Italo Nofroni

MicroRNA profiling in human medulloblastoma

Medulloblastoma is an aggressive brain malignancy with high incidence in childhood. Current treatment approaches have limited efficacy and severe side effects. Therefore, new risk‐adapted therapeutic strategies based on molecular classification are required. MicroRNA expression analysis has emerged as a powerful tool to identify candidate molecules playing an important role in a large number of malignancies. However, no data are yet available on human primary medulloblastomas. A high throughput microRNA expression profiles was performed in human primary medulloblastoma specimens to investigate microRNA involvement in medulloblastoma carcinogenesis. We identified specific microRNA expression patterns which distinguish medulloblastoma differing in histotypes (anaplastic, classic and desmoplastic), in molecular features (ErbB2 or c‐Myc overexpressing tumors) and in disease‐risk stratification. MicroRNAs expression profile clearly differentiates medulloblastoma from either adult or fetal normal cerebellar tissues. Only a few microRNAs displayed upregulated expression, while most of them were downregulated in tumor samples, suggesting a tumor growth‐inhibitory function. This property has been addressed for miR‐9 and miR‐125a, whose rescued expression promoted medulloblastoma cell growth arrest and apoptosis while targeting the proproliferative truncated TrkC isoform. In conclusion, misregulated microRNA expression profiles characterize human medulloblastomas, and may provide potential targets for novel therapeutic strategies.

Reduction pneumoplasty versus respiratory rehabilitation in severe emphysema: a randomized study

BACKGROUND The purpose of the study was to determine in a prospective randomized trial the independent short-term physiologic impact of reduction pneumoplasty (RP) on respiratory rehabilitation (RR). METHODS Sixty patients eligible for RP were randomly selected by computer to receive either RP (n = 30) or comprehensive RR (n = 30). Pulmonary function tests, analysis of blood gas levels, measurement of respiratory muscle strength (maximal inspiratory and expiratory pressures), 6-minute walk test (6MWT), and incremental treadmill test (ITT), were performed at baseline and at 3 and 6 months. RESULTS Two treatment-related deaths occurred after RP and one after RR. At 6 months dyspnea index, maximal inspiratory pressure, 6MWT, ITT, and PaO2 were significantly improved in both groups whereas forced expiratory volume in 1 second and residual volume were significantly improved only in the surgical arm. In addition at 6 months, dyspnea index, 6MWT, maximal ITT, and PaO2 improved significantly more after RP than after RR. CONCLUSIONS In our study short-term improvements in dyspnea index, oxygenation, inspiratory muscle strength, and exercise capacity occurred after either RP and RR. However dyspnea index, PaO2, and exercise capacity improved more after RP than after RR whereas pulmonary function improved only after RP.

Thoracoscopic thymectomy in autoimmune myasthenia : Results of left-sided approach

BACKGROUND We undertook to analyze the results of video-assisted thoracoscopic thymectomy through a left-sided approach in patients with autoimmune myasthenia. METHODS Between 1993 and 1997, 31 patients underwent thoracoscopic thymectomy by a uniform left-sided approach. There were 8 men and 23 women with a mean age of 34 +/- 12 years. RESULTS Preoperative duration of disease was 14.8 +/- 11 months. There were no operative deaths or major complications. The mean hospital stay was 5.2 +/- 2.8 days. Mean follow-up was 39.6 +/- 15 months and was 100% complete. At 48 months, remission and improvement rates were 36% and 96%, respectively. Shorter duration of symptoms (< 12 months) correlated with improved outcome (13 of 13 patients versus 10 of 14 patients; p = 0.036). Age, sex, Osserman class, corticosteroid therapy, presence of ectopic thymic tissue, and temporary postoperative symptom increase (deterioration) did not affect outcome. CONCLUSIONS Thoracoscopic thymectomy facilitated the goal of early thymectomy. Through a left-sided approach, improvement or remission was achieved in more than 95% of the patients. Thoracoscopic thymectomy should be considered a valid less invasive alternative to the most radical open approaches.

Stenosis of lumbar intervertebral foramen: anatomic study on predisposing factors.

Study Design. In Study 1 the authors measured the vertical and sagittal dimensions of the intervertebral foramen in dried lumbar vertebrae. In Study 2 the dimensions of the intervertebral foramen were measured in fresh cadaveric spines in which the soft tissues forming the foraminal walls were preserved. Objectives. To investigate whether disc narrowing, or other factors related to the morphometry of lumbar vertebrae, may predispose to foraminal stenosis. Summary of Background Data. Predisposing factors to foraminal stenosis have been little investigated. Previous studies suggested that narrowing of the disc space might cause a reduction in the foraminal dimensions; however, it is not clear whether such a reduction is to such an extent as to compress the nerve root within the foramen. Methods. In Study 1 the vertical and sagittal dimensions of 160 intervertebral foramens were measured on dried white spines. Measurements were performed in the presence of a normal height of the disc space, obtained using a silicone rubber disc, and repeated in the same specimen after disc removal. Foraminal dimensions were then related to the sagittal diameter of the spinal canal and the pedicle length. In Study 2, the authors evaluated the dimensions of 50 intervertebral foramens of fresh cadaveric spines, in which the soft tissues forming the foraminal walls and the nerve root were preserved. In specimens showing normal or slightly decreased disc height, the foraminal dimensions were measured before and after disc excision. Results. In Study 1 the reduction in the foraminal height after disc removal was, on average, 6.5 mm (P < 0.0001). In both Studies 1 and 2 the sagittal dimensions of the foramen were not significantly reduced after disc removal. No significant difference was found in Study 1 in the sagittal dimensions of the foramen between specimens showing normal or degenerated facet joints. In Study 2 a compression of the nerve root within the foramen was found in one specimen, showing a concomitant central stenosis at multiple levels. A significant correlation was found between the sagittal diameters of the foramen and the sagittal diameter of the spinal canal and the pedicle length. Conclusions. Narrowing of the disc space significantly reduces the vertical diameter of the foramen but has no significant effects on its sagittal dimensions. In contrast, the sagittal dimensions of the foramen are strictly related to the sagittal diameter of the spinal canal and the pedicle length. These results suggest that in patients with developmental or combined stenosis of the central spinal canal, a concomitant foraminal stenosis is likely to be present, or at least should be suspected.

Low absolute lymphocyte count is a poor prognostic factor in diffuse-large-B-cell-lymphoma

The prognostic value of absolute lymphocytic count (ALC), has been a recent matter of debate in non-Hodgkin-lymphoma (NHL). We assessed prospectively the value of ALC at diagnosis and also after the completion of immuno-chemotherapy in 101 diffuse-large-B-cell-lymphoma (DLBCL). Analysis of prognostic factors with respect to overall survival (OS), event free survival (EFS) and progression free survival (PFS) was done by two-tailed log-rank test. The ALC cut-off value was calculated as <0.84 × 109/L at diagnosis: this was a strong negative prognostic factor for OS (p = 0.0004), EFS (p < 0.00001) and PFS (p < 0.00001) and in multivariate analysis was independent from the revised-international-prognostic-index (R-IPI). ALC after chemo-immunotherapy was not of prognostic value. As R-IPI and ALC < 0.84 × 109/L, were the factors better discriminating poor prognosis, a new trichotomous score (ALC/R-IPI) was built up: (1) low risk: R-IPI = very good or good and ALC < 0.84 × 109/L; (2) intermediate risk: patients with at least one risk factor (R-IPI = poor or ALC < 0.84 × 109/L). (3) high risk: patients with both risk factors. This new prognostic score was highly significant in univariate analysis for OS (p = 0.0002), EFS (p < 0.00001) and PFS (p < 0.00001). In multivariate analysis ALC/R-IPI was the most predictive factor for OS (OR = 2.954; p = 0.002) and EFS (OR = 2.381; p < 0.00001) and the only predictive factor for PFS (OR = 4.018; p < 0.00001).Our data, show that ALC at diagnosis has a strong prognostic relevance and is independent from the R-IPI. The new score including both values proved the most powerful predictor at multivariate analysis.

Longterm results after resection of simultaneous and sequential lung and liver metastases from colorectal carcinoma.

BACKGROUND Although simple lung or liver metastasectomy from colorectal cancer have proved effective in selected patients, the value of simultaneous biorgan metastasectomies is still debated. STUDY DESIGN Of 155 patients who underwent operation for lung or liver colorectal metastases between March 1987 and December 1998, we retrospectively reviewed 29 patients who presented simultaneous (n = 12) or sequential liver-->lung (n = 10) and lung-->liver (n = 7) metastases. All metastases were successfully resected in a total of 56 separate procedures. In 35 thoracic procedures, 45 metastases were removed by wedge resection (n = 36) or lobectomy (n = 9). In addition, 47 liver metastases were resected with wedge (n = 24), segmentectomy (n = 13), or lobectomy (n = 10). There were no perioperative deaths and the morbidity rate was low (10.7%). All patients were followed for a minimum of 3 years. Factors possibly influencing survival were evaluated by univariate and subsequently by multivariate analyses. RESULTS Median survival from the second metastasectomy was 41 months, with a 5-year survival rate of 51.3%. Risk factor distribution among the three metastastic pattern groups was insignificant. Premetastasectomy elevated levels of both CEA and CA19-9 (p = 0.0001), and mediastinal or celiac lymph node status (p = 0.03) were significantly associated with survival in the univariate analysis, although number of metastasectomies, disease-free interval, and simultaneous versus sequential diagnosis were not. In the multivariate analysis, only elevated CEA plus CA19-9 (p = 0.01) was significantly associated with survival. CONCLUSIONS We conclude that either simultaneous or sequential lung and liver metastasectomy can be successfully treated by surgery. Poor results were obtained in the presence of high levels of CEA plus CA19-9.

Quality of life in ambulatory postmenopausal women: the impact of reduced bone mineral density and subclinical vertebral fractures

Health-related quality of life (HRQOL) in postmenopausal women with osteoporosis has hitherto been mainly assessed in patients with clinically recognized vertebral fractures. Our study aimed to investigate the QOL perception in 361 asymptomatic ambulant postmenopausal women who came to our center for an osteoporosis screening program planned with their general practitioners. The Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) was administered to all subjects. The participants underwent bone mineral density (BMD) measurements by DXA of either the lumbar spine and/or the femoral neck, as well as X-ray examination of the thoracolumbar spine to identify subclinical vertebral fractures. According to the WHO definition, where subjects are subdivided by BMD values into three groups (women with normal BMD, osteopenia, and osteoporosis), a significant difference was found only for the domains which explore general health perception (p<0.01 by ANOVA) and mental function (p<0.001 by ANOVA). When we segregated both osteopenic and osteoporotic women according to whether or not they had vertebral fractures, a significant difference was found only in osteoporotic patients for domains which explore physical function (p<0.001), social function (p<0.001), general health perception (p<0.02), and total QUALEFFO score (p<0.01). Stepwise multiple logistic regression analysis of the whole sample showed that both vertebral fractures and a low femoral BMD impairs QOL perception, while age did not exert a significant influence. ROC curves analysis demonstrated a low discriminating capacity of individual domains and total QUALEFFO score for both vertebral deformities and BMD categorization. Our results showed that QUALEFFO is not able to discriminate between patients with or without subclinical vertebral fractures. However, some aspects of QOL appear to be impaired in patients with subclinical vertebral fractures or reduced BMD.

Absolute lymphocyte count is a prognostic factor in diffuse large B-cell lymphoma

imab is associated with a reduction in IgG antibodies to ADAMTS13. British Journal of Haematology, 136, 451–461. Yarranton, H., Lawrie, A.S., MacKie, I.J., Pinkoski, L., Corash, L. & Machin, S.J. (2005) Coagulation factor levels in cryosupernatant prepared from plasma treated with amotosalen hydrochloride (S-59) and ultraviolet A light. Transfusion, 45, 1453–1458.

RIFLE Criteria and Hepatic Function in the Assessment of Acute Renal Failure in Liver Transplantation

Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney.

Atherosclerotic ischemic renal disease. Diagnosis and prevalence in an hypertensive and/or uremic elderly population

BackgroundAtherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; Its prevalence is inferred from autopsy or retrospective arteriographic studies. This study has been conducted on 269 subjects over 50 with hypertension and/or CRF, unrelated to other known causes of renal disease.MethodsAll 269 patients were studied either by color-flow duplex sonography (n = 238) or by renal scintigraphy (n = 224), and 199 of the 269 patients were evaluated using both of these techniques. 40 patients, found to have renal artery stenosis (RAS), were subjected to 3D-contrast enhancement Magnetic Resonance Angiography (MRA) and/or Selective Angiography (SA). An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or SA).ResultsColor-duplex sonography, carried out in 238 patients, revealed 49 cases of RAS. MR or SA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography showed a PPV value of 94.3% and NPV of 87.0% while renal scintigraphy, carried out in 224 patients, had a PPV of 72.2% and a NPV of 29.4%. Patients with RAS showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in proteinuria. RAS, based on color-duplex sonography studies, was present in 11% of patients in the age group 50–59, 18% in the 60–69 and 23% at age 70 and above.ConclusionsA relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by RAS and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis.