Molecular cytogenetic characterization of a complex rearrangement involving chromosomes 9 and 22 in a case of Ph-negative chronic myeloid leukemia

The "golden path", produced by the Human Genome Project effort, is composed of a collection of overlapping and fully sequenced BAC/PAC clones covering almost completely the human genome. These clones can be advantageously exploited as fluorescence in situ hybridization (FISH) probes for the characterization of rearrangements frequently found in tumors. Breakpoint characterization can be further refined by generating additional smaller FISH probes through LONG-PCR amplification of specific DNA segments, 5-10 kb in size, using appropriate BAC/PAC probes as template. We report here an example of this approach that has been used to characterize a complex Ph-negative chronic myeloid leukemia (CML Ph-) case in which the BCR/ABL fusion gene was found located on chromosome 9.     

Risk factors for urinary incontinence in women

OBJECTIVES: To review the epidemiological evidence on risk factors for urinary incontinence (UI) in women. METHODS: Using Medline and a manual search we identified the main papers published in English up to 1998. RESULTS: There is consistent evidence that the frequency of UI increases with age, but there is little information on the frequency of different types of UI in different age groups. With regard to other risk factors, there is a clinical consensus that vaginal delivery and, more in general, obstetric traumas are associated with UI, although epidemiological studies are not always consistent. Less defined is the role of race, menopausal status, history of gynecological surgery, body mass index, smoking, and coffee and alcohol consumption on the risk of UI. CONCLUSION: In the coming years, epidemiological research should focus particularly on the potential differences in the epidemiological characteristics of different types of UI in order to gain insight into the pathogenic mechanisms.     

The surgical treatment of fractures of the proximal end of the tibia: a review of cases as related to prognostic factors

It is the purpose of this retrospective study to analyze factors capable of influencing clinical-functional and radiographic results, such as type of fracture, age of the patients, type of trauma, delay in treatment, associated lesions. A total of 33 fractures treated by open reduction and internal stabilization for fractures of the proximal tibia classified according to the AO were re-evaluated. Clinical and radiographic evaluation were obtained by assessing arthrosis, axis, and sinking of the tibial plateau. The clinical and functional results were satisfactory in 72.2% of cases, and radiographic ones were satisfactory in 63.6% for gonarthrosis, in 81.6% for axis, and in 84.8% for sinking. In conclusion, factors capable of influencing the results, such as type of fracture, age of the patient, and type of trauma, in addition to variables that the surgeon must monitor, such as reconstruction of the joint, alignment, synthesis, treatment of meniscal lesions, were observed.     

Early predictors of mortality in refractory cardiogenic shock following acute coronary syndrome treated with extracorporeal membrane oxygenator

We aimed to analyze the outcome and identify predictors of hospital mortality in patients with refractory cardiac arrest (CA) complicating acute coronary syndromes (ACS) and requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. Between Jan-2005 and Dec-2019, 51 patients underwent urgent VA-ECMO implantation for CA in ACS. Patients were divided in two groups: “in-hospital” cardiac arrest (IHCA) and “out-of-hospital” cardiac arrest (OHCA). Prospectively collected data were retrospectively analyzed and compared between groups. Predictors for hospital mortality were investigated. IHCA and OHCA patients were 32 (62.7%) and 19 (37.3%), respectively. The groups differed for: male gender (72% vs 95%; p?=?0.070), lactate peak level (8.5?±?4.3vs10.7?±?2.9; p?=?0.023), total elapsed time from CA to VA-ECMO implantation in both groups (p?<?0.001) and elapsed time from CA (IHCA group) or hospital arrival (OHCA group) to VA-ECMO implantation (38 min vs 80 min; p?=?0.001). At logistic regression analysis, concomitant lactate level greater than 8.0 mmol/L and elapsed time from CA to VA-ECMO?≥?30 min were predictors of increased mortality (OR 3.9; 95% CI 1.19–12.79; p?=?0.025) for the entire population. In-hospital mortality was 60.8% (31/51 patients): 68.4% in OHCA group and 56.2% in IHCA group. No risk factors related to 30-day mortality resulted significant at univariable analysis. When rapidly instituted, VA-ECMO improves survival in patients with refractory cardiac arrest allowing coronary syndrome treatment. The association of an elapsed time from CA to VA-ECMO implantation longer than 30 min and a preoperative lactate peak level over 8.0 mmol/L predict a poor outcome, independently from being IHCA or OHCA.

     

Atrioventricular canal defect in patients with RASopathies

Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124 A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies.     

Congenital heart defects in recurrent reciprocal 1q21.1 deletion and duplication syndromes: Rare association with pulmonary valve stenosis

Microdeletion 1q21.1 (del 1q21.1) and the reciprocal microduplication 1q21.1 (dup 1q21.1) are newly recognized genomic disorders, characterized by developmental delay, dysmorphic features and congenital malformations. Congenital heart defect (CHD) is a major feature of del 1q21.1, and has been occasionally reported in dup 1q21.1. We report here a family segregating del 1q21.1 in 3 members. Two of the affected family members had CHD, including the proband with syndromic atrial septal defect, pulmonary valve stenosis (PVS), and muscular ventricular septal defects, and the maternal uncle with non-syndromic PVS. This finding prompted investigation of the role of recurrent rearrangements of chromosome 1q21.1 in the pathogenesis of PVS. We gathered 38 patients with PVS (11 syndromic and 27 non-syndromic), and searched for genomic rearrangements of 1q21.1. A dup 1q21.1 was detected in a single sporadic non-syndromic patient. Review of the CHDs in published del 1q21.1 and dup 1q21.1 subjects showed a great heterogeneity in anatomic types. In conclusion, the present family illustrates recurrent CHD in del 1q21.1, expressing either as syndromic in one family member or as non-syndromic in the another one. The spectrum of CHDs associated with del 1q21.1 and dup 1q21.1 can occasionally include PVS.     

Current practice of chronic hepatitis B treatment in Southern Italy

BackgroundTreatment choice for chronic HBV infection is a continuously evolving issue, with a wide range of options. We aimed to evaluate the current practice of HBV therapies in the real world in Southern Italy.MethodsA prospective study enrolling over a six month period (February–July 2010) all consecutive HBsAg positive subjects, never previously treated, referred to 16 liver units in two Southern Italy regions (Calabria and Sicily).ResultsOut of 247 subjects evaluated, 116 (46.9%) had HBV-DNA undetectable or lower than 2000 UI/ml. There were 108 (43.7%) inactive carriers, 103 (41.7%) chronic hepatitis, and 36 (14.6%) liver cirrhosis. Antiviral treatment was planned in 94 (38.0%) patients (26 cases with Interferon or Pegylated Interferon and 68 with nucleos(t)ides analogues). As many as 49.5% of subjects with chronic hepatitis did not receive antiviral treatment.DiscussionThe majority of chronic HBsAg carrier referring centres for evaluation were not considered suitable for antiviral treatment. Nucleos(t)ides analogues are the preferred first choice for therapy. A long-lasting period of observation may be needed to make appropriate therapeutic decisions in several cases.     

Coventry Award paper. Backsurface wear and deformation in polyethylene tibial inserts retrieved postmortem

Wear and deformation were characterized at the backsurface of 25 posterior cruciate-retaining total knee arthroplasty polyethylene inserts retrieved postmortem from 20 subjects. The mean implantation time was 64.1 months (range, 4-156 months). The backsurface of the inserts was inspected using a stereomicroscope with a digital optical system. Coronal histologic sections of 13 proximal tibias were inspected for the presence and extent of penetration of granuloma. Damage to the backsurface was limited. Polishing was recorded on 21 (84%) of the inserts and abrasive wear on five (20%) inserts. Pitting was present in 21 (84%) components, but involved less than 1% of the area in all but one of these components. Delamination and cracking were not observed. Extrusions were seen in all 10 of the components that had screw holes in the tibial tray. A correlation was found between the depth of penetration of the granuloma along the posteromedial screw and the height of the corresponding extrusion. The anteroposterior profiles showed a concave deformation of the backsurface in 24 (96 %) of the cases. The concave deformation of tibial inserts may facilitate accumulation and transportation of wear debris to the tibial bone-implant interface through the screw holes in implants designed for cementless fixation.