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M Sanna

Publications and source records attributed to M Sanna.

At least 19 recordsLinked to original sources
PubMed2025

Identification and Validation of Novel Combinatorial Genetic Risk Factors for Endometriosis across Multiple UK and US Patient Cohorts.

BACKGROUND: Endometriosis affects about 10% of women usually of reproductive age. It often has severe negative impacts on patients' quality of life, but the average time to a definitive diagnosis remains 7-9 years, and there are few effective therapeutic options. Relatively little is known about the genetic drivers of the disease even though its heritability is fairly high. A recent large genome wide association study (GWAS) meta-analysis identified 42 genomic loci associated with risk of endometriosis, but together these explain only 5% of disease variance. METHODS: We used the PrecisionLife&#xae; combinatorial analytics platform to identify multi-SNP disease signatures significantly associated with endometriosis in a white European UK Biobank (UKB) cohort. We assessed the reproducibility of these multi-SNP disease signatures as well as 35 of the 42 meta-GWAS SNPs in a multi-ancestry American endometriosis cohort from All of Us (AoU) after controlling for population structure. RESULTS: We identified 1,709 disease signatures, comprising 2,957 unique SNPs in combinations of 2-5 SNPs, that were associated with increased prevalence of endometriosis in UKB. Pathways enriched in the disease signatures included cell adhesion, proliferation and migration, cytoskeleton remodeling, angiogenesis as well as biological processes involved in fibrosis and neuropathic pain.We observed a significant enrichment of these signatures (58-88%, p<0.04) that are also positively associated with endometriosis in the AoU cohort, including one 2-SNP signature that is individually significant. Reproducibility rates were greatest for higher frequency signatures, ranging from 80-88% for signatures with greater than 9% frequency (p<0.01) in AoU. Encouragingly, the disease signatures also show high reproducibility rates in non-white European AoU sub-cohorts (66-76%, p<0.04 for signatures with greater than 4% frequency).A total of 195 unique SNPs mapping to 98 genes were identified in the high frequency reproducing signatures (>9%). Of these, 7 genes were previously identified in the endometriosis meta-GWAS study and 16 genes have a previous association with endometriosis. 75 novel genes were identified in this study.We characterized 9 novel genes that occur at the highest frequency in reproducing signatures and that do not contain any SNPs linked to known GWAS genes, providing new evidence for links between endometriosis and autophagy and macrophage biology. Reproducibility rates, ranging between 73% to 85%. are especially strong for the signatures that contain these 9 genes independently of any SNPs mapping to the meta-GWAS genes. CONCLUSION: Although using much smaller, less well-characterized datasets than the previous whole genome meta-GWAS study, combinatorial analysis has provided important new insights into the genetics and biology of endometriosis including reproducible biologically relevant genes that are overlooked by GWAS approaches.The 75 novel gene associations provide new insights and routes for study of the disease and potential new therapies. Several of the novel genes identified are credible targets for drug discovery, repurposing and/or repositioning. Using the disease signatures identified as genetic biomarkers in trials of candidates drugs targeting specific mechanisms will enable precision medicine-based approaches. We hope this will encourage new targeted therapy discovery efforts.

Endometriosis↗
PubMed1992

Surgery of the 'only hearing ear' with chronic ear disease.

The management of chronic ear disease affecting the only hearing ear is a controversial subject. The relative scarcity of literature on the subject prompted us to prepare a questionnaire which was sent to European and American otologists and to review 19 cases operated at the ENT Clinic of the University of Parma, Italy, and 16 cases operated at The Baptist Memorial Hospital, Memphis, U.S.A. Surgery of cholesteatoma involving the only hearing ear is advised by all the interviewed otologists without exception, even in the presence of a labyrinthine fistula. The cases from the University of Parma were managed as follows: a classic modified radical mastoidectomy was performed in 10 cases, a staged intact canal wall tympanoplasty was done in four cases, an open tympanoplasty in three and a radical mastoidectomy in the remaining two cases. The cases from The Baptist Memorial Hospital were managed with an intact canal wall tympanoplasty (ICWT) in nine and with an open procedure in seven cases. All the otologists interviewed agreed that surgery of the only hearing ear requires particular attention and experience, and should be performed with extreme care by a very experienced surgeon.

Attitude of Health Personnel↗
PubMed1992

[Role of penile ultrasonography in erection deficit].

The presence of penile nodule, curvature, disorders in blood flow to and from the corpora cavernosa is often correlated with organic sexual impotence. Echography allows to obtain a clear imaging of penile structures: diameters of corpora cavernosa can be measured before and after injection of vasoactive drugs. In our study penile structure were evaluated using a Combison 310 and a Toshiba with 7.5 MHz probe. In a lot of cases echography was repeated after intracavernous injection of PGE 1 or papaverine. The equipment needed for this evaluation is expensive but echography is undoubtedly less invasive than other equivalent examinations like cavernosography. Although the sensitivity and specificity of penile echography have not yet been clearly established this test is generally considered to be an useful and objective one. Penile echography is particularly usefull in discriminating between echogenic and not-echogenic nodules in case of Peyronie disease.

Adult↗
PubMed1990

Primary intratemporal tumours of the facial nerve: diagnosis and treatment.

Benign primary tumours of the facial nerve are uncommon. A slowly progressive facial palsy should be considered the result of a nerve tumour until proven otherwise. Improvements in diagnostic imaging techniques of the temporal bone have increased the possibility of a correct pre-operative diagnosis but facial nerve tumours remain a frequently ignored or misdiagnosed entity as a consequence of their subtle and protean clinical manifestations. A series of 12 cases of primary facial nerve tumours is presented. The clinical features, diagnostic modalities and treatment are discussed in relation to a review of the literature.

Adult↗
PubMed1990

Inner ear cholesteatoma and the preservation of cochlear function.

Labyrinthine destruction by direct cholesteatoma invasion has always been considered a serious threat to the inner ear function. A number of reports in the literature have cited both patients who had preservation of hearing despite widespread erosion of the labyrinth by cholesteatoma and patients who had retained auditory function despite surgical removal of the matrix from the labyrinth. In most cases the vestibular portion of the inner ear was invaded but cases of cochlear involvement have been described as well. Twelve cases with pre-operative auditory function preservation despite extensive labyrinthine destruction treated at our Institution are reported. Seven cases retained cochlear function post-operatively. Possible explanations of this occurrence and implications of related with hearing preservation in the presence of widespread inner ear destruction by chronic inflammatory disease are discussed.

Adult↗
PubMed1988

Retrolabyrinthine versus middle fossa vestibular neurectomy.

The authors' experience in treating incapacitating peripheral vertigo using the middle cranial fossa (MCF) and the retrolabyrinthine (RL) approaches is presented. Among 94 operated cases, 56 have been treated using the MCF approach and 38 the RL approach. In 18 of the RL cases, a simple vestibular neurectomy has been associated with different adjunctive techniques (i.e., drainage of the endolymphatic sac, section of the Wrisberg intermediary nerve, and neurovascular decompression of the eight nerve) in an attempt to influence the disease from a pathogenetic viewpoint. The RL approach has demonstrated to be a valid alternative to the MCF approach, since it allows the same results to be obtained in the control of vertigo, with fewer risks to the facial nerve and hearing functions. Moreover, it allows the association, although still in an experimental way, of the simple vestibular neurectomy and the other "pathogenetic" methods mentioned above.

Adult↗
PubMed1988

Closed versus open technique in the management of labyrinthine fistulae.

A labyrinthine fistula is the most common complication of cholesteatomatous chronic ear disease. Its treatment remains a controversial subject. The present paper reports our approach to the management of this complication. Operations were performed on 1,226 cases of chronic otitis media with cholesteatoma between January 1971 and December 1985. A labyrinthine fistula was detected in 158 cases. We favor intact canal wall tympanoplasty even in the presence of medium or large fistulas: in the latter case, the matrix is not removed but is trimmed to cover only the bony defect and it is left in place. Open procedures with the preservation of the matrix over the fistula are done in an only-hearing ear with fistula, in ears with a wide defect of the posterior canal wall, and in ears with multiple labyrinthine fistulas. The management of the matrix over the fistula and the anatomic and functional results following each type of procedure are presented and discussed.

Cholesteatoma↗
PubMed1987

The surgical management of childhood cholesteatoma.

The results of treatment of 124 cases of childhood cholesteatoma are reported in the present study and compared with an adult group of patients. Intact canal wall tympanoplasty was performed in over 90 per cent of cases in children and the procedure was staged in nearly 80 per cent of cases. The children had a 43.8 per cent incidence of residual cholesteatoma and an 8.8 per cent incidence of recurrent cholesteatoma in intact canal wall tympanoplasty cases. Intact canal wall tympanoplasty remains the technique of choice in our hands for the treatment of childhood cholesteatoma; pre-planned staging of the operation is mandatory for the detection and elimination of residual cholesteatoma which occurs more frequently in children.

Adolescent↗
PubMed1987

[Various aspects and problems in surgery of the parotid gland: experience in 70 cases].

The pathology and the relative surgical treatment, performed in all the swellings of the parotid gland observed in our clinic, are reported. Particularly the most important topics and problematics, both of short and long term, connected to the surgical therapy carried out, are described. Finally the actual diagnostic aspects and the necessity of an accurate preoperatory staging are discussed.

Female↗
PubMed1987

Hearing preservation in acoustic neuroma surgery. Middle fossa versus suboccipital approach.

Over the past few years there have been reports discussing the preservation of hearing after the removal of acoustic neuromas through the middle cranial fossa or the suboccipital approaches. This is a complex issue with many facets and controversies. In an attempt to answer at least some of these controversies, this article reviews the experience of our group. Preservation of hearing was attempted in thirty-four cases out of 220 acoustic neuromas. In twenty cases the middle fossa approach was used: All tumors were less than 2 cm from the fundus, and in four patients the tumor was bilateral. In sixteen of the twenty (80%) the cochlear nerve was spared; in ten of twenty (50%) measurable hearing was retained, but in only four (20%) was the postoperative hearing serviceable according to the 50/50 rule. In fourteen cases the suboccipital approach was used: All but two of the tumors were smaller than 2 cm. In three patients the tumor was bilateral. The cochlear nerve was preserved in ten of the fourteen cases (71.4%). Measurable hearing was present in four of fourteen cases postoperatively (28.6%); none had serviceable hearing according to the 50/50 rule. Hearing was not preserved in any bilateral tumor case. The middle fossa and the suboccipital approaches are discussed as well as the relative merits of each procedure in preservation of hearing.

Adult↗
PubMed1986

Regenerated middle ear mucosa after tympanoplasty. Part I. Transmission electron microscopy.

The ultrastructural appearance of the regenerated middle ear mucosa--found at the second operation of staged intact canal wall tympanoplasty (ICWT) with mastoidectomy--has been evaluated with the transmission electron microscope. The regenerated epithelium showed all the morphologic characteristics of the normal middle ear mucosa: ciliated cells, nonciliated cells, and secretory cells. All of these (including goblet cells) have been found in the specimens. It is concluded that a normal middle ear mucosa regenerates to cover all denuded bone surfaces after the first operation of staged ICWT with mastoidectomy, when silicone rubber sheeting has been used to prevent adhesions and maintain an air-containing middle ear space.

Biopsy↗
PubMed1986

Regenerated middle ear mucosa after tympanoplasty. Part II. Scanning electron microscopy.

The ultrastructural appearance of the regenerated middle ear epithelium, found at the second operation of staged ICWT with mastoidectomy, has been investigated herein with the scanning electron microscope. The regenerated epithelium consists of flat nonciliated cells, "elevated" nonciliated cells with microvilli, and ciliated cells. Secretory material is present on the surface of the "elevated" nonciliated cells surrounding the ciliated ones. Regeneration of the mucosa occurs following precise topographic differences that mimic the distribution of epithelial cells in the normal middle ear. It is confirmed that a morphologically normal middle ear epithelium regenerates to cover all denuded bone surfaces within 12 months--after first stage ICWT with mastoidectomy--when silicone rubber sheeting has been used to maintain an aerated middle ear and mastoid space.

Cilia↗