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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↗
PubMed2004

Canalplasty for severe external auditory meatus exostoses.

Exostoses of the external auditory meatus is a well known condition which infrequently requires surgical correction. However, the stenosis caused by severe exostosis can affect quality of life considerably and may require surgical intervention. Canalplasty, in such a situation, is a valid and effective management option. In our series the commonest indication for surgery was recurrent otitis externa. The detailed surgical technique is described and a retrospective analysis of 65 such procedures is presented. There were only two significant complications, both post-operative stenosis, requiring further corrective surgery. In conclusion, canalplasty for the exostosis of the external auditory meatus is a safe surgical option.

Adolescent↗
PubMed2003

Glomus tympanicum tumour: an alternative surgical technique.

Glomus tympanicum tumour is one of the commonest neoplasms of the middle ear. It is more common in females. The most common presenting symptom is pulsatile tinnitus. A retrotympanic mass is found in the middle ear in all the cases. Computed tomography (CT) scan is the investigation of choice, however in difficult cases magnetic resonance imaging (MRI) can be helpful. Surgery is regarded as the gold standard of treatment in spite of the fact that radiation therapy has also been advocated in the literature. In this series 17 cases of glomus tympanicum treated at Gruppo Otologico Piacenza - Rome (Italy) were analysed retrospectively. A simple and safe technique has been described. All the cases were female and treated by surgery. The tumour was removed completely in all the cases and the ossicular chain kept intact. Recurrence was encountered in only one case after nine years. Surgical removal of the tumour is recommended as the treatment of choice with the following advantages: complete removal, a low complication rate, a low recurrence rate, acceptable hearing level and minimum morbidity.

Adult↗
PubMed2003

Technique to prevent post-operative CSF leak in the translabyrinthine excision of vestibular schwannoma.

Cerebrospinal fluid (CSF) leak following VS removal is a challenging complication. With experience, it can be seen that anatomical factors such as the extent of pneumatization of the petrous temporal bone and posterior wall of the internal auditory canal play an important role in contributing to CSF leak. Nevertheless, the risk of post-operative CSF leak remains a major concern for both the surgeon and patient. This paper describes a technique, which we have used since 1994, and which has helped us to achieve the lowest reported rate of post-operative CSF leak in translabyrinthine excision of vestibular schwannoma in the world literature.

Cerebrospinal Fluid Otorrhea↗
PubMed2002

[Preoperative imaging in chronic otitis surgery].

High resolution computed tomography (CT) is presently the most accurate technique to study the temporal bone. Nevertheless, there is no general agreement about its usefulness in pre-operative evaluation of chronic otitis media. Indeed, if we rule out some exceptions, CT is not fundamental for diagnosis which can often be obtained through an accurate otomicroscopy. The Otology Group in Piacenza applies the following absolute indications for pre-operative CT in chronic otitis media: 1) difficult otomicroscopy evaluation; 2) suspected petrous bone cholesteatoma; 3) dubious diagnosis; 4) suspect of malformations; 5) review of cases that had previously undergone mastoidectomy; 6) suspected intracranial complications and/or meningoencephalic herniation (in this case also a magnetic resonance imaging must be performed). With the exception of these specific conditions, pre-operative CT is useless in cases of simple chronic otitis. However, when a cholesteatoma is suspected, CT can provide the surgeon, particularly when inexperienced, useful, but not indispensable, informations. Pre-operative knowledge of these informations can allow a more accurate evaluation of the case, with a better planning of the surgical procedure, in order to ensure a more specific informed consent. Finally, the Authors point out the fact that surgeon must be able to interpret by his own the CT data to have a real advantage by this examination.

Ear↗
PubMed2001

Meningiomas intrinsic to the geniculate ganglion.

Geniculate ganglion meningiomas are extremely rare lesions-only 14 cases have been reported in the literature. Two new cases of these tumors are described. On computed tomography and magnetic resonance imaging, both lesions appeared centered on the area of the geniculate ganglion, extending to the tympanic cleft and eroding the middle cranial fossa floor. The first case was treated through a middle cranial fossa approach. Because the tumor was so large in the second case, a subtotal petrosectomy was used. The authors review the literature to clarify the clinical and radiological characteristics of these tumors and their surgical treatment.

Case Reports↗
PubMed2001

Identification of internal acoustic canal in the middle cranial fossa approach: a safe technique.

BACKGROUND: The middle cranial fossa approach (MCFA) is a very valuable functional approach in the armamentarium of the neuro-otologic surgeon. Identification of the internal acoustic canal (IAC) in MCFA is one of the most tedious steps. Many techniques have been described to locate the IAC safely when using the MCFA. OBJECTIVE: We sought to describe a safe technique for identification of the IAC and to demonstrate its feasibility in temporal bone dissections, as well as to discuss our clinical experience with this technique. METHODS: The surgical anatomy of the 20 temporal bones were evaluated and measured, especially by defining the medial and lateral ends of the IAC and relations to the nearby located structures. Measurements were obtained at 3 levels: the width of the IAC at the level of the fundus, the width of the IAC at the level of the porus, and the safe distance around the IAC at the meatal level. The medial and lateral IAC end widths were compared with each other and with the safe area at the meatal level. RESULTS: The smallest, the largest, and the mean values were recorded. The mean width of the IAC at the level of the porus was found to be more than 3-fold that of the width of the IAC at the level of the Bill's bar, and the ratio between the width of the medial safe area around the IAC and the lateral end of the IAC was found to be more than 7-fold as wide. CONCLUSION: This technique offers direct quick exposure of the IAC, without handling the facial nerve and the inner ear structures. Forty-five cases of operations with the same technique showed excellent ease and safety of identifying the IAC medially in the MCFA.

Craniotomy↗
PubMed2001

Electromyographic evaluation of facial nerve damage in acoustic neuroma surgery.

OBJECTIVE: This study aimed to determine whether postoperative facial nerve paralysis or surgical manipulation causing paralysis could be predicted on train responses during intraoperative facial nerve monitoring in acoustic neuroma surgery. STUDY DESIGN AND SETTING: This was a prospective study performed at a tertiary referral center. PATIENTS AND METHODS: Train responses were recorded on a floppy disk and compared with postoperative facial nerve function in 51 patients who underwent enlarged translabyrinthine acoustic neuroma surgery. MAIN OUTCOME MEASURES: The number, duration, frequency, and peak-to-peak amplitude of train responses were analyzed and compared with postoperative facial nerve function. RESULTS: Trains were observed in 42 of 51 patients. Six of seven patients with high-amplitude trains more than 250 microV, and three of five patients with bomber-type high-frequency trains elicited during tumor dissection from the facial nerve or stretching the nerve, showed severe facial nerve dysfunction. On the other hand, seven of the nine patients with no trains also showed severe facial nerve dysfunction. CONCLUSIONS: The presence of high-amplitude or high-frequency trains elicited by surgical manipulation to the facial nerve seems to indicate a critical situation for the facial nerve. However, certain types of mechanical trauma resulting in severe facial nerve paralysis cannot be identified by train responses.

Adult↗
PubMed2001

[Enlarged translabyrinthine approach in large acoustic neurinomas].

The translabyrinthine approach has long been, and in some centers is still, considered inadequate for the removal of large acoustic neuromas (AN). Over the years, with experience, the original technique has been modified, extending the approach to what is now called the enlarged translabyrinthine (ET) approach. Applying these modifications, between April 1987 and February 2000, the Gruppo Otologico in Piacenza, Italy removed 132 ANs, 3 cm or larger, from the cerebello-pontine angle. These tumors accounted for 25.9% of the 510 cases of AN to undergo surgery during that period. Of the 132 cases only one patient died and the percentage of complications was very low, generally lower than analogous series published in the literature. Such complications were progressively reduced in time, leading to a significant reduction in the length of post-operative hospitalization: on the average the 8.8 days were reduced to 5.7 in the last 43 cases. Ipsilateral preoperative hearing, inevitably sacrificed using the ET approach, was already significantly compromised in more than 65% of the cases. On the basis of the present data, it can be asserted that tumor diameter does not in any way preclude the use of the ET approach in AN surgery, rather the reduced morbility and shorter post-operative hospitalization make it the approach of choice for large ANs.

Adult↗
PubMed2000

Fast-growing vestibular schwannoma.

A case of a Jehovah's witness affected by an intracanalicular vestibular schwannoma with an extremely fast growth rate is presented. Nine months after presentation, the tumor reached 23 mm in the cerebellopontine angle. A partial removal through a retrosigmoid approach was planned. Because of the presence of a dominant high jugular bulb masquering the internal auditory canal, the intracanalicular portion of the tumor was left in place. The residual tumor grew 12 mm in 2 months. Even after a gross total removal through a middle cranial fossa approach, the tumor recurred, reaching the size of 30 mm in 17 months. A modified transcochlear approach was then performed, and the patient was free of disease at the last radiologic follow-up, 8 months after the surgery. We illustrate our strategy in treating this aggressive benign lesion with unusual behavior.

Case Reports↗
PubMed2000

[Treatment of residual acoustic neurinomas].

Generally the main objective of acoustic neurinoma (AN) surgery is to totally remove the tumor associated with minimum morbidity. Nevertheless, in some cases residual tumor fragments are intentionally or accidentally left in place. These residues can lead to new growth. The present study provides a retrospective analysis of 14 cases of residual AN have undergone surgery at the Otology Group in Piacenza from 1987 to 1999. All these patients had previously undergone at least one retrosigmoidal exeresis although only one had been performed at the Otology Group. All patients except 1 were affected by anacusia at the time of surgery. The list of post-operative deficits included 2 hemipareses, 3 irreversible facial paralysis with consequent corneal opacity in 2 cases, 1 dysmetria and 1 paralysis of the abducent nerve. The patients had also undergone the following additional treatments: 1 emergency revision to drain a cerebellar hematoma, 3 ventricle-peritoneal derivations, 1 double application of stereotactic radiotherapy and 2 surgical procedures for facial plasty. Ten cases underwent the revision surgery at the Otologic Group using a translabyrinthine approach and 4 using a transcochlear approach. Tumor removal was deemed complete in all cases. The sole post-operative complications were a subcutaneous hematoma at the point where abdominal fat was removed and a temporary paralysis of the abducent nerve. Post-operative hospitalization was an average of 6.9 days. Analysis of the results showed that AN must be operated at selected centers in order to reduce the post-operative neurological deficit and the percentage of residual tumor. It also indicated that the retrosigmoid approach has a higher risk of accidentally leaving tumor residues than the other approaches. Finally, in the presence of a residual AN, the translabyrinthine approach offers the greatest advantages.

Adult↗
PubMed1999

Subtemporal exposure of the intrapetrous internal carotid artery. An anatomical study with surgical application.

This work describes the exposure of the intrapetrous internal carotid artery (ICA) through the subtemporal approach. The anatomical details of 25 fresh temporal bones were studied and provided the initial background for this procedure. Bone drilling in the meatal plane anterior to the internal auditory canal could create a four-sided quadrangular area. The exposure of the ICA through this area was applied on three occasions. It proved safe as regards the surrounding structures and also provided an ample working space for the extirpation of tumours surrounding the artery.

Adult↗