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Background: Liberal or overtransfusion (OT) may be regarded as "inappropriate," but it is not reported as a transfusion-related adverse event. A definition of OT is lacking. OT may include overdosing of components, giving the incorrect component, or unnecessary administration without evidence of need for transfusion. OT can be associated with hypercoagulability, thrombosis, alloimmunization, increased mortality, longer hospital stay, increased infection rates, and adverse cardiocirculatory events., Study Design and Methods: In 2023, an expert panel formed a hemovigilance international taskforce embedded in the German Interdisciplinary Taskforce for Clinical Hemotherapy (IAKH). The group was charged with proposing simple criteria to be used by hemovigilance systems to document instances of OT., Results: This international initiative combined a narrative review of the literature for the rate and outcomes of OT with transfusion error reports to propose a definition for OT, including a definition for transfusion-induced hypercoagulopathy (TIH), three new codes for OT/TIH and subcodes A to G, three severity categories (serious adverse event, adverse event, near miss), and four incident codes (definite, probable, possible, not determinable). These codes can be used by hemovigilance systems to appropriately document instances of OT., Conclusions: Global adoption of these codes within hemovigilance systems would assist with the recognition and reporting of instances of OT, promote effective policies for adequate clinical administration techniques, and support technical guidelines for avoidance of OT. Thereby, incorporation of OT into hemovigilance strategies could support adequate use of blood products, increase patient safety, and facilitate blood supply and availability., (© 2024 AABB.)

In recent years, GLP-1 receptor agonists (GLP-1RA), and SGLT-2 inhibitors (SGLT-2i) have become available, which have become valuable additions to therapy for type 2 diabetes as they are associated with low risk for hypoglycemia and cardiovascular benefits. Indeed, SGLT-2i have emerged as a promising class of agents to treat heart failure (HF). By inhibiting SGLT-2, these agents lead to excretion of glucose in urine with subsequent lowering of plasma glucose, although it is becoming clear that the observed benefits in HF cannot be explained by glucose-lowering alone. In fact, multiple mechanisms have been proposed to explain the cardiovascular and renal benefits of SGLT-2i, including hemodynamic, anti-inflammatory, anti-fibrotic, antioxidant, and metabolic effects. Herein, we review the available evidence on the pathophysiology of the cardiological benefits of SGLT-2i. In diabetic heart disease, in both clinical and animal models, the effect of SGLT-2i have been shown to improve diastolic function, which is even more evident in HF with preserved ejection fraction. The probable pathogenic mechanisms likely involve damage from free radicals, apoptosis, and inflammation, and therefore fibrosis, many of which have been shown to be improved by SGLT-2i. While the effects on systolic function in models of diabetic heart disease and HF with preserved ejection fraction is limited and contrasting, it is a key element in patients with HF and reduced ejection fraction both with and without diabetes. The significant improvement in systolic function appears to lead to subsequent structural remodeling of the heart with a reduction in left ventricle volume and a consequent reduction in pulmonary pressure. While the effects on cardiac metabolism and inflammation appear to be consolidated, greater efforts are still warranted to further define the entity to which these mechanisms contribute to the cardiovascular benefits of SGLT-2i., (© 2023. The Author(s).)

We report a case of a 12-year-old girl who presented with acute-onset diplopia, dizziness, and upbeat nystagmus. On examination, she had right internuclear ophthalmoplegia with right eye hypertropia and exotropia and impaired convergence. In addition, she also had spontaneous primary position symmetric upbeat nystagmus. In this report, we discuss the clinical approach with meticulous neuro-ophthalmologic examination and neuroanatomic localization in pediatric patients with acute-onset diplopia., (© 2022 American Academy of Neurology.)

Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, glycemia is a very stable parameter, while in poorly controlled DM patients, it oscillates greatly throughout the day and between days. Clinically, GV could be measured by different parameters, but there are no guidelines on standardized assessment. Nonetheless, DM patients with high GV experience worse cardiovascular disease outcomes. In vitro and in vivo studies showed that high GV causes several detrimental effects, such as increased oxidative stress, inflammation, and apoptosis linked to endothelial dysfunction. However, the evidence that treating GV is beneficial is still scanty. Clinical trials aiming to improve the diagnostic and prognostic accuracy of GV measurements correlated with cardiovascular outcomes are needed. The present review aims to evaluate the clinical link between high GV and cardiovascular diseases, taking into account the underlined biological mechanisms. A clear view of this challenge may be useful to standardize the clinical evaluation and to better identify treatments and strategies to counteract this DM aspect.

Background: Current knowledge regarding the relationship between aortic valve sclerosis (AVSc), cardiovascular risk factors, and mortality in patients with known coronary artery disease (CAD) is still unclear. The present study aimed at investigating the prevalence of AVSc as well as its association with long-term all-cause mortality in high-risk CAD patients that has never been explored in large cohorts thus far. Methods and Results: In this retrospective and observational cohort study we enrolled high-risk CAD patients, hospitalized at Centro Cardiologico Monzino (CCM), Milan, Italy, between January 2006 and December 2016. The morphology and function of the aortic valve were assessed from the recorded echocardiographic images to evaluate the presence of AVSc, defined as a non-uniform thickening of the aortic leaflets with no consequences on hemodynamics. Data on 5-year all-cause mortality was retrieved from a Regional database. Of the 5,489 patients initially screened, 4,938 (mean age 67 ± 11 years, 3,954 [80%] men) were enrolled in the study. In the overall population, AVSc was detected in 2,138 (43%) patients. Multivariable LASSO regression revealed that age, female gender, diabetes mellitus, previous MI, and left ventricular ejection fraction were independently associated with AVSc. All-cause mortality (adjusted hazard ratio: 1.29, 95%CI: 1.05-1.58) was significantly higher in AVSc than in non-AVSc patients. Conclusions: AVSc is frequently detected in high-risk CAD patients and is associated with long-term mortality. Our findings corroborate the hypothesis that AVSc is an underestimated marker of systemic cardiovascular risk. Thus, AVSc detection may be used to improve long-term risk stratification of high-risk CAD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Myasoedova, Genovese, Cavallotti, Bonomi, Chiesa, Campodonico, Rondinelli, Cosentino, Baldassarre, Veglia, Pepi, Alamanni, Colombo, Marenzi and Poggio.)

Background: High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM., Methods: We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint., Results: Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients., Conclusions: This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.

Objective: ST-segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (DM) have higher in-hospital mortality than those without. Since cardiac and renal functions are the main variables associated with outcome in STEMI, we hypothesized that this prognostic disparity may depend on a higher rate of cardiac and renal dysfunction in DM patients., Research Design and Methods: We retrospectively analyzed 5,152 STEMI patients treated with primary angioplasty. Left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were evaluated at hospital admission. The primary end point was in-hospital mortality. A composite of in-hospital mortality, cardiogenic shock, and acute kidney injury was the secondary end point., Results: There were 879 patients (17%) with DM. The incidence of LVEF ≤40% (30% vs. 22%), eGFR ≤60 mL/min/1.73 m 2 (27% vs. 18%), or both (12% vs. 6%) was higher ( P < 0.001 for all comparisons) in DM patients. In-hospital mortality was higher in DM patients than in non-DM patients (6.1% vs. 3.5%; P = 0.002), with an unadjusted odds ratio (OR) of 1.81 (95% CI 1.31-2.49; P < 0.001). However, DM was no longer associated with an increased mortality risk after adjustment for cardiac and renal function (OR 1.03, 95% CI 0.68-1.56; P = 0.89). A similar behavior was observed for the secondary end point, with an unadjusted OR for DM of 1.52 (95% CI 1.25-1.85; P < 0.001) and an OR after adjustment for cardiac and renal function of 1.07 (95% CI 0.85-1.36; P = 0.53)., Conclusions: The study indicates that the increased in-hospital mortality and morbidity of DM patients with STEMI is mainly driven by their underlying cardio-renal dysfunction., (© 2019 by the American Diabetes Association.)

Wolfram syndrome (WFS) is a rare autosomal premature aging syndrome that shows signs of diabetes mellitus, optic atrophy, and deafness in addition to central nervous system and endocrine complications. The frequent form of WFS type 1 (WFS1) harbors causative mutations in the WFS1 gene, whereas the rare form or WFS type 2 (WFS2) involves CISD2. Mutations in these two genes are recognized by a subset of variable clinical symptoms and a set of overlapping features. In this study, we report on the generation of stable human-induced pluripotent stem cells (hiPSCs) derived from primary fibroblasts of a previously reported Italian family with CISD2 mutation (c.103 + 1G>A), occurring in the consensus intron 1 splicing site in two sisters, deleting the first exon of the transcript. The generated hiPSCs provide a cell model system to study the mutation's role in the multisystemic clinical disorders previously described and test eventual drug effects on the specific and associated clinical phenotype.

Liddle syndrome is considered a rare Mendelian hypertension. We have previously described 3 reportedly unrelated families, native of an Italian area around the Strait of Messina, carrying the same mutation (βP617L) of the epithelial sodium channel. The aims of our study were (1) to evaluate whether a close genomic relationship exists between the 3 families through the analysis of mitochondrial DNA and Y chromosome; and (2) to quantify the genomic relatedness between the patients with Liddle syndrome belonging to the 3 families and assess the hypothesis of a mutation shared through identity by descent. HVRI (the hypervariable region I) of the mitochondrial DNA genome and the Y chromosome short tandem repeats profiles were analyzed in individuals of the 3 families. Genotyping 542 585 genome-wide single nucleotide polymorphisms was performed in all the patients with Liddle syndrome of the 3 families and some of their relatives. A panel of 780 healthy Italian adult samples typed for the same set of markers was used as controls. espite different lineages between the 3 families based on the analysis of mitochondrial DNA and Y chromosome, the 3 probands and their 6 affected relatives share the same ≈5 Mbp long haplotype which encompasses the mutant allele. Using an approach based on coalescent theory, we estimate that the 3 families inherited the mutant allele from a common ancestor ≈13 generations ago and that such an ancestor may have left ≈20 carriers alive today. The prevalence of Liddle syndrome in the region of origin of the 3 families may be much higher than that estimated worldwide., (© 2017 American Heart Association, Inc.)

Background: Mutations in the gene that encodes CDGSH iron sulfur domain 2 (CISD2) are causative of Wolfram syndrome type 2 (WFS2), a rare autosomal recessive neurodegenerative disorder mainly characterized by diabetes mellitus, optic atrophy, peptic ulcer bleeding and defective platelet aggregation. Four mutations in the CISD2 gene have been reported. Among these mutations, the homozygous c.103 + 1G > A substitution was identified in the donor splice site of intron 1 in two Italian sisters and was predicted to cause a exon 1 to be skipped., Methods: Here, we employed molecular assays to characterize the c.103 + 1G > A mutation using the patient's peripheral blood mononuclear cells (PBMCs). 5'-RACE coupled with RT-PCR were used to analyse the effect of the c.103 + 1G > A mutation on mRNA splicing. Western blot analysis was used to analyse the consequences of the CISD2 mutation on the encoded protein., Results: We demonstrated that the c.103 + 1G > A mutation functionally impaired mRNA splicing, producing multiple splice variants characterized by the whole or partial absence of exon 1, which introduced amino acid changes and a premature stop. The affected mRNAs resulted in either predicted targets for nonsense mRNA decay (NMD) or non-functional isoforms., Conclusions: We concluded that the c.103 + 1G > A mutation resulted in the loss of functional CISD2 protein in the two Italian WFS2 patients.

Purpose: An observational retrospective study was conducted by 2 diabetes clinics in Italy to assess patterns of use and long-term effectiveness of liraglutide on established and emerging parameters., Methods: Data from 261 patients with type 2 diabetes who started treatment with liraglutide between 2010 and 2014 were collected. Hierarchical linear regression models were applied to assess trends over time of clinical parameters. Factors associated with higher likelihood of dropout were identified through multivariate logistic analysis., Findings: Liraglutide was initiated as a switch in 42.5% of patients and as an add-on in 49.8%; in 7.7% of the patients initiation of liraglutide was associated with a reduction in the number of pharmacologic agents. A statistically significant reduction after 36 months was found for the following parameters (mean change [95% CIs]): glycosylated hemoglobin (HbA 1c ; -1.01% [1.34% to -0.68%]), fasting blood glucose (-27.5 [-40.6 to -14.4] mg/dL), weight (-2.9 [-4.5 to -1.3] kg), body mass index (-1.13 [-1.76 to -0.50] kg/m 2 ), waist circumference (-1.74 [-3.85 to -0.37] cm), and LDL-C (-24.7 [-36.67 to -12.8] mg/dL). Improvements in systolic (-3.5 mm Hg) and diastolic (-2.3 mm Hg) blood pressures were observed at 24 months. Albuminuria was reduced by -16.6 mg/L during 36 months, although statistical significance was not reached. Glomerular filtration rate and heart rate were unchanged. Reductions in HbA 1c between -0.6% and -1.3% were obtained in specific subgroups. Treatment was effective also in patients with >20 years of diabetes duration, although the likelihood of dropout was 6% higher for each additional year of disease duration (RR = 1.06; 95% CI, 1.01-1.12). The likelihood of dropout was almost four times higher for subjects treated with insulin (RR = 3.82; 95% CI, 1.22-11.96) and more than twice for those treated with sulfonylureas (RR = 2.39; 95% CI, 1.16-4.94) compared with patients not treated with these agents., Implications: Liraglutide used in routine clinical conditions maintains its effectiveness on metabolic control and weight after 3 years. Improvements in terms of metabolic control were found when liraglutide was used as both switch and add-on treatment. In addition, improvements were sustained when liraglutide replaced sulfonylureas or insulin. Diabetes duration had no impact on drug efficacy. Long-term benefits relative to blood pressure and LDL-C were also found, which could not be entirely explained by antihypertensive/lipid-lowering treatment intensification. No major effect on renal parameters was documented. Diabetes duration and some concomitant treatments were associated with a higher likelihood of liraglutide discontinuation. These data can contribute to improve appropriateness and cost-effectiveness profile of liraglutide., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Background: In type 2 diabetes, acute hyperglycemia worsens endothelial function and inflammation,while resistance to GLP-1 action occurs. All these phenomena seem to be related to the generation of oxidative stress. A Mediterranean diet, supplemented with olive oil, increases plasma antioxidant capacity, suggesting that its implementation can have a favorable effect on the aforementioned phenomena. In the present study, we test the hypothesis that a Mediterranean diet using olive oil can counteract the effects of acute hyperglycemia and can improve the resistance of the endothelium to GLP-1 action., Methods: Two groups of type 2 diabetic patients, each consisting of twelve subjects, participated in a randomized trial for three months, following a Mediterranean diet using olive oil or a control low-fat diet. Plasma antioxidant capacity, endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels were evaluated at baseline and at the end of the study. The effect of GLP-1 during a hyperglycemic clamp, was also studied at baseline and at the end of the study., Results: Compared to the control diet, the Mediterranean diet increased plasma antioxidant capacity and improved basal endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels. The Mediterranean diet also reduced the negative effects of acute hyperglycemia, induced by a hyperglycemic clamp, on endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels. Furthermore, the Mediterranean diet improved the protective action of GLP-1 on endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels, also increasing GLP-1-induced insulin secretion., Conclusions: These data suggest that the Mediterranean diet, using olive oil, prevents the acute hyperglycemia effect on endothelial function, inflammation and oxidative stress, and improves the action of GLP-1, which may have a favorable effect on the management of type 2 diabetes, particularly for the prevention of cardiovascular disease.

Liddle's syndrome (LS) is a rare heritable form of hypertension that often affects young patients. It is caused by gain-of-function mutations of the kidney epithelial sodium channel (ENaC) and it is classically associated with hypokalemia and suppression of renin and aldosterone. LS is characterized by responsiveness to ENaC inhibitors but not to mineralocorticoid receptor inhibitors. Consequently the most effective treatment is amiloride. This drug is not used in pregnancy, as it has not been sufficiently studied during gestation. However for pregnant LS patient amiloride is the most effective drug in decreasing blood pressure. Herein we report the case of a LS patient, who has been followed up by a multidisciplinary teamwork during her first pregnancy. Hypertension worsened after the 25th week of gestation and amiloride was safely administered, firstly in combination with hydrochlorothiazide (the only formulation commercially available in Italy) and, thereafter, as a single drug. Genetic testing was performed in the patient's family in order to support diagnosis and clinical management.

Objective: To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1 diabetes., Research Design and Methods: A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced., Results: At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced., Conclusions: This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress.

Background: It has been reported that hyperglycemia following hypoglycemia produces an ischemia-reperfusion-like effect in type 1 diabetes. In this study the possibility that GLP-1 has a protective effect on this phenomenon has been tested., Methods: 15 type 1 diabetic patients underwent to five experiments: a period of two hours of hypoglycemia followed by two hours of normo-glycemia or hyperglycemia with the concomitant infusion of GLP-1 or vitamin C or both. At baseline, after 2 and 4 hours, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2alpha, sCAM-1a, IL-6 and flow mediated vasodilation were measured., Results: After 2 h of hypoglycemia, flow mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine and IL-6 significantly increased. While recovering with normoglycemia was accompanied by a significant improvement of endothelial dysfunction, oxidative stress and inflammation, a period of hyperglycemia after hypoglycemia worsens all these parameters. These effects were counterbalanced by GLP-1 and better by vitamin C, while the simultaneous infusion of both almost completely abolished the effect of hyperglycemia post hypoglycemia., Conclusions: This study shows that GLP-1 infusion, during induced hyperglycemia post hypoglycemia, reduces the generation of oxidative stress and inflammation, improving the endothelial dysfunction, in type 1 diabetes. Furthermore, the data support that vitamin C and GLP-1 may have an additive protective effect in such condition.

Objective: The aim of this study was to measure plasmatic concentrations of vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF) in pregnant women, and to evaluate their relationship with age, hormonal status, gestational age, and different diseases of pregnancy., Methods: We selected a control group of 163 patients (96 fertile and 67 in menopause) and a group of 214 pregnant patients during the whole gestational period. VEGF-A and PlGF were assayed by ELISA and EIA methods, respectively. Statistical analysis was performed using the Mann-Whitney test., Results: The control group showed mean VEGF-A and PlGF values of 89.87 pg/ml and 10.22 pg/ml, respectively; PlGF showed the highest values in menopausal patients. The group of pregnant patients showed VEGF-A values of 27.05 pg/ml and PlGF values of 231.36 pg/ml respectively, with lower (for the VEGF-A) and higher (for the PlGF) statistical significance. These values were not influenced by biological age, but were related to gestational age: VEGF-A showed a decrease and PlGF an increase particularly after the 20th gestational week. PlGF showed a statistically significant decrease compared to physiological gestation in spontaneous and threatened abortions (p < 0.0001) and in ectopic pregnancies (p < 0.0001), an increase in ultrasound and CTG alterations (p < 0.05), and threatened premature delivery and uterine hypercontractility (p < 0.01); on the other hand VEGF-A showed a statistically significant increase in ectopic pregnancies (p < 0.05)., Conclusions: VEGF-A and PlGF may play a diagnostic and prognostic role in pregnancy. Further studies are required to better understand the meaning of variability of their values.

Background: Uterine sarcomas are relatively rare tumors that account for approximately 1-3% of female genital tract malignancies and between 4-9% of uterine cancers. Less than 8% of all cases are Mullerian adenosarcoma, a distinctive uterine neoplasm characterized by a benign, but occasionally atypical, epithelial and a malignant, usually low-grade, stromal component, both of which should be integral and neoplastic constituents of the tumor. Mullerian adenosarcoma with sarcomatous overgrowth (MASO) is a very aggressive variant, associated with post-operative recurrence, metastases, even when diagnosed in early stage., Case Presentation: We present a fourth MASO case derived from uterine cervix in a 72-year-old woman with metrorrhagia and a polypoid mass protruding through the cervical ostium. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, systematic pelvic lymph node dissection, omental biopsy and appendectomy were performed. Surgery treatment was associated with adjuvant whole-pelvis radiation (45 Gy) and adjuvant chemotherapy (cisplatin/ifosfamide). After nine months of follow up, the patient was free of tumor., Conclusions: The rarity of MASO of the cervix involves a management difficult. Most authors recommend total abdominal hysterectomy, usually accompanied by bilateral salpingo-oophorectomy. There is no common agreement on staging by lymphadenectomy during primary surgery and adjuvant chemo-radio therapy.

Cartilage is the grafting material of choice in advanced disorders of the middle ear while the indications for its routine use remain controversial due to the possible detrimental effect on post-operative hearing. Aim of the present study was to report personal experience with "tragal cartilage shield" tympanoplasty. The study focused on 306 adult patients (236 primary procedures and 70 revisions from January 2003 to June 2007). Mean post-operative follow-up was 37 months (range 1-66). The following parameters were evaluated: graft take, change between the pre- and post-operative pure-tone average air-bone gap (PTA-ABG), post-operative complications. Graft take was achieved in 304 patients (99.35%) and there were no immediate post-operative complications. The overall average pre-operative pure-tone average air-bone gap was 43.79 +/- 7.07 dB, whereas the post-operative (1 year after surgery) pure-tone average air-bone gap was 10.43 +/- 5.25 dB (p < 0.0001). Statistically significant improvement was observed up to 5 years after surgery. This study reveals that tragal cartilage shield tympanoplasty is a reliable technique, in fact it has a high degree of graft take and hearing results are satisfactory. Furthermore, the cartilage is a satisfactory grafting material because it is easily accessible, easy to adapt, resistant to negative middle ear pressures, stable, elastic, well tolerated by the middle ear, resistant to resorption. Therefore, we also recommend its use in less severe middle ear disorders, in which the functional outcome is more essential.

We report 72 blastic crises (BC), occurring in 238 Ph+ chronic myeloid leukemia (CML) patients treated in chronic phase (CP) with alpha-interferon (IFN) for a median time of 51 months (range 7-96). The 238 patients were grouped by Sokal's risk at diagnosis in low- (LR), intermediate- (IR) and high-risk (HR), and by CP treatment. Group 1: 160 patients (57% LR, 31% IR, 12% HR) given IFN alone in early CP. Group 2: 31 patients (65% LR, 32% IR, 3% HR) given IFN alone in late CP. Group 3: 23 patients (78% LR, 22% IR) given IFN before and after autologous stem cell transplantation (ASCT). Group 4: 24 patients (83% LR, 17% IR) given IFN after ASCT. Of the 72 BC, 52 (72%) were myeloid (My), and 20 (28%) lymphoid (Ly). Overall BC incidence was similar in all CP treatment groups, although with a prevalence of Ly BC in groups 3 + 4 vs groups 1 + 2, (p = NS); the incidence of BC was higher in HR patients (P = NS), but on the whole it was lower than expected on the basis of historical controls. Lymphoid BC was more frequent in LR than in IR + HR patients (P < 0.05), and was more frequent in responders to IFN, than in non-responders (P < 0.05). In conclusion, a subset of patients with low risk at diagnosis, better response to IFN and proneness to evolve into Ly BC can be identified. The role played by IFN in this context remains to be defined.

We describe the application of fluorescence in situ hybridization (FISH) in a case of suspected chronic myelogenous leukemia (CML), cytogenetically characterized by a t(21;22) with no clear involvement of chromosome 9. The dual color FISH technique, performed using specific painting probes for chromosomes 9,21,22 and a BCR/ABL translocation probe, enabled us to confirm the diagnosis of CML by detecting the BCR/ABL rearrangement on chromosome 22q and the involvement of chromosome 9 in a variant translocation t(9;21;22).

A case of acute nonlymphocytic leukemia after radiochemotherapy for Hodgkin's disease, with a rearrangement of 6p23 region, is described. This chromosome change, which has been previously reported in secondary leukemias or myelodysplastic syndromes, was an isolated karyotypic anomaly in our case, which strongly supports the nonrandom involvement of chromosome 6p in induced leukemias.

There is ample documentation that breech full-term infants delivered vaginally have a higher perinatal morbidity and mortality rate than breech infants born via cesarean section. Until now, little emphasis has been placed on the risks to premature newborns born in breech presentation. Therefore, the authors have considered all singleton pregnancies with infants in breech presentation admitted to the Department of Obstetrics, University of Padova, from January 1978 to December 1979 and delivered before 36-weeks gestation. On the basis of obstetric management, the authors have obtained two groups: Group A comprised 36 infants born by vaginal delivery; Group B totaled 32 newborns delivered by cesarean section. Mean gestational age and birthweight were comparable. Of the neonatal events considered, the following were significantly different: Apgar score at 5 minutes less than 7 (A = 30.6%; B = 9.3%), mortality (A = 13.8%; B = 0), neurologic sequelae in the infants discharged from the neonatal intensive care unit (NICU) (A = 50%; B = 9.1%) and the sum of mortality and long term sequelae (A = 22.2%; B = 3.1%). The authors conclude that cesarean section performed in mothers with impending preterm breech delivery decreases the neonatal mortality rate and improves the long-term outcome.

The administration of betamethasone to the mother in order to accelerate maturation of foetal lungs induces significant modifications in the foeto-placental hormonal secretion. Both the total estriol and unconjugated estriol present a sharp fall in the days immediately following the administration and a rise 10-12 days later, depending on a rebound effect. The HPL levels do not variate except for a progressive and constant rising due probably to better cardiocirculatory maternal condition with, consequently, a higher utero-placental blood-flow. All these phenomena increase when the administration of betamethasone to the mother is repeated more then once. The AA. believe that the sharp fall of the estriol doesn't represent a danger for the foetus being only an effect of maternal and fetal adrenal depression. Consequently the AA. suggest to drive the management during and after the administration of betamethasone to the mother on the basis of other foeto-placental functional tests, as cardiotocography. The results were analysed.

The possibility of influencing the fetal uptake of free fatty acids (FFA), beta-hydroxybutyrate (beta-OH), and glycerol was demonstrated by enhancing the maternal blood level of these substances by means of 10% intralipid infusions to the mothers during delivery. The FFA uptake, which was not significant in fetuses of control mothers, became positive in fetuses born after maternal infusion with intralipid. The uptake of beta-OH and glycerol, which were positive in normal conditions, increased in fetuses from intralipid-infused mothers. These studies demonstrate that, after intralipid infusions to the mothers, the fetal FFA uptake could be correlated with the FFA concentration difference between maternal arterial, and fetal umbilical arterial blood. Since the fetal uptake of FFA subsequent to intralipid infusions is not negligible, we consider the possibility that lipid infusions to the mothers could be an approach to the treatment of the fetus with poor intrauterine growth.

85 high risk pregnant women were evaluated by RIA of total estriol, unconjugated estriol and HPL by ultrasonic measurement of foetal BPD and by NST and Fischer's score. In all, 277 evaluations were made. The Authors found a good correlation between results of the cardiotocographic tests and levels of HPL and measurements of foetal BPD. A low correlation was noticed between the levels of total and unconjugated estriol and the characteristics of cardiotocography. The evaluation of the cardiotocographic tests, according to Lee and Coll., resulted better than according to Fischer's score. The contemporary qualitative and quantitative evaluation of the cardiotocograms seems to reduce significantly the false-positive results and to half the false-negative results of the other tests for foeto-placental function. Result were analysed.