Synchronous Primary Synovial Chondromatosis of the Hip: An Integrated Perspective on Physiotherapeutic Support.

abstract: Primary synovial chondromatosis of the hip is a rare joint condition characterized by the abnormal proliferation of cartilaginous tissue within the synovial membrane, which leads to the formation of clusters of chondrocytes floating in the joint space. This commentary provides a comprehensive overview of the pathology, including symptoms, diagnosis, treatment options and long-term management. Patients with primary synovial chondromatosis complaint pain and functional impairment, together with a peculiar joint popping sensation during movement, so determining early disability. The early treatment can lead to better clinical outcomes, with increased preservation of joint function and reduced risk of long-term disability, but strictly depend on symptoms acknowledgement and proper imaging interpretation. As a chronic pathology, surgical approach must necessarily be part of a larger medical and rehabilitative care planning, with long period follow-up. Multidisciplinary team management, with the active involvement of the patient is pivotal in improving the clinical outcomes and quality of life.

Radial head prosthesis disassembly: case report and medico-legal implications.

BACKGROUND: The aim of the treatment of radial head comminuted fractures is the restoration of anatomical normalcy to avoid the risk of several complications such as joint instability. Among the options for the treatment of such fractures, it is worth mentioning osteosynthesis, resection of the radial head or prosthetic replacement. In the presence of comminution or severe dislocation of the fracture's fragments, as in our patient's type III Mason fracture, prosthesis implantation is the treatment of choice. CASE REPORT: This clinical case reports a 22-year-old volleyball player, who during training suffered a comminuted fracture of the radial head, type III according to Mason's classification. A prosthesis was implanted. The post-operative course took place regularly. However, approximately three months after surgery, the patient experienced sudden pain and functional limitation following a normal elbow extension movement, so much so that he required medical attention in our emergency room. Following all the appropriate clinical-instrumental tests, a complete dissociation of the bipolar prosthesis of the radial head was found. CONCLUSIONS: Our clinical case shows the disassembly of a bipolar radial head prosthesis, a rather rare complication. From a medicolegal perspective, the patients should be aware of the increased risk of requiring further surgery after radial head replacement. When patients are thoroughly informed, they can cooperate and comply with indications more effectively, thus taking an active role in recovery management.

Prevalencia del Estrés Postraumático en médicos residentes, expuestos al SARS-COV-2 / Prevalence of posttraumatic stress in resident doctors, exposed to SARS-COV-2

Objetivo: Determinar la prevalencia del trastorno de estrés postraumático (TEPT) en una muestra de médicos residentes del Hospital de Clínicas, José de San Martín, Buenos Aires, Argentina, un año después del cierre total durante la cuarentena por COVID-19. Materiales y métodos: Se administraron los siguientes cuestionarios autoadministrados: una encuesta demográfica, el cuestionario de la Escala de Trauma de Davidson y la Escala de Experiencias Disociativas (EED). Se excluyeron a los residentes de primer año de especialidades básicas, a aquellos que por su especialidad no tienen contacto con pacientes y a los médicos con licencia fueron excluidos. Resultados: La prevalencia de TEPT fue de 24.3% (n=25). Las medianas de las puntuaciones de DES fueron mayores en los participantes con puntaje positivo para TEPT en comparación con los que no lo presentaban (Mann-Whitney U:13.30, p = 0.001). Se encontraron asociaciones entre el género (X2:6.074, p = 0.013), el TEPT y el tipo de especialidad (prueba exacta de Fisher, p = 0.017). No se encontraron otras asociaciones entre las demás variables analizadas y el TEPT. Conclusion: La prevalencia del TEPT fue similar a los informes previos. Se hallaron asociaciones entre este desorden, el género y el tipo de especialidad. Estos resultados deberían llamar la atención de los sistemas de salud para establecer medidas preventivas y terapéuticas para manejar esta situación.

Objective: Determine the prevalence of posttraumatic stress disorder (PTSD) in a sample of resident doctors of the Hospital de Clínicas, José de San Martín, Buenos Aires, Argentina, one year after the total closure during the quarantine by COVID-19. Materials and Methods: The following self-administered questionnaires were dispensed: a demographic survey, the Davidson Trauma Scale questionnaire, and the Scale of Dissociative Experiences (EED). First year residents of basic specialties were excluded, those who for their specialty do not have contact with patients and licensed doctors were excluded. Results: PTSD prevalence was 24.3% (n = 25). The medium-sized ones were greater in the participants with positive score for PTSD compared to those who did not present it (Mann-Whitney U: 13.30, p = 0.001). Associations between the genre were found (X2: 6,074, p = 0.013), the PTSD and the type of specialty (Fisher's exact test, p = 0.017). No other associations were found between the other variables analyzed and the PTSD. Conclusion: The prevalence of the PTSD was similar to the previous reports. Associations between this disorder, gender and type of specialty were found. These results should draw the attention of health systems to establish preventive and therapeutic measures to handle this situation

Genetic Drift Versus Climate Region Spreading Dynamics of COVID-19.

Background: The current propagation models of COVID-19 are poorly consistent with existing epidemiological data and with evidence that the SARS-CoV-2 genome is mutating, for potential aggressive evolution of the disease. Objectives: We looked for fundamental variables that were missing from current analyses. Among them were regional climate heterogeneity, viral evolution processes versus founder effects, and large-scale virus containment measures. Methods: We challenged regional versus genetic evolution models of COVID-19 at a whole-population level, over 168,089 laboratory-confirmed SARS-CoV-2 infection cases in Italy, Spain, and Scandinavia at early time-points of the pandemic. Diffusion data in Germany, France, and the United Kingdom provided a validation dataset of 210,239 additional cases. Results: Mean doubling time of COVID-19 cases was 6.63 days in Northern versus 5.38 days in Southern Italy. Spain extended this trend of faster diffusion in Southern Europe, with a doubling time of 4.2 days. Slower doubling times were observed in Sweden (9.4 days), Finland (10.8 days), and Norway (12.95 days). COVID-19 doubling time in Germany (7.0 days), France (7.5 days), and the United Kingdom (7.2 days) supported the North/South gradient model. Clusters of SARS-CoV-2 mutations upon sequential diffusion were not found to clearly correlate with regional distribution dynamics. Conclusion: Acquisition of mutations upon SARS-CoV-2 spreading failed to explain regional diffusion heterogeneity at early pandemic times. Our findings indicate that COVID-19 transmission rates are rather associated with a sharp North/South climate gradient, with faster spreading in Southern regions. Thus, warmer climate conditions may not limit SARS-CoV-2 infectivity. Very cold regions may be better spared by recurrent courses of SARS-CoV-2 infection.

Economic evaluation of Zepatier for the management of HCV in the Italian scenario.

BACKGROUND: Hepatitis C virus (HCV) is a major health issue worldwide. New generation of direct-active antiviral medications is an epoch-making turning point in the management of HCV infections. OBJECTIVE: Conducing a cost-effectiveness analysis comparing the combination of elbasvir/grazoprevir and sofosbuvir + pegylated interferon/ribavirin for the management of all HCV patients (even those in the initial stages of fibrosis). METHODS: A Markov model was built on the natural history of the disease to assess the efficacy of the alternatives. The outcomes are expressed in terms of quality adjusted life-years (QALYs) and result in terms of incremental cost-effectiveness ratio). RESULTS: Elbasvir/grazoprevir implies an expenditure of €21,104,253.74 with a gain of 19,287.90 QALYs and sofosbuvir + pegylated interferon/ribavirin implies an expenditure of €31,904,410.11 with a gain of 18,855.96 QALYs. Elbasvir/grazoprevir is thus a dominant strategy. CONCLUSION: Consideration should be given to the opportunity cost of not treating patients with a lower degree of fibrosis (F0-F2).

Cost-Effectiveness Analysis of Lesinurad/Allopurinol Versus Febuxostat for the Management of Gout/Hyperuricemia in Italy.

BACKGROUND: Until very recently the only therapeutic alternative for the management of patients affected by gout/hyperuricemia that did not respond to a first-line treatment based on allopurinol alone or who cannot tolerate allopurinol was febuxostat, a xanthine oxidase non-purine-selective inhibitor. Lately, however, a new therapeutic alternative has become available for the management of this pathology: lesinurad, a urate transporter inhibitor. OBJECTIVE: To objective of this study was to evaluate the cost effectiveness of lesinurad/allopurinol in comparison with febuxostat as a second-line therapeutic strategy for the management of patients affected by gout and hyperuricemia that did not respond to a first-line therapy based on allopurinol alone. METHODS: A Markov model was built based on the natural history of the pathology; patients entered the model according to their level of serum uric acid concentration and flowed across it according to their response to the therapy. The analysis was carried out considering the perspective of the Italian National Health Service on a lifetime horizon and 6-month cycles. Costs and quality-adjusted life-years (QALYs) were discounted at a 3.5% yearly rate. The results of the model were expressed in terms of incremental cost-effectiveness ratio (ICER). Both a one-way and a multi-way Monte-Carlo analysis were carried out in order to check the robustness of the results achieved. RESULTS: The ICER derived from the comparison was equal to €77.53/QALY on the lifetime horizon, as there was a higher level of costs associated with the combination as compared with febuxostat (€10,658.27 vs. €10,645.87, for a differential of €12.40) and a higher level of QALYs achieved (7.77 vs. 7.61, for a differential of 0.16). CONCLUSIONS: The lesinurad/allopurinol combination is recommended for the treatment of patients affected by gout/hyperuricemia in the Italian Health System as it appears to be cost effective and thus sustainable for the Italian healthcare sector.

Maternal hemodynamics early in labor: a possible link with obstetric risk?

OBJECTIVE: To determine if hemodynamic assessment in 'low-risk' pregnant women at term with an appropriate-for-gestational age (AGA) fetus can improve the identification of patients who will suffer maternal or fetal/neonatal complications during labor. METHODS: This was a prospective observational study of 77 women with low-risk term pregnancy and AGA fetus, in the early stages of labor. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor (USCOM® ) system. Patients were followed until the end of labor to identify fetal/neonatal and maternal outcomes, and those which developed complications of labor were compared with those delivering without complications. RESULTS: Eleven (14.3%) patients had a complication during labor: in seven there was fetal distress and in four there were maternal complications (postpartum hemorrhage and/or uterine atony). Patients who developed complications during labor had lower cardiac output (5.6 ± 1.0 vs 6.7 ± 1.3 L/min, P = 0.01) and cardiac index (3.1 ± 0.6 vs 3.5 ± 0.7 L/min/m2 , P = 0.04), and higher total vascular resistance (1195.3 ± 205.3 vs 1017.8 ± 225.6 dynes × s/cm5 , P = 0.017) early in labor, compared with those who did not develop complications. Receiver-operating characteristics curve analysis to determine cut-offs showed cardiac output ≤ 5.8 L/min (sensitivity, 81.8%; specificity, 69.7%), cardiac index ≤ 2.9 L/min/m2 (sensitivity, 63.6%; specificity, 76.9%) and total vascular resistance > 1069 dynes × s/cm5 (sensitivity, 81.8%; specificity, 63.6%) to best predict maternal or fetal/neonatal complications. CONCLUSIONS: The study of maternal cardiovascular adaptation at the end of pregnancy could help to identify low-risk patients who may develop complications during labor. In particular, low cardiac output and high total vascular resistance are apparently associated with higher risk of fetal distress or maternal complications. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Economic Analysis and Budget Impact of Tenofovir and Entecavir in the First-Line Treatment of Hepatitis B Virus in Italy.

BACKGROUND: Chronic hepatitis B is a common, progressive disease, particularly when viral replication is detected. Oral antivirals can suppress viral replication and prevent or delay the development of cirrhosis and liver-related complications. The treatments of chronic hepatitis B cannot totally cure the disease but can prevent its progression to hepatocellular carcinoma, decreasing the levels of both morbidity and mortality. To date, there are several therapies indicated by the international guidelines as first-line treatments for the management of hepatitis B; two of the most effective are those based on either tenofovir or entecavir. OBJECTIVE: The aim of this study is to evaluate the cost-effectiveness of tenofovir and entecavir in the treatment of naïve patients with chronic hepatitis B. The two treatments are compared with the "no treatment" and to one another. METHODS: The cost-effectiveness analysis was conducted using a Markov model; patients entered one of the following health states: chronic hepatitis, cirrhosis (compensated or decompensated), hepatocellular carcinoma, liver transplantation or death. The analysis was carried out from the perspective of the Italian National Health Service by considering a life-time horizon with cycles lasting 1 year and with costs and QALYs (quality-adjusted life years) discounted at a rate of 3.5%. The results of the model were analysed in terms of incremental cost-effectiveness ratio (ICER). RESULTS: ICERs for tenofovir and entecavir emerging from the comparison versus "no treatment" were equal to €10,274.73 and €16,300.44 per QALY gained, respectively, on the life-time horizon. Tenofovir was dominant in the direct comparison with entecavir, indicating more QALYs and a lower consumption of resources. The Monte Carlo simulation demonstrated that in 97% (tenofovir) and in 85% (entecavir) of the scenarios performed, the cost per QALY fell below the threshold of €30,000/QALY. The budget impact analysis showed savings for tenofovir amounting to 33% compared to entecavir in the first year on treatment and to 31% in following years. CONCLUSIONS: Entecavir and tenofovir are recommended for the treatment of patients with chronic Hepatitis B in the Italian Health System. In particular, tenofovir appeared to be the more cost-effective drug for the management of chronic hepatitis B virus (HBV) infections. These results could help decision makers and clinicians to address their decision when choosing a first-line treatment for the management of people affected by chronic HBV.

Child Abuse and Neglect and its Psycho-Physical and Social Consequences: A Review of the Literature.

Child maltreatment is a complex life experience occurs when a parent or caregiver does an intentional or potential damage to a child, including acts of commission and omission. Child abuse is not an uncommon event, but it is not always recognized. Identifying the real number of maltreated children is a challenge because of the large variability in reported prevalence data across studies. Unfortunately, in the United States, it affects 1 in 8 children, by the age of 18 years, annually. Paediatricians may encounter a variety of forms of maltreatment such as neglect, emotional, physical and sexual abuse. These aspects should be recognised, examined and evaluated by employing a systematic approach and focusing on basic needs of children that may not be met. Child maltreatment is a global problem with serious life-long physical and psychological or psychiatric outcomes. It is associated with important economic and social costs (such as physical and mental health, productivity losses, child welfare, criminal justice and special education costs) due to its high prevalence and its long-term and short-term consequences. In the United States, the average cost of nonfatal maltreatment is $210,012 per children and the cost of fatal maltreatment is $1,272,900. General Practitioners are quite prepared to face the problem of child maltreatment: since they have the opportunity to meet several members of the same family, they can detect stressors that put children at risk of maltreatment. All health professionals have the responsibility to protect children from abuse and neglect.

Effectiveness of 3D T2-Weighted FLAIR FSE Sequences with Fat Suppression for Detection of Brain MR Imaging Signal Changes in Children.

BACKGROUND AND PURPOSE: T2-weighted FLAIR can be combined with 3D-FSE sequences with isotropic voxels, yielding higher signal-to-noise ratio than 2D-FLAIR. Our aim was to explore whether a T2-weighted FLAIR-volume isotropic turbo spin-echo acquisition sequence (FLAIR-VISTA) with fat suppression shows areas of abnormal brain T2 hyperintensities with better conspicuity in children than a single 2D-FLAIR sequence. MATERIALS AND METHODS: One week after a joint training session with 20 3T MR imaging examinations (8 under sedation), 3 radiologists independently evaluated the presence and conspicuity of abnormal areas of T2 hyperintensities of the brain in FLAIR-VISTA with fat suppression (sagittal source and axial and coronal reformatted images) and in axial 2D-FLAIR without fat suppression in a test set of 100 3T MR imaging examinations (34 under sedation) of patients 2-18 years of age performed for several clinical indications. Their agreement was measured with weighted κ statistics. RESULTS: Agreement was "substantial" (mean, 0.61 for 3 observers; range, 0.49-0.69 for observer pairs) for the presence of abnormal T2 hyperintensities and "fair" (mean, 0.29; range, 0.23-0.38) for the comparative evaluation of lesion conspicuity. In 21 of 23 examinations in which the 3 radiologists agreed on the presence of abnormal T2 hyperintensities, FLAIR-VISTA with fat suppression images were judged to show hyperintensities with better conspicuity than 2D-FLAIR. In 2 cases, conspicuity was equal, and in no case was conspicuity better in 2D-FLAIR. CONCLUSIONS: FLAIR-VISTA with fat suppression can replace the 2D-FLAIR sequence in brain MR imaging protocols for children.

Sonographic diagnosis of hepatic erosion caused by umbilical catheterization.

The use of umbilical venous catheter (UVC) is common practice in neonatal units. The traumatic injury of the hepatic parenchyma is a rare complication. We present a case of a preterm newborn underwent ultrasound examination revealing a hyperechogenic focal lesion at the confluence of the hepatic veins This finding, according to patient's history, was suspected to be a traumatic injury of the liver parenchyma caused by umbilical catheterization. During sonographic follow-up this lesion gradually reduced until complete resolution. Finally, when focal hyperechogenic hepatic lesion is incidentally detected in newborn with history of UVC placement, the radiologists must consider the traumatic etiology.

Transanal anopexy with HemorPex System (HPS) is effective in treating grade II and III hemorrhoids: medium-term follow-up.

BACKGROUND: Hemorrhoidal disease is a common proctologic disorder. The HemorPex System(®) (HPS) (Angiologica, S. Martino Siccomario PV, Italy) is an innovative surgical technique based on muco-hemorrhoidopexy without Doppler guidance. The aim of this study was to evaluate the efficacy of HPS in on the treatment of grade II and III hemorrhoids. METHODS: One hundred patients with grade II and III hemorrhoidal disease were included in the study and operated on using HPS without Doppler guidance. The procedure consists of a mucopexy carried out by means of a dedicated rotating anoscope in the 6 relatively constant positions of the terminal branches of the superior hemorrhoidal artery. A direct follow-up was carried out on 100 patients for up to 3 months. A late analysis (>12 months postoperatively) was conducted by telephone interview. At follow-up the following parameters were considered: pain, bleeding, prolapse, difficulties with hygiene and patient satisfaction with treatment. RESULTS: Operative time was 16 ± 5 min. Three-month follow-up showed significant improvement of symptoms: pain was present in 10 (10 %) patients versus 45 (45 %) preoperatively; bleeding in 13 (13 %) of patients versus 57 (57 %) preoperatively; prolapse in 13 (13 %) of patients versus 45 (45 %) preoperatively and difficulties with hygiene in 1 (1 %) versus 24 (24 %) preoperatively (all p < 0.05). At longer follow-up which was available in 67 patients, 5 patients (7.5 %) had recurrence and were reoperated on at 8, 10, 24, 26 and 36 months, respectively after the first procedure. As regards patient satisfaction, complete satisfaction was reported by 95/100 patients (95 %) at 3 months, 62/67 (92.5 %) at 12 months and 8/56 (85.7 %) at 24 months; partial satisfaction was reported by 3/100 patients (3 %) with intermittent bleeding at 3 months, 3/67 (4.4 %) patients at 12 months and 6/56 (10.7 %) patients at 24 months, all with either intermittent bleeding or prolapse. Dissatisfaction with the procedure was reported by in 1/100 (1 %) patient at 3 months, 2/67 (2.9 %) at 12 months and 2/56 (3.6 %) at 24 months including patients who underwent reintervention. CONCLUSIONS: HPS can be used in the treatment of grade II and III hemorrhoidal disease. Our results show that this simple technique may be an effective but due to the important limitations of this study (loss to follow-up, non-comparative study) further studies are required.

Isolation and characterization of the [Ga2Al18O8(OH)36(H2O)12](8+) cluster: cationic variations on the Wells-Dawson topology.

The structural chemistry of Group 13 polyoxometalates lags far behind related negatively charged transition metal species and limits the development of advanced materials. A novel heterometallic cluster [Ga2Al18O8(OH)36(H2O)12](8+) (Ga2Al18) has been isolated using a supramolecular approach and structurally characterized using single-crystal X-ray diffraction. Ga2Al18 represents the Wells-Dawson structure polycations and variations in the structural topology may be related to the initial stabilization of the Keggin isomer. DFT calculations on the related ε-Keggins (GaAl12 and Al13), Ga2Al18, and theoretical Al2Al18 clusters reveal similar features of electronic structure, suggesting additional heteroatom substitution in other isostructural clusters should be possible.

Chemical controls on uranyl citrate speciation and the self-assembly of nanoscale macrocycles and sandwich complexes in aqueous solutions.

Uranyl citrate forms trimeric species at pH > 5.5, but exact structural characteristics of these important oligomers have not previously been reported. Crystallization and structural characterization of the trimers suggests the self-assembly of the 3 : 3 and 3 : 2 U : Cit complexes into larger sandwich and macrocyclic molecules. Raman spectroscopy and ESI-MS have been utilized to investigate the relative abundance of these species in solution under varying pH and citrate concentrations. Additional dynamic light scattering experiments indicate that self-assembly of the larger molecules does occur in aqueous solution.

Assessing Serum Concentrations of 25-Hydroxy-Vitamin D in North-Western Italy.

OBJECTIVES: Backgound: Most of the published studies on vitamin D levels in Italy have been performed in specific age- or disease- subgroups. Few data are available on the status of vitamin D in the adult general population. OBJECTIVE: We report on vitamin D levels of a large sample of adults from North-Western Italy. Association with age, sex, and season is also evaluated. PARTICIPANTS: 13,110 cases (24% men, 76% women; median age 67 [interquartile range, IQR, 56-77] years old) were collected in the North-Eastern of Piedmont (Italy). MEASUREMENTS: 25-OH-vitamin D levels were measured by chemiluminescent immunoassay. RESULTS: Median total vitamin D level was 19.9 ng/ml (IQR 11.2-28.8 ng/ml) with up to 3,592 (27.4%) and 10,185 (77.7%) subjects respectively below 12 and 30 ng/ml. Vitamin D levels were significantly higher in women than in men (20.5 vs 18.1 ng/ml; p<0.001), in summer than in winter (21.4 vs 18.5 ng/ml; p<0.001), and in individuals aged ≤45years or 46-64 years than in those older than 65 years (20.3 and 21.3 vs 18.8 ng/ml). The lowest mean vitamin D levels were reported during the winter season by men aged ≥65 years (14.7 ng/ml) and 46-64 years (16.8 ng/ml). Multivariate analysis confirmed that age (p<0.001), sex (p=0.002), season (p<0.001) and their interaction (p=0.03) were independently associated to vitamin D concentrations. CONCLUSIONS: This study clearly shows that the majority of adult Italian population, living in a sunny and highly urbanized area of North-Western Italy, have an important deficiency in vitamin D. However, these data must be interpreted with caution if considering the lack of standardization of vitamin D assays.

Safety and efficacy of oral vinorelbine and capecitabine combination for metastatic breast cancer.

The aim of this prospective open-label study was to evaluate the efficacy and safety of oral vinorelbine in combination with capecitabine in patients with metastatic breast cancer (MBC). 51 patients with MBC received oral vinorelbine and capecitabine. The safety profile was analyzed through NCI-CTCAE v3.0 and response was evaluated using RECIST criteria. The overall response rate was 37.2%: there were four complete responders (8%) and fifteen partial responders (29.4%); practically all the responders were patients previously treated with anthracyclines and taxanes. Sixteen patients (31.3%) experienced stable disease. The clinical benefit rate was 68.5%. The median time to progression was 8 months (range 2-43; 95% CI: 6-10.8). Vinorelbine in combination with capecitabine is an effective and safe schedule for patients with MBC especially after pretreatment with anthracycline/ taxane-based regimens. The clinical benefit suggests that this may be a promising schedule in the MBC initial treatment.

Weekly combination of non-pegylated liposomal doxorubicin and taxane in first-line breast cancer: wALT trial (phase I-II).

BACKGROUND: Through different pharmacodynamic-kinetic interactions, weekly administration of proved efficacy agents can overcome resistance with lower toxicity and greater benefit. Based on this assumption, we designed a phase I-II trial with weekly non-pegylated liposomal anthracycline and taxane in first-line breast cancer patients. PATIENTS AND METHODS: We enrolled 56 previously untreated metastatic breast cancer patients; they were randomly assigned to receive paclitaxel (Taxol) (50 mg/mq) or docetaxel (Taxotere) (30 mg/mq) combined with non-pegylated liposomal anthracycline (25 mg/mq) on days 1, 8 and 15 every 4 weeks. The primary end points were the clinical benefit and treatment-related toxic effects assessment. Secondary end points were time-to-disease progression (TTP) and overall survival (OS). RESULTS: The overall clinical benefit was 87.04%. World Health Organization G3-4 toxic effects included neutropenia (45%), anemia (44%), complete alopecia (83%), severe onycholysis and neuropathy. The 24% of patients developed left ventricular ejection fraction reduction but none >10% with recover after treatment completion. The median absolute decrease from baseline was 1%. Median TTP was 11 months and median OS was 23 months. CONCLUSIONS: Combined weekly administration of taxane and non-pegylated liposomal anthracycline is well tolerated and clinical benefit data encourage phase III study design.

Catechols in post-mortem brain of patients with Parkinson disease.

BACKGROUND: Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the 'catecholaldehyde hypothesis' about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum - especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease - and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease. METHODS: Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end-stage Parkinson disease (N=15) and control subjects (N=14) of similar age with similar post-mortem intervals. RESULTS: Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (P=0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients. CONCLUSIONS: Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.

Prognostic role of sub-clinical hypothyroidism in chronic heart failure outpatients.

BACKGROUND: It has been suggested that low thyroid hormones levels may be associated with increased mortality in patients with cardiovascular disease. AIM: To evaluate the prognostic role of thyroid function deficiency in patients with chronic heart failure (CHF). METHODS: We evaluated 338 consecutive outpatients with stable CHF receiving conventional therapy, all of whom underwent a physical examination, electrocardiography and echocardiography. Blood samples were drawn to assess renal function, and Na+, hemoglobin, NT-proBNPs, fT3, fT4 and TSH levels. Patients with hyperthyroidism were excluded. RESULTS: During the follow-up (15+/-8 months), heart failure progression was observed in 79 patients (including 18 who died of heart failure after hospitalisation and six who underwent transplantation). Univariate regression analysis showed that TSH (p<0.0001), fT3 (p<0.0001), fT4 (p=0.016) and fT3/fT4 (p<0.0001) were associated with heart failure progression but multivariate analysis showed that only TSH considered as a continuous variable (p = 0.001) as well as subclinical hypothyroidism (TSH > 5.5 mUI/l; p=0.014) remained significantly associated with the events. CONCLUSIONS: In CHF patients TSH levels even slightly above normal range are independently associated with a greater likelihood of heart failure progression. This supports the need for prospective studies aimed at clarifying the most appropriate therapeutic approach to sub-clinical hypothyroidism in such patients.

Inclusive K(S);(0)K(S);(0) resonance production in ep collisions at HERA.

Inclusive K_{S};{0}K_{S};{0} production in ep collisions at the DESY ep collider HERA was studied with the ZEUS detector using an integrated luminosity of 0.5 fb;{-1}. Enhancements in the mass spectrum were observed and are attributed to the production of f_{2}(1270)/a_{2};{0}(1320), f_{2};{'}(1525) and f_{0}(1710). Masses and widths were obtained using a fit which takes into account theoretical predictions based on SU(3) symmetry arguments, and are consistent with the Particle Data Group values. The f_{0}(1710) state, which has a mass consistent with a glueball candidate, was observed with a statistical significance of 5 standard deviations. However, if this state is the same as that seen in gammagamma-->K_{S};{0}K_{S};{0}, it is unlikely to be a pure glueball state.