. No implants were lost in the control group, whereas one implant failed in the test group. At the 12-month examination, no statistically significant differences were seen between the two groups for periodontal parameters, marginal soft tissue level change, or papilla height (P > .05), but greater marginal bone loss was observed at the control sites (0.51 ± 0.24 mm) compared to the test sites (0.2 ± 0.17 mm) (P = .0004). CONCLUSION: Although the control group demonstrated a slight increase in marginal bone loss compared to the test group, the peri-implant soft tissues were very stable with both types of implant-abutment connection after 12 months of loading.

Delayed otogenic pneumocephalus complicating ventriculoperitoneal shunt.

Tension pneumocephalus complicating ventriculoperitoneal shunt is extremely rare. We report an elderly male who developed delayed tension pneumocephalus 12 months after ventriculoperitoneal shunt for hydrocephalus complicating aneurysmal subarachnoid hemorrhage. Fine-cut reformatted computer tomography scan revealed a large pneumatocele on the petrous apex associated with tegmen tympani defect. The shunt valve pressure was temporarily raised from 120 mm H 2 O to 200 mm H 2 O, and the patient underwent successful subtemporal extradural repair of the bony defect in the temporal bone. Although extremely rare, otogenic tension pneumocephalus is a potentially life-threatening condition, and urgent surgical repair of the bony defect in the temporal bone reduces the risk of both the morbidity and mortality.

Thoracic extradural haematoma after epidural anaesthesia.

The administration of analgesics to the thoracic spine is established practice in the operating room, minimizing the need for systemic anaesthetic administration during thoracic surgery. Complications arising from thoracic epidural anaesthesia are uncommon but potentially disastrous. Here, we report the case of a 43-year-old woman who developed a thoracic epidural haematoma with paraplegia a few hours after the removal of an epidural catheter. The patient underwent emergency thoracic laminectomy and clot evacuation. After a 4 months period, there was almost complete neurological recovery. Epidural haematoma is a rare complication that must be heeded and urgently treated in case of clinical deterioration after the epidural analgesia.

Sex-related differences in exercise performance and outcome of patients with hypertrophic cardiomyopathy.

AIMS: Exercise performance is known to predict outcome in hypertrophic cardiomyopathy (HCM), but whether sex-related differences exist is unresolved. We explored whether functional impairment, assessed by exercise echocardiography, has comparable predictive accuracy in females and males with HCM. METHODS: We retrospectively evaluated 292 HCM patients (46 ± 16 years, 72% males), consecutively referred for exercise echocardiography; 242 were followed for 5.9 ± 4.2 years. RESULTS: Peak exercise capacity was 6.5 ± 1.6 metabolic equivalents (METs). Sixty patients (21%) showed impaired exercise capacity (≤5 METs). Exercise performance was reduced in females, compared with males (5.6 ± 1.6 vs 6.9 ± 1.5 METs, p < 0.001; peak METs ≤ 5 in 40% vs 13%, p < 0.001), largely driven by a worse performance in women >50 years of age. At multivariable analysis, female sex was independently associated with impaired exercise capacity (odds ratio: 4.67; 95% confidence interval (CI): 1.83-11.90; p = 0.001). During follow-up, 24 patients (10%) met the primary endpoint (a combination of cardiac death, heart failure requiring hospitalization, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator discharge, resuscitated sudden cardiac death and cardioembolic stroke). Event-free survival was reduced in females (p = 0.035 vs males). Peak METs were inversely related to outcome in males (hazard ratio (HR) per unit increase: 0.57; 95% CI: 0.39-0.84; p = 0.004) but not in females (HR: 1.22; 95% CI: 0.66-2.24; p = 0.53). CONCLUSIONS: Female patients with HCM showed significant age-related impairment in functional capacity compared with males, particularly evident in post-menopausal age groups. While women were at greater risk of HCM-related complications and death, impaired exercise capacity predicted adverse outcome only in men. These findings suggest the need for sex-specific management strategies in HCM.

Inkjet-printed graphene Hall mobility measurements and low-frequency noise characterization.

We report room temperature Hall mobility measurements, low temperature magnetoresistance analysis and low-frequency noise characterization of inkjet-printed graphene films on fused quartz and SiO2/Si substrates. We found that thermal annealing in vacuum at 450 °C is a necessary step in order to stabilize the Hall voltage across the devices, allowing their electrical characterization. The printed films present a minimum sheet resistance of 23.3 Ω sq-1 after annealing, and are n-type doped, with carrier concentrations in the low 1020 cm-3 range. The charge carrier mobility is found to increase with increasing film thickness, reaching a maximum value of 33 cm2 V-1 s-1 for a 480 nm-thick film printed on SiO2/Si. Low-frequency noise characterization shows a 1/f noise behavior and a Hooge parameter in the range of 0.1-1. These results represent the first in-depth electrical and noise characterization of transport in inkjet-printed graphene films, able to provide physical insights on the mechanisms at play.

Immediate occlusal loading of immediately placed implants supporting fixed restorations in completely edentulous arches: a 1-year prospective pilot study.

BACKGROUND: The aims of this pilot study were to evaluate the efficacy of treatment consisting of the immediate loading of implants placed immediately after tooth extraction in full-arch restorations and to compare the clinical and radiographic outcomes of implants placed in healed versus postextraction sites in the same group of patients. METHODS: Twenty-three patients who needed full-arch restorations were treated. One hundred forty-four implants were placed: 59 after tooth extraction (test group) and 85 in healed sites (control group). Within 48 to 72 hours of implant placement, nine maxillary and 15 mandibular arches received screw-retained fixed prostheses, consisting of a titanium framework fabricated with a computer-aided design and manufacturing techniques and composite resin teeth. The insertion torque for implants was >or=30 Ncm. Implant stability measurements (ISQ) and radiographs of the marginal bone level (MBL) change were performed at prosthesis delivery and after 1 year. RESULTS: One implant in the test group and one implant in the control group failed, giving a cumulative success rate of 98.6%; the prosthesis survival rate was 100%. At the 1-year follow-up, no statistically significant difference was found between the control and test sites with respect to MBL change (0.47 +/- 0.18 mm versus 0.57 +/- 0.27 mm) or mean ISQ values (62.24 +/- 1.92 versus 61.34 +/- 2.15). CONCLUSION: These preliminary data suggest that immediate loading of implants placed immediately after extraction may be a viable treatment option for edentulous arches when implants are stable at insertion and are rigidly splinted with screw-retained titanium-resin prostheses.

Evaluation of survival and success rates of dental implants placed at the time of or after alveolar ridge augmentation with an autogenous mandibular bone graft and titanium mesh: a 3- to 8-year retrospective study.

PURPOSE: The purpose of this retrospective longitudinal study was to evaluate the survival and success rates of 56 implants consecutively placed in alveolar ridges following a one- or two-stage augmentative procedure, using autogenous bone and titanium micromeshes. MATERIALS AND METHODS: This study included 24 consecutive patients treated with 27 micromeshes and mandibular particulated bone. In 13 patients, 20 implants were placed at the time of the reconstructive procedure. In the remaining 11 patients, 36 implants were positioned in a second surgery 8 to 9 months after grafting. Follow-up data (implant survival, success rate, marginal bone resorption) were collected after 3 to 8 years of prosthetic loading. RESULTS: Four of the 27 micromeshes (complication rate, 14.8%) were exposed prematurely and were removed before the intended time. The mean vertical bone augmentation obtained was 5.4 +/- 1.81 mm for implants placed in simultaneous procedures and 4.5 +/- 1.16 mm in delayed procedures. None of the 56 implants was lost during the observation period (cumulative implant survival rate, 100%). Radiographic analysis showed stable marginal bone levels, with a mean bone resorption of 1.58 +/- 0.48 mm after 3 to 8 years. Only two implants demonstrated increased bone loss (3.12 and 3.37 mm) over the follow-up period, whereas the remaining 54 implants were considered clinically successful, resulting in a cumulative success rate of 96.4%. CONCLUSIONS: This study revealed that implant placement in augmented ridges using micromeshes and autogenous bone provided satisfactory long-term survival and success rates, with minimal bone resorption.

Effect of mesenchymal stem cells and platelet-rich plasma on the healing of standardized bone defects in the alveolar ridge: a comparative histomorphometric study in minipigs.

PURPOSE: The purpose of this study was to test the effect of the combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) incorporated into a fluorohydroxyapatite (FHA) scaffold on bone regeneration in cylindrical defects in the edentulous mandibular ridge of minipigs. MATERIALS AND METHODS: Two mandibular premolar teeth were extracted bilaterally in 8 adult minipigs. After 2 months, 4 standardized defects of 3.5 mm diameter and 8 mm depth were created in each root site. The defects were randomly grafted with autogenous mandibular bone, FHA alone, PRP-FHA, or MSCs-PRP-FHA. A resorbable collagen membrane was placed over the defect area and the flaps were sutured. The animals were sacrificed 3 months later and biopsy samples were taken from the defect sites for histologic and histomorphometric assessment. RESULTS: There was no evidence of inflammation or adverse tissue reaction with either treatment. MSCs-PRP-FHA-treated sites showed new vital bone between residual grafting particles. PRP-FHA- and FHA-treated sites showed residual particles in a background of marrow soft tissue with a moderate quantity of newly formed bone. Autogenous bone (46.97%) and MSCs-PRP-FHA (45.28%) produced a significantly higher amount of vital bone than PRP-FHA (37.95%), or FHA alone (36.03%). Further, the MSCs-PRP-FHA-treated defects showed a significantly higher percentage of contact between graft particles and newly formed bone compared with PRP-FHA and FHA group (59.23% vs 48.37% and 46.43%, respectively). CONCLUSIONS: Our results suggest that, in this animal model, the addition of MSCs to PRP-FHA enhances bone formation after 3 months.

Acute Symptomatic Sinus Bradycardia in High-Dose Methylprednisolone Therapy in a Woman With Inflammatory Myelitis: A Case Report and Review of the Literature.

High dose corticosteroid therapy is widely used as attack therapy of inflammatory central nervous system disorders and can induce several adverse reactions. Bradycardia is an infrequent event after corticosteroids administration and is often asymptomatic. We report a case of a woman admitted to the neurological department of our hospital for paraesthesias of the lower limbs. She received adiagnosis of inflammatory myelitis and high dose corticosteroid therapy was prescribed. During the therapy she complained of chest tightness, dyspnoea, weakness and malaise. An electrocardiogram revealed sinus bradycardia. A significant increase in body weight, probably due to plasma volume expansion, was detected. Bradycardia and high blood pressure spontaneously resolved in few days. We provide a collection and a statistical analysis of literature data about steroid induced bradycardia. We found that higher total doses are associated with lower pulse rate and symptomatic bradycardia. Bradycardia is more frequent in older patients and those with underlying cardiac disease or with autonomic disturbance. However clinicians must be aware about the occurrence of symptomatic bradycardia in all patients who undergo high dose corticosteroid therapy, not only in those at risk, to early detect and treat this potentially dangerous condition.