Search

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a promising biodegradable bio-based material, which is designed for a vast range of applications, depending on its composite. This study aims to assess the degradability of a PHBV-based compound under different conditions. The research group followed different methodological approaches and assessed visual and mass changes, mechanical and morphological properties, spectroscopic and structural characterisation, along with thermal behaviour. The Ph-Stat (enzymatic degradation) test and total dry solids (TDS)/total volatile solids (TVS) measurements were carried out. Finally, the team experimentally evaluated the amount of methane and carbon dioxide produced, i.e., the degree of biodegradation under aerobic conditions. According to the results, different types of tests have shown differing effects of environmental conditions on material degradation. In conclusion, this paper provides a summary of the investigations regarding the degradation behaviour of the PHBV-based compound under varying environmental factors. The main strengths of the study lie in its multi-faceted approach, combining assessments of PHBV-based compound degradability under different conditions using various analytical tools, such as visual and mass changes, mechanical and morphological properties, spectroscopic and structural characterization, and thermal behavior. These methods collectively contribute to the robustness and reliability of the undertaken work.

BACKGROUND: Pituitary tumors are a heterogeneous group of lesions that are usually benign. Therefore, a proper understanding of the anatomy, physiology, and pathology is mandatory to achieve favorable outcomes. Accordingly, diagnostic tests and treatment guidelines should be determined and implemented. Thus, we decided to perform a multicenter study among Italian neurosurgical centers performing pituitary surgery to provide an actual depiction from the neurosurgical standpoint. METHODS: On behalf of the SINch (Società Italiana di Neurochirurgia), a survey was undertaken with the participants to explore the activities in the field of pituitary surgery within 41 public institutions. RESULTS: Of the 41 centers, 37 participated in the present study. The total number of neurosurgical procedures performed in 2016 was 1479. Most of the procedures were performed using the transsphenoidal approach (1320 transsphenoidal [1204 endoscopic, 53 microscopic, 53 endoscope-assisted microscopic] vs. 159 transcranial). A multidisciplinary tumor board is convened regularly in 32 of 37 centers, and a research laboratory is present in 18 centers. CONCLUSIONS: Diagnosing pituitary/hypothalamus disorders and treating them is the result of teamwork, composed of several diverse experts. Regarding neurosurgery, our findings have confirmed the central role of the transsphenoidal approach, with preference toward the endoscopic technique. Better outcomes can be expected at centers with a multidisciplinary team and a full, or part of a, residency program, with a greater surgical caseload.

Leksell Gamma Knife is a mini-invasive technique to obtain a complete destruction of cerebral lesions delivering a single high dose radiation beam. Positron Emission Tomography (PET) imaging is increasingly utilized for radiation treatment planning. Nevertheless, lesion volume delineation in PET datasets is challenging because of the low spatial resolution and high noise level of PET images. Nowadays, the biological target volume (BTV) is manually contoured on PET studies. This procedure is time expensive and operator-dependent. In this article, a fully automatic algorithm for the BTV delineation based on random walks (RW) on graphs is proposed. The results are compared with the outcomes of the original RW method, 40% thresholding method, region growing method, and fuzzy c-means clustering method. To validate the effectiveness of the proposed approach in a clinical environment, BTV segmentation on 18 patients with cerebral metastases is performed. Experimental results show that the segmentation algorithm is accurate and has real-time performance satisfying the physician requirements in a radiotherapy environment.

MR Imaging is being increasingly used in radiation treatment planning as well as for staging and assessing tumor response. Leksell Gamma Knife® is a device for stereotactic neuro-radiosurgery to deal with inaccessible or insufficiently treated lesions with traditional surgery or radiotherapy. The target to be treated with radiation beams is currently contoured through slice-by-slice manual segmentation on MR images. This procedure is time consuming and operator-dependent. Segmentation result repeatability may be ensured only by using automatic/semi-automatic methods with the clinicians supporting the planning phase. In this paper a semi-automatic segmentation method, based on an unsupervised Fuzzy C-Means clustering technique, is proposed. The presented approach allows for the target segmentation and its volume calculation. Segmentation tests on 5 MRI series were performed, using both area-based and distance-based metrics. The following average values have been obtained: DS = 95.10, JC = 90.82, TPF = 95.86, FNF = 2.18, MAD = 0.302, MAXD = 1.260, H = 1.636.

Nowadays, radiation treatment is beginning to intensively use MRI thanks to its greater ability to discriminate healthy and diseased soft-tissues. Leksell Gamma Knife® is a radio-surgical device, used to treat different brain lesions, which are often inaccessible for conventional surgery, such as benign or malignant tumors. Currently, the target to be treated with radiation therapy is contoured with slice-by-slice manual segmentation on MR datasets. This approach makes the segmentation procedure time consuming and operator-dependent. The repeatability of the tumor boundary delineation may be ensured only by using automatic or semiautomatic methods, supporting clinicians in the treatment planning phase. This article proposes a semiautomatic segmentation method, based on the unsupervised Fuzzy C-Means clustering algorithm. Our approach helps segment the target and automatically calculates the lesion volume. To evaluate the performance of the proposed approach, segmentation tests on 15 MR datasets were performed, using both area-based and distance-based metrics, obtaining the following average values: Similarity Index=95.59%, Jaccard Index=91.86%, Sensitivity=97.39%, Specificity=94.30%, Mean Absolute Distance=0.246[pixels], Maximum Distance=1.050[pixels], and Hausdorff Distance=1.365[pixels].

Lesion volume delineation of Positron Emission Tomography images is challenging because of the low spatial resolution and high noise level. Aim of this work is the development of an operator independent segmentation method of metabolic images. For this purpose, an algorithm for the biological tumor volume delineation based on random walks on graphs has been used. Twenty-four cerebral tumors are segmented to evaluate the functional follow-up after Gamma Knife radiotherapy treatment. Experimental results show that the segmentation algorithm is accurate and has real-time performance. In addition, it can reflect metabolic changes useful to evaluate radiotherapy response in treated patients.

Contains fulltext : 173083.pdf (Publisher’s version ) (Open Access), All laboratory tests have test performance characteristics (TPCs), whether or not they are explicitly known to the laboratorian or the pathologist. TPCs are thus also an integral characteristic of immunohistochemistry (IHC) tests and other in situ, cell-based molecular assays such as DNA or RNA in situ hybridization or aptamer-based testing. Because of their descriptive, in situ, cell-based nature, IHC tests have a limited repertoire of appropriate TPCs. Although only a few TPCs are relevant to IHC, proper selection of informative TPCs is nonetheless essential for the development of and adherence to appropriate quality assurance measures in the IHC laboratory. This paper describes the TPCs that are relevant to IHC testing and emphasizes the role of TPCs in the validation of IHC tests. This is part 2 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Contains fulltext : 173020.pdf (Publisher’s version ) (Open Access), Technical progress in immunohistochemistry (IHC) as well as the increased utility of IHC for biomarker testing in precision medicine avails us of the opportunity to reassess clinical IHC as a laboratory test and its proper characterization as a special type of immunoassay. IHC, as used in current clinical applications, is a descriptive, qualitative, cell-based, usually nonlinear, in situ protein immunoassay, for which the readout of the results is principally performed by pathologists rather than by the instruments on which the immunoassay is performed. This modus operandi is in contrast to other assays where the instrument also performs the readout of the test result (eg, nephelometry readers, mass spectrometry readers, etc.). The readouts (results) of IHC tests are used either by pathologists for diagnostic purposes or by treating physicians (eg, oncologists) for patient management decisions, the need for further testing, or follow-up. This paper highlights the distinction between the original purpose for which an IHC test is developed and its subsequent clinical uses, as well as the role of pathologists in the analytical and postanalytical phases of IHC testing. This paper is the first of a 4-part series, under the general title of "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Contains fulltext : 173084.pdf (Publisher’s version ) (Open Access), Validation of immunohistochemistry (IHC) assays is a subject that is of great importance to clinical practice as well as basic research and clinical trials. When applied to clinical practice and focused on patient safety, validation of IHC assays creates objective evidence that IHC assays used for patient care are "fit-for-purpose." Validation of IHC assays needs to be properly informed by and modeled to assess the purpose of the IHC assay, which will further determine what sphere of validation is required, as well as the scope, type, and tier of technical validation. These concepts will be defined in this review, part 3 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Background and objectives: Nowadays, clinical practice in Gamma Knife treatments is generally based on MRI anatomical information alone. However, the joint use of MRI and PET images can be useful for considering both anatomical and metabolic information about the lesion to be treated. In this paper we present a co-segmentation method to integrate the segmented Biological Target Volume (BTV), using [11C]-Methionine-PET (MET-PET) images, and the segmented Gross Target Volume (GTV), on the respective co-registered MR images. The resulting volume gives enhanced brain tumor information to be used in stereotactic neuro-radiosurgery treatment planning. GTV often does not match entirely with BTV, which provides metabolic information about brain lesions. For this reason, PET imaging is valuable and it could be used to provide complementary information useful for treatment planning. In this way, BTV can be used to modify GTV, enhancing Clinical Target Volume (CTV) delineation. Methods: A novel fully automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife® treatments is proposed. This approach improves and combines two computer-assisted and operator-independent single modality methods, previously developed and validated, to segment BTV and GTV from PET and MR images, respectively. In addition, the GTV is utilized to combine the superior contrast of PET images with the higher spatial resolution of MRI, obtaining a new BTV, called BTVMRI. A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is also presented. Overlap-based and spatial distance-based metrics were considered to quantify similarity concerning PET and MRI segmentation approaches. Statistics was also included to measure correlation among the different segmentation processes. Since it is not possible to define a gold-standard CTV according to both MRI and PET images without tre

Contains fulltext : 173084.pdf (Publisher’s version ) (Open Access), Validation of immunohistochemistry (IHC) assays is a subject that is of great importance to clinical practice as well as basic research and clinical trials. When applied to clinical practice and focused on patient safety, validation of IHC assays creates objective evidence that IHC assays used for patient care are "fit-for-purpose." Validation of IHC assays needs to be properly informed by and modeled to assess the purpose of the IHC assay, which will further determine what sphere of validation is required, as well as the scope, type, and tier of technical validation. These concepts will be defined in this review, part 3 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Contains fulltext : 173083.pdf (Publisher’s version ) (Open Access), All laboratory tests have test performance characteristics (TPCs), whether or not they are explicitly known to the laboratorian or the pathologist. TPCs are thus also an integral characteristic of immunohistochemistry (IHC) tests and other in situ, cell-based molecular assays such as DNA or RNA in situ hybridization or aptamer-based testing. Because of their descriptive, in situ, cell-based nature, IHC tests have a limited repertoire of appropriate TPCs. Although only a few TPCs are relevant to IHC, proper selection of informative TPCs is nonetheless essential for the development of and adherence to appropriate quality assurance measures in the IHC laboratory. This paper describes the TPCs that are relevant to IHC testing and emphasizes the role of TPCs in the validation of IHC tests. This is part 2 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Contains fulltext : 173020.pdf (Publisher’s version ) (Open Access), Technical progress in immunohistochemistry (IHC) as well as the increased utility of IHC for biomarker testing in precision medicine avails us of the opportunity to reassess clinical IHC as a laboratory test and its proper characterization as a special type of immunoassay. IHC, as used in current clinical applications, is a descriptive, qualitative, cell-based, usually nonlinear, in situ protein immunoassay, for which the readout of the results is principally performed by pathologists rather than by the instruments on which the immunoassay is performed. This modus operandi is in contrast to other assays where the instrument also performs the readout of the test result (eg, nephelometry readers, mass spectrometry readers, etc.). The readouts (results) of IHC tests are used either by pathologists for diagnostic purposes or by treating physicians (eg, oncologists) for patient management decisions, the need for further testing, or follow-up. This paper highlights the distinction between the original purpose for which an IHC test is developed and its subsequent clinical uses, as well as the role of pathologists in the analytical and postanalytical phases of IHC testing. This paper is the first of a 4-part series, under the general title of "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Contains fulltext : 173083.pdf (Publisher’s version ) (Open Access), All laboratory tests have test performance characteristics (TPCs), whether or not they are explicitly known to the laboratorian or the pathologist. TPCs are thus also an integral characteristic of immunohistochemistry (IHC) tests and other in situ, cell-based molecular assays such as DNA or RNA in situ hybridization or aptamer-based testing. Because of their descriptive, in situ, cell-based nature, IHC tests have a limited repertoire of appropriate TPCs. Although only a few TPCs are relevant to IHC, proper selection of informative TPCs is nonetheless essential for the development of and adherence to appropriate quality assurance measures in the IHC laboratory. This paper describes the TPCs that are relevant to IHC testing and emphasizes the role of TPCs in the validation of IHC tests. This is part 2 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Contains fulltext : 173020.pdf (Publisher’s version ) (Open Access), Technical progress in immunohistochemistry (IHC) as well as the increased utility of IHC for biomarker testing in precision medicine avails us of the opportunity to reassess clinical IHC as a laboratory test and its proper characterization as a special type of immunoassay. IHC, as used in current clinical applications, is a descriptive, qualitative, cell-based, usually nonlinear, in situ protein immunoassay, for which the readout of the results is principally performed by pathologists rather than by the instruments on which the immunoassay is performed. This modus operandi is in contrast to other assays where the instrument also performs the readout of the test result (eg, nephelometry readers, mass spectrometry readers, etc.). The readouts (results) of IHC tests are used either by pathologists for diagnostic purposes or by treating physicians (eg, oncologists) for patient management decisions, the need for further testing, or follow-up. This paper highlights the distinction between the original purpose for which an IHC test is developed and its subsequent clinical uses, as well as the role of pathologists in the analytical and postanalytical phases of IHC testing. This paper is the first of a 4-part series, under the general title of "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Contains fulltext : 173084.pdf (Publisher’s version ) (Open Access), Validation of immunohistochemistry (IHC) assays is a subject that is of great importance to clinical practice as well as basic research and clinical trials. When applied to clinical practice and focused on patient safety, validation of IHC assays creates objective evidence that IHC assays used for patient care are "fit-for-purpose." Validation of IHC assays needs to be properly informed by and modeled to assess the purpose of the IHC assay, which will further determine what sphere of validation is required, as well as the scope, type, and tier of technical validation. These concepts will be defined in this review, part 3 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Background and objectives: Nowadays, clinical practice in Gamma Knife treatments is generally based on MRI anatomical information alone. However, the joint use of MRI and PET images can be useful for considering both anatomical and metabolic information about the lesion to be treated. In this paper we present a co-segmentation method to integrate the segmented Biological Target Volume (BTV), using [11C]-Methionine-PET (MET-PET) images, and the segmented Gross Target Volume (GTV), on the respective co-registered MR images. The resulting volume gives enhanced brain tumor information to be used in stereotactic neuro-radiosurgery treatment planning. GTV often does not match entirely with BTV, which provides metabolic information about brain lesions. For this reason, PET imaging is valuable and it could be used to provide complementary information useful for treatment planning. In this way, BTV can be used to modify GTV, enhancing Clinical Target Volume (CTV) delineation. Methods: A novel fully automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife® treatments is proposed. This approach improves and combines two computer-assisted and operator-independent single modality methods, previously developed and validated, to segment BTV and GTV from PET and MR images, respectively. In addition, the GTV is utilized to combine the superior contrast of PET images with the higher spatial resolution of MRI, obtaining a new BTV, called BTVMRI. A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is also presented. Overlap-based and spatial distance-based metrics were considered to quantify similarity concerning PET and MRI segmentation approaches. Statistics was also included to measure correlation among the different segmentation processes. Since it is not possible to define a gold-standard CTV according to both MRI and PET images without tre

Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogeneic bone marrow transplantation (BMT). Thalidomide was found to have immunosuppressive properties and it has been used in a limited number of children with cGVHD. We report our experience with refractory and/or high-risk cGVHD in 14 children. Six children showed complete clinical response to thalidomide in a median time of 2 months. Four children had partial responses and four failed. Side-effects were usually mild (somnolence, constipation) and only two patients developed sensory peripheral neuropathy. An increased incidence of infectious complications attributable to thalidomide was not observed. Nine out of 10 responding patients are alive 49-111 months post-BMT. Thalidomide can be effective particularly in children with prevailing mucocutaneous cGVHD. All patients should be carefully monitored to detect peripheral neuropathy early.

Contains fulltext : 137112.pdf (publisher's version ) (Open Access), The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Contains fulltext : 137112.pdf (publisher's version ) (Open Access), The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the 'Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Tr

One hundred and 43 consecutive pediatric patients (June 1985-December 1996) with at least 18 months of follow-up, were considered: most of the patients (111/143, 77.6%) underwent allogeneic BMT. The median follow-up was 5.7 years. Overall survival and 5 years EFS were 48.6% and 46.9%, respectively. For patients who underwent allogeneic BMT from HLA-identical siblings, the 5 years EFS for ALL was 75% in 1st CR, 60.4% in 2nd CR, 22.3% in > 2nd CR and 86.7% for AML in 1st CR. The EFS for Allo-BMT in "good" and "poor" prognosis patients was 68.6% and 21.8%, respectively (p value = 0.001). Early mortality in Allo-BMT patients was 17.7% between 1985-1990 and 10.3% between 1991-1996. Early treatment-related organ complications occurred mostly in patients who underwent BMT from an unrelated or a mismatched family donor. Late toxicity was evaluated in 57 patients (median follow-up of 82 months): none of the patients complained of significant late cardiac or respiratory dysfunction. With regards to growth, 18/57 patients (31.6%) lost more than two height centile channels. Three cases of thyroid neoplasms were observed. Evaluation of psychosocial functioning, studied in 39 patients who had at least 2 years of follow-up in CR, did not reveal any evident quality of life impairment. The possibility of curing childhood hematological malignancies is based on a global pediatric and multidisciplinary approach. A continuous need to improve results in terms of EFS and quality of life suggests that further multicenter prospective studies should be carried out., One hundred and 43 consecutive pediatric patients (June 1985-December 1996) with at least 18 months of follow-up, were considered: most of the patients (111/143, 77.6%) underwent allogeneic BMT. The median follow-up was 5.7 years. Overall survival and 5 years EFS were 48.6% and 46.9%, respectively. For patients who underwent allogeneic BMT from HLA-identical siblings, the 5 years EFS for ALL was 75% in 1st CR, 60.4% in 2nd CR, 22.3% in > 2nd CR and 86.7% for AML in 1st CR. The EFS for Allo-BMT in "good" and "poor" prognosis patients was 68.6% and 21.8%, respectively (p value = 0.001). Early mortality in Allo-BMT patients was 17.7% between 1985-1990 and 10.3% between 1991-1996. Early treatment-related organ complications occurred mostly in patients who underwent BMT from an unrelated or a mismatched family donor. Late toxicity was evaluated in 57 patients (median follow-up of 82 months): none of the patients complained of significant late cardiac or respiratory dysfunction. With regards to growth, 18/57 patients (31.6%) lost more than two height centile channels. Three cases of thyroid neoplasms were observed. Evaluation of psychosocial functioning, studied in 39 patients who had at least 2 years of follow-up in CR, did not reveal any evident quality of life impairment. The possibility of curing childhood hematological malignancies is based on a global pediatric and multidisciplinary approach. A continuous need to improve results in terms of EFS and quality of life suggests that further multicenter prospective studies should be carried out.

One hundred fifty-six episodes of fever occurred in 102 children during the first 100 days after bone marrow transplantation (BMT) performed at a single institution: fever of undetermined origin (FUO), 40.3%; septicemia, 7.1%; pneumonia, 19.2%; other infections, 33.4% of cases. The overall incidence of mortality was 22.6% and of mortality due to infections 17.4%. All FUO episodes resolved. Pneumonia was the major cause of death; 60% of recipients who developed pneumonia died, accounting for 90% of deaths attributable to febrile complications. Interstitial pneumonia occurred rarely, in 3.9% of all febrile episodes. The Cox model showed that the presence of graft-versus-host disease (GVHD) was related to an approximately ninefold increase in the risk of a first episode of FUO (P value .03). The risk of developing pneumonia was fourfold greater in children who received a transplant from a matched unrelated donor or a mismatched family donor (P value .01). Developments in diagnostic tools are needed to diagnose febrile episodes earlier and more precisely with the aim of reducing early mortality after BMT., One hundred fifty-six episodes of fever occurred in 102 children during the first 100 days after bone marrow transplantation (BMT) performed at a single institution: fever of undetermined origin (FUO), 40.3%; septicemia, 7.1%; pneumonia, 19.2%; other infections, 33.4% of cases. The overall incidence of mortality was 22.6% and of mortality due to infections 17.4%. All FUO episodes resolved. Pneumonia was the major cause of death; 60% of recipients who developed pneumonia died, accounting for 90% of deaths attributable to febrile complications. Interstitial pneumonia, occurred rarely, in 3.9% of all febrile episodes. The Cox model showed that the presence of graft-versus-host disease (GVHD) was related to an approximately ninefold increase in the risk of a first episode of FUO (P value .03). The risk of developing pneumonia was fourfold greater in children who received a transplant from a matched unrelated donor or a mismatched family donor (P value .01). Developments in diagnostic tools are needed to diagnose febrile episodes earlier and more precisely with the aim of reducing early mortality after BMT

The aim of this study was to compare the Hickman and Groshong central venous catheters (CVCs) for incidence and severity of catheter-related complications in children. Seventy-three patients with hematological malignancies were observed, 42 with Groshong CVCs and 31 with Hickman CVCs. The number of infective episodes per 100 CVC-days was not significantly different (0.25 in the Hickman group versus 0.13 in the Groshong group; P = 0.24). The most frequent type of CVC-related infection in both groups was microbiologically documented sepsis; in most cases Gram-positive bacteria were isolated. Neutropenia (P < 0.001 for both CVCs) and hospital CVC management (P = 0.0047 for the Hickman group, P < 0.001 for the Groshong group) emerged as the major risk factors for the outbreak of infections. The rate of mechanical complication episodes per 100 CVC-days was similar in both groups (1.01 in the Hickman group versus 1.1 in the Groshong group; P = 0.58). Some complications (fissures, ruptures, total lumen obstruction by clots) occurred only in the Groshong group. Our study did not demonstrate any statistically significant difference in the incidence of mechanical and infective CVC-related complications between these two types of catheter., The aim of this study was to compare the Hickman and Groshong central venous catheters (CVCs) for incidence and severity of catheter-related complications in children. Seventy-three patients with hematological malignancies were observed, 42 with Groshong CVCs and 31 with Hickman CVCs. The number of infective episodes per 100 CVC-days was not significantly different (0.25 in the Hickman group versus 0.13 in the Groshong group; P = 0.24). The most frequent type of CVC-related infection in both groups was microbiologically documented sepsis; in most cases Gram-positive bacteria were isolated. Neutropenia (P < 0.001 for both CVCs) and hospital CVC management (P = 0.0047 for the Hickman group, P < 0.001 for the Groshong group) emerged as the major risk factors for the outbreak of infections. The rate of mechanical complication episodes per 100 CVC-days was similar in both groups (1.01 in the Hickman group versus 1.1 in the Groshong group: P = 0.58). Some complications (fissures, ruptures, total lumen obstruction by clots) occurred only in the Groshong group. Our study did not demonstrate any statistically significant difference in the incidence of mechanical and infective CVC-related complications between these two types of catheter

Pulmonary thromboembolism (PTE) in leukemic children undergoing intensive chemotherapy should be promptly recognized so that specific therapy can be started. Our experience with the two cases reported here has led us to propose guidelines for the treatment of initial PTE in a pediatric hematology unit. Two children with leukemia developed PTE, the first during the relapse for acute lymphoblastic leukemia and the second at the onset of acute promyelocytic leukemia. In both cases, the diagnosis of PTE was based on clinical assessment of sudden acute respiratory failure with positive pulmonary perfusional scintigraphy in spite of a negative chest X-ray. The subintensive supervision consisted of instrumental monitoring with the assistance of an intensive care anesthetist. The clinical monitoring was based on the serial registration of respiratory rate, cardiac rate, SaO2 and body temperature. The thrombolytic therapy, together with heparin prophylaxis, was successfully administered in the hematology ward without the need for intensive care support (i.e. mechanical ventilation). The success of the treatment was documented by the criterion of a return to the normal cardiorespiratory parameters a few hours after the start of the thrombolytic treatment. Furthermore, a chest CT scan in case 1 and an arteriography in case 2 confirmed the PTE-related hypoperfusion. On the basis of this experience, the authors point out that in the course of acute respiratory failure in leukemic children, the combination of a negative chest X-ray and a positive pulmonary perfusional scintigraphy (compared whenever possible with ventilatory scintigraphy) in the presence of a negative CT scan could be a reliable diagnostic tool for PTE. This pathology should be treated promptly and with specific therapy to avoid progression to a severe, massive PTE

Minimal data about oral and dental health in long-term survivors after BMT are available. We studied the dental status of 27 children (19 males, eight females) with leukaemia, followed up with a routine oral examination, panoramic tomogram and, when necessary, an endoral radiograph at a median of 2 years (range 1-10) after BMT. Community periodontal index treatment necessity (CPITN), dental caries, missing or filled permanent teeth (DMFT) and dento-facial alterations according to WHO criteria were registered and evaluated. Median age of the patients at BMT was 9 years (range 1.1-17.9), The mean DMFT score ranged from 1.6 to 12.4 according to age at examination and was slightly higher than that which we previously reported in children who received chemotherapy alone, CPITN showed the presence of soft deposits in 77.7%, serious gingivitis in 59.2% and parodontal involvement in 3.7% of cases, Dento-facial abnormalities were found in 55.5% of patients, while 62.9% of the patients had tooth abnormalities or agenesis. Nine out of 27 patients (33%) had root hypoplasia, A negative impact on DMFT index due to multiple post-BMT factors was found. Age is the crucial factor in determining a developmental defect of enamel and root, The follow-up of long-term survivors after BMT should include regular dental examination., Minimal data about oral and dental health in long-term survivors after BMT are available. We studied the dental status of 27 children (19 males, eight females) with leukaemia, followed up with a routine oral examination, panoramic tomogram and, when necessary, an endoral radiograph at a median of 2 years (range 1-10) after BMT. Community periodontal index treatment necessity (CPITN), dental caries, missing or filled permanent teeth (DMFT) and dento-facial alterations according to WHO criteria were registered and evaluated. Median age of the patients at BMT was 9 years (range 1.1-17.9). The mean DMFT score ranged from 1.6 to 12.4 according to age at examination and was slightly higher than that which we previously reported in children who received chemotherapy alone. CPITN showed the presence of soft deposits in 77.7%, serious gingivitis in 59.2% and parodontal involvement in 3.7% of cases. Dento-facial abnormalities were found in 55.5% of patients, while 62.9% of the patients had tooth abnormalities or agenesis. Nine out of 27 patients (33%) had root hypoplasia. A negative impact on DMFT index due to multiple post-BMT factors was found. Age is the crucial factor in determining a developmental defect of enamel and root. The follow-up of long-term survivors after BMT should include regular dental examination

N/A

Between 1976 and 1982, 59 patients with locally advanced breast cancer were treated with preoperative supervoltage radiotherapy, adjuvant preoperative and postoperative hormonochemotherapy, and modified radical mastectomy. Systemic treatment, which was started simultaneously with radiotherapy, consisted of a combination of daily oral tamoxifen and a monthly alternation of Doxorubicin + vincristine and cyclophosphamide + methotrexate + 5-fluorouracil (CMF). One of each cycle was given preoperatively at half dosage and five of each were repeated postoperatively at full dosage. All patients became operable. Results of pathologic examination of the operative specimen, available in 51 patients, showed complete disappearance of tumor tissue in breast areas in eight patients, of which three still had positive axillary nodes. After a median follow-up time of 6 years locoregional failure was observed in 12 patients (20%) but in only three (5%) did it occur before distant failure. The actuarial median survival of the entire patient population is close to 4 years. Seven patients are alive without recurrence at greater than 9 years. This aggressive multidisciplinary treatment approach is associated with a projected 30% long-term survival (10 years), excellent local control, but substantial toxicity., Journal Article, Research Support, Non-U.S. Gov't, FLWIN, info:eu-repo/semantics/published

Between 1976 and 1982, 59 patients with locally advanced breast cancer were treated with preoperative supervoltage radiotherapy, adjuvant preoperative and postoperative hormonochemotherapy, and modified radical mastectomy. Systemic treatment, which was started simultaneously with radiotherapy, consisted of a combination of daily oral tamoxifen and a monthly alternation of Doxorubicin + vincristine and cyclophosphamide + methotrexate + 5-fluorouracil (CMF). One of each cycle was given preoperatively at half dosage and five of each were repeated postoperatively at full dosage. All patients became operable. Results of pathologic examination of the operative specimen, available in 51 patients, showed complete disappearance of tumor tissue in breast areas in eight patients, of which three still had positive axillary nodes. After a median follow-up time of 6 years locoregional failure was observed in 12 patients (20%) but in only three (5%) did it occur before distant failure. The actuarial median survival of the entire patient population is close to 4 years. Seven patients are alive without recurrence at greater than 9 years. This aggressive multidisciplinary treatment approach is associated with a projected 30% long-term survival (10 years), excellent local control, but substantial toxicity., Journal Article, Research Support, Non-U.S. Gov't, FLWIN, info:eu-repo/semantics/published

Nel soggetto anziano la perdita uditiva si accompagna a forme di degrado extrauditivo che inficiano il rapporto sociale del soggetto isolandolo dall’ambiente in cui vive. La presbiacusia riduce infatti l’intellegibilità delle parole e la comprensione del messaggio verbale. La perdita uditiva dell’anziano è, nella maggioranza dei casi, rimediabile attraverso l’applicazione di un sussidio protesico; le tipiche modificazioni uditive di tale paziente rendono questa fase particolarmente complessa e obbligano ad un periodo di adattamento e riabilitazione che va condotto da personale specializzato. Tale periodo riabilitativo è utile per far si che il soggetto familiarizzi con i nuovi suoni amplificati dalla protesi acustica e associ a questi i segni acustici che aveva immagazzinati nella memoria. L’esperienza ottenuta dagli AA evidenzia come un migliore adattamento della protesi abbia migliorato l’accettabilità di questa da parte del presbiacusico. Inoltre si evidenzia come la riabilitazione debba risvegliare il desiderio alla comunicazione e all’identificazione delle voci e dei rumori ambientali. L’opera riabilitativa deve infondere nell’anziano fiducia nel suo nuovo modo di sentire rendendo il soggetto consapevole che la perdita uditiva è un evolversi fisiologico di una ulteriore fase della vita. PAROLE CHIAVI Sordità, Protesi acustica, Riabilitazione acustica.

Gli A.A. espongono i vantaggi delle nuove protesi acustiche a doppio range di amplificazione attraverso le loro modalità operative. Illustrano le metodiche con cui è possibile evitare gli inconvenienti (senso di fastidio), rilevati dai soggetti affetti da sordità neurosensoriali in situazioni di comunicabilità in campi sonori diffusi. Vengono valutati i tempi di intervento dei controlli automatici di guadagno (AGC) e le loro interazioni con la dinamica dell’espressione vocale. Si soffermano, infine, sui vantaggi offerti dall’audiometria vocale con logotomi che permette di dedurre, meglio dell’audiometria tonale, le reali capacità comunicazionali del paziente sordo, portatore di protesi acustica.

Gli Autori osservano che gli audiolesi presentano spesso difficoltà notevoli nella percezione dei gruppi consonantici, mentre raramente rilevano delle difficoltà nella intellegibilità delle vocali. In talune circostanze poi gli audiolesi palesano anche una tendenza funzionale alla nasalizzazione. Questi problemi spesso sussistono anche in presenza di una protesizzazione. Dopo avere analizzato la struttura spettrale delle consonanti e delle vocali gli Autori forniscono una interpretazione delle anomalie osservate.

Gli AA evidenziano come nel caso di protesizzazione monoaurale la deprivazione uditiva controlaterale comporti una ridotta capacità del cervello a decodificare i suoni provenienti dall’orecchio rimasto a lungo privato dagli stimoli uditivi. In particolar modo si evidenzia una ridotta discriminazione delle parole in competizione o in presenza di rumore di fondo. La possibilità di regressione dagli effetti negativi della deprivazione uditiva è tempo-dipendente. I 12 soggetti protesizzati adattati binauralmente hanno, inoltre, evidenziato una migliore localizzazione spaziale dei suoni con un apprezzabile miglioramento riconoscitivo e delle capacità attentive di una voce di interesse rispetto ad altre. Alla luce degli studi e delle conoscenze fin’oggi acquisite si ritiene che il ripristino fisiologico binaurale debba essere raccomandato sin dalla prima protesizzazione per evitare di compromettere l’abilità funzionale residua. PAROLE CHIAVE Sordità; Protesizzazione monoaurale; Protesizzazione binaurale.

Gli A.A. hanno studiato il fenomeno del riverbero sonoro ambientale correlando i valori di latenza dell’onda sonora (r) con le capacità discriminative di 10 soggetti presbiacusici in varie condizioni di ascolto. L’esperienza è stata condotta utilizzando l’effetto di riverbero prodotto da due ambienti di diverso volume, e con conseguente diverso valore di r, in cui sono stati testati i soggetti facendo loro ascoltare parole non a senso compiuto emesse attraverso un altoparlante ad intensità costante. Si sono quindi ricavati le percentuali medie di comprensibilità sia con ascolto senza protesi acustica che con l’ausilio di protesi. Si è poi passati dalla protesizzazione monaurale alla binaurale con microfono omnidirezionale e da questa all’impiego di microfono direzionale, Si è pertanto evidenziato il vantaggio che, offre la protesi binaurale, in particolare la direzionale, in presenza di un alto tempo di riverbero. Infine gli A.A. hanno effettuato un test di intellegibilità con protesi filtrate sulle basse frequenze range in cui sono presenti i fenomeni di risonanza dell’ambiente, rilevando percentuali di intellegibilità ancora più alte. Concludono ritenendo di grande interesse la correlazione fra i tempi medi di riverbero degli ambienti abitati con i sistemi di audioprotesizzazione.

Le caratteristiche della voce di ognuno di noi seguono le trasformazioni fisiologiche del procedere dell’età. Nell’anziano sovente la voce si fa debole, tremante e priva di inflessioni espressive. Il soggetto avverte le trasformazioni ma non riesce a concretizzare il desiderio di tornare alla fonazione degli anni migliori. Le modificazioni vocali sono, infatti, dovute a una sommatoria di problemi: respiratori, cardiovascolari e, spesso, neurologici. Nel soggetto normale il feead-back acustico da la possibilità di autocontrollare la propria voce. Nell’anziano la presbiacusia interrompe questa reazione naturale. L’anziano perde la possibilità di modulare la propria espressività vocale; la fonazione perde la dinamica e si accompagna spesso a rumore inespressivo su tutto lo spettro frequenziale. Il ripristino della funzionalità uditiva, con l’impiego della protesi acustica personalizzata, restituisce all’anziano la possibilità di ascoltarsi ripristinando, nella maggior parte dei casi, una voce modulata e completa della corretta tessitura armonica. Gli AA descrivono una indagine fatta su dodici soggetti di età compresa tra 65 e 75 anni confrontando, attraverso l’indagine elettroacustica, la voce in presenza e in assenza di protesi acustica. Gli stessi concludono ritenendo necessaria una corretta protesizzazione dell’anziano al fine di restituire fiducia nelle proprie capacità sensoriali, uditive e fonatorie e mantenere i normali rapporti sociali.

A study about the acoustic characteristcs of phonation gives us a further interpretation of why deaf people haven’t a correct language. The Authors have established, by spectral analysis, the variability field of the vowel formantic frequencies, essential to recognize the phonemes. The correlation between the signal emitted during the normal phonation and the ability to perceive and to discriminat by the choclea allowed to establish a new interpretation of the difficulties of deaf people to have a correct language. For this reason we have classified the values of the vowel frequencies, which are necessary to recognize the language, in relation to the dislocation of the risonance points on the basilar membrana (MEL scale). This membrana, in fact, reacts to the sound according to a semilogarithmic disposition of the stimolated points. So, if the membrana has a low number of sensory cells, low will be the language discrimination and intellegibility.

The authors have developed a research about letting in noise into a house situated at ground floor from external vehicles. During the day the AA have measured too high sound pressure level while during the night the sound pressure have just seen acceptable. Particularly the AA have measured a high sound energy in low frequency range; these lowe signals are not pointed out by weighting curve A. The AA consider dangerous this sound level for human body and advise to make measures of noise by linear range level sound meter.

The authors have developed a research about letting in noise into a house situated at ground floor from external vehicles. During the day the AA have measured too high sound pressure level while during the night the sound pressure have just seen acceptable. Particularly the AA have measured a high sound energy in low frequency range; these lowe signals are not pointed out by weighting curve A. The AA consider dangerous this sound level for human body and advise to make measures of noise by linear range level sound meter.

Gli A.A. espongono i vantaggi delle nuove protesi acustiche a doppio range di amplificazione attraverso le loro modalità operative. Illustrano le metodiche con cui è possibile evitare gli inconvenienti (senso di fastidio), rilevati dai soggetti affetti da sordità neurosensoriali in situazioni di comunicabilità in campi sonori diffusi. Vengono valutati i tempi di intervento dei controlli automatici di guadagno (AGC) e le loro interazioni con la dinamica dell’espressione vocale. Si soffermano, infine, sui vantaggi offerti dall’audiometria vocale con logotomi che permette di dedurre, meglio dell’audiometria tonale, le reali capacità comunicazionali del paziente sordo, portatore di protesi acustica.

Nel soggetto anziano la perdita uditiva si accompagna a forme di degrado extrauditivo che inficiano il rapporto sociale del soggetto isolandolo dall’ambiente in cui vive. La presbiacusia riduce infatti l’intellegibilità delle parole e la comprensione del messaggio verbale. La perdita uditiva dell’anziano è, nella maggioranza dei casi, rimediabile attraverso l’applicazione di un sussidio protesico; le tipiche modificazioni uditive di tale paziente rendono questa fase particolarmente complessa e obbligano ad un periodo di adattamento e riabilitazione che va condotto da personale specializzato. Tale periodo riabilitativo è utile per far si che il soggetto familiarizzi con i nuovi suoni amplificati dalla protesi acustica e associ a questi i segni acustici che aveva immagazzinati nella memoria. L’esperienza ottenuta dagli AA evidenzia come un migliore adattamento della protesi abbia migliorato l’accettabilità di questa da parte del presbiacusico. Inoltre si evidenzia come la riabilitazione debba risvegliare il desiderio alla comunicazione e all’identificazione delle voci e dei rumori ambientali. L’opera riabilitativa deve infondere nell’anziano fiducia nel suo nuovo modo di sentire rendendo il soggetto consapevole che la perdita uditiva è un evolversi fisiologico di una ulteriore fase della vita. PAROLE CHIAVI Sordità, Protesi acustica, Riabilitazione acustica.

Le caratteristiche della voce di ognuno di noi seguono le trasformazioni fisiologiche del procedere dell’età. Nell’anziano sovente la voce si fa debole, tremante e priva di inflessioni espressive. Il soggetto avverte le trasformazioni ma non riesce a concretizzare il desiderio di tornare alla fonazione degli anni migliori. Le modificazioni vocali sono, infatti, dovute a una sommatoria di problemi: respiratori, cardiovascolari e, spesso, neurologici. Nel soggetto normale il feead-back acustico da la possibilità di autocontrollare la propria voce. Nell’anziano la presbiacusia interrompe questa reazione naturale. L’anziano perde la possibilità di modulare la propria espressività vocale; la fonazione perde la dinamica e si accompagna spesso a rumore inespressivo su tutto lo spettro frequenziale. Il ripristino della funzionalità uditiva, con l’impiego della protesi acustica personalizzata, restituisce all’anziano la possibilità di ascoltarsi ripristinando, nella maggior parte dei casi, una voce modulata e completa della corretta tessitura armonica. Gli AA descrivono una indagine fatta su dodici soggetti di età compresa tra 65 e 75 anni confrontando, attraverso l’indagine elettroacustica, la voce in presenza e in assenza di protesi acustica. Gli stessi concludono ritenendo necessaria una corretta protesizzazione dell’anziano al fine di restituire fiducia nelle proprie capacità sensoriali, uditive e fonatorie e mantenere i normali rapporti sociali.

Gli AA evidenziano come nel caso di protesizzazione monoaurale la deprivazione uditiva controlaterale comporti una ridotta capacità del cervello a decodificare i suoni provenienti dall’orecchio rimasto a lungo privato dagli stimoli uditivi. In particolar modo si evidenzia una ridotta discriminazione delle parole in competizione o in presenza di rumore di fondo. La possibilità di regressione dagli effetti negativi della deprivazione uditiva è tempo-dipendente. I 12 soggetti protesizzati adattati binauralmente hanno, inoltre, evidenziato una migliore localizzazione spaziale dei suoni con un apprezzabile miglioramento riconoscitivo e delle capacità attentive di una voce di interesse rispetto ad altre. Alla luce degli studi e delle conoscenze fin’oggi acquisite si ritiene che il ripristino fisiologico binaurale debba essere raccomandato sin dalla prima protesizzazione per evitare di compromettere l’abilità funzionale residua. PAROLE CHIAVE Sordità; Protesizzazione monoaurale; Protesizzazione binaurale.

Gli Autori osservano che gli audiolesi presentano spesso difficoltà notevoli nella percezione dei gruppi consonantici, mentre raramente rilevano delle difficoltà nella intellegibilità delle vocali. In talune circostanze poi gli audiolesi palesano anche una tendenza funzionale alla nasalizzazione. Questi problemi spesso sussistono anche in presenza di una protesizzazione. Dopo avere analizzato la struttura spettrale delle consonanti e delle vocali gli Autori forniscono una interpretazione delle anomalie osservate.

Gli A.A. hanno studiato il fenomeno del riverbero sonoro ambientale correlando i valori di latenza dell’onda sonora (r) con le capacità discriminative di 10 soggetti presbiacusici in varie condizioni di ascolto. L’esperienza è stata condotta utilizzando l’effetto di riverbero prodotto da due ambienti di diverso volume, e con conseguente diverso valore di r, in cui sono stati testati i soggetti facendo loro ascoltare parole non a senso compiuto emesse attraverso un altoparlante ad intensità costante. Si sono quindi ricavati le percentuali medie di comprensibilità sia con ascolto senza protesi acustica che con l’ausilio di protesi. Si è poi passati dalla protesizzazione monaurale alla binaurale con microfono omnidirezionale e da questa all’impiego di microfono direzionale, Si è pertanto evidenziato il vantaggio che, offre la protesi binaurale, in particolare la direzionale, in presenza di un alto tempo di riverbero. Infine gli A.A. hanno effettuato un test di intellegibilità con protesi filtrate sulle basse frequenze range in cui sono presenti i fenomeni di risonanza dell’ambiente, rilevando percentuali di intellegibilità ancora più alte. Concludono ritenendo di grande interesse la correlazione fra i tempi medi di riverbero degli ambienti abitati con i sistemi di audioprotesizzazione.