Identification of recurrent genetic patterns from targeted sequencing panels with advanced data science: a case-study on sporadic and genetic neurodegenerative diseases.

BACKGROUND: Targeted Next Generation Sequencing is a common and powerful approach used in both clinical and research settings. However, at present, a large fraction of the acquired genetic information is not used since pathogenicity cannot be assessed for most variants. Further complicating this scenario is the increasingly frequent description of a poli/oligogenic pattern of inheritance showing the contribution of multiple variants in increasing disease risk. We present an approach in which the entire genetic information provided by target sequencing is transformed into binary data on which we performed statistical, machine learning, and network analyses to extract all valuable information from the entire genetic profile. To test this approach and unbiasedly explore the presence of recurrent genetic patterns, we studied a cohort of 112 patients affected either by genetic Creutzfeldt-Jakob (CJD) disease caused by two mutations in the PRNP gene (p.E200K and p.V210I) with different penetrance or by sporadic Alzheimer disease (sAD). RESULTS: Unsupervised methods can identify functionally relevant sources of variation in the data, like haplogroups and polymorphisms that do not follow Hardy-Weinberg equilibrium, such as the NOTCH3 rs11670823 (c.3837 + 21 T > A). Supervised classifiers can recognize clinical phenotypes with high accuracy based on the mutational profile of patients. In addition, we found a similar alteration of allele frequencies compared the European population in sporadic patients and in V210I-CJD, a poorly penetrant PRNP mutation, and sAD, suggesting shared oligogenic patterns in different types of dementia. Pathway enrichment and protein-protein interaction network revealed different altered pathways between the two PRNP mutations. CONCLUSIONS: We propose this workflow as a possible approach to gain deeper insights into the genetic information derived from target sequencing, to identify recurrent genetic patterns and improve the understanding of complex diseases. This work could also represent a possible starting point of a predictive tool for personalized medicine and advanced diagnostic applications.

Clinical aspect and survival rates in subject with oral cancer: a retrospective cohort study.

AIM: The aim of this study was to describe and evaluate survival in a group of patients with oral malignant neoplasias, observed at the Unit of Oral Pathology and Medicine, University of Milan, between February 1995 and September 2005. METHODS: This retrospective study considered the clinical histories and anamnestic profiles of a group of 108 patients with malignant oral neoplasms. A sample of 72 out of these 108 patients was identified, for whom follow-up data were available for at least 4 months from the date of diagnosis. Survival times for this group were then evaluated. RESULTS: In this group of 108 patients, 103 were affected by squamous cell carcinoma. The ratio of male to female patients was 1.1:1.0 and the average age at the time of diagnosis was 64.9 years. In 44 out of 91 cases, the site affected was the tongue and in 28 out of 45 cases, the lesion was at an early stage (TNM 1 and 2) at the time of diagnosis. Survival in the group of 72 considered was 84% at 2 years from diagnosis and 55% at 5 years. Diagnosis before the age of 65 favoured a positive prognosis (P=0.01), as did lesions diagnosed at TNM 1 stage, though this was not statistically significant (P=0.1). CONCLUSION: The data provided in this retrospective study were consistent with previous reports of survival rates at 5 years from diagnosis and the improved prognosis for patients diagnosed before the age of 65. The only finding that was different from previous studies was the gender distribution, which in this study was almost equal.

Miconazole as adjuvant therapy for oral lichen planus: a double-blind randomized controlled trial.

BACKGROUND: Topical steroids are the first choice for the treatment of oral lichen planus (OLP). Antifungal drugs are often employed together with them, to prevent secondary oral candidosis, although it has been suggested anecdotally that they can also be beneficial for OLP itself. OBJECTIVES: To compare the effect of clobetasol propionate with and without a topical antifungal drug (miconazole) on the symptoms and extension of OLP. METHODS: A randomized, parallel, double-blind trial was conducted at the Unit of Oral Medicine and Pathology of the University of Milan. Thirty-five outpatients with histologically proven OLP were randomly assigned to receive either clobetasol propionate and miconazole, or clobetasol propionate and placebo for 6 weeks. Primary outcomes included symptoms and extension of lesions; adverse effects were also recorded. RESULTS: All the patients who concluded the study (30 of 35) showed clinical and subjective improvement within 3 weeks. The addition of miconazole did not affect in a significant way the signs and symptoms of OLP. No cases of clinical candidosis were seen in the patients taking miconazole, while one-third (five of 15) of the placebo group were affected. CONCLUSIONS: Although effective in preventing iatrogenic candidosis, the addition of miconazole to topical steroid treatment does not improve the efficacy of the therapy.

The effect of levosulpiride in burning mouth syndrome.

AIM: This paper evaluated the efficacy of the systemic administration of levosulpiride, an antipsychotic and antidepressant drug, in the management of burning mouth syndrome. METHODS: Forty-four subjects suffering from idiopathic burning mouth syndrome were enrolled in the study. Patients underwent a thorough clinical examination, including salivary flow rate measurements, laboratory tests (complete blood cell counts, blood glucose levels, serum iron and transferrin levels, serum vitamin B(12), and folate levels), patch tests for contact allergy to denture materials, and isolation of Candida species from oral mucosal scrapes. Oral symptoms before and after treatment were assessed using a visual analogue scale. All the patients used systemic levosulpiride (100 mg/daily) for 8 weeks. RESULTS: Of the 39 patients who completed the protocol, none reported complete remission of the oral burning sensation. However, 28 patients reported at least some improvement, and these patients had had oral symptoms for significantly less time than those who reported no improvement. CONCLUSIONS: These preliminary data suggest that levosulpiride is more effective in patients who have recently developed burning/stinging oral sensation.