Variable clinical expression of Stickler Syndrome: A case report of a novel COL11A1 mutation

Background: Stickler Syndrome is a rare connective tissue disorder, characterized by clinical, and genetic heterogeneity. The clinical expression is highly variable, including moderate to severe myopia in childhood, hearing loss, facial dysmorphic features, cleft palate, and early osteoarthritis. COL2A1, COL11A1, and COL11A2 mutations account of the majority of autosomal dominant Stickler Syndrome and, in particular, a heterozygous mutation in COL11A1 gene is identified in about 10 to 20% of Stickler Syndrome patients. Methods: Herein, we report a case of an 8-year- old child with Stickler Syndrome, presenting with early-onset of myopia with vitreal abnormalities, facial dysmorphic characteristics, and mild hearing loss later in childhood. To identify the underlying genetic cause, Whole Exome Sequencing was carried out for COL11A1 gene. Results: A novel de novo heterozygous splice site variant (NM_001854: c.1845 + 5G> C) of the COL11A1 gene, which had not been previously reported, was identified by Whole Exome Sequencing. Conclusion: We reported a novel COL11A1 mutation in a child with Stickler Syndrome presenting a phenotype of early-onset of ocular anomalies and mild hearing loss later in childhood. Our findings confirm the variability of the expression of the disease, even in the contest of the same gene-related disorder, thus, contributing to improve the knowledge on clinical and molecular basis of this rare disease

The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice

Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We conducted a single-institution cross-sectional study. Patients were categorized according to IOR Classification, which identifies three patients' classes on the presence/absence of deformities and/or limitations. The present dataset was compared with our previously published data, to refine the classification. Nine hundred sixty-eight patients were included: 243 children (<10 years), 136 adolescents (10–15 years), and 589 adults. Of the entire population, half patients presented at least one deformity, and one quarter reported at least one limitation. Compared with our previous study, the amount of children was more than doubled and the percentage of mild/moderate cases was notably increased, giving a better disease overview throughout the lifespan and suggesting a different cut-off for dividing Class II in subclasses. We confirmed that MO is characterized by phenotypic heterogeneity, suggesting that an early classification of the disease may offer a useful tool to follow disease pattern and evolution, to support clinical practice, and to propose timely interventions

Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series

Melorheostosis (MEL) is an uncommon, sclerosing disease, characterised by hyperostosis of long bones, resembling the flowing of candle wax. The disease is sporadic and the pathogenesis is still poorly understood. Occasionally, the same family can include individuals with MEL and Osteopoikilosis (OPK), a disease characterised by multiple round foci of increased bone density. LEMD3 gene mutations are related to OPK and Buschke\u2013Ollendorff Syndrome, a genetic condition in which an association between MEL, OPK and skin lesions is observed. In rare cases, LEMD3 mutations and recently mosaic MAP2K1 gene mutations have been correlated to MEL suggesting that somatic mosaicism could be causative of the disease. In this study, we described the clinical, radiological and molecular findings of 19 individuals with MEL and 8 with OPK and compared the results to the medical literature. The molecular analyses of this case series corroborate the available data in the medical literature, indicating that LEMD3 germline mutations are not a major cause of isolated MEL and reporting five further cases of OPK caused by LEMD3 germline mutations

Does hub-and-spoke organization of healthcare system promote workers’ satisfaction?

The healthcare services network is a recent organizational structure of healthcare services that are interdependent and organized as a network on the basis of the Hub-and-Spoke model. This questionnaire-based study analyzed socio-psychological well-being of health workers both in terms of team-related experience and individual satisfaction and engagement with one's work in a Hub-and-Spoke healthcare service in comparison to non-network healthcare service. Workers from two different public healthcare services involved in the treatment of the same skeletal rare diseases participated in the Study. We expected that working under a Hub-and-Spoke healthcare service-involving teamwork and cooperation among different healthcare services within the units, as well as among workers belonging to different units-would lead to greater psychological team-related and individual benefits. In line with predictions, the findings showed that under a Hub-and-Spoke healthcare service, health workers felt highly interdependent by their team fellows and developed shared cognitions (i.e., team mental models) about their integration and their tasks to a higher extent than non-network ones. They were also individually more satisfied of their job and displayed higher work engagement than non-network workers. Beneficial team-related dynamics, such as perceived interdependence, were responsible for the differences between the Hub-and-Spoke workers and non-network ones. The implications of the present findings were discussed in terms of promotion of health workers' satisfaction and well-being

Does Hub-and-Spoke organization of healthcare system promote workers\u2019 satisfaction?

The healthcare services network is a recent organizational structure of healthcare services that are interdependent and organized as a network on the basis of the Hub-and-Spoke model. This questionnaire-based study analyzed socio-psychological well-being of health workers both in terms of team-related experience and individual satisfaction and engagement with one's work in a Hub-and-Spoke healthcare service in comparison to non-network healthcare service. Workers from two different public healthcare services involved in the treatment of the same skeletal rare diseases participated in the Study. We expected that working under a Hub-and-Spoke healthcare service-involving teamwork and cooperation among different healthcare services within the units, as well as among workers belonging to different units-would lead to greater psychological team-related and individual benefits. In line with predictions, the findings showed that under a Hub-and-Spoke healthcare service, health workers felt highly interdependent by their team fellows and developed shared cognitions (i.e., team mental models) about their integration and their tasks to a higher extent than non-network ones. They were also individually more satisfied of their job and displayed higher work engagement than non-network workers. Beneficial team-related dynamics, such as perceived interdependence, were responsible for the differences between the Hub-and-Spoke workers and non-network ones. The implications of the present findings were discussed in terms of promotion of health workers' satisfaction and well-being

Sarcoma primitivo del cuore. Descrizione di un caso

Primary cardiac tumors are rare events. We describe here a case of undifferentiated pleomorphic sarcoma (so-called pleomorphic malignant fibrous histiocytoma) obliterating mostly the left side and the anterior wall of pericardium in a 84-year-old man admitted for mild dyspnea at rest. The diagnosis was suspected after excluding the lung origin of the mass (observed by plain chest radiography) by thorax computed tomography but it was confirmed only by cardiac-gated magnetic resonance imaging and transthoracic biopsy. Considering both patient's age and comorbidity, and local extension of the lesion, after counseling with cardiac surgeons and oncologists, the patient was treated only by conservative medical therapy. The patient died 6 months after the diagnosis due to a superior vena cava syndrome as an effect of infiltration and obstruction of superior vena cava by the tumor at the site of vein entry in the right atrium. This case is an example of a primary cardiac tumor that causes relative myocardial sufferance both by infiltration and by limitation of normal heart diastolic function

Urinary coproporhyrin isomers during therapy with IFn-RIBA in patients with chronic hepatitis due to HCV infection

Background : MRP2 transporter has a proven role in biliary export of many different products of hepatocytic metabolism. Particularly, human and animal models have demonstrated MRP2 role in biliary excretion of coproporhyrins: its preference for isomer I (CPI) export with respect to isomer III (CPIII) is responsable for the biliary CPI/CPIII ratio about 2-3:1 and the plasma and urinary CPI/CPIII ratio about 1:2-3. A significant reduction of MRP2 expression has been described in many different acquired cholestatic liver diseases and in patients with chronic hepatitis (CH) due to HCV infection. Aim of our study was to evaluate quantitative and qualitative (CPI/CPIII ratio) urinary CP excretion in patients with CH due to HCV before (T0), at 3 months (T3) and at the end of antiviral therapy (ET) (peg-IFN + Ribavirin)Materials and Methods: 60 patients (18 females, aged 46±11 years, genotype: 1 (31); 2(10); 3(15); 4(4); 51 naive) with istologically proven HCV-inducted CH were consecutively enrolled; 5 (8.4%) did not conclude the study. 10 healthy subjects sex- and age-matched were also considered for comparing the basal values. None of considered subjects had overt laboratory [i.e. serum alkaline phosphatase (AP) over the normal range] or clinical signs of cholestasis. All patients underwent a urinary evaluation (HPLC) of CPI excretion at T0, T3 and ET. SVR (n=34) was defined as serum HCV-RNA undetectable after 6 months of follow-up. Results: Basal serum FA levels resulted significantly related both to basal urinary total CPI (r=.405, p=.001), and basal CPI/CPIII ratio (r=.692, p=.000). Table I show Total urinary CPI e urinary CPI/CPIII ratio in controls and in HCV patients with respect to serum PA percentile.Table IPA ≥ 75°percentile(≥ 232 u/L) (n=16)(group A)PA 60% at T3 showed a 88% PPV for SVR, reaching 95% if considering only patients in group A.Our data indirectly confirm the effect of liver chronic infection due to HCV on MRP2 expression, whose alteration may be considered as the main responsible for the observed urinary CPI modifications (greater excretion with CPI/CPIII ratio inversion). Even if more confirmative data are needed, monitoring of urinary CPI excretion (especially CPI/CPIII ratio) may be a useful, cheap and simple tool in early prediction of the response to antiviral therapy in subjects affected by HCV CH, especially in the presence of mild laboratory signs of cholestasis

Case of melorheostosis associated with ipsilateral verrucous epidermal nevus, linear connective tissue nevus, diffuse hyperpigmentation and hypertrichosis: A fortuitous coincidence?

Melorheostosis (MEL) is a rare benign bone disorder that can be associated with several anomalies, including vascular abnormalities, nevus sebaceus, unilateral nevoid telangiectasia, linear scleroderma and hypertrichosis. We report the case of a 6-year-old patient who showed an unusual co-occurrence of bone hyperostosis and different skin lesions affecting the same side of the body: MEL, verrucous epidermal nevus, connective tissue nevus, linear scleroderma-like disorder, hyperpigmentation and hypertrichosis. The spatial co-occurrence of these conditions made us speculate as to whether they originated from a common genetic mechanism or if their co-occurrence was completely accidental

Radiofrequency ablation combined with transcatheter arterial chemioembolization in the treatment of advanced hepatocellular carcinoma

Background : Treatment of HCC complicating liver cirrhosis still remains a controversial issue, due to both the characteristics of the malignant disease per se and to the problems of underlying associated chronic liver disease. In particular, for patients with HCC not elegible for “curative” options (advanced HCC) (who, despite of surveillance programs, still remain a relevant amount in the clinical practice) there is no standard therapy. Aim: to evaluate efficacy of combined treatment with radiofrequency ablation (RFA) and transcatether arterial chemio-embolization (TACE) in the treatment of advanced hepatocellular carcinoma.Materials and Methods: We compared the treatment efficacy (cumulative survival rate after treatment) in 30 HCC-confirmed (imaging and/or histological proven) patients treated with combined therapy (simultaneous application of TACE and RFA; RFA was performed on to the greatest node in case of multiple nodes) [RFA-TACE group] with HCC-confirmed patients treated only by TACE [TACE group] or by conservative option [Control group]. Patients in TACE and Control groups were chosen as matching more as possible with patients in RFA-TACE group with regard to all possible factors influencing survival. Patients in TACE group could not undergo RFA due to technical (site of tumour, lesion undetectable at ultrasound, etc) and/or refuse of treatment. Control group could not undergo TACE due to portal complete or partial thrombosis or site of tumour. All patients were monitored at one-three months after treatment and every six months by imaging to control for treatment success and neoplasm relapse.Results: Characteristics of the considered groups are resumed in the table below. No patients were lost at follow-up. Survival rates were better in TACE-RFA group than TACE and control group. The median survival time was 16.1 months for TACE-RFA, 12.1 for TACE and 8.4 for Controls. The 6-month, 1-year and 2-years survival rate was 78%, 71% and 47% TACE-RFA group vs. 72%, 66% and 40% and 65%, 55% and 39% in TACE and Control group (p=.025 and p=.002 with respect to TACE-RFA group, i.e significant after Bonferroni correction for multiple comparisons).RFA-TACE (n=30)TACE (n=34)Controls (n=35)Age67±764±868±10Sex (males)22 (73.3%)25 (73.5%)26 (74.3%)Child score6.8±1.56.8±1.37.1±1.9Child group A/B11/1911/2310/25Nodes (mean)3.1±1.23.2 ±1.13.4±1.6Major node dimension3.9±1.53.8±1.63.9±1.8Single / Multiple node8/209/269/26BCLC stage ( B/C)16/1416/1815/20Milan criteria1 2/ 3 17/1315/1915/20Duration of Liver Disease (years) 8.4±4.48.7±3.58.6±3.5Etiology : Viral vs. Nonviral22/828/628/71 2= Single node > 3 and 5 cm or multiple nodes (more than 3 or up to 3 with the greatest > 3 cm)Conclusion: The combination of RFA and TACE is a promising approach for the treatment of advanced HCC complicating liver cirrhosis, nevertheless a better definition of patient’s characteristics and technical approaches are needed together with large scale-randomized trial for confirmation of results