Cataract and optic disk drusen in a patient with glycogenosis and di George syndrome: clinical and molecular report

Background We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD). Case presentation A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. The patient has been followed from birth, attending the day-hospital every six months at the San Paolo Hospital, Milan, outpatient clinic for metabolic diseases and previously at another eye center. During the last day-hospital visit, a complete eye examination showed ONHD and cataract in both eyes. Next Generation Sequencing (NGS) was subsequently done to check for any association between the eye problems and metabolic aspects. Conclusions This is the first description of ocular changes in a patient with GSD Ia and DGS. Mutations explaining GSD Ia and DGS were found but no specific causative mutation for cataract and ONHD. The metabolic etiology of her lens changes is known, whereas the pathogenesis of ONHD is not clear. Although the presence of cataract and ONHD could be a coincidence; the case reported could suggest that hypocalcemia due to DGS could be the common biochemical pathway

Prevention of bisphosphonate-related mandibular fractures = Prevenzione delle fratture mandibolari conseguenti alla necrosi ossea da difosfonati

La frattura della mandibola rappresenta solitamente l\u2019evento finale nei pazienti che presentano una progressione della necrosi ossea derivante dall\u2019impiego dei difosfonati. Si tratta di una grave complicanza molto dolorosa che impedisce ai pazienti di alimentarsi correttamente, essendo pertanto un fattore che peggiora notevolmente la loro qualit\ue0 di vita. L\u2019obiettivo del trattamento dei pazienti che presentano la necrosi ossea legata ai difosfonati (BRONJ) dovrebbe essere rallentare la progressione della malattia. Presentiamo una soluzione tecnica per il trattamento dei pazienti che presentano necrosi mandibolare in stadio 3 ad alto rischio di sviluppare una frattura, avendo un\u2019altezza mandibolare residua di osso sano inferiore a 6 mm. Il trattamento consiste nel posizionamento di una placca ricostruttiva mandibolare per via extra-orale in un piano superficiale al muscolo platisma per tenere i mezzi di sintesi separati dal sito infettivo e non farli contaminare con conseguente necessit\ue0 di doverli rimuovere, seguito dal courettage per via endorale della necrosi mandibolare. Il rispetto della vascolarizzazione mandibolare e l\u2019assenza di contatto diretto tra il sito di osteonecrosi e la placca ricostruttiva rappresentano alcuni dei vantaggi di questa metodica. La placca ricostruttiva rinforza la mandibola e consente di aggredire energicamente l\u2019area di necrosi mandibolare, senza esporre il paziente a rischio di frattura iatrogena. Questo garantisce al paziente un rallentamento della progressione della malattia e impedisce la frattura patologica della mandibola, inevitabile epilogo delle necrosi ossee mandibolari.Mandibular fracture is usually the clinical end of bisphosphonate-related osteonecrosis of the jaw. This is a painful complication and patients cannot feed as usual, with a worsening of their quality of life. The goal of treatment in bisphosphonate related osteonecrosis of jaw (BRONJ) patients is to slow progression of bone necrosis. We present a novel technique for treatment of severe mandibular BRONJ in stage 3 patients that present with a high risk to develop fracture, since they have a residual unaffected mandibular bone height less than 6 mm. We treated 10 patients in this clinical situation with an extra-oral application of a reconstructive plate superficial to the platysma, to keep the plate separated from the infected site to avoid contamination and consequent need of removal, followed by an intraoral approach for active curettage of mandibular necrosis. The preservation of blood supply to the mandible and avoidance of direct contact of the infected site with the reconstructive plate are some advantages of this technique. This plate allows enhancement of mandibular strength, allowing proper treatment of the BRONJ site on the oral side without fear of causing a mandibular fracture when the residual mandible is thin. This technical solution guarantees these patients an extended disease-free period since it is effective in preventing mandibular fractures in patients with low mandibular residual height left after the BRONJ onset

Prevenzione delle fratture mandibolari conseguenti alla necrosi ossea da difosfonati

La frattura della mandibola rappresenta solitamente l'evento finale nei pazienti che presentano una progressione della necrosi ossea derivante dall'impiego dei difosfonati. Si tratta di una grave complicanza molto dolorosa che impedisce ai pazienti di alimentarsi correttamente, essendo pertanto un fattore che peggiora notevolmente la loro qualità di vita. L'obiettivo del trattamento dei pazienti che presentano la necrosi ossea legata ai difosfonati (BRONJ) dovrebbe essere rallentare la progressione della malattia. Presentiamo una soluzione tecnica per il trattamento dei pazienti che presentano necrosi mandibolare in stadio 3 ad alto rischio di sviluppare una frattura, avendo un'altezza mandibolare residua di osso sano inferiore a 6 mm. Il trattamento consiste nel posizionamento di una placca ricostruttiva mandibolare per via extra-orale in un piano superficiale al muscolo platisma per tenere i mezzi di sintesi separati dal sito infettivo e non farli contaminare con conseguente necessità di doverli rimuovere, seguito dal courettage per via endorale della necrosi mandibolare. Il rispetto della vascolarizzazione mandibolare e l'assenza di contatto diretto tra il sito di osteonecrosi e la placca ricostruttiva rappresentano alcuni dei vantaggi di questa metodica. La placca ricostruttiva rinforza la mandibola e consente di aggredire energicamente l'area di necrosi mandibolare, senza esporre il paziente a rischio di frattura iatrogena. Questo garantisce al paziente un rallentamento della progressione della malattia e impedisce la frattura patologica della mandibola, inevitabile epilogo delle necrosi ossee mandibolari

LINE-1 methylation in cleft lip tissues:influence of infant MTHFR c.677C>T genotype

Objective: To investigate the influence of MTHFR c.677C>T genotype on LINE-1 methylation in lateral and medial tissues from cleft lip (CL). Methods: Forty-five consecutive non-syndromic cleft lip with or without cleft palate (nsCL/P) cases were included in the study. Genomic DNA was extracted from tissues at both sides of cleft lip, and LINE-1 methylation was detected by bisulfite conversion and pyrosequencing. MTHFR c.677C>T genotyping was carried out using the TaqMan genotyping assay. Results: LINE-1 methylation level was significantly higher on medial side of cleft lip compared with lateral side (p = 0.001). This difference was not significantly influenced by the case's sex or cleft type. However, MTHFR c.677C>T genotyping revealed that the difference in LINE-1 methylation across cleft lip was restricted to carriers of C allele of MTHFR c.677C>T and was not apparent in TT homozygous cases (p = 0.027). Conclusion: This integrated analysis supports the previous finding of differences in DNA methylation across the two sides of cleft lip and further suggests a possible role of MTHFR c.677C>T genotype in establishing this difference

Technical refinements in mandibular reconstruction with free fibula flaps: Outcome-oriented retrospective review of 99 cases = Accorgimenti tecnici nelle ricostruzioni mandibolari con lembi liberi di fibula: analisi retrospettiva dei risultati su 99 casi

Congenital disease, major trauma, tumour resection and biphosphonate-related osteonecrosis can lead to partial, subtotal, or total loss of the mandibular bone. Minor defects can be easily reconstructed using bone grafts, whereas microvascular free tissue transfer may be unavoidable in the case of major bone loss or poor quality of soft tissue. Simple bone or composite osteocutaneous fibula free flaps have proven invaluable and remain the workhorse for microvascular mandibular reconstruction in daily practice. Our experience with 99 consecutive fibular free flaps confirms the available data in terms of high success rate. In these cases, 90% had total success, while 7 had complete flap failures. Three of our patients showed skin paddle necrosis with bony conservation. This report focuses on the technical refinements used by the authors that can prove valuable in obtaining predictable and precise results: in particular, we discuss surgical techniques that avoid vascular pedicle ossification by removing the fibular periosteum from the vascular pedicle itself and reduce donor site morbidity and aid in management of the position in the new condylar fossa. Finally, new technologies such as intraoperative CT and custom premodelled fixation plates may also increase the predictability of morpho-functional results

Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network

Testicular germ-cell tumours and penile squamous cell carcinoma: Appropriate management makes the difference

Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well defined entities in terms of management, where specific recommendations - in the form of continuously up-to-dated guide lines-are provided. Impact of these tumour is relevant. Testicular GCT affects young, healthy men at the beginning of their adult life. PeSCC affects older men, but a proportion of these patients are young and the personal consequences of the disease may be devastating. Deviation from recommended management may be a reason of a significant prognostic worsening, as proper treatment favourably impacts on these tumours, dramatically on GCT and significantly on PeSCC. RARECAREnet data may permit to analyse how survivals may vary according to geographical areas, histology and age, leading to assume that non-homogeneous health-care resources may impact the cure and definitive outcomes. In support of this hypothesis, some epidemiologic datasets and clinical findings would indicate that survival may improve when appropriate treatments are delivered, linked to a different accessibility to the best health institutions, as a consequence of geographical, cultural and economic barriers. Finally, strong clues based on epidemiological and clinical data support the hypothesis that treatment delivered at reference centres or under the aegis of a qualified multi-institutional network is associated with a better prognosis of patients with these malignancies. The ERN EURACAN represents the best current European effort to answer this clinical need

Treatment challenges in and outside a network setting: Head and neck cancers

Head and neck cancer (HNC) is a rare disease that can affect different sites and is characterized by variable incidence and 5-year survival rates across Europe. Multiple factors need to be considered when choosing the most appropriate treatment for HNC patients, such as age, comorbidities, social issues, and especially whether to prefer surgery or radiation-based protocols. Given the complexity of this scenario, the creation of a highly specialized multidisciplinary team is recommended to guarantee the best oncological outcome and prevent or adequately treat any adverse effect. Data from literature suggest that the multidisciplinary team-based approach is beneficial for HNC patients and lead to improved survival rates. This result is likely due to improved diagnostic and staging accuracy, a more efficacious therapeutic approach and enhanced communication across disciplines. Despite the benefit of MTD, it must be noted that this approach requires considerable time, effort and financial resources and is usually more frequent in highly organized and high-volume centers. Literature data on clinical research suggest that patients treated in high-accrual centers report better treatment outcomes compared to patients treated in low-volume centers, where a lower radiotherapy-compliance and worst overall survival have been reported. There is general agreement that treatment of rare cancers such as HNC should be concentrated in high volume, specialized and multidisciplinary centers. In order to achieve this goal, the creation of international collaboration network is fundamental. The European Reference Networks for example aim to create an international virtual advisory board, whose objectives are the exchange of expertise, training, clinical collaboration and the reduction of disparities and enhancement of rationalize migration across Europe. The purpose of our work is to review all aspects and challenges in and outside this network setting planned for the management of HNC patients

Compass : clinical evaluation of a new instrument for the diagnosis of glaucoma

Aims: To evaluate Compass, a new instrument for glaucoma screening and diagnosis that combines scanning ophthalmoscopy, automated perimetry, and eye tracking. Materials and Methods: A total of 320 human subjects (200 normal, 120 with glaucoma) underwent full ophthalmological evaluation and perimetric evaluation using the Humphrey SITA standard 24\ub0 test (HFA), and the Compass test that consisted of a full-threshold program on the central 24\ub0with a photograph of the central 30\ub0 of the retina. A subgroup of normal subjects and glaucoma patients underwent a second Compass test during the same day in order to study test-retest variability. After exclusion of 30 patients due to protocol rules, a database was created to compare the Compass to the HFA, and to evaluate retinal image quality and fixation stability. Results: The difference inmean sensitivity between Compass and HFA was -1.02 \ub1 1.55 dB in normal subjects (p65% of cases; Image-based diagnosis was in accordance with the initial diagnosis in 85%of the subjects. Conclusions: Based on preliminary results, Compass showed useful diagnostic characteristics for the study of glaucoma, and combined morphological information with functional data

Blindness and glaucoma: A multicenter data review from 7 academic eye clinics

Purpose To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. Methods This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (''controls''). Blindness was defined as visual acuity-0.05 and/or visual field loss to less than 10°. Results Unilateral and bilateral blindness were respectively 11.0% and 1.6%at the beginning, and 15.5%and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years)//conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14%in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). Conclusions In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved//it could be predicted by high initial MD, high initial IOP, and old age