Isolated Large Glenoid Fracture and Acute Glenohumeral Dislocation in Elderly Patients: A Case Series Treated Surgically With Reverse Shoulder Arthroplasty and Augmented Glenoid.

Background: One of the most frequent complications in patients affected by traumatic anterior dislocations is bony Bankart lesion. This study evaluates the clinical and functional outcomes of 10 patients with isolated large glenoid fracture and acute glenohumeral dislocation treated with reverse shoulder arthroplasty. Methods: Patients older than 69 years who underwent reverse shoulder arthroplasty after isolated large glenoid fracture and acute glenohumeral dislocation between 2016 and 2022 at the same institute were selected. Shoulder range of motion and pain level was assessed. The impact on quality of life has been evaluated through four measures: the constant scale, the simple shoulder test (SST), the OXFORD scale, and The University of California-Los Angeles (UCLA) shoulder scale. Results: The mean Constant score was 77.1 (range 68-84), the mean SST score was 9.4 (range 8-10), the Oxford score was 44.3 (range 35-48), and the UCLA shoulder scale was 27.1 (range 24-30). No reoperation was performed on any patient in this series. Conclusion: Reverse shoulder arthroplasty for elderly patients with bony Bankart lesion and acute glenohumeral dislocation represents a valuable option in terms of clinical results, patient satisfaction and early- to medium-term complications.

Impact of tuberosity treatment in reverse shoulder arthroplasty after proximal humeral fractures: A multicentre study.

BACKGROUND: To assess how tuberosity treatment affects the short-term clinical outcome of patients with complex proximal humeral fractures (PHFs) treated with reverse shoulder arthroplasty (RSA). METHODS: This is a multicentre study on 90 patients affected by acute PHFs (Neer type-4/11C3.2 in 80% of patients, and a Neer type 3/11B3.2 in 20%) treated with RSA and followed at an average of 34 months. Patients were divided into two groups (reconstructed and non-reconstructed tuberosity) according to the surgical fixation of the tuberosities. Then, the "reconstructed tuberosity" was divided into "healed" and "non-healed" groups. All patients were clinically evaluated in terms of ROM and strength in elevation, as well as with 0-10 numerical rating scale (NRS), Constant and Murley Score (CMS), DASH Score, and EQ-VAS. X-rays in anteroposterior and Neer views were performed. RESULTS: Based on the status of the tuberosities, 18.9% were non-reconstructed (17 patients) and 81.1% were reconstructed (73 patients): out of these, 11 were correctly healed, 42 healed with malposition, and 20 were reabsorbed. Instability was found in 2/73 patients in the reconstructed group, and in 4/17 patients in the non-reconstructed group. NRS (1.4 vs 0.5), DASH (23.1 vs 13.9), and EQ-VAS (78.1 vs 83.7) scores had better final values in the non-reconstructed group (p < 0.05). However, the non-correctly healed tuberosity group (excision + resorption + malposition/migration) showed worse strength, as well as clinical scores when compared to the correctly healed tuberosity group. CONCLUSION: RSA ensures satisfactory functional results for PHFs. Patients with a successfully reconstructed tuberosity have an overall better outcome. However, in this series most of the reconstructed cases presented tuberosity reabsorption, malposition, or migration, which led to lower results. Thus, tuberosity reconstruction must be carefully considered and tuberosity reabsorption or migration factors should be investigated, to optimize tuberosity reconstruction and provide to a higher number of patients a better outcome of RSA for the treatment of PHFs.

Minimally Invasive HEROS (Higher External ROtator Sparing) Posterior-lateral Approach for Total Hip Arthroplasty: Surgical Technique and Preliminary Results.

BACKGROUND: Minimally invasive approaches for Total Hip Arthroplasty (THA) are extremely popular among both patients and surgeons. Even though many surgical techniques have been described with overall satisfactory results, one of the most feared complications that still burdens THA is early dislocation, particularly for the most popular, posterior-lateral, approach. OBJECTIVES: The purpose of this report is to describe an original, minimally invasive, posterior-lateral technique, which spares the proximal external rotator muscle tendons of the hip (Higher External ROtator-Sparing; HEROS), while presenting its preliminary clinical and radiographic results. METHODS: From 2018 to 2020, 100 patients underwent THA, performed by the same surgeon using the HEROS technique. In all cases, the same cementless prosthesis was implanted. The Modified Harris Hip Score (MHHS) was obtained before surgery and at the last follow-up visit. The osteointegration and orientation of the prosthetic components were radiographically evaluated, and the restoration of the femoral offset was analyzed. RESULTS: Seventy-seven patients were assessed at a mean follow-up of 28 months. At the time of surgery, the average age of the patients was 72 years. There were 36 females and 41 males with a mean BMI of 27. The diagnoses were primary arthritis, avascular necrosis of the femoral head and fracture of the femoral neck. The mean surgical time was 76 minutes. The average MHHS score at follow-up was excellent. The mean offset variation was approximately 1 mm. There was an intra-operative fracture and an early infection of the wound. There were no dislocations. All patients returned to activities of daily living and were satisfied with the cosmetic appearance of the wound. CONCLUSIONS: The present study confirmed that this simple, minimally invasive approach is effective for restoring pain-free joint function and preventing implant dislocation with a low incidence of complications.

Posterior Shoulder Dislocation with Engaging Reverse Hill-Sachs Lesion: A Retrospective Study of Ten Patients Treated with Arthroscopy or Open Reduction and Stabilization.

This study compares two surgical techniques used to treat patients with posterior shoulder dislocation with an engaging reverse Hill-Sachs lesion. We assessed ten patients who were treated at the Surgical Orthopedic and Traumatological Institute (ICOT) of Latina and the Clinic of Orthopedic and Traumatological Surgery of the ASST Sette Laghi of Varese between 2016 and 2019. The patients were divided into two groups: the first comprising six patients who underwent the open surgery McLaughlin procedure as modified by Neer, the second including four patients who underwent the arthroscopic McLaughlin procedure. All patients received postoperative rehabilitation to achieve the best possible functional recovery of the affected shoulder. We then assessed the shoulder range of motion, the pain level, and the impact on quality of life with four tests: the Constant Scale, the Simple Shoulder Test (SST), the OXFORD Scale, and The University of California-Los Angeles (UCLA) Shoulder Scale. The mean scores of the first group were: 81.3 ± 9.8 SD (Constant Scale), 10.8 ± 1.06 SD (SST), 42.5 ± 5.4 SD (Oxford Scale), 30.8 ± 3.02 SD (UCLA Shoulder Scale); we calculated the following mean scores in the second group: 80.25 ± 4.1 SD (Constant Scale), 11.5 ± 0.8 SD (SST), 42 ± 4.06 SD (Oxford Scale), 32 ± 2.9 SD (UCLA Shoulder Scale). We found no significant differences between the two groups.

Beneficial Metabolic Effect of a Nutraceuticals Combination (Monacolin K, Yeasted Red Rice, Polyphenolic Extract of Annurca Apple and Berberine) on Acquired Hypercholesterolemia: A Prospective Analysis.

Hypercholesterolemia represents a serious public health problem as it significantly increases the risk of developing cardiovascular diseases. Its treatment with statin is limited by costs, side effects, and drugs interactions. Nutraceuticals appear to have an important metabolic effect on cholesterol reduction as well as on body weight and glycemia. The aim of this study was to evaluate the effect of a nutraceutical combination (Melasterol) in eighty-seven patients with acquired hypercholesterolemia. Clinically relevant parameters were collected at baseline and after three and six months of Melasterol treatment, one tablet per day. The primary endpoint was the change in cholesterol and triglyceride levels. Six months of treatment resulted in a 19.2% decrease in total cholesterol, accompanied by a 19.8% decrease in low-density lipoprotein (LDL) and a 23% reduction in triglycerides (p < 0.001) but not in high-density lipoprotein (HDL) levels (p > 0.05). These results were paralleled by a significative blood glucose (108.3 ± 21.3 vs. 98.4 ± 18.6 mg/dL p < 0.001) and body mass index (BMI) reduction (27.8 ± 4.4 vs. 27.0 ± 4.2 mg/dL, p < 0.001). A subgroup of 12 patients performed flow-mediated dilation, with values increasing by 1.8% (p < 0.05). No significant side effects were reported. Besides its cholesterol-lowering effect, Melasterol was associated with a significant improvement in other relevant metabolic parameters such as BMI and glycemia.

Identification of novel BRCA1 large genomic rearrangements by a computational algorithm of amplicon-based Next-Generation Sequencing data.

BACKGROUND: Genetic testing for BRCA1/2 germline mutations in hereditary breast/ovarian cancer patients requires screening for single nucleotide variants, small insertions/deletions and large genomic rearrangements (LGRs). These studies have long been run by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). The recent introduction of next-generation sequencing (NGS) platforms dramatically improved the speed and the efficiency of DNA testing for nucleotide variants, while the possibility to correctly detect LGRs by this mean is still debated. The purpose of this study was to establish whether and to which extent the development of an analytical algorithm could help us translating NGS sequencing via an Ion Torrent PGM platform into a tool suitable to identify LGRs in hereditary breast-ovarian cancer patients. METHODS: We first used NGS data of a group of three patients (training set), previously screened in our laboratory by conventional methods, to develop an algorithm for the calculation of the dosage quotient (DQ) to be compared with the Ion Reporter (IR) analysis. Then, we tested the optimized pipeline with a consecutive cohort of 85 uncharacterized probands (validation set) also subjected to MLPA analysis. Characterization of the breakpoints of three novel BRCA1 LGRs was obtained via long-range PCR and direct sequencing of the DNA products. RESULTS: In our cohort, the newly defined DQ-based algorithm detected 3/3 BRCA1 LGRs, demonstrating 100% sensitivity and 100% negative predictive value (NPV) (95% CI [87.6-99.9]) compared to 2/3 cases detected by IR (66.7% sensitivity and 98.2% NPV (95% CI [85.6-99.9])). Interestingly, DQ and IR shared 12 positive results, but exons deletion calls matched only in five cases, two of which confirmed by MLPA. The breakpoints of the 3 novel BRCA1 deletions, involving exons 16-17, 21-22 and 20, have been characterized. CONCLUSIONS: Our study defined a DQ-based algorithm to identify BRCA1 LGRs using NGS data. Whether confirmed on larger data sets, this tool could guide the selection of samples to be subjected to MLPA analysis, leading to significant savings in time and money.

Next-generation sequencing of BRCA1 and BRCA2 genes for rapid detection of germline mutations in hereditary breast/ovarian cancer.

BACKGROUND: Conventional methods used to identify BRCA1 and BRCA2 germline mutations in hereditary cancers, such as Sanger sequencing/multiplex ligation-dependent probe amplification (MLPA), are time-consuming and expensive, due to the large size of the genes. The recent introduction of next-generation sequencing (NGS) benchtop platforms offered a powerful alternative for mutation detection, dramatically improving the speed and the efficiency of DNA testing. Here we tested the performance of the Ion Torrent PGM platform with the Ion AmpliSeq BRCA1 and BRCA2 Panel in our clinical routine of breast/ovarian hereditary cancer syndrome assessment. METHODS: We first tested the NGS approach in a cohort of 11 patients (training set) who had previously undergone genetic diagnosis in our laboratory by conventional methods. Then, we applied the optimized pipeline to the consecutive cohort of 136 uncharacterized probands (validation set). RESULTS: By minimal adjustments in the analytical pipeline of Torrent Suite Software we obtained a 100% concordance with Sanger results regarding the identification of single nucleotide alterations, insertions, and deletions with the exception of three large genomic rearrangements (LGRs) contained in the training set. The optimized pipeline applied to the validation set (VS), identified pathogenic and polymorphic variants, including a novel BRCA2 pathogenic variant at exon 3, 100% of which were confirmed by Sanger in their correct zygosity status. To identify LGRs, all negative samples of the VS were subjected to MLPA analysis. DISCUSSION: Our experience strongly supports that the Ion Torrent PGM technology in BRCA1 and BRCA2 germline variant identification, combined with MLPA analysis, is highly sensitive, easy to use, faster, and cheaper than traditional (Sanger sequencing/MLPA) approaches.

Coexistence of three EGFR mutations in an NSCLC patient: A brief report.

BACKGROUND: The epidermal growth factor receptor (EGFR) represents a molecular target for tyrosine kinase inhibitors for non-small cell lung cancer (NSCLC) patients with a mutation in the EGFR gene. Mutations of the EGFR gene that occur at a single position in NSCLC tissue are found as single, whereas two or more mutations on the same allele are poorly detected and investigated. PATIENT AND METHODS: We investigated the presence of the EGFR gene mutations in tumor tissue by Sanger sequencing and ion torrent sequencing in an NSCLC patient at Stage IV of disease. RESULTS: We found the presence of three coexisting mutations on the EGFR gene-two of which on exon 21 are present on the same allele, and the third, on exon 20, was analyzed by Sanger sequencing of the peripheral blood lymphocytes. The patient staged as cT4N0M1c (Stage IV) and started afatinib 40 mg daily 8 months ago, showing a clinical benefit. CONCLUSION: In this report we describe the case of an NSCLC patient harboring three coexisting mutations on the EGFR gene, two of which are present on the same allele. This mutation pattern may represent, for patient progeny, a genetic risk of cancer development. Therefore it should be possible to obtain screening guidelines to improve the risk calculation for lung cancer susceptibility in the future.

Optimizing the identification of risk-relevant mutations by multigene panel testing in selected hereditary breast/ovarian cancer families.

The introduction of multigene panel testing for hereditary breast/ovarian cancer screening has greatly improved efficiency, speed, and costs. However, its clinical utility is still debated, mostly due to the lack of conclusive evidences on the impact of newly discovered genetic variants on cancer risk and lack of evidence-based guidelines for the clinical management of their carriers. In this pilot study, we aimed to test whether a systematic and multiparametric characterization of newly discovered mutations could enhance the clinical utility of multigene panel sequencing. Out of a pool of 367 breast/ovarian cancer families Sanger-sequenced for BRCA1 and BRCA2 gene mutations, we selected a cohort of 20 BRCA1/2-negative families to be subjected to the BROCA-Cancer Risk Panel massive parallel sequencing. As a strategy for the systematic characterization of newly discovered genetic variants, we collected blood and cancer tissue samples and established lymphoblastoid cell lines from all available individuals in these families, to perform segregation analysis, loss-of-heterozygosity and further molecular studies. We identified loss-of-function mutations in 6 out 20 high-risk families, 5 of which occurred on BRCA1, CHEK2 and ATM and are esteemed to be risk-relevant. In contrast, a novel RAD50 truncating mutation is most likely unrelated to breast cancer. Our data suggest that integrating multigene panel testing with a pre-organized, multiparametric characterization of newly discovered genetic variants improves the identification of risk-relevant alleles impacting on the clinical management of their carriers.

Characterization of medulloblastoma in Fanconi Anemia: a novel mutation in the BRCA2 gene and SHH molecular subgroup.

Fanconi Anemia (FA) is an inherited disorder characterized by the variable presence of multiple congenital somatic abnormalities, bone marrow failure and cancer susceptibility. Medulloblastoma (MB) has been described only in few cases of FA with biallelic inactivation in the tumor suppressor gene BRCA2/FANCD1 or its associated gene PALB2/FANCN. We report the case of a patient affected by Fanconi Anemia with Wilms tumor and unusual presentation of two medulloblastomas (MB1 and MB2). We identified a new pathogenetic germline BRCA2 mutation: c.2944_2944delA. Molecular analysis of MBs allowed us to define new features of MB in FA. MBs were found to belong to the Sonic Hedgehog (SHH) molecular subgroup with some differences between MB1 and MB2. We highlighted that MB in FA could share molecular aspects and hemispheric localization with sporadic adult SHH-MB. Our report provides new findings that shed new light on the genetic and molecular pathogenesis of MB in FA patients with implications in the disease management.

Validation of the Ion Torrent PGM sequencing for the prospective routine molecular diagnostic of colorectal cancer.

OBJECTIVES: Treatment individualization based on specific molecular biomarkers is becoming increasingly important in oncology. In colorectal cancer (CRC), the molecular characterization of RAS and BRAF mutation status for prognostic and predictive purposes is commonly performed by different validated methods. However, as the number of clinically relevant mutations to be analyzed increases, the definition of new approaches for more sensitive, rapid and economic patient selection urges. To this aim, we evaluated the Ion Semiconductor sequencing using the Ion Torrent Personal Genome Machine (IT-PGM) in our routine molecular diagnostics for CRC in comparison with the gold standard direct Sanger sequencing. DESIGN AND METHODS: Formalin-fixed and paraffin-embedded tumor tissues obtained by surgery or biopsy of 66 CRCs were collected. DNA was extracted and sequenced by IT-PGM and Sanger method. RESULTS: The proposed IT-PGM sequencing strategy exceeded the 500 reads of coverage for all clinically relevant RAS/BRAF amplicons in most samples and thus guaranteed optimal determination. Indeed, the frequencies and the mutational spectrum of RAS and BRAF mutations were in agreement with literature data and revealed 100% concordance between the IT-PGM and routine Sanger sequencing approaches. Turnaround time and cost evaluation indicate that the IT-PGM sequencing permits the characterization of the clinically relevant mutational spots at lower cost and turnaround time compared to Sanger sequencing and allows inclusion of additional amplicons whose characterization may acquire significance in the very next future. CONCLUSION: The IT-PGM is a valid, flexible, sensitive and economical method alternative to the Sanger sequencing in routine diagnostics to select patients for anti-epidermal growth factor receptor therapy for metastatic CRC.

Efficacy of sildenafil in HIV-related pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is one of the long-term complications of HIV infection. The incidence of HIV-PAH is estimated at 0.5% of HIV-infected individuals. The mechanism by which infection leads to full-blown PAH is unknown. We describe a 44-year-old female patient with HIV infection diagnosed in 2004. Pulmonary hypertension was diagnosed in 2006. Seven months after the first cardiovascular clinical signs had started, the patient was referred to hospital because she was in New York Heart Association functional class IV. She commenced treatment with sildenafil. After increasing the sildenafil dose to ensure therapeutic drug levels over 24 h, the PAH and physical performance of the patient improved significantly. Our experience confirms long-term benefits of sildenafil monotherapy in PAH-HIV adult patients with improvements in symptoms and echocardiographic findings.

Masquelet technique for the treatment of a severe acute tibial bone loss.

The "induced membrane" technique described by Masquelet has been used successfully for many years for posttraumatic bone defect reconstruction, non-unions and osteomyelitis. The main advantages are the two-step surgical procedure that in case of primary infection allows repeated debridement if necessary, in case of internal fixation early weight bearing with decreased malalignment risk and it has a short learning curve. A theoretical application of this procedure is the management of acute severe traumatic bone loss of the limbs despite the lack of this experience in literature. We report on a Gustilo IIIB meta-epiphyseal fracture (AO 43-C3) of the leg with a 6 cm in length bone loss that was treated with the Masquelet technique.

Novel and recurrent BRCA2 mutations in Italian breast/ovarian cancer families widen the ovarian cancer cluster region boundaries to exons 13 and 14.

Hereditary breast and ovarian cancer are mainly linked to mutations in BRCA1 and BRCA2 genes which confer a similar cumulative risk of developing breast cancer. Importantly, while BRCA2 mutation carriers generally have a lower cumulative risk for ovarian cancer, mutations clustered in the central portion of BRCA2 are associated with a higher proportion of ovarian compared with breast cancer cases. The boundaries of this ovarian cancer cluster region (OCCR) have been tentatively defined within a 3.3 kb region of BRCA2 exon 11, and herein, we reassessed these boundaries using our series of Italian breast/ovarian cancer families. We used direct sequencing to investigate BRCA mutations in 367 breast/ovarian cancer families. We also studied the association between the location of the mutations and the ovarian cancer phenotype in our cohort of BRCA2-mutated families. We observed the novel c.7309_7309delA frameshift mutation and the c.7007G>A deleterious mutation in BRCA2 exons 14 and 13, respectively, in five independent Italian families characterized by a high proportion of ovarian cancer cases. Of note, a significantly higher proportion of ovarian versus breast cancer cases was associated not only with mutations in the previously defined OCCR (OR = 5.91; p = 0.004), but also with the exon 13-14 region (OR = 7.37; p = 0.001) in our BRCA2-mutated families. Our data provide initial evidence for a novel putative OCCR in BRCA2 exons 13-14.

Imaging of articular cartilage: current concepts.

Magnetic resonance imaging (MRI) is the gold standard method for non-invasive assessment of joint cartilage, providing information on the structure, morphology and molecular composition of this tissue. There are certain minimum requirements for a MRI study of cartilage tissue: machines with a high magnetic field (> 1.5 Tesla); the use of surface coils; and the use of T2-weighted, proton density-weighted fast-spin echo (T2 FSE-DP) and 3D fat-suppressed T1-weighted gradient echo (3D-FS T1W GRE) sequences. For better contrast between the different joint structures, MR arthography is a method that can highlight minimal fibrillation or fractures of the articular surface and allow evaluation of the integrity of the native cartilage-repair tissue interface. To assess the biochemical composition of cartilage and cartilage repair tissue, various techniques have been proposed for studying proteoglycans [dGEMRIC, T1rho mapping, sodium (23Na) imaging MRI, etc.], collagen, and water distribution [T2 mapping, "magnetisation transfer contrast", diffusion-weighted imaging (DWI), and so on]. Several MRI classifications have been proposed for evaluating the processes of joint degeneration (WORMS, BLOKS, ICRS) and post-surgical maturation of repair tissue (MOCART, 3D MOCART). In the future, isotropic 3D sequences set to improve image quality and facilitate the diagnosis of disorders of articular structures adjacent to cartilage.

[Effect of antiretroviral therapy on carotid intima-media thickness in HIV-infected patients]. / Influenza di terapie antiretrovirali sullo spessore medio-intimale carotideo in pazienti HIV-positivi.

BACKGROUND: The introduction of highly active antiretroviral therapy reduced HIV-associated morbidity and mortality, at the cost of adverse metabolic effects that increase cardiovascular risk. The aim of this study was to evaluate the impact of exposure to protease inhibitors (PI) compared with exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI) on carotid intima-media thickness (IMT) and blood flow velocity and to measure vascular involvement over a 2-year follow-up in HIV-infected patients treated with PI. METHODS: Thirty-five HIV-infected patients treated with PI (group I) and 15 patients treated with NNRTI (group II) underwent epiaortic vessel ultrasonography. The same evaluation was obtained in a group of 20 healthy subjects. After 20 +/- 2 months, 22 patients of group I were re-evaluated and the follow-up data were compared with those obtained at baseline. RESULTS: The ANOVA test showed a significant difference among the three groups for IMT and flow velocities. Bonferroni analyses showed significant differences in IMT and flow velocities in group I vs group II vs controls: IMT of the right common carotid artery was 0.742 +/- 0.135 mm in group I vs 0.642 +/- 0.131 mm in group II (p < 0.05) and 0.616 +/- 0.069 mm in controls (p = 0.002); IMT of left common carotid artery was 0.720 +/- 0.108 vs 0.659 +/- 0.066 mm (p < 0.05) and 0.640 +/- 0.081 mm (p < 0.01), respectively. There were no differences in group II vs healthy subjects. At follow-up examinations of group I, no significant differences were observed in both IMT and blood flow velocity when compared with baseline values. CONCLUSIONS: The HIV-infected patients treated with PI show earlier vascular involvement as compared to those treated with NNRTI and to healthy subjects with similar distribution of cardiovascular risk factors. However, such damage seems to have no significant progression over a 2-year follow-up in HIV-infected patients treated with PI. These data emphasize the need for follow-up studies assessing whether these changes are predictive of adverse cardiac events.

Cardiovascular effects of antiretroviral drugs: clinical review.

In HIV infected patients an increased occurence of cardiac events has been demontrated from the introduction of highly active antiretroviral therapy (HAART). Antiretroviral drugs' regimens are, in fact, associated with several metabolic side effects, such as dyslipidemia, impaired glucose metabolism and abnormal body fat distribution, that increase the cardiovascular risk of HIV subjects. In addition, HIV infection itself, the chronic inflammatory status and the relevant presence in this population of some of the traditional cardiovascular risk factors contribute to an higher incidence of cardio and cerebrovascular events. In last years several studies showed the occurence of carotid vascular impairment in patients in treatment with protease inhibitors (PI). Similarly the DAD Study reported an increase of 26% of the risk of myocardial infarction in patients on HAART and that this risk is indipendently associated with longer exposure to PI, even after multivariate adjustments. A correct evaluation of the metabolic status before starting HAART and an adeguate control of the drugs-related metabolic abnormalities may reduce the incidence of cardiac events and still improve HIV patients prognosis. This review will focus on the metbolic effects of antiretroviral drugs and to the contribution of combination antiretroviral therapy on cardiovascular risk.

Prevalence of BRCA1 and BRCA2 genomic rearrangements in a cohort of consecutive Italian breast and/or ovarian cancer families.

Germline point mutations in BRCA1 and BRCA2 genes account for about 30% of the inherited breast and ovarian cancers. Germline genomic rearrangements have been found in both BRCA1 and BRCA2 genes, but the extent to which these alterations might contribute to increasing the actual mutation detection rate is still debated. Here we screened a cohort of 112 consecutive Italian families at moderate-to-high risk for breast and/or ovarian cancer for BRCA1 and BRCA2 point mutations and genomic rearrangements. Of the 83 point mutation negative probands, two (2.4%) showed BRCA1 rearrangements, accounting for 10.5% of the BRCA1 mutations. BRCA1 del18-19 has been previously described in another Italian family, while the molecular characterization of the BRCA1 del23-24 is given here for the first time. Conversely, we failed to identify any BRCA2 rearrangements even in the hereditary breast cancer families, where we detected an higher prevalence of BRCA2 compared to BRCA1 point mutations. Our results support the idea that search for BRCA1 rearrangements should be included in the genetic screening of even moderate risk breast/ovarian cancer families. In contrast, they suggest BRCA2 rearrangements might be very rare out of the high risk families including a male breast cancer.