Osteonecrosis of the jaw after long-term oral bisphosphonates, followed by short-term denosumab treatment for osteoporosis: a case report

Bisphosphonates and denosumab are antiresoptive agents and are mainly used for management of metastatic bone cancer, osteoporosis and other diseases. Bisphosphonates (BP) can reduce skeletal related events (SRE) by 30–50%1; denosumab (D) has been found even more effective than BP2. BP and D have been both associated to osteonecrosis of the jaw (ONJ). We report a case of an osteoporotic woman (62 yrs), complaining maxillary intense pain after a recent tooth molar extraction, observed in July 2013 at our centre. She mentioned previous treatments with monthly ibandronate (Bonviva ® 150 mg) per os (from January 2003 to April 2010), risedronate (35 mg weekly, from May 2010 to May 2012) and two administrations (in August 2012 and in January 2013) of denosumab (Prolia ®, 60 mg sc every 6 months). Of note, she also reported a previous incisor extraction that was performed in July 2012 (before denosumab) without ONJ onset. No further systemic or local risk factors were referred. Intraorally, bone exposure of right emimaxilla was present; osteolysis area was observed in in CT scans. According to Bedogni et al.3, the ONJ case was classified as stage II B. Medical therapy (ampicillin/sulbactam im 2 times/die, metronidazole per os 3 times/die, chlorhexidine 0.2% mouth rinses) was administered. One week later, the patient was asymptomatic but within the same stage (IIA); she was referred to Oral and Maxillofacial surgery for surgical management

On the notion of conditional symmetry of differential equations

Symmetry properties of PDE's are considered within a systematic and unifying scheme: particular attention is devoted to the notion of conditional symmetry, leading to the distinction and a precise characterization of the notions of ``true'' and ``weak'' conditional symmetry. Their relationship with exact and partial symmetries is also discussed. An extensive use of ``symmetry-adapted'' variables is made; several clarifying examples, including the case of Boussinesq equation, are also provided.Comment: 18 page

Identification of a variant hotspot in MYBPC3 and of a novel CSRP3 autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy

INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, compound heterozygosity, or double heterozygosity has also been described. Most of the HCM pathogenic variants are missense and unique, but truncating mutations of the MYBPC3 gene have been reported as founder pathogenic variants in populations from Finland, France, Japan, Iceland, Italy, and the Netherlands. OBJECTIVES This study aimed to assess the genetic background of HCM in a cohort of Polish patients. PATIENTS AND METHODS Twenty–nine Polish patients were analyzed by a next–generation sequencing panel including 404 cardiovascular genes. RESULTS Pathogenic variants were found in 41% of the patients, with ultra–rare MYBPC3 c.2541C>G (p.Tyr847Ter) mutation standing for a variant hotspot and correlating with a lower age at HCM diagnosis. Among the nonsarcomeric genes, the CSRP3 mutation was found in a single case carrying the novel c.364C>T (p.Arg122Ter) variant in homozygosity. With this finding, the total number of known HCM cases with human CSRP3 knockout cases has reached 3

MicroRNA-21 Expression as a Prognostic Biomarker in Oral Cancer: Systematic Review and Meta-Analysis

Oral carcinoma represents one of the main carcinomas of the head and neck region, with a 5-year survival rate of less than 50%. Smoking and tobacco use are recognized risk factors. Prognostic survival biomarkers can be a valid tool for assessing a patient’s life expectancy and directing therapy towards specific targets. Among the biomarkers, the alteration of miR-21 expression in tumor tissues is increasingly reported as a valid prognostic biomarker of survival for oral cancer. The purpose of this meta-analysis was, therefore, to investigate and summarize the results in the literature concerning the potential prognostic expression of tissue miR-21 in patients with OSCC. Methods: The systematic review was conducted following the PRISMA guidelines using electronic databases, such as PubMed, Scopus, and the Cochrane Central Register of Controlled Trials, with the use of combinations of keywords, such as miR-21 AND oral cancer, microRNA AND oral cancer, and miR-21. The meta-analysis was performed using the RevMan 5.41 software. Results: At the end of the article-selection process, 10 studies were included in the meta-analysis, and the result for the main outcome was a pooled HR per overall survival (OS) of 1.29 (1.16–1.44) between high and low expression of miR-21. Conclusions: The data in the literature and the results emerging from the systematic review indicate that miR-21 can provide a prognostic indication in oral cancer

The Prognostic Role of miR-31 in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis with Trial Sequential Analysis

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with high recurrence, metastasis, and poor treatment outcome. Prognostic survival biomarkers can be a valid tool for assessing a patient’s life expectancy and directing therapy toward specific targets. Recent studies have reported microRNA (miR) might play a critical role in regulating different types of cancer. The main miR used as a diagnostic and prognostic biomarker and reported in the scientific literature for HNSCC is miR-21. Other miRs have been investigated to a lesser extent (miR-99a, miR-99b, miR-100, miR-143, miR-155, miR-7, miR-424, miR-183), but among these, the one that has attracted major interest is the miR-31. Methods: The systematic review was conducted following the PRISMA guidelines using electronic databases, such as PubMed, Scopus, and the Cochrane Central Register of Controlled Trials, with the use of combinations of keywords, such as miR-31 AND HNSCC, microRNA AND HNSCC, and miR-31. The meta-analysis was performed using the RevMan 5.41 software (Cochrane Collaboration, Copenhagen, Denmark). Results: This search produced 721 records, which, after the elimination of duplicates and the application of the inclusion and exclusion criteria, led to 4 articles. The meta-analysis was conducted by applying fixed-effects models, given the low rate of heterogeneity (I2 = 40%). The results of the meta-analysis report an aggregate hazard ratio (HR) for the overall survival (OS), between the highest and lowest miR-31 expression, of 1.59, with the relative intervals of confidence (1.22 2.07). Heterogeneity was evaluated through Chi2 = 5.04 df = 3 (p = 0.17) and the Higgins index I2 = 40; testing for the overall effect was Z = 3.44 (p = 0.00006). The forest plot shows us a worsening HR value of OS, in relation to the elevated expression of miR-31. Conclusions: In conclusion, the data resulting from the current meta-analysis suggest that miR-31 is associated with the prognosis of patients with HNSCC and that elevated miR-31 expression could predict a poor prognosis in patients with this type of neoplasm