Endometriosis: seeking optimal management in women approaching menopause.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

Radiomic biomarkers informative of cancerous transformation in neurofibromatosis-1 plexiform tumors.

BACKGROUND: This study explores whether objective, quantitative radiomic biomarkers derived from magnetic resonance (MR), positron emission tomography (PET), and computed tomography (CT) may be useful in reliably distinguishing malignant peripheral nerve sheath tumors (MPNST) from benign plexiform neurofibromas (PN). METHODS: A registration and segmentation pipeline was established using a cohort of NF1 patients with histopathological diagnosis of PN or MPNST, and medical imaging of the PN including MR and PET-CT. The corrected MR datasets were registered to the corresponding PET-CT via landmark-based registration. PET standard-uptake value (SUV) thresholds were used to guide segmentation of volumes of interest: MPNST-associated PET-hot regions (SUV≥3.5) and PN-associated PET-elevated regions (2.0

Regulating the communication of genetic risk information: the Italian legal approach to questions of confidentiality and disclosure.

Communication of genetic risk is a complex process in which the rights of the individual and those of relatives may conflict with regard to the information revealed by DNA testing. If patients who participate in clinical genetic testing refuse to share their genetic information with at-risk relatives, healthcare professionals need to reach a proper ethical balance between the right of individual patients regarding the confidentiality of their genetic test result and the right of families to be informed about their genetic risk. Rules and legislation in most countries generally protect the confidentiality of medical information but allow limited disclosure of genetic test results without the patient's consent in specific cases when certain conditions are met. The aim of this article is to draw attention to how Italian policymakers have attempted to balance protection of autonomy and confidentiality, and protection of health by means of a hybrid instrument. Furthermore, we show that some of the requirements of that instrument depart from the most widely recognized standards for non-consensual disclosure of genetic risk information, while at the same time allowing an unusually high level of discretion to healthcare professionals involved in genetic counseling and testing.

An unusual observation of tetragametic chimerism: forensic aspects.

A 41-year-old healthy Caucasian male showed an unidentifiable direct AB0 group and a B group by an indirect method revealing the presence of natural antibodies anti-A1 and anti-A2. Mixed fields with anti-B and anti-A+B antisera led to the conclusion that blood group B and 0 cell populations were present in a 1:1 ratio. A negative anamnesis for both transplantation and transfusion suggested a chimerism. DNA analysis of tissues revealed a tetragametic chimerism due to an apparent double parental contribution of nuclei in a phenotypically normal man.

Audit of litigation against the accident and emergency radiology department.

PURPOSE: The aims of this study were to reduce and monitor litigation due to failure to diagnose a fracture, to evaluate whether the cases were due to radiological error or other problems in the diagnostic and therapeutic management of patients and to identify organisational, technical or functional changes or guidelines to improve the management of patients with suspected fracture and their expectations. MATERIALS AND METHODS: We analysed the litigation database for the period 2004-2006 and extracted all episodes indicating failure to diagnose a fracture at the accident and emergency radiology department of our centre. The radiographs underwent blinded review by two experts, and each case was jointly analysed by a radiologist and a forensic physician to see what led to the compensation claim. RESULTS: We identified 22 events (2004 seven cases; 2005 eight cases; 2006 seven cases). Six cases were unrelated to radiological error. Six were due to imperceptible fractures at the time of the examination. These were accounted for by the presence of a major lesion distracting the examiner's attention from a less important associated lesion in one case, a false negative result in a patient examined on a incompletely radiolucent spinal board and underexposure of the coccyx region in an obese patient. Six cases were related to an interpretation error by the radiologist. In the remaining cases, the lesion being referred to in the compensation claim could either not be established or the case was closed by the insurance company without compensation. Corrective measures were adopted. These included planning the purchase of a higher performance device, drawing up a protocol for imaging patients on spinal boards, reminding radiologists of the need to carefully scrutinise the entire radiogram even after having identified a lesion, and producing an information sheet explaining to patients the possibility of false negative results in cases of imperceptible lesions and inviting them to return to the department if symptoms persist. CONCLUSIONS: We believe the clinical and administrative analysis we performed is useful. It reviewed some administrative practices and identified critical features. We identified tools that we trust will reduce litigation.

Obesity treatment in elderly outpatients: predictors of efficacy and drop-out.

OBJECTIVE: Obesity is increasing in the elderly and it is associated with an increased risk of medical complications, decline in physical function and disability. Very few studies specifically evaluated the outcome of obesity treatment in the aging patients. Aim of this work is therefore the evaluation of the efficacy of medical therapy in a group of obese patients >or=65 years old. METHODS: The study has been performed on the clinical records of obese outpatients treated at the medical branch of the Unit for Medical and Surgical Therapy of Obesity at the University of Padova. Patients were recruited from January 1st, 2001 to June 30th, 2006 in order to have patients with at least one year of potential follow-up. In particular two groups were enrolled: 100 patients >or=65 years old and 200 patients <65 years old. The baseline characteristics, the prescriptions and the treatment outcome were compared. RESULTS: Mean age of the elderly patients was 69.1+/-3.7 years (range 65-80 years). We did not find any significant difference between elderly and adult patients in the sex distribution (female patients 76% in the elderly group and 72% in the adult group; p=0.276) and in the severity of overweight (body mass index: 37.8+/-6.0 kg/m2 in the elderly; 37.2+/-6.3 kg/m2 in adults; p=0.425). The elderly group was characterized by a higher incidence of comorbidities and a lower incidence of eating behavior disorders at baseline. No significant differences in the dietary prescription were found, whereas physical activity was prescribed in 27/100 elderly patients (27%) and in 97/200 (48%) adults patients (p<0.000). Weight loss was evaluated by analyzing the percentage of patients reaching at least a 10% weight loss from baseline after 12 months of treatment. In elderly patients still in active treatment after 12 months, only 5/28 (18%) patients reached the specified goal, whereas in adult patients still in treatment, 18/47 (38%) patients reached the goal (p<0.05). Lower age at baseline, female sex, and lower body mass index were found to be the only significant predictors of 10% weight loss in logistic regression. In our experience, drop-out rate after 12 months was similar in adults (77%) and in older patients (72%). In a multivariate Cox regression model, the risk of drop-out was reduced by married or widowed status, the prescription of physical activity at baseline, and the presence of type 2 diabetes. The risk of drop-out was increased by the presence of osteoarthritis. Even after adjustments for these confounding variables, age did not play any significant role as drop-out predictor. CONCLUSION: Advanced age seems to be a predictor of poor response to treatment in obese outpatients treated by conventional medical therapy. Drop-out rate was not significantly influenced by age.

Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma.

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based immunosuppressive regimen to allow engraftment of HLA-sibling donors' mobilized stem cells and induction of a graft-versus-lymphoma effect for patients with advanced resistant Hodgkin's disease and non-Hodgkin's lymphoma. PATIENTS AND METHODS: Fifteen patients with Hodgkin's disease (n = 10) and non-Hodgkin's lymphoma (n = 5) were studied. All patients received cyclophosphamide and granulocyte colony-stimulating factor to mobilize autologous hematopoietic stem cells (HSCs). Subsequently, they received high-dose therapy with carmustine, etoposide, cytarabine, and melphalan and reinfusion of HSCs. At a median of 61 days after engraftment, patients were given fludarabine 30 mg/m(2) with cyclophosphamide 300 mg/m(2) daily for 3 days. Donor-mobilized HSC collections were prepared for fresh infusion and were not T-cell depleted. Methotrexate and cyclosporine were used to prevent graft rejection and as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Combined treatment was well tolerated. After mini-allografting, hematologic recovery was prompt. Thirteen patients had 100% donor cell engraftment. Eleven patients achieved complete remission (CR) after the combined procedure. Nine patients, who were in partial remission after autografting, achieved CR after mini-allografting. Seven patients developed >/= grade 2 acute GVHD (aGVHD) and two developed extensive chronic GVHD (cGVHD). Three patients who received the highest number of donor lymphocyte infusions (DLIs) developed grade 3 GVHD (two patients) and extensive cGVHD (one patient). Ten patients are currently alive, and five are in continuous CR. Seven patients received DLI, with five CRs. Five patients died: one of progressive disease, two of progressive disease combined with aGVHD or cGVHD, one of extensive cGVHD, and one of infection. CONCLUSION: Fludarabine/cyclophosphamide was well tolerated and allowed consistent engraftment in lymphoma allografted patients. Response rates were high in this group of refractory and heavily pretreated patients. This dual procedure seems to be most promising in patients with end-stage malignant lymphomas.

Obesity, Muscular Strength, Muscle Composition and Physical Performance in an Elderly Population.

OBJECTIVE: To evaluate the association between BMI levels, muscular strength, muscle composition and physical performance in the elderly. DESIGN: Italians subjects from the Progetto Veneto Anziani (ProVA) study were analyzed. SETTING: The ProVa was a population study focused on chronic diseases and functional limitations in Italian subjects aged ≥65 years living in two Northeast Italian cities. PARTICIPANTS: The ProVa study included 3099 subjects. ProVa participants with unknown information on BMI or disability status were excluded. The final sample was thus represented by 1.188 men, and 1.723 women. MEASUREMENTS: Physical performance was measured with the Short Physical Performance Battery (SPPB) and leg muscular strength with dynamometry. Fat distribution and skeletal muscle composition were measured in an abdominal single-scan magnetic resonance (MRI) in a randomly selected sample of 348 subjects. Study population was stratified by BMI classes. RESULTS: An association between BMI levels and SPPB was observed. Normal weight subjects showed the best SPPB scores (8.29±0.03), with significant differences compared to underweight (7.50±0.15; p<0.001), overweight (8.12±0.02; p<0.001), class I (7.72±0.04; p<0.001), class II (6.67±0.09; p<0.001) and class III obesity (5.88±0.24; p<0.001). This pattern was not modified by adjustment for possible confounders. Compared to normal weight subjects (22.9±0.1 kg), leg muscular strength was higher in overweight (23.8±0.1; p<0.001) and in class I obesity (24.5±0.1; p<0.001), but it was reduced in class II (21.4±0.3; p<0.001) and class III (19.8±0.9; p<0.001). The association between BMI and impaired physical performance was not affected by adjustment for muscular strength. An inverse association between SPPB scores and fat infiltration in skeletal muscle was observed in patients with abdominal MRI. CONCLUSION: A poor physical performance was observed in overweight and obese elderly subjects. Leg strength was reduced only in subjects with severe obesity. Physical performance was negatively influenced by the degree of fat infiltration in skeletal muscle.

Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation.

Malignant autosomal recessive (AR) osteopetrosis represents an absolute indication for bone marrow transplantation (BMT). Over the last 15 years, almost 100 BMTs for osteopetrosis have been reported. The median age at transplant of most patients is 4 months. Very few cases of mild AR osteopetrosis have been described. Here, we report the good outcome of two cases of mild AR osteopetrosis with a follow-up of 5 and 6 years, respectively, after an HLA-identical sibling transplant undergone at 5 and 12 years of age, respectively. At the time of BMT, severe visual impairment was present in both children. Bone biopsy demonstrated hypermineralization with virtual obliteration of the medullary spaces, rare microfoci of hematopoiesis and marked deficiency in osteoclastic activity. Successful engraftment was complicated by hypercalcemia, controlled by a combination of bisphosphonate, phosphate infusions, vigorous hydration and calcitonin. Following BMT, radiological and histological findings showed extensive bone resorption with marked augmentation of the osteoclasts in normalized marrow. No improvement was observed in visual acuity, despite complete remodeling of skeletal abnormalities. We conclude that allogeneic BMT is the only chance of curing mild AR osteopetrosis.

Treatment of allergic diseases during pregnancy.

Pregnancy may variously modify the natural history of allergic disorders through occurring endocrinologic, functional and immunological changes. A pharmacologic treatment of allergic diseases (mainly asthma) is often necessary during pregnancy. On the other hand, a drug should be not potentially teratogenic and should not have serious side effects, both for the mother and the fetus. This paper reviews current knowledge about allergic diseases during pregnancy, considering the points of view of the different specialists involved in their management. Topical mucosal agents seem to be the safest, due to their minimal or absent absorption which should reflect reduced side effects. Preferred agents should be topical antihistamines (for rhinitis and conjunctivitis), and cromones and topical steroids (for asthma), as they are both safe and effective.

HLA-DQA1 allele and genotype frequencies in a northern Italian population.

HLA-DQA1 typing of 227 randomly selected Northern Italian people by the use of polymerase chain reaction are reported. The combined use of commercial Amplitype HLA-DQalpha system and four sequence-specific oligonucleotide probes allows the definition of 8 alleles and 36 genotypes, arranged according to World Health Organisation nomenclature. Seven of these genotypes are not observed among the analyzed samples. Allele frequencies range from 1.5 to 35.7% and genotype observations do not deviate significantly from Hardy-Weinberg equilibrium; observed heterozygosity is 0.8238 with an allelic diversity value of 0.79 and the power of discrimination is 0.925. Our Italian population sample shows differences from other Caucasian samples both for allele and genotype frequencies. This locus typing for the 8 defined alleles provides a rapid and sensitive method in individual identification and paternity investigation.

Y-chromosome haplotypes in Italy: the GEFI collaborative database.

A sample of 1176 males from 10 Italian regions have been typed for DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, and DYS385. Individual haplotype data are available on line. A low degree of variation is present among regions. Use of this database is specifically recommended for forensic applications in Italy.

HLA-DQA1 and amelogenin coamplification: a handy tool for identification.

A protocol for HLA-DQA1 and gender identification by single amplification is described. The use of the commercial HLA-DQA1 amplification kit (Perkin Elmer) permits a positive response for sex determination by adding primers for a short sequence on the first intron of Amelogenin gene. The suggested amplification protocol results in PCR products easily and clearly detectable on ethidium bromide stained agarose gel or silver stained polyacrylamide gel. In both gels the HLA-DQA1 observations at 242-239 bp are accomplished with a single band at 106 bp in females and a doublet 112-106 bp in males. HLA-DQA1 reverse dot-blot hybridization is unaffected by the presence of X and Y amplified fragments.

[Flaccid paralysis surveillance in the Latium Region]. / La sorveglianza della paralisi flaccida nella Regione Lazio.

The goal of World Health Organization is to reach the global eradication of poliomyelitis during the first decade of the third millennium. To achieve the certification of the eradication of the disease the main strategy is the Acute Flaccid Paralysis (AFP) surveillance. In Italy the active AFP surveillance was performed at national level since 1997. In the Latium region the active surveillance was performed since January 1997 by the laboratory of virology of Institute of Hygiene G Sanarelli which established a regional hospital network. During the years of survey 7 cases were found in 1997 (0.87/100,000), 4 in 1998 (0.5/100,000), 2 in 1999 (0.25/100,000) and 2 in 2000. No wild polioviruses were detected.

Informed consent for tracheostomy procedures in Intensive Care Unit: an Italian national survey.

BACKGROUND: Critically ill patients in Intensive Care Unit (ICU), due to their temporary or permanent incompetence, are often not capable to provide informed consent (IC), although required, for not emergency invasive procedures, like elective tracheostomy. By Italian law, a person with partially/temporarily physical/mental impairment needs a legal tutorship appointed by the court (Support Administrator, SA). We performed a national survey in Italy to investigate IC practice for elective tracheostomy procedure in critically ill conscious and unconscious patients in ICU. METHODS: Questions about IC were included in a survey concerning the clinical practice of tracheostomy in ICU. The survey was approved by the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI, n° 434 - 28 March 2012) and sent by e-mail to all members included in its mailing list. The duration of the survey was three months from April to June 2012. All required information was referred to the year 2011. RESULTS: The mailed questionnaire correctly fulfilled was sent back by 131/427 (30%) national ICUs. Our data showed 1) in conscious patients, IC was obtained by 82.4% of ICUs; 2) in unconscious patients, IC was obtained in only 61.8% with different procedures not following the current Italian law, 3) for surgical tracheostomy performed in operating room, IC was obtained in conscious and unconscious patients in only 69.8% and 47.2% of ICUs, respectively, 4) risk/benefit informative document was provided in 61.1% ICUs, but available only in 47.2% of ICUs performing tracheostomy in operating room. CONCLUSION: In Italian ICUs, participating to this study, the procedures related to IC for conscious and unconscious critically ill patients requiring surgical or percutaneous tracheostomy are not in line with current legal rules and procedures.

The 2011 GeFI collaborative exercise. Concordance study, proficiency testing and Italian population data on the new ENFSI/EDNAP loci D1S1656, D2S441, D10S1248, D12S391, D22S1045.

The 2011 collaborative exercise of the ISFG Italian Working Group GeFI was aimed at validating the five ENFSI/EDNAP miniSTR loci D1S1656, D2S441, D10S1248, D12S391 and D22S1045. The protocol required to type at least 50 multilocus profiles from locally resident individuals and two blind bloodstains in duplicate (i.e., using at least two different commercial kits), and to send the electropherograms to the Organizing Committee. Nineteen laboratories distributed across Italy participated, collecting a total of 960 samples. Full concordance was found for the five new miniSTRs as observed from the comparison of 13,150 alleles. The inspection of the electropherograms allowed the identification of a very limited number of mistypings in the miniSTR genotypes thus contributing to the establishment of an high quality Italian database of frequencies.

Allogeneic hemopoietic SCT for patients with primary myelofibrosis: a predictive transplant score based on transfusion requirement, spleen size and donor type.

A total of 46 patients with primary myelofibrosis (PMF) (median age 51 years), underwent an allogeneic hemopoietic SCT (HSCT) after a thiotepa-based reduced-intensity conditioning regimen. The median follow-up for surviving patients is 3.8 years. In multivariate analysis, independent unfavorable factors for survival were RBC transfusions >20, a spleen size >22 cm and an alternative donor-24 patients had 0-1 unfavorable predictors (low risk) and 22 patients had 2 or more negative predictors (high risk). The overall actuarial 5-year survival of the 46 patients is 45%. The actuarial survival of low-risk and high-risk patients is, respectively, 77 and 8% (P<0.0001); this is because of a higher TRM for high-risk patients (RR, 6.0, P=0.006) and a higher relapse-related death (RR, 7.69; P=0.001). In multivariate Cox analysis, the score maintained its predictive value (P=0.0003), even after correcting for donor-patient age and gender, Dupriez score, IPSS (International Prognostic Scoring System) score pre-transplant and splenectomy. In conclusion, PMF patients undergoing an allogeneic HSCT may be scored according to the spleen size, transfusion history and donor type; this scoring system may be useful to discuss transplant strategies.