Biomedical subjects

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® 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↗

PubMed1998

Titration streptomycin therapy in Meniere's disease: long-term results.

As soon as the use of streptomycin was started for the treatment of tuberculosis, its ototoxic effect was discovered. Initial reports demonstrated that streptomycin was successful in reducing vestibular responses while preserving cochlear activity. Streptomycin sulfate has been used for almost half a century for the treatment of vertigo in patients with Meniere's disease. At the Gruppo Otologico, Piacenza, Italy, between 1987 and 1995 we treated 16 patients with either bilateral Meniere's disease or with Meniere's disease in their only hearing ear, adopting the titration streptomycin therapy protocol of Graham et al. Three patients with follow-up periods of less than 2 years were not included in this study. The ages of the patients ranged from 36 to 64 years with a mean of 49.2 years. The patients were observed for 2 to 8.8 years. The dose of administered streptomycin varied from 14 to 49 gm. Episodic vertigo was totally relieved in all of the patients after initial treatment, whereas hearing remained the same or was improved when compared with the pretreatment levels. Five of the patients experienced recurring vertigo during a period of 4 to 24 months after initial treatment. Oscillopsia persisted in two patients and ataxia in darkness persisted in another two patients. Hearing was unchanged in 14 ears, improved in 2 ears, and worsened in 4 ears at the last follow-up evaluation. The overall outcome indicated that intramuscular titration streptomycin therapy seems to be one of the most important therapeutic options in the treatment of disabling vertigo in patients with either bilateral Meniere's disease or Meniere's disease in an only hearing ear.

Adult↗

PubMed1998

The system of the modified transcochlear approach: a lateral avenue to the central skull base.

OBJECTIVE: This study aimed to update the authors' experience with the modified transcochlear approach for the management of lesions of the central skull base. The surgical technique, classification, indications, and results also are presented. STUDY DESIGN: A retrospective review of the charts of 66 consecutive patients treated in our centers by the modified transcochlear approach was conducted. SETTING: The study was performed in two tertiary referral centers. PATIENTS: All patients treated by the modified transcochlear approach were included. Thirty-five patients had extradural lesions, whereas 31 lesions were intradural. INTERVENTION: All patients were treated surgically using the modified transcochlear approach either in its basic form (type A) or with its extensions (types B, C, and D). MAIN OUTCOME MEASURES: The outcome of surgery is evaluated with particular emphasis on the incidence of morbidity, mortality, and the degree of total tumor removal. RESULTS: Total tumor removal was accomplished in 58 cases either in single or staged procedures. A second-stage procedure for total tumor removal is planned in five other patients. Subtotal tumor removal was performed in three patients. Mortality occurred in two cases. Ipsilateral hearing loss and immediate facial nerve palsy constituted the major drawbacks of this approach. However, 67.5% recovered to grade III facial function or better 1 year after surgery. CONCLUSIONS: The modified transcochlear approach provides a relatively safe, wide, and versatile access to large lesions of the central skull base.

Adolescent↗

PubMed1997

Mastoidectomy in noncholesteatomatous chronic suppurative otitis media: is it necessary?

Chronic suppurative otitis media (CSOM) without cholesteatoma, the surgical treatment of which is still controversial, is a common diagnosis in otologic practice. A retrospective analysis of 323 patients who underwent surgery for noncholesteatomatous chronic otitis media in the Gruppo Otologica, Piacenza, Italy, between April 1983 and December 1993 is presented. Cases were separated into three groups according to different surgical treatment modalities and conditions of the ears at the time of operation. Group I (n = 53) consisted of cases of CSOM treated by tympanoplasty without mastoidectomy (TLWOM). Group II (n = 28) included cases of CSOM treated by tympanoplasty with mastoidectomy (TLWM). Intact canal wall technique was used in these cases. The ears in both these groups were discharging severely at the time of surgery. Group III (n = 242) included patients whose ears were dry at the time of surgery but who had had previous recurrent episodes of suppuration and who were treated by TLWOM. At the last follow-up, graft success rates for groups I, II, and III were 90.5%, 85.7%, and 89.2%, respectively, and mean residual gaps were 17.2 dB, 20.1 dB, and 19.4 dB, respectively. There was no statistically significant difference between the three groups either on graft success rates (p > 0.05) or on final functional hearing outcome (p > 0.05). TLWM is the preferable treatment modality for most surgeons in noncholesteatomatous CSOM. Nevertheless, in our experience TLWOM yields comparable results for this group of patients. In addition, we could not find any significant difference in results of graft success and final functional hearing rates between dry and discharging ears (p > 0.05).

Adolescent↗

PubMed1997

Clinical observations on coexistence of sudden hearing loss and vestibular schwannoma.

It has long been recognized that sudden hearing loss (SHL) may be a harbinger of vestibular schwannoma (VS). Among 192 VS patients who underwent operation in the Gruppo Otologico, Piacenza, Italy, from April 1987 to October 1995, the charts of 14 (7.3%) cases with a history of SHL were examined. SHL was the first symptom in 8 (4.2%) patients. Eight (57.1%) of 14 VS cases with SHL anamnesis had reported recovery of their previous hearing either totally or partially before establishment of tumor diagnosis. Five (35.7%) cases had recurrent bouts of SHL. SHL was observed less frequently in cases with large tumors (>3 cm). However, the frequency of SHL in patients with small tumors did not differ from that of medium-sized tumors. Awareness about coexistence of SHL and VS, as well as concomitant use of auditory brain stem response and magnetic resonance imaging, is crucial to rule out the diagnosis of VS in a patient with SHL.

Adult↗

PubMed1997

Anatomical considerations of high jugular bulb in lateral skull base surgery.

In order to study high jugular bulb management in lateral skull base surgery, an anatomical study was conducted on 30 temporal bones by examining the relationship between the internal auditory canal (IAC) and the jugular bulb. The following parameters were measured: 1) Height of the jugular bulb (H)... distance between the level of jugular bulb dome and the line passing through the confluence of the sigmoid sinus with the jugular bulb (SS-JB), 2) Mastoid length (ML)... distance between the mastoid process and middle cranial fossa dura, 3) Distance between the most inferior part of the porus acousticus and jugular bulb dome (A), 4) Distance between the porus acousticus and SS-JB (B). The jugular bulb was defined as high when it occupied more than two thirds of (B). The incidence of a high jugular bulb was 23 per cent in this study. When the jugular bulb was high, the mean (H) and (A) were 9.4 +/- 1.9 mm and 2.7 +/- 0.5 mm, respectively. (H) was higher on the right side than on the left side. No statistically significant difference was found between small and large mastoids (t-test: p > 0.05). It was concluded that when a high jugular bulb was encountered during lateral skull base surgery, the jugular bulb position allows a very small working area inferior to the IAC. In these cases, a 3 or 4 mm depression of the jugular bulb is necessary in order to expose the lower cranial nerves. This can be accomplished by lowering the jugular bulb with the technique already described.

Humans↗

PubMed1997

Lower cranial nerve schwannomas involving the jugular foramen.

Schwannomas involving the jugular foramen are rare lesions, and no consensus exists on their management. This paper reports on 20 such cases treated in our centers. Nineteen cases were operated on for removal of the tumors, and the remaining case is being managed by watchful expectancy. Fifteen cases were operated on by the petro-occipital trans-sigmoid approach with or without labyrinthectomy, 2 by the infratemporal fossa approach, 1 by the modified transcochlear approach, and 1 by the jugulo-petrosectomy approach. The petro-occipital trans-sigmoid approach allowed single-stage, total tumor removal with preservation of the facial nerve and of middle and inner ear functions. Lower cranial nerve paralysis was the major complication and seemed to be inherent to the disease rather than to the approach used. No cerebrospinal fluid leak or meningitis occurred in the present series. So far, no recurrence has been detected.

Adult↗

PubMed1997

Retrolabyrinthine vestibular nerve section: a current appraisal.

We report our experience (1987-1993) with Meniere's disease patients treated with a retrolabyrinthine vestibular neurectomy. The current literature was reviewed and our results have been compared with those of previous reports. The overall success rate for vertigo relief was 96.7%, with no serious or permanent complications resulting from the procedure. The technical elements of the operation, as they apply to our approach and those of others, have been analyzed, with special attention given to the anatomical features of the region and their influence on success or failure. We conclude that the retrolabyrinthine approach for vestibular nerve section remains a safe and highly successful technique which merits continued use.

Adult↗

PubMed1996

Vestibular schwannoma and the only hearing ear.

With the recent advances in the management of vestibular schwannomas, it is possible not only to save the facial nerve function but also preserve hearing in a small percentage of cases. Difficulties arise while managing patients with vestibular schwannoma in their only hearing ear. In this article we summarize our experience in managing seven of these patients. We recommended a watch and wait policy with a regular follow-up with audiometric testing and gadolinium-enhanced magnetic resonance imaging (MRI). Gamma knife radiosurgery is advised in cases with deterioration of hearing or increase in tumour size. Surgery is usually avoided unless there are brainstem compression symptoms.

Adult↗

PubMed1996

The retroangular flap for nasal reconstruction.

Many techniques can be used for nasal reconstruction. This paper describes the preliminary results of our study and shows a one-stage method for partial nasal reconstruction performed with a fasciocutaneous island flap with a retrograde blood supply based on the angular artery. This flap is called the retroangular flap. Six patients had been treated from January of 1993 to January of 1994. The technique is illustrated, and the correlated complications and results are also shown. The flap's color and texture have always been satisfactory. In one patient, the thickness of the flap required a secondary defatting. No sequelae were observed in the donor site.

Aged↗

PubMed1996

Measurement of endocochlear DC potentials in ears with acoustic neuromas: a preliminary report.

The pathogenesis of hearing loss in acoustic neuromas remains to be elucidated. To obtain more detailed information about inner ear damage in this disease, especially that dealing with the possibility of ischemia of the inner ear due to compression of the blood supply in the internal auditory canal by acoustic neuromas, measurement of endocochlear DC potential (EP) was attempted in three ears with acoustic neuromas during surgical removal of the tumors by the translabyrinthine approach. The size of each tumor was 3.0, 0.8, and 1.8 cm, respectively. An EP with a positive value was recorded in each of the three ears, i.e., 54, 57, and 38 mV, respectively, although the first and third patients were profoundly deaf on the side with a tumor. These findings were interpreted as being evidence of retention of function by the stria vascularis and the existence of blood supply to the inner ear in spite of the presence of tumors. Measurement of the EP seems to provide a new tool with which to analyze the causes of hearing loss in acoustic neuromas. Relatively low EP values may suggest mild dysfunction of the stria vascularis with acoustic neuromas.

Aged↗

PubMed1996

Normal hearing in acoustic neuroma patients: a critical evaluation.

A series of 128 acoustic neuromas (ANs) managed in our center in the last 6 years were evaluated. Sixteen cases (12.5%) were found to have normal pure tone audiograms. A comparatively younger age was an important characteristic of these patients. Tinnitus, dysequilibrium, and subjective hearing loss or distortion were their most common complaints. Pure tone audiometry showed a mean pure tone average of 14.5 dB. Speech discrimination score and performance intensity phonetically balanced index were very insensitive and showed very high false-negative results. Auditory brainstem responses proved to be a reliable test, being positive in 93.8% of cases. The mean tumor size did not show any significant difference when compared with acoustic neuroma cases with abnormal hearing. The combination of otologic and neurotologic symptoms in a young patient should prompt the clinician to investigation further even if hearing is within normal limits. A high index of suspicion is a prerequisite for the early diagnosis of such subtle lesions.

Adult↗

PubMed1996

Congenital cholesteatomas of the middle ear: a different experience.

A retrospective analysis is presented of 44 cases of congenital cholesteatoma of the middle ear. Twenty-one patients had cholesteatoma localized to the posterosuperior mesotympanum in complete contrast to the commonly reported anterosuperior location seen in only two cases. The remaining 21 patients had cholesteatoma involving either the entire mesotympanum or epitympanum or both. The posteriorly located congenital cholesteatomas might represent a completely different entity and originate from the trapped epithelial cell rests in the posterior mesotympanum during the development of temporal bone. All but one patient were treated by using a closed tympanoplasty. Eight patients underwent a single-stage surgery. A preplanned second-stage procedure was performed in 33 patients, and three are awaiting their second stage. Residual disease was seen in 19 (57%) patients undergoing second-stage surgery. No patient has had recurrent disease so far. Thirty-eight (85%) patients had a preoperative air-bone gap of > or = 30 dB. Of the 33 patients considered for hearing results, 16 (48%) had a postoperative gap within 10 db.

Adolescent↗

PubMed1996

[Vestibular neurectomy by retrolabyrinthine approach in cases of untreatable Meniere's disease].

We report on a series of 35 Ménière's disease patients, all of whom had undergone retrolabyrinthine vestibular neurectomy between 1987-1993. The overall success rate of vertigo relief was 96.7% with no serious or permanent complications resulting from the procedure. The current literature is reviewed and our results are compared with those of previous reports. The technical elements of the operation, regarding our approach and those of the others are analyzed with special attention given to the anatomical features of the region and their influence on success or failure. We conclude that the retrolabyrinthine approach for nerve section remains a safe and highly successful technique which continues to be widely used.

Adult↗

PubMed1995

Surgical treatment of cholesteatoma in children.

Treating cholesteatoma in children is still controversial. This article reviews 93 cases of pediatric cholesteatoma operated on from 1983 to 1991 in the Gruppo Otologico, Placenza, Italy, and details the results in 83 children who underwent the intact canal wall technique. During second-stage surgery, residual cholesteatoma was detected in 38% of patients. Recurrent cholesteatoma was detected in 10% of patients treated with the intact canal wall technique. Residual cholesteatoma was seen in the middle ear cleft in 63%, in the epitympanum in 26%, and in the mastoid in 11% of cases. Social hearing level (< 25 dB) was achieved in 85% of cases with suprastructure, whereas only 53% of patients without suprastructure had these levels. In the treatment of cholesteatoma in children by use of the intact canal wall technique, a preplanned second-look operation is mandatory to eradicate the disease.

Adolescent↗

PubMed1995

Cerebrospinal fluid leak after translabyrinthine acoustic neuroma surgery.

Cerebrospinal fluid leakage is the most common complication of translabyrinthine acoustic neuroma surgery. This retrospective study reviews patients who had translabyrinthine acoustic neuroma surgery at the Gruppo Otologico, Piacenza, Italy, and ENT Department of Bergamo General Hospital, Bergamo, Italy, during the last 6 years. The incidence of postoperative cerebrospinal fluid leakage was 6.2%, and 75% of these patients underwent another surgery to control the cerebrospinal fluid leakage. A modification of translabyrinthine approach was used in patients with highly pneumatized temporal bones to prevent cerebrospinal fluid leakage in these high-risk patients.

Adolescent↗

PubMed1995

Hearing preservation in vestibular schwannoma surgery: fact or fantasy?

This study reviews 57 papers dealing with the issue of hearing preservation in vestibular schwannoma surgery published in otolaryngologic and neurosurgical literature between the years 1977 and 1994. The authors', in this review, have made an attempt to verify whether the claims of hearing preservation are real, whether there is a price to be paid in terms of morbidity and whether there are univocal criteria for reporting results. The review shows that there is a wide disarray in reporting hearing results and the claims of hearing preservation are often unreal and misleading. On retabulating the results of a few series according to the minimal prerequisites for normal hearing (PTA < or = 30 dB and SDS > or = 70 per cent) and according to other various commonly reported criteria, it became evident that rates of hearing preservation differed a lot depending upon criteria. While any measurable hearing could be preserved in many cases, only a few had normal hearing preserved.

Audiometry, Pure-Tone↗

PubMed1995

Benign osteoblastoma of the mastoid part of the temporal bone: case report.

Osteoblastoma is a benign bone lesion that mainly affects the long bones and rarely the temporal bones. Very few cases have been reported in the literature. This paper reviews the literature, discusses the differential diagnosis, clinical presentation, and CT scan findings of such a condition and details our experience with a young patient who had a temporal bone (mastoid process) osteoblastoma.

Adolescent↗