What is the Incidence of Late Complications Associated With Lower Third Molar Coronectomy? 10-Year Follow-Up Results.

PURPOSE: Coronectomy is an operation to manage impacted third molars (M3s) considered at high risk for mandibular nerve injury but long-term outcomes are still lacking. The purpose of this study was to estimate the risk of late complications occurring within 10 years following lower M3 coronectomy. METHODS: The investigators designed a prospective cohort study and enrolled a sample of 94 patients treated with coronectomy of third mandibular molars at the Unit of Oral and Maxillofacial Surgery of the University of Bologna, from 2009 to 2012. This follow-up study included all of the patients from the original study who completed 10 years of follow-up. The primary outcome variables is postoperative late complication occurring between 5 and 10 years after coronectomy coded as present or absent. Late complications were defined as root exposure, nerve injury, pulpitis, periapical infection, and reoperation. The secondary outcome variable was probing pocket depth. Covariates examined were age, smoking and type of M3 impaction. Descriptive statistical analyses were performed. RESULTS: The inception cohort was composed of 94 subjects who had 116 coronectomies (k) completed. The study cohort was composed of subjects with 10 years of follow-up and included 48 subjects (k = 60) with a mean age of 28.99 ± 8.9 years. Between years 5 and 10 of follow-up, 2 subjects (4%) have complications; all root exposures diagnosed at years 8 or 9 after surgery. In another case root removal was required for orthodontics reason. No case of nerve injury to the inferior alveolar nerve occurred, and no periapical infection was observed around the residual roots. The mean 10-year probing pocket depth was 3.31 ± 0.92 mm (1,66-5,66 mm). There were too few complications to identify risk factors for late complications. CONCLUSIONS: Within all the limitations of this study, the results of this prospective study imply that coronectomy is a useful surgical technique for the treatment of M3s at high neurological risk, to avoid nerve injury to the inferior alveolar nerve. In addition, after coronectomy, retained roots did not develop late infection or periapical infection in the long term. However, in a few cases, removal of retained roots was required at 10 years, due to root migration in the oral cavity. The risk for late complications is uncommon, but persistent.

Postmarketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12 to 39 years in Italy: A multi-database, self-controlled case series study.

BACKGROUND: Myocarditis and pericarditis following the Coronavirus Disease 2019 (COVID-19) mRNA vaccines administration have been reported, but their frequency is still uncertain in the younger population. This study investigated the association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccines, BNT162b2, and mRNA-1273 and myocarditis/pericarditis in the population of vaccinated persons aged 12 to 39 years in Italy. METHODS AND FINDINGS: We conducted a self-controlled case series study (SCCS) using national data on COVID-19 vaccination linked to emergency care/hospital discharge databases. The outcome was the first diagnosis of myocarditis/pericarditis between 27 December 2020 and 30 September 2021. Exposure risk period (0 to 21 days from the vaccination day, subdivided in 3 equal intervals) for first and second dose was compared with baseline period. The SCCS model, adapted to event-dependent exposures, was fitted using unbiased estimating equations to estimate relative incidences (RIs) and excess of cases (EC) per 100,000 vaccinated by dose, age, sex, and vaccine product. Calendar period was included as time-varying confounder in the model. During the study period 2,861,809 persons aged 12 to 39 years received mRNA vaccines (2,405,759 BNT162b2; 456,050 mRNA-1273); 441 participants developed myocarditis/pericarditis (346 BNT162b2; 95 mRNA-1273). Within the 21-day risk interval, 114 myocarditis/pericarditis events occurred, the RI was 1.99 (1.30 to 3.05) after second dose of BNT162b2 and 2.22 (1.00 to 4.91) and 2.63 (1.21 to 5.71) after first and second dose of mRNA-1273. During the [0 to 7) days risk period, an increased risk of myocarditis/pericarditis was observed after first dose of mRNA-1273, with RI of 6.55 (2.73 to 15.72), and after second dose of BNT162b2 and mRNA-1273, with RIs of 3.39 (2.02 to 5.68) and 7.59 (3.26 to 17.65). The number of EC for second dose of mRNA-1273 was 5.5 per 100,000 vaccinated (3.0 to 7.9). The highest risk was observed in males, at [0 to 7) days after first and second dose of mRNA-1273 with RI of 12.28 (4.09 to 36.83) and RI of 11.91 (3.88 to 36.53); the number of EC after the second dose of mRNA-1273 was 8.8 (4.9 to 12.9). Among those aged 12 to 17 years, the RI was of 5.74 (1.52 to 21.72) after second dose of BNT162b2; for this age group, the number of events was insufficient for estimating RIs after mRNA-1273. Among those aged 18 to 29 years, the RIs were 7.58 (2.62 to 21.94) after first dose of mRNA-1273 and 4.02 (1.81 to 8.91) and 9.58 (3.32 to 27.58) after second dose of BNT162b2 and mRNA-1273; the numbers of EC were 3.4 (1.1 to 6.0) and 8.6 (4.4 to 12.6) after first and second dose of mRNA-1273. The main study limitations were that the outcome was not validated through review of clinical records, and there was an absence of information on the length of hospitalization and, thus, the severity of the outcome. CONCLUSIONS: This population-based study of about 3 millions of residents in Italy suggested that mRNA vaccines were associated with myocarditis/pericarditis in the population younger than 40 years. According to our results, increased risk of myocarditis/pericarditis was associated with the second dose of BNT162b2 and both doses of mRNA-1273. The highest risks were observed in males of 12 to 39 years and in males and females 18 to 29 years vaccinated with mRNA-1273. The public health implication of these findings should be considered in the light of the proven mRNA vaccine effectiveness in preventing serious COVID-19 disease and death.

Stability of Periodontal Healing Distal to the Mandibular Second Molar After Third Molar Coronectomy: A 3-Year Follow-Up Study.

PURPOSE: The stability of the periodontal attachment distal to the mandibular second molar after coronectomy of the third molar is still unclear. This study addressed the question of whether periodontal measures are stable over time among patients undergoing coronectomy. MATERIALS AND METHODS: This prospective cohort study enrolled 30 patients treated at the Unit of Oral and Maxillofacial Surgery of the University of Bologna. The predictor variables were the probing pocket depth (PPD), distance between the marginal crest and the bottom of the osseous defect (BOD), and distance between the cementoenamel junction and the BOD. Three points on the distal surface of the second molar were recorded: distobuccal, distomedial, and distolingual sites. The distobuccal site was used as the statistical unit. The Wilcoxon test for paired data and Kendall τb were used to evaluate all variables. The significance level was set at P < .05. RESULTS: The 3-year follow-up was completed by 27 patients (7 male and 20 female patients; mean age, 28 ± 7 years) with 30 third molars. At 3 years, the PPD was 4 ± 1.25 mm; no significant changes in PPD were recorded for all sites from 9 months to 3 years. For the marginal crest-BOD distance and the cementoenamel junction-BOD distance, significant reductions were evident between preoperative values and those at 9 to 36 months (P = .001) and between values at 9 and 36 months (P = .02). CONCLUSIONS: A clinical healthy periodontium distal to the second molar was observed 36 months after coronectomy. However, further studies are necessary to confirm these preliminary clinical results.

Coronectomy: A Surgical Option for Impacted Third Molars in Close Proximity to the Inferior Alveolar Nerve-A 5-Year Follow-Up Study.

PURPOSE: The extraction of third molars is the most common surgical procedure performed in the oral cavity. Coronectomy is a surgical protocol to reduce the risk of neurologic lesions to the inferior alveolar nerve (IAN). We evaluated early (up to 1 month) and late (from 2 to 60 months) postoperative complications. MATERIALS AND METHODS: This prospective cohort study enrolled patients treated at the Unit of Oral and Maxillofacial Surgery, University of Bologna. The predictor variable was the time after coronectomy with up to 5 years' follow-up. To assess the rate of postoperative complications, the outcome variables were neurologic injuries, postoperative pain, swelling, fever, alveolitis, pulpitis, and root exposure. The success rate, need for a second surgical procedure, probing pocket depth, and bleeding on probing also were investigated. Univariate and bivariate descriptive statistics, Kaplan-Meier analysis, and Cox hazards modeling were performed to evaluate the variables. RESULTS: We performed 116 coronectomies in 94 healthy patients (37 men and 57 women; mean age, 28.99 ± 8.9 years). At 5 years' follow-up, we re-evaluated 63 patients with 76 coronectomies. In total, 30 complications were verified. No cases of neurologic lesions to the IAN or lingual nerve were observed after surgery. In the first 3 years, the surgeons extracted migrated roots in 5 cases (6%) without any neurologic lesions to the IAN. No complications were observed from the third to fifth year. CONCLUSIONS: This prospective study on coronectomy of third molars in a close relationship with the mandibular canal found no cases of neurologic lesions, no cases of late infection of the retained roots at 5 years, and a low rate of immediate postoperative complications. Further investigations should include a follow-up study at 10 years and more research about the mechanism of pulp healing.

Periodontal Healing Distally to Second Mandibular Molar After Third Molar Coronectomy.

PURPOSE: Coronectomy of mandibular third molars is a procedure that still raises a number of questions. The aim of the present study was to answer one unsolved question: the periodontal healing distal to the mandibular second molar after third molar coronectomy. MATERIALS AND METHODS: A prospective cohort study was performed of 30 patients treated at the Unit of Oral and Maxillofacial Surgery of the Department of Biomedical and Neuromotor Science of the University of Bologna. The predictor variables were the probing pocket depth (PPD), the distance between the marginal crest (MC) and the bottom of the osseous defect (BOD), and the distance between the cementum enamel junction (CEJ) and the BOD. These clinical indexes were recorded on 3 points of the distal surface of second molar: the distobuccal (DB), distomedial (DM), and distolingual (DL) sites. The other variables evaluated included root migration and postoperative complications. The Wilcoxon test for paired data and Kendall's tau-b correlation coefficient was used to evaluate all variables. The significance level was set at P = .05. RESULTS: The cohort was composed of 30 patients with 34 high-risk mandibular third molars (9 men and 21 women), with a mean age of 28 ± 7 years. At 9 months, a statistically significant reduction in the PPD of 2 ± 3, 1 ± 2, and 2 ± 2 mm and a statistically significant reduction in the MC-BOD distance of 4 ± 4, 4 ± 4, and 4 ± 5 mm for the DB, DM, and DL sites, respectively, was observed (P = .001). Also, the intraoperative CEJ-BOD distance showed a statistically significant reduction for the DB, DM, and DL sites. CONCLUSIONS: After coronectomy, restoration of a clinical healthy periodontium distal to the second molar was observed. However, further studies are necessary to confirm these preliminary clinical results and to compare periodontal healing between coronectomy and complete extraction.

Root Fragment Vitality After Coronectomy: Histological Evidence in a Case.

PURPOSE: Coronectomy is a well-documented surgical technique for the treatment of high-risk third molars, but the fate of retained roots remains controversial. This case report describes the histologic analysis of retained root fragments. PATIENT AND METHODS: A 44-year-old man treated with coronectomy of a left mandibular third molar requested the extraction of the retained roots. The patient was asymptomatic and the retained roots were extracted 18 months after coronectomy at the patient's request. RESULTS: The extracted roots were histologically evaluated and the results showed the presence of vital pulp tissue. CONCLUSION: Histologic analysis showed that retained roots remain vital after coronectomy.

What Are the Types and Frequencies of Complications Associated With Mandibular Third Molar Coronectomy? A Follow-Up Study.

PURPOSE: Coronectomy has been proposed for impacted third molars in close proximity to the inferior alveolar nerve (IAN) to avoid neurologic injury. Immediate (up to 1 month) and late (2 to 36 months) postoperative complications were investigated. MATERIALS AND METHODS: A prospective cohort study was performed on healthy patients treated in the dental clinic of the Department of Oral Surgery, University of Bologna. The predictor variables examined were experience of the surgeon (<10 vs ≥10 yr), length of surgery, type of mandibular third molar inclusion, and patient age. To assess the rate of postoperative complications, outcome variables were neurologic injuries, postoperative pain, swelling, fever, alveolitis, pulpitis, and root exposure. The success rate and need for a second surgery also were investigated. Univariate and bivariate descriptive statistics, Kaplan-Meier analysis, and Cox hazards modeling were performed to evaluate the variables. RESULTS: The study involved 94 healthy patients (mean age, 28.99 ± 8.9 yr; range, 17 to 56 yr; 37 men and 57 women) who had 116 third mandibular molars treated with coronectomy. During the 3-year follow-up period, 28 patients (29 coronectomy procedures) dropped out of the study. There was no case of neurologic injury to the inferior alveolar nerve (IAN) or to the lingual nerve (LN). In total, 30 complications were observed (25 within 1 month; 5 at 2 to 12 months). Surgeons with less than 10 years of training exposed patients to a greater risk of complications (hazard ratio = 2.069; 95% confidence interval, 1.004-4.263). An overall success rate of 74% at 6 months was estimated, and a second surgery was needed in 6% of cases. Of the retained roots analyzed, 80% showed postoperative root migration. CONCLUSIONS: In this study, coronectomy of mandibular third molars did not result in temporary or permanent injury to the IAN or LN. Coronectomy showed a low rate of postoperative complications. However, within the first year, a second surgery was needed in 6% of coronectomy procedures to remove migrated root fragments. Additional studies with larger patient samples are recommended to further investigate differences in postoperative complications in relation to patient age.

Piezosurgery or conventional rotatory instruments for inferior third molar extractions?

PURPOSE: The purpose of this study was to compare the discomfort and surgical outcomes of a piezosurgery device with those of rotatory instruments in lower third molar extraction. MATERIALS AND METHODS: A split-mouth, randomized, unblinded clinical study was designed; the 2 molars had to have the same extraction difficulty score. The test side was extracted using a piezosurgery technique and the control side was extracted using a conventional handpiece. The primary endpoint was patient discomfort evaluated with the Postoperative Symptom Severity (PoSSe) scale, which was administered to each patient; secondary endpoints were pain, trismus, swelling, and surgical time evaluation. Paired-samples t test and repeated-measures analysis of variance were used to compare outcomes within patients. RESULTS: Ten consecutive patients (6 female, 4 male; mean age, 22.4 ± 2.3 yr) were recruited. The total score on the PoSSe scale was significantly lower for piezosurgery compared with the conventional rotating handpiece (24.7 ± 10.3 vs 36.0 ± 7.6; t = -4.27; P = .002). Moreover, postoperative swelling 1 week after surgery was significantly lower for piezosurgery than for the conventional rotating handpiece (2.75 ± 0.23 vs 3.1 ± 0.39 cm; t = -2.63; P = .027). CONCLUSIONS: Piezosurgery was associated with less postoperative discomfort and yielded better results for swelling. Piezosurgery seems to be a good technique in daily surgical practice, especially if applied in the critical steps in which safety and respect for soft tissue, bone, and nerves are necessary.

A laboratory based investigation of a new elastic toothbrush head.

PURPOSE: To demonstrate the noninferiority of a new toothbrush head with retractile bristles compared to traditional toothbrush heads on dental models. METHODS: The new toothbrush head, mounted on manual and electrical handles, presents retractile bristle groups that can singularly retract over its entire length and offer calibrated resistance. Fourteen gypsum models of dental arches, twelve with and two without anatomical impairments, were spread with a "plaque simulator." Each arch was brushed twice with each of the four toothbrushes, one minute by the same operator, blinded to the study. The plaque index (PI) was recorded at the end of each brushing session. GLM for repeated measures analysed the data. RESULTS: On all the casts, the manual prototype and the electric prototype, removed 11% and 14% more "plaque simulator" compared to the standard toothbrush. In presence of dental anomalies, the prototypes removed 13% and 16% more plaque, respectively, compared to standard toothbrushes (P = 0.04). In both situations, the 95% confidence intervals of PI did not include -10% (the minimal margin of clinical relevance). CONCLUSIONS: The prototype is more effective in removing plaque from the casts with anomalies. The noninferiority of the prototype with respect to the standard toothbrushes was demonstrated.

Post-marketing active surveillance of Guillain Barré Syndrome following COVID-19 vaccination in persons aged ≥12 years in Italy: A multi-database self-controlled case series study.

BACKGROUND: Recently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy. METHODS: Study population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020-30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods. RESULTS: Increased risk of GBS was found after first (RI = 6.83; 95% CI 2.14-21.85) and second dose (RI = 7.41; 2.35-23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88-14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08-31.03) and second dose (RI = 7.71; 2.38-24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40-59 (RI = 4.50; 1.37-14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56-18.28). CONCLUSIONS: mRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events.

Incidence of Delayed Infections after Lower Third Molar Extraction.

PURPOSE: This retrospective study aimed to verify that the onset of delayed infection after lower third molar extraction was influenced by the amount of distal space. PATIENTS AND METHODS: We evaluated 265 patients (age range 12-55 years), who had one or two mandibular third molars to be extracted. All 380 third molars were removed for orthodontic reasons, periodontal disease, or pericoronitis and were evaluated by the Pell and Gregory classification using the panoramic radiographs. RESULTS: Delayed infection, characterized from purulent exudates from the alveolus and swelling, was reported in 21 extractions between 2 and 8 weeks after surgery. In 16 of the 21 cases of infection, a class III of Pell and Gregory was observed, and this anatomic condition evidenced an extremely reduced space distal to the second molar. CONCLUSION: This study confirmed that the absence of distal space was significantly correlated with delayed infection. These data are important for proper examination of a patient because, in the case of class I or II of Pell and Gregory, a delayed infection was less likely to occur, while a class III of Pell and Gregory could indicate a greater likelihood of this type of infection.

Evans Syndrome Presenting as an Atypical Complication of SARS-CoV-2 Vaccination.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drastically affected our daily lives, causing millions of deaths worldwide. The early and late complications of this infection are being increasingly revealed on a regular basis; however, an important brake on the spread and especially the lethality of the disease has been guaranteed by the introduction of mRNA-based and viral vector-based COVID-19 Vaccines. Also, an increasing number of adverse effects of the vaccination have been reported to specific pharmacovigilance boards, most of them totally non-serious events that are resolved within one to three days after the administration of the vaccine. In this report, we present a case of Evans syndrome (ES) secondary to SARS-CoV-2 vaccination in an 85-year-old male patient. To the best of our knowledge, this is the first case of ES caused by the COVID-19 vaccination to be reported in the literature.

Mandibular third molar removal in young patients: an evaluation of 2 different flap designs.

PURPOSE: To evaluate the influence of 2 different flap designs on periodontal healing and postoperative complications, after inferior third molar removal in young patients. PATIENTS AND METHODS: Twenty-four mandibular third molars were extracted from 12 patients with an average age of 16 years. Patients were included in the study when radiographs at the time of surgery showed that only the crown of the germ was formed. Each patient underwent 2 extractions, using a triangular flap on one side and an envelope flap on the other. Periodontal probing was recorded at the preoperative visit, and 7 days, 3 months, and 6 months after extraction. Postoperative complications were recorded using a questionnaire completed by the patient for the week after the extraction. RESULTS: The examination performed 7 days after the extraction demonstrated a deeper probing depth in all teeth examined. This increase was statistically greater (P < .05) for the first and second molars when an envelope flap was used. After 3 months, the probing depths returned to preoperative values. No significant differences were seen between the 2 flap designs when postoperative complications were considered. The average operating time was 30.66 minutes with the triangular flap, versus 35.66 minutes with the envelope flap. This difference was not significant. After 6 months, the 2 flap designs resulted in no difference in periodontal healing or complications, but 30% of the surgical extractions resulted in a debilitating postoperative period for the patients treated. CONCLUSIONS: Although we observed statistically significant differences in probing depth between triangular and envelope flaps 7 days after the extraction of third molars with no root development, this was not important from a clinical perspective, because periodontal healing at 3 and 6 months was comparable. We believe that this is also the case with the extraction of third molars with fully formed roots. Another important finding was the presence of a debilitating postoperative period in most of the patients who underwent extraction, contrary to the beliefs of many surgeons.

Evaluation of antibiotic prophylaxis in reducing postoperative infection after mandibular third molar extraction in young patients.

PURPOSE: This study evaluated the influence of antibiotic prophylaxis on postoperative complications after inferior third molar removal in young patients. PATIENTS AND METHODS: We extracted 59 mandibular third molars from 59 patients with a mean age of 15 years (range, 12-19 years). The patients were included in the study when radiographs at the time of surgery showed that only the crown of the tooth germ was formed. Patients were randomized into 2 groups, the test group and the control group. The test group received 2-g amoxicillin tablets 1 hour before surgery, and the control group received no antibiotic therapy. The test group included 32 patients, 20 of whom were female and 12 were male; the mean age was 15 years. The control group included 27 patients, 12 of whom were female and 15 were male; the mean age was 15 years. Postoperative complications such as pain, swelling, wound infection, and fever were recorded by use of a questionnaire completed by the patient for the week after the extraction. Suture removal and questionnaire evaluation were performed by a surgeon who did not know the preoperative regimen. RESULTS: The mean operating time was 34 minutes in the control group and 31 minutes in the test group. This difference was not significant. In the test group there was a statistically significant reduction of postoperative pain in the 7 days after the extraction, and the patients had a consistent minor consumption of analgesics. Swelling was always present in the control and test groups in the postoperative week, but in the test group it was a minor sequela and was absent in 2 patients. Wound infection was a sequela reported in 4 patients in the control group and in 1 patient in the test group; this difference was statistically significant (P < .01). Fever was present in 2 patients in the control group and in 1 patient in the test group; this difference was not statistically significant. CONCLUSIONS: A statistically significant difference was found between patients receiving preoperative amoxicillin and the control group in the incidence of postoperative pain, fever, and wound infection. Another important finding was the statistically minor consumption of analgesics in the test group in the postoperative week.

Liposome-incorporated Grb2 antisense oligodeoxynucleotide increases the survival of mice bearing bcr-abl-positive leukemia xenografts.

We previously demonstrated that liposome-incorporated antisense oligodeoxynucleotide specific for the grb2 mRNA (L-Grb2) inhibited Grb2 protein expression and the proliferation of bcr-abl-positive leukemia cell lines. To determine whether L-Grb2 has the potential of being a therapeutic modality against bcr-abl-positive leukemia, we studied the tissue distribution of L-Grb2 in normal mice before studying its effects in mice bearing bcr-abl-positive leukemia xenografts. L-Grb2 was widely distributed in the body. The highest tissue concentrations of L-Grb2 were found in the spleen and liver, which are the organs where the tumor mass of bcr-abl-positive leukemia is mainly found. At 4 h post-injection, the amount of L-Grb2 detected per g of tissue was 64 microg in spleen and 50 microg in liver. Intravenous injection of bcr-abl-positive 32D mouse leukemia cells into radiated NOD/scid mice caused a lethal leukemia syndrome; we determined whether L-Grb2 could prolong the survival of mice bearing such xenografts. One day after leukemia cell inoculation, mice received twice weekly intravenous injections of L-Grb2. At an injection dose of 15 mg of L-Grb2 per kg of mouse body weight, 80% of mice treated with L-Grb2 survived to 48 days (end of study) whereas 0% of mice treated with the same dose of liposomal control oligonucleotide survived; the mean survival duration of these groups was 44 and 20 days, respectively. Our data indicate that L-Grb2 prolonged the survival of mice bearing bcr-abl-positive leukemia xenografts. L-Grb2 may be used as a novel cancer therapeutic modality.

Kawasaki disease and immunisation: A systematic review.

BACKGROUND: Kawasaki disease is a complex and potentially serious condition. It has been observed in temporal relation to immunisation. METHODS: We conducted a systematic literature review using various reference sources to review the available evidence published in the literature. RESULTS: We identified twenty seven publications reporting a temporal association between immunisation and Kawasaki disease. We present a systematic review of data drawn from randomised controlled trials, observational studies, case series and reports, and reviews. Overall there was a lack of standardised case definitions, making data interpretation and comparability challenging. CONCLUSIONS: Although a temporal relationship between immunisation and Kawasaki disease is suggested, evidence for an increased risk or a causal association is lacking. Implementation of a standardised Kawasaki disease case definition would increase confidence in the findings and add value to future studies of pre- or post-licensure vaccine safety studies.

Bcr-Abl-mediated suppression of normal hematopoiesis in leukemia.

A variety of experimental evidence including findings in various mouse models indicates that the BCR-ABL oncogene is the cause of chronic myeloid leukemia (CML). Since normal hematopoietic cells in marrow and spleen are replaced with proliferating leukemic blasts, we determined whether this is an active process mediated by the leukemia cells. The lipocalin 24p3 was reported to be secreted by mouse hematopoietic cells deprived of IL-3, resulting in apoptosis induction in a variety of hematopoietic cells including bone marrow cells. Here, we show that BCR-ABL+ mouse hematopoietic cells induced persistent expression and secretion of 24p3. Importantly, BCR-ABL+ hematopoietic cells were resistant to the apoptotic effects of 24p3. The expression of the Bcr-Abl oncoprotein and its tyrosine kinase were required for induction of 24p3 expression. Co-culture studies showed that BCR-ABL+ cells induced apoptosis in BCR-ABL negative cells. Antisense 24p3/siRNA expression reduced the level of 24p3 protein in both BCR-ABL+ cells and in conditioned medium (CM) obtained from these cells. CM from BCR-ABL+ cells expressing antisense 24p3/siRNA had reduced apoptotic activity for target cells; 24p3 antibody also reduced the apoptotic activity of the CM. Leukemic mice induced by BCR-ABL+ cells expressing either antisense 24p3 or 24p3 siRNA had increased levels of normal hematopoiesis and reduced invasion of leukemia cells in marrow and spleen tissues. These findings indicate that suppression of normal hematopoiesis in BCR-ABL-induced leukemia is an active process involving secretion of the cell death-inducing factor 24p3 by mouse leukemia cells, raising the possibility that similar factors are involved in BCR-ABL+ CML.

The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces caspase-dependent and -independent apoptosis in acute myelogenous leukemia.

In acute myeloid leukemia (AML), resistance to chemotherapy is associated with defects in both the extrinsic and intrinsic pathways of apoptosis. Novel agents that activate endogenous apoptosis-inducing mechanisms directly may be potentially useful to overcome chemoresistance in AML. We examined the mechanisms of apoptosis induction by the novel synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) in AML cells. CDDO-induced apoptosis was associated with the loss of mitochondrial inner transmembrane potential, caspases activation, the translocation of apoptosis-inducing factor to the nucleus, and DNA fragmentation in AML cells. Apoptosis was equally evident in cells deficient in caspase-9 or caspase-8 after exposure to CDDO, suggesting caspase-independent cell death. The use of small interfering RNA to reduce the expression of apoptosis-inducing factor partially inhibited CDDO-induced apoptosis in AML cells. Cells overexpressing Bcl-2 were markedly resistant to CDDO-induced apoptosis. Moreover, CDDO promoted the release of cytochrome c from isolated mitochondria, suggesting that CDDO targets the mitochondria directly to trigger the intrinsic pathway of cell death in intact cells. Together, these results suggest that CDDO functions by activating the intrinsic pathway of apoptosis and initiates caspase-dependent and independent cell death. The direct modulation of mitochondrial-mediated, caspase-independent apoptosis by CDDO may be advantageous for overcoming chemoresistance in AML.

Spontaneous reports of vasculitis as an adverse event following immunization: A descriptive analysis across three international databases.

BACKGROUND: Vasculitides have been reported as adverse events following immunization (AEFI) following various vaccines. We describe reports of vasculitis to three international spontaneous reporting systems. METHODS: All spontaneous reports of vasculitis following immunization between January 2003 and June 2014 were retrieved from Eudravigilance (EV), the Vaccine Adverse Event Reporting System (VAERS), and VigiBase®. A Standard MedDRA Query (SMQ) for vasculitis was used and vaccine types were categorized using the Anatomical Therapeutic Chemical classification system. We performed a descriptive analysis by source, sex, age, country, time to onset, vaccine, and type of vasculitis. RESULTS: We retrieved 1797 reports of vasculitis in EV, 1171 in VAERS, and 2606 in VigiBase®. Vasculitis was predominantly reported in children aged 1-17 years, and less frequently in the elderly (>65 years). The generic term "vasculitis" was the most frequently reported AEFI in this category across the three databases (range 21.9% to 27.5% of all reported vasculitis for vaccines). For the more specific terms, Henoch-Schoenlein Purpura (HSP) was most frequently reported, (19.1% on average), followed by Kawasaki disease (KD) (16.1% on average) and polymyalgia rheumatica (PMR) (9.2% on average). Less frequently reported subtypes were cutaneous vasculitis (CuV), vasculitis of the central nervous system (CNS-V), and Behcet's syndrome (BS). HSP, PMR and CuV were more frequently reported with influenza vaccines: on average in 29.3% for HSP reports, 61.5% for PMR reports and in 39.2% for CuV reports. KD was reported with pneumococcal vaccines in 32.0% of KD reports and with rotavirus vaccines in more than 20% of KD reports. BS was most frequently reported after hepatitis and HPV vaccines and CNS-V after HPV vaccines. CONCLUSION: Similar reporting patterns of vasculitides were observed in different databases. Implementation of standardized case definitions for specific vasculitides could improve overall data quality and comparability of reports.

Coronectomy of mandibular third molars: A clinical protocol to avoid inferior alveolar nerve injury.

Coronectomy is a surgical procedure for the treatment of mandibular third molars in close proximity to the mandibular canal. Unfortunately, often the surgical protocol is not described step by step and it is difficult for the clinician to assess the key factors that are important for the success of this procedure. The aim of this paper is to propose and describe a standardized surgical protocol to improve the success of the technique. The treatment approach, for the most common types of third molars impaction is analysed. Each step of the surgical procedure is described in details and a new type of crown section is proposed. The presented protocol is proposed in order to define a clinical practitioner's guide that could help the surgeon who approaches coronectomy for the first times.