A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes,different faces of the same disease?

Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.     

Assessing inter- and intra-individual cognitive variability in patients at risk for cognitive impairment: the case of minimal hepatic encephalopathy

Recent evidence reveals that inter- and intra-individual variability significantly affects cognitive performance in a number of neuropsychological pathologies. We applied a flexible family of statistical models to elucidate the contribution of inter- and intra-individual variables on cognitive functioning in healthy volunteers and patients at risk for hepatic encephalopathy (HE). Sixty-five volunteers (32 patients with cirrhosis and 33 healthy volunteers) were assessed by means of the Inhibitory Control Task (ICT). A Generalized Additive Model for Location, Scale and Shape (GAMLSS) was fitted for jointly modeling the mean and the intra-variability of Reaction Times (RTs) as a function of socio-demographic and task related covariates. Furthermore, a Generalized Linear Mixed Model (GLMM) was fitted for modeling accuracy. When controlling for the covariates, patients without minimal hepatic encephalopathy (MHE) did not differ from patients with MHE in the low-demanding condition, both in terms of RTs and accuracy. Moreover, they showed a significant decline in accuracy compared to the control group. Compared to patients with MHE, patients without MHE showed faster RTs and higher accuracy only in the high-demanding condition. The results revealed that the application of GAMLSS and GLMM models are able to capture subtle cognitive alterations, previously not detected, in patients’ subclinical pathologies.     

The grandfather’s fever

Clinical Rheumatology - An 86-year-old Caucasian man had prior episodes of fever (up to 38 °C), mild abdominal pain, tachycardia, and malaise in the last 3 months, lasting...     

Laparoscopic repair of perforated peptic ulcer: single-center results

Background

Perforated peptic ulcer (PPU), the most common indication for emergency gastric surgery, is associated with high morbidity and mortality rates. Outcomes might be improved by performing this procedure laparoscopically, but no consensus exists on whether the benefits of laparoscopic repair (LR) of PPU outweigh the disadvantages.

Methods

From January 2002 to December 2012, 111 patients underwent surgery for perforated ulcer. A “laparoscopy-first” policy was attempted and then applied for 56 patients. The exclusion criteria for LR ruled out patients who had shock at admission, severe cardiorespiratory comorbidities, or a history of supramesocolic surgery. The aim of this study was a retrospective analysis of the 56 patients treated laparoscopically.

Results

The patient distribution was 30 men and 26 women, who had a mean age of 59 years (range 19–95 years). The mean ulcer size was 10 mm, and the Mannheim peritonitis index (MPI) was 21. LR was performed for 39 (69.6 %) of the 56 patients and included peritoneal lavage, suturing of the perforation, and omental patching. Conversion to laparotomy was necessary in 17 cases (30.4 %). The “conversion group” showed significant differences in ulcer size (larger ulcers: 1.9 vs 0.7 mm; p < 0.01), ulcer-site topography (higher incidence of posterior ulcers: 5 vs 0; p < 0.01), and MPI score (higher score: 24 vs 20; p < 0.05). The LR group had a mean operating time of 86 min (range 50–125 min), an in-hospital morbidity rate of 7.6 %, a mortality rate of 2.5 %, and a mean hospital stay of 6.7 days (range 5–12 days). None of these patients required reintervention.

Conclusions

The results showed that LR for PPU is feasible with acceptable mortality and morbidity rates. Skill in laparoscopic abdominal emergencies is required. Perforations 1.5 cm or larger, posterior duodenal ulcers, and an MPI higher than 25 should be considered the main risk factors for conversion.     

Mapping protein signal pathway interaction in sarcoma bone metastasis: linkage between rank, metalloproteinases turnover and growth factor signaling pathways

We applied reverse phase protein microarrays technology to map signal pathway interactions in a discovery set of 34 soft tissue sarcoma (STS) bone metastases compared to healthy bone. Proteins associated with matrix remodeling (MMP), adhesion (FAK Y576/577, Syndecan-1), and growth/survival (IGF1R Y1135/1136, PI3K, EGFR) were elevated in metastasis compared to normal bone. Linkage between Syndecan-1, FAK Y576/577, Shc Y317, and EGFR, IGF Y1135/1136, PI3K/AKT was a prominent feature of STS bone metastasis. Elevated linkage between RANKL and 4EBP1 T37/46, EGFR, IGF1R Y1135/1136, Src Y41, Shc Y317, PI3Kp110γ was associated with short survival. Finally, we tested the hypothesis that signal pathway proteins augmented in the STS bone metastasis may provide clues to understand the subset of primary STS that metastasize. The most representative molecules identified in the discovery set were validated on an independent series of 82 primary STS by immunohistochemistry applied to a tissue microarray. The goal was to correlate the molecular profile in the primary tumors with a higher likelihood of metastasis. Elevation of activated kinase substrate endpoints IRS1 S612, 4EBP1 T37/46, FAK Y576/577 and loss of Fibronectin, were associated with a higher likelihood of metastases. These data indicate that the linkage between matrix remodeling, adhesion, and growth signaling may drive STS metastasis and can be the basis for prognostic and therapeutic strategies.     

Role of mandibular displacement and airway size in improving breathing after rapid maxillary expansion

Background

Oral breathing and maxillary deficiency are often associated with steep mandibular plane angle, and retrognathic mandible compared with the faces of healthy controls. Some studies suggested that after rapid maxillary expansion, improvement in nasal breathing and repositioning of mandible with transitory increasing of facial height and, in some cases, spontaneous forward repositioning might occur. The abovementioned mandibular effects could contribute to enlarge oropharynx volume with repositioning of tongue and soft palate with an improvement of upper airway volume after treatment. The aim of this study was to investigate by cone beam computed tomography the role of oropharyngeal volume and mandibular position changes after rapid maxillary expansion in patients showing improved breathing pattern confirmed by polysomnography exam.

Methods

The final sample of this retrospective study comprised 14 Caucasian patients (mean age 7.6 years) who undergone rapid maxillary expansion with Haas-type expander banded on second deciduous upper molars. Cone beam computed tomography scans and polysomnography exams were collected before placing the appliance (T0) and after 12 months (T1). Mandibular landmarks localization and airway semiautomatic segmentation on cone beam computed tomography scans allowed airway volume computing and measurements.

Results

No significant differences were found between oropharyngeal airway changes and mandibular displacement after rapid maxillary expansion in growing patients.

Conclusions

The suggested improvement in upper airway and breathing after rapid maxillary expansion should be further related to different compartments of airway such as rhinopharynx and nasal cavity.