Blood-brain barrier damage associates with glia-related cytokines in the cerebrospinal fluid of patients with Multiple Sclerosis.

BACKGROUND: The presence of Blood-Brain Barrier (BBB) dysfunction is defined by albumin quotient (QALB) and characterize a group of Multiple Sclerosis (MS) patients at clinical onset. We evaluated the concentration in cerebrospinal fluid (CSF) of 87 cytokines, to better characterize the CSF inflammatory pattern in presence of BBB damage. MATERIALS AND METHOD: In an exploratory cohort, CSF cytokines were evaluated by means of Multiplex technology (Bio-Plex Pro-Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro-Human Chemokines 40-Plex Panel, Bio-Plex Pro-Human Inflammation Assays 37-Plex Panel) in a cohort of Other Not Inflammatory Neurological Disorders (ONIND) and in cohort of patients with MS, stratified according to BBB damage into QALB+ and QALB- MS patients. In the validation cohort, we evaluated the relevant molecules in a cohort of MS patients, stratified again into QALB+ and QALB-, including also Neurofilament Light (NfL) and Chitinase 3-like 1 (CHI3L1) CSF concentration. RESULTS: While MIP-1α, CXCL-13, and CCL-22 CSF concentrations were higher in both MS groups compared to ONIND, in QALB+ MS CSF concentrations of CXCL-9 (17.85 ± 4.69 pg/mL), CXCL-10 (476.5 ± 324.3 pg/mL), and IL-16 (96.08 ± 86.17 pg/mL) were higher than in QALB- MS (8.98 ± 5368 pg/mL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.05, and 47.35 ± 36.87 pg/mL, p < 0.005, respectively) and ONIND (8.98 ± 5368 pg/mlL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.005, and 47.35 ± 36.87 pg/mL, p < 0.001, respectively). A strong correlation was observed between CXCL-9 and CXCL-10 in all MS groups (all r>0.75, all p < 0.001). In the validation cohort again CXCL-10 CSF concentration were higher in QALB+ MS than in QALB- MS (94.25 ± 64.75 vs 153.8 ± 99.52, p < 0.05), while no difference was observed in serum. CSF NfL (1642 ± 1963 vs 3231 ± 3492 pg/mL, p < 0.05) and CHI3L1 (183.9 ± 86.62 vs 262 ± 137.5 ng/mL, p < 0.05) were increased in QALB+ MS. CONCLUSIONS: BBB damage in MS is linked to a specific CSF cytokines pattern (CXCL-9, CXCL-10, IL-16), that are also involved in astrocyte-microglia interaction. To what extent their continuous production in the CNS may mark a more severe disease course merits to be investigated.

Whole genome sequencing in ROHHAD trios proved inconclusive: what's beyond?

Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) is a rare, life-threatening, pediatric disorder of unknown etiology, whose diagnosis is made difficult by poor knowledge of clinical manifestation, and lack of any confirmatory tests. Children with ROHHAD usually present with rapid onset weight gain which may be followed, over months or years, by hypothalamic dysfunction, hypoventilation, autonomic dysfunction, including impaired bowel motility, and tumors of neural crest origin. Despite the lack of evidence of inheritance in ROHHAD, several studies have been conducted in recent years that have explored possible genetic origins, with unsuccessful results. In order to broaden the search for possible genetic risk factors, an attempt was made to analyse the non-coding variants in two trios (proband with parents), recruited in the Gaslini Children's Hospital in Genoa (Italy). Both patients were females, with a typical history of ROHHAD. Gene variants (single nucleotide variants, short insertions/deletions, splice variants or in tandem expansion of homopolymeric tracts) or altered genomic regions (copy number variations or structural variants) shared between the two probands were searched. Currently, we have not found any potentially pathogenic changes, consistent with the ROHHAD clinical phenotype, and involving genes, regions or pathways shared between the two trios. To definitively rule out the genetic etiology, third-generation sequencing technologies (e.g., long-reads sequencing, optical mapping) should be applied, as well as other pathways, including those associated with immunological and autoimmune disorders, should be explored, making use not only of genomics but also of different -omic datasets.

Are glucose and insulin levels at all time points during OGTT a reliable marker of diabetes mellitus risk in pediatric obesity?

PURPOSE: Childhood overweight and obesity associated with insulin resistance and metabolic syndrome represent the new global pandemic and the main causative factors for dysglycemia, prediabetes, and Type 2 Diabetes Mellitus (T2DM). Predictors, such as HOMA-IR, HOMA-ß%, and QUICKI lack specific reference values in children. OGTT is a gold standard for glycometabolic assessment. Recently, a glycemic level higher than 155 mg/dl at + 60' after glucose ingestion has been defined as a risk factor for T2DM in obese adolescents. We aim to analyze and correlate fasting insulin-resistance markers with OGTT results in overweight/obese children and adolescents. METHODS: We retrospectively evaluated glucose and insulin values during a 2-h OGTT every 30 min in 236 overweight/obese patients. Glucose values and insulin sum during OGTT were compared to glycometabolic indexes and different cut-off values for insulin sum. RESULTS: A 1-h glucose > 155 mg/dl and insulin sum > 535 microU/ml at all times during OGTT are the best predictors of diabetes risk in obese youths. A1-h glucose > 155 mg/dl is significantly associated with HbA1c > 5.7%, while no association was observed between HbA1c > 5.7% and glucose levels at baseline and 2 h. The ability of the standardized HOMA-IR to predict the prediabetes status is clearly lower than the total insulin sum at OGTT. CONCLUSION: Our study demonstrates that also 1-h post-OGTT glucose, together with HbA1c, is an effective diabetes predictor.

Measurement of electromagnetic waves from runaway electrons.

Electromagnetic waves emitted during a tokamak discharge can be partially ascribed to coupling with plasma waves. In particular, in the presence of runaway electrons, the electromagnetic waves deliver information, otherwise inaccessible, about kinetic instabilities excited by the fast particles. Experiments aimed at studying radio frequency emissions from runaway electron scenarios during different stages of plasma discharge have been carried out at the Frascati Tokamak Upgrade. Frequencies in the range of lower hybrid and whistler waves have been explored, in the presence of relativistic electrons with different energies, ranging from a few to tens of MeV. A pronounced sensitivity of the radio frequency measurements in detecting driven instabilities is observed, providing the possibility to exploit this kind of technique as a monitor of the instability processes and for studies of the fast electron activity. In particular, in this work, we propose a simplified analysis of the frequency scaling of a specific family of kinetic instabilities arising at the lower hybrid frequency range during the current ramp-up stage. The study is performed with respect to the density profile and the wave vector coupling conditions and is aimed at obtaining a rough estimate of the most likely radial location of the interaction between the runaway electron beam and plasma waves at the emission times of the observed signals.

First Intrashot Observation of Runaway-Electron-Driven Instabilities at the Lower-Hybrid Frequency Range under ITER-Relevant Plasma-Wave Dispersion Conditions.

Kinetic instabilities driven by runaway electrons (REs) have recently received attention in the fusion community as a means to control and diagnose REs in a tokamak. Experiments aimed at studying such kinetic instabilities have been performed at the Frascati Tokamak Upgrade (FTU), where different families of waves have been identified, from wide-band bursting emissions to quasi-monochromatic waves and sharp lines, in the presence of REs with energies from a few to tens of MeV. A specific family of waves with intense kinetic drive was directly observed for the first time, during both the early Ohmic plasma start-up and the current ramp-up. A clear wave frequency scaling with respect to the electron density was demonstrated. This scaling, with the complementary analysis of signals observed at different magnetic fields, allowed the identification of these instabilities as lower-hybrid waves. The relevant analysis shown in this Letter is based on a continuous intrashot detection of the RE-driven wave, which is reported for the first time for this kind of instability. We demonstrated that unstable waves are excited already at the very beginning of a tokamak discharge, opening the way to new possible research on the exploitation of this kind of measurement for monitoring seed REs formation at the early plasma stage, while most diagnostics still have limited capabilities. The conditions for plasma wave dispersion at the early phase of the FTU discharge are very similar to the ones expected during the ITER start-up, when analogous instabilities might, hence, come to light, in case of formation of suprathermal populations.

Radio-frequency current drive for thermonuclear fusion reactors.

Principal research on energy from thermonuclear fusion uses Deuterium-Tritium plasmas magnetically trapped in toroidal devices. As major scientific problem for an economic (i.e., really feasible) reactor, we must understand how to lead strongly heated plasmas to sustain a high fusion gain while large fraction of current is self-produced via the presence of strong pressure gradient. To suppress turbulent eddies that impair thermal insulation and pressure tight of the plasma, current drive (CD) is necessary. However, tools envisaged so far in ITER (International Thermonuclear Experiment Rector) are unable accomplishing this task that requires efficiently and flexibly matching the natural current profiles of plasma. Consequently, viability of a thermonuclear reactor should be problematic. Multi-megawatt radio-frequency (RF) power coupled to plasma would produce the necessary CD, but modelling results based on previous understanding found difficult the extrapolation of this CD concept to reactor conditions of high temperature plasma, and greater flexibility of method would also be required. Here we present new model results based on standard quasilinear (QL) theory that allow establish conditions to drive efficiently and flexibly the RF-driven current at large radii of the plasma column, as necessary for the goal of a reactor.

Micro-fragmented adipose tissue injection associated with arthroscopic procedures in patients with symptomatic knee osteoarthritis.

BACKGROUND: The social impact of degenerative diseases is steadily increasing, because of the continued rise in the mean age of the active population. Articular cartilage lesions are generally associated with disability and symptoms such as joint pain and reduced function, and remain a challenge for the orthopaedic surgeon. Several non-invasive solution have been proposed, but the results achieved to date are far from being completely satisfactory. Recently, new therapeutic approaches, such as the use of mesenchymal stem cells, have been developed. Among the many sources, the adipose tissue is nowadays considered one of the smartest, due to its abundance and easy access. The aim of this retrospective study is to explore whether patients affected by symptomatic knee osteoarthritis treated with micro-fragmented adipose tissue associated with a chondral shaving procedure experience an improvement in symptoms and function. METHODS: Thirty-eight patients affected by symptomatic knee osteoarthritis were treated in 2015 with an arthroscopic procedure associated with an injection of autologous and micro-fragmented adipose tissue. Micro-fragmented adipose tissue was obtained using a minimal manipulation technique in a closed system. Clinical outcomes were determined at 1, 3, 6, and 12 months follow-up using Knee Injury and Osteoarthritis Outcome Score questionnaire and direct physical examination. Safety of the procedure, recording type and incidence of any adverse event, was also assessed. RESULTS: A steady and statistically significant improvement of all the clinical scores from pre-operative evaluation to 1, 3, 6, and 12 months follow-up was observed, with KOOS sport and quality of life being the most improved scores. On average, 92% of the patients clinically improved and 100% of them were satisfied with the treatment. No adverse events nor relevant complications were recorded. CONCLUSION: The result of the study pointed to micro-fragmented adipose tissue as a safe and beneficial adjuvant in the surgical treatment of degenerative knee chondropathy. The procedure is simple, sustainable, quick, minimally invasive, one-step, and safe. After one year, the results are very satisfactory and promising. A longer follow-up is needed to draw definitive conclusions and enlarge the indications. TRIAL REGISTRATION: Registered at clinicaltrials.gov as NCT03527693 on 27 April 2018 (retrospectively registered).

Validation of the Italian Quality of Life in Short Stature Youth (QoLISSY) questionnaire.

PURPOSE: The Quality of Life in Short Stature Youth (QoLISSY) questionnaire is a disease-specific instrument developed to assess health-related quality of life (HrQoL) in children with short stature. While the original instrument was simultaneously developed in five European countries, this study describes the results of the Italian QoLISSY translation, cultural adaptation, and validation. METHODS: Focus group discussions and a cognitive debriefing process with children (N = 12) diagnosed with growth hormone deficiency or idiopathic short stature and one parent each, as well as parents of younger children (N = 20) were conducted to examine the linguistic and content validity of the Italian version. Psychometric testing was performed using data from the subsequent field- and re-test (N = 32). RESULTS: The results of the qualitative testing of the Italian sample revealed comparability of content to data of the original five European countries. The following field- and re-test results were psychometrically satisfactory including good item and scale operating characteristics, sufficient evidence of reliability, and acceptable evidence of construct validity. CONCLUSION: In conclusion, the Italian QoLISSY HrQoL-dimensions are comparable to other European countries. The psychometric quality of the Italian QoLISSY version is satisfactory and the instrument is ready for use in Italian patients and their parents.

Growth factors and metabolic markers in cord blood: relationship to birth weight and length.

Low birth weight and length for gestational age are associated with a high risk of short stature and metabolic syndrome in adulthood. The mechanisms that link prenatal growth to adult stature and metabolic syndrome have not yet been entirely clarified. The aim of our study was to evaluate the relationship between standardized anthropometric measures at birth and insulin-like growth factor (IGF)-I, IGF-II, insulin, adiponectin, and non-esterified fatty acid (NEFA) cord blood levels in the general population. One hundred fifty-eight random newborn subjects (77F, 81M) from Genoa, Italy, were analyzed. Anthropometric parameters were measured and standardized according to standard Italian tables. Insulin values were treated as categorical, since in several cases the results fell below detection cut-off. Mean birth weight was 3,214.23∓488.99 gr and mean length was 49.82∓2.17 cm. Females had higher mean IGF-I (p=0.04), and were more likely to have insulin values either <2 μU/ml or >4.5μU/ml (p= 0.04) compared to males. Weight and length SD scores (SDS) were higher in subjects with elevated insulin levels (p=0.002). A moderate correlation was found between weight and IGF-II (r=0.354). Multivariable analysis demonstrated that standardized birth weight was associated with IGFII and insulin values. Our data highlight the importance of IGF-II in fetal growth and suggest that gender differences should be taken into consideration when evaluating prenatal growth.

Serie de paciente con escabiosis tratados con azufre precipitado al 6% / Series of patient with scabies treated with 6% precipitated sulfur

OBJETIVOS: reportar los resultados de la estrategia que incluye "el tratamiento tópico con azufre precipitado al 6% sumado a medidas no farmacológicas" en la población de Villa Verde, Pilar, Buenos Aires, Argentina. MÉTODOS: Serie de casos tratados entre Marzo de 2007 y marzo de 2008 de una muestra de conveniencia integrada por toda la población con signos y síntomas sugestivos de escabiosis durante dicho período. RESULTADOS: Fueron incluidos 161 pacientes, pero sólo se pudo realizar la evaluación completa en 110 de ellos (68,3%). De éstos, 74 se encontraba curado a los 15 días de iniciado el tratamiento y otros 23, al mes, lo que implica una tasa global de curación de 88%. Sólo 12,7% de la muestra evaluada presentó efectos adversos. El 20% de los encuestados percibió la intervención como de bajo costo, el 32,6 de costo moderado y el 47,5 alto. El autorreporte de adherencia al tratamiento farmacológico fue de 95% y del no farmacológico, 96%. CONCLUSIONES: Estos resultados contribuyen a avalar una estrategia terapéutica ampliamente utilizada en nuestro medio (por su bajo precio y amplia disponibilidad), que por el momento posee escasa evidencia científica y es utilizada por motivos fundamentalmente empíricos.

OBJECTIVES: Report the results of the strategy that includes "the topical treatment with precipitated sulfur at 6% plus non-pharmacological measures" in the population of Villa Verde, Pilar, Buenos Aires, Argentina. METHODS: A series of cases treated between March 2007 and March 2008 of a sample of convenience integrated by the entire population with signs and symptoms suggestive of scabies during this period. RESULTS: A total of 161 patients were included, but only 110 of them could complete the complete evaluation (68.3%). Of these, 74 were cured 15 days after starting treatment and another 23, a month, which implies an overall cure rate of 88%. Only 12.7% of the sample evaluated had adverse effects. 20% of respondents perceived the intervention as low cost, 32.6 moderate cost and 47.5 high. Self-reported adherence to pharmacological treatment was 95% and non-pharmacological self-report was 96%. CONCLUSIONS: These results contribute to endorse a therapeutic strategy widely used in our environment (due to its low price and wide availability), which at the moment has little scientific evidence and is used for fundamentally empirical reasons.

Estimation of genetic risk for Type 1 diabetes mellitus in newborns on dried blood spot.

BACKGROUND: The main contribution to genetic susceptibility for Type 1 Diabetes Mellitus (T1DM) is conferred by the Human Leukocyte Antigens (HLA). AIM: We evaluated the feasibility of large scale screening on Dried Blood Spot (DBS) to estimate the genetic risk for T1DM in newborns. SUBJECTS AND METHODS: Peripheral blood DBS samples from 256 newborns, were genotyped for HLA DRB1 and DQB1 alleles identification by a commercially available assay based on a dissociation enhancer lanthanide fluorescence system available in many newborn screening laboratories. Results were compared with those obtained in two wide multicentric studies on cord blood (DIABFIN and PREVEFIN). RESULTS: Genotyping on DBS revealed 6 subjects at high risk for T1DM, 99 at moderate risk for T1DM and the remaining at low risk for T1DM. We found 100% concordance between both techniques for HLA-DQB1 and DRB1 determination, confirming the feasibility of large scale screening on DBS. CONCLUSIONS: DBSs represent a resource for future studies about new genetics markers. This assay for estimate the genetic risk of T1DM on DBS showed an excellent sensitivity, specificity and accuracy compared with conventional techniques. Moreover, this assay resulted less expensive, and it could be easily performed on material already collected for newborn screening programs.

Quantitative ultrasound detects bone changes following bone marrow transplantation in pediatric subjects with hematological diseases: a longitudinal study.

BACKGROUND: Bone marrow transplantation (BMT) is associated with bone morbidity. We investigated bone status with quantitative ultrasound (QUS) in pediatric patients with hematological diseases prior to and up to 3 yr following BMT. METHODS: Phalangeal QUS measures for amplitude- dependent speed of sound (Ad-SoS) and bone transmission time (BTT) were obtained in 40 hematological patients (25 with malignant, 15 with non-malignant disease; 9.7+/-4.9 yr) before BMT and 6, 12, 24, and 36 months after BMT. Bone parameters were expressed as Z-scores based on age-sex-matched normal controls. RESULTS: Mean Ad-SoS and BTT Z-scores were normal before BMT and reduced at 36 months (analysis of variance: p=0.0542 and p=0.0233). Ad-SoS and BTT Z-scores remained relatively stable in the first 6 months after BMT and then progressively decreased reaching a plateau at 12-36 months. In non-malignant patients, BTT Z-score decreased at 6-12 months (p=0.029) and subsequently increased, while in malignant patients BTT Z-score showed a decrease at 12-24 months. Pre-pubertal subjects displayed a drop of BTT Z-Score values at both 12 (p=0.023) and 36 months after BMT (p=0.049), while BTT Z-score remained relatively unchanged in pubertal subjects. Early impairment of BTT Z-score was found in patients who suffered acute graft versus host disease (GVHD) compared to patients without this clinical condition; BTT Z-score was lower at 36 months (p=0.045). CONCLUSIONS: Longitudinal assessment by QUS of pediatric BMT survivors evidenced that bone status is mildly affected up to 36 months after BMT, mainly in malignant patients, in pre-pubertal subjects at BMT and in patients who suffered acute GVHD.

Folic acid, vitamin B12, and homocysteine levels during fasting and after methionine load in patients with Type 1 diabetes mellitus.

AIMS: To assess plasma concentrations of folic acid, vitamin B12, and total plasma homocysteine (tHCY) during fasting and after methionine load in young patients with Type 1 diabetes mellitus (T1DM). METHODS: We enrolled 41 young patients with T1DM without any sign of microvascular complications and 123 healthy controls in a 1:3 case-control study. Fasting and post-methionine load (PML) tHCY, folic acid, and vitamin B12 levels were measured in both groups. Data regarding chronological age, metabolic control (assessed by mean values of glycated hemoglobin in the last 12 months) and disease duration were also recorded. RESULTS: Fasting and PML tHCY levels were significantly lower in patients than in controls: 7.3+/-2.7 micromol/l vs 8.3+/-2.5 micromol/l (p=0.01), and 16.7+/-5.8 micromol/l vs 17.3+/-4.3 micromol/l (p=0.01), respectively. No correlation was found between fasting and PML tHCY levels and chronological age, disease duration, metabolic control, and insulin requirement. Patients had significantly higher vitamin B12 levels compared to controls: 767+/-318 pg/ml vs 628+/-236 pg/ml (p=0.003), while folic acid turned out to be lower in patients than in controls: 5.3+/-1.9 nmol/l vs 7.5+/-2.6 nmol/l (p<0.0001). CONCLUSIONS: Adolescents and young adults with T1DM without microvascular complications showed lower tHCY both during fasting and after methionine load. Lower folate concentrations in these patients might benefit from food fortification.

Effects of anti-CD20 monoclonal antibody as a rescue treatment for ANCA-associated idiopathic systemic vasculitis with or without overt renal involvement.

BACKGROUND: Cyclophosphamide (CYC) is thought to be the most effective treatment for antineutrophil cytoplasmatic antibody (ANCA)-associated idiopathic systemic vasculitis with severe organ or life threatening presentation. The key mechanism of action of CYC is suppression of the B lymphocyte activity. However, a considerable minority of patients either remains refractory to conventional therapy or experiences dose-limiting side effects. METHODS: In the present study, rituximab (4 weekly doses of 375 mg/m2 and 2 more doses at 1-month interval) was intravenously administered as a rescue therapy to 7 patients (4 affected by idiopathic systemic microscopic polyangiitis, 2 by Wegener's granulomatosis, and 1 affected by Churg Strauss syndrome). The study group was made up of 3 women and 4 men, mean age 61.5 years (39-71), intolerant or refractory to more conventional therapy. Four patients had histologically confirmed paucimmune necrotizing glomerulonephritis. RESULTS: Significant decreases were observed in levels of serum creatinine, proteinuria, erythrocyte sedimentation rate, C-reactive protein, and ANCA titers within the first 12 months of follow-up. Arthralgia and weakness rapidly disappeared in all patients. Four out of five patients reported a decrease in the degree of paresthesia, paralleled by an improvement in the electrodiagnostic parameters. A significant improvement was observed in both Birmingham Vasculitis Activity Score and Vasculitis Damage Index. Side effects were negligible. CONCLUSION: In this sample of patients with idiopathic systemic vasculitis that was refractory or intolerant to conventional treatment, rituximab was found to be a safe and effective rescue therapy.

Anti-neuronal antibodies in patients with HCV-related mixed cryoglobulinemia.

Mixed cryoglobulinemia (MC) is an immunological disorder characterized by immune-complex-mediated systemic vasculitis involving small vessels, which may present with renal, cutaneous, rheumatologic, and/or neurological manifestations. Until recently, the possible appearance of anti-neuronal autoantibodies in peripheral neuropathy occurring in the context of hepatitis C virus (HCV)-associated IgMk/IgG MC has not been extensively addressed. Therefore, a sample of these patients were evaluated by means of immuno-enzyme methods of anti-neuronal autoantibody detection. A significant increase in plasma titers of both anti-GM1 ganglioside and anti-sulfatide was observed. Abnormal titers were associated with evidence of active neuropathy as assessed by electrophysiologic studies. While peripheral neuropathy was traditionally thought to result from axonal ischemic damage caused by deposits of cryoprecipitable immune complexes in the vasa nervorum, a significant association between anti-GM1 and anti-sulfatide antibodies and involvement of the peripheral nervous system was observed in HCV-associated mixed IgMk/IgG cryoglobulinemia. Anti-neuronal reactivity could be a direct trigger of neurologic injury in this disorder.

Rupture of an isolated true superficial femoral artery aneurysm: case report.

True isolated atherosclerotic aneurysm of the superficial femoral artery is a rare pathology. We report a case of ruptured superficial femoral artery aneurysms (SFAA) not associated with aortic, common femoral or popliteal artery aneurysms. An emergency surgical procedure was performed and, after endoaneurysmal branches ligation, a ePTFE graft interposition was performed. The literature review shows a prevalence of rupture as compared with ischemic complications and the need for surgical repair in case of SFAA with diameter twice the normal vessel size. Early diagnosis and management are recommended because of the lower morbility and mortality rates associated with elective surgery by comparison with emergency procedures.

[Lymphedema secondary to breast cancer treatment: possibility of diagnostic and therapeutic prevention]. / Linfedema secondario al trattamento del cancro mammario: possibilità di prevenzione diagnostica e terapeutica.

We performed a prospective randomized study upon 50 patients who had undergone a breast cancer treatment, considering particularly the possibility of appearance of arm secondary lymphedema. The patients were divided in two groups of 25 patients each. In the 1st group, we performed only a clinical follow-up, whilst in the 2nd one, we used also lymphoscintigraphy. The aim of the study was to compare the incidence of arm secondary lymphedema in the two groups, and relate the data with those of the international literature, in order to identify diagnostic procedures indicative of the risk of development of lymphedema and find proper therapeutic preventive measures. It is certainty complex to foresee the appearance of arm lymphedema due to breast cancer treatment. No specific preventive therapeutic methods based upon particular diagnostic investigations were ever reported. Patients had undergone surgery and radiation for breast cancer in the period between April 1992 and June 1994, and controlled at over 5 years after operation. Upper limb lymphoscintigraphy was performed only in one of the two groups of 25 patients, before operation and, furthermore, after 1-3-6 months and 1-3 years from the treatment. Patients who presented lymphoscintigraphic alterations (dermal back flow, diffused or delayed transit of the tracer, etc.), before edema appeared clinically, underwent physical and rehabilitative therapy (bandages, manual lymphatic drainage, mechanical lymph drainage, elastic garments, etc.) and microsurgery (lymphatic-venous anastomoses at the arm), performed early (stages Ib and II) in patients not responsive to physical therapy. In the first group followed only clinically, secondary arm lymphedema occurred in 9 cases (36%), and appeared after a period variable from 1 week to 2 years (3-6 months averagely). In the second group, lymphoscintigraphy, performed preoperatively, permitted to find lymphatic impairment (absence of deltoid way, reduced axillary lymph nodal tracer uptake, delayed transit of the tracer) at the upper limb in 4 patients (15%). After breast cancer surgery, lymphoscintigraphy pointed out alterations of lymphatic circulation in 5 patients (20%) after 1 month, in other 6 cases (56%) at 6 months, other 5 (76%) after 1 year and 3 (88%) at 3 and 5 years. Physical preventive therapy performed in patients with positive lymphoscintigraphy, even before the clinical appearance of edema, allowed to find a clinically evident lymphedema only in 2 cases (8%). The last two patients underwent early (at stage Ib and II) microsurgical operation of lymphatic-venous anastomoses, with complete regression of edema and improved lymphatic drainage of the arm controlled by lymphoscintigraphy (appearance of preferential lymphatic pathways, absence of dermal back flow). Secondary arm lymphedema due to breast cancer treatment appears in 20-25% of cases till 35% when surgery is associated with radiotherapy. Lymphoscintigraphy allows to pointout alterations of lymphatic drainage before the clinical appearance of edema. Preventive physical and rehabilitative measures allows to reduce the clinical appearance of lymphedema significantly. Microsurgical operation performed precociously, at the early stages of the disease, permits to obtain the complete regression of the pathology thanks to the repair of preferential lymphatic pathways before of fibrosclerotic tissural alterations occur, which cause progressive worsening of clinical conditions, together with recurrent attacks of acute lymphangitis.

Long-term results after lymphatic-venous anastomoses for the treatment of obstructive lymphedema.

Over the past 25 years, 665 patients with obstructive lymphedema have been treated with microsurgical lymphatic-venous anastomoses; of these, 446 patients were available for long-term follow-up study. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Lymphangioscintigraphy, lymphangiography (in patients with gravitational reflux pathology), and echo-Doppler were used preoperatively. Subjective improvement was noted in 578 patients (87%). Objectively, volume changes showed a significant improvement in 552 patients (83%), with an average reduction of 67% of the excess volume. Of those patients followed up, 379 patients (85%) have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was a 87% reduction in the incidence of cellulitis after microsurgery. In those patients who improved, drainage resulted in increased softness of the limbs. Peripheral edema (hand and foot) diminished considerably in most patients. These long-term results indicate that lymphatic-venous anastomoses have a place in the treatment of obstructive lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. Improved results can be expected with earlier operations because patients referred earlier usually have fewer lymphatic alterations.

The use of vein grafts in the treatment of peripheral lymphedemas: long-term results.

This study evaluates long-term results of the treatment of peripheral lymphedemas by the microsurgical reconstructive technique of interposed vein grafts. The technique consists of the use of autologous vein grafts to reconstruct lymphatic pathways where there is a block to the lymphatic circulation of the limb, whether of congenital or acquired etiology. The venous segment represents a sort of "bridge" between afferent and efferent lymphatic collectors (lymphatic-venous-lymphatic plasty [LVLA]). The results also proved to have positive long-term effects after microsurgical operation. Follow-up evaluation was performed clinically by water volumetry and instrumentally by lymphangioscintigraphy. With this LVLA technique, peripheral lymphedemas can be treated when derivative lymphovenous shunts cannot be used because of impaired venous circulation in the same lymphedematous limb. The new aspect of the study is that we report long-term clinical and instrumental results.

Percent achieved of predicted peak exercise oxygen uptake and kinetics of recovery of oxygen uptake after exercise for risk stratification in chronic heart failure.

To investigate whether percent achieved of predicted peak exercise oxygen uptake (%VO2max) and recovery of oxygen consumption after exercise may provide prognostic information in chronic heart failure (CHF), we prospectively studied 196 patients with mild to moderate CHF. The following variables were examined: age, etiology of CHF, functional class, ejection fraction (EF), peak exercise oxygen uptake normalized for body weight (VO2max), %VO2max, time to reach 50% of the peak oxygen uptake after exercise (T1/2VO2max), presence of nonsustained ventricular tachycardia (NSVT) and inability to take ACE-inhibitors. VO2max was the most powerful predictor of cardiac death (P<0.0001). Other independent predictors of death were EF, T1/2VO2max, NSVT and inability to take ACE-inhibitors. The discriminatory accuracy of VO2max for cardiac death was not significantly greater than that of %VO2max. In conclusion, the determination of %VO2max does not enhance risk stratification in CHF whereas the kinetics of oxygen consumption after exercise can provide prognostic information.