Pain, symptoms and therapy satisfaction in adult oncologic patients at admission to palliative care: An Italian prospective, multicenter, observational study.

BACKGROUND: Pain in cancer patients is a complex clinical problem. Pain is systematically assessed and treated during palliative care, but little is known about how it is addressed before starting palliative care. AIM: This study primarily analyzed pain, symptoms, ongoing therapy at patients' admittance to the palliative care unit, and the relationships between pain and tumor, comorbidities, performance status and quality of life (QoL). Notably, patient satisfaction with the received antalgic therapy was assessed. METHODS: A multicentric, prospective, observational study was conducted in seven Italian palliative centers. The population consisted of adult cancer patients admitted to specialist palliative care units in hospice and home care. RESULTS: The sample consisted of 476 patients. Ninety-three patients reported moderate pain of 4.0 and worst pain of 5.9 at the initial medical examination. The pain was high, and QoL was lower in breakthrough pain. The pain was lower in older subjects when it was discontinuous and when it was also treated with corticosteroids. A total of 61% of the patients were unsatisfied with the prescribed pain therapy. CONCLUSIONS: Before the beginning of palliative care, physicians do not manage pain adequately. We support the idea that palliative care is not only intended for the last days of life but must be started early and simultaneously with oncological treatments. All that, in our opinion, is often ignored, and we hope that our study could have a positive influence and that the study results stimulate further research in this area with in-depth studies.

Ongoing Research Protocols for the Pharmacological Treatment of Neuropsychiatric Symptoms in Dementia.

The implementation of effective interventions for neuropsychiatric symptoms (NPS) is perceived as one of the most pressing research priorities in the field of dementia and one of the main unmet needs from the perspective of affected individuals and their caregivers and relatives. Nevertheless, to date, only a relatively marginal part of dementia research has focused on NPS. This study aimed to describe and discuss the state of the art concerning the identification and development of new pharmacological treatments for NPS in dementia. A review of 320 ongoing phase 1, 2, 3, and 4 protocols registered in the clinicaltrials.gov database was performed. All the trials enrolling patients with dementia were selected. Only studies adopting clinical measures of NPS frequency and/or severity as primary outcome were retained and analyzed. Overall, only a minority of ongoing phase 1, 2, 3 and 4 protocols on dementia (i.e., 9.0%) is primarily targeting NPS. Most of these studies are adopting a placebo-controlled parallel assignment design, testing oral compounds, and targeting specific NPS (mostly agitation and/or aggression). A total of 3,445 subjects with dementia will tentatively be recruited in these trials. The methodologies adopted in these studies, the characteristics of the tested interventions, the eligibility criteria, and the operational definitions of NPS are presented and discussed. The relevance of NPS is not yet matched by an adequate research effort. The current tendency at privileging disease-modifying approaches and other symptoms of dementia and the methodological complexity of studying NPS are still substantially contributing to the gap between research activities and clinical needs.

High-resolution ultrasound in the assessment of the distal biceps brachii tendinous complex.

OBJECTIVE: To establish a high-resolution US technique that enables a systematic morphometric examination of the three components that form the distal biceps brachii tendinous complex; the internal bicipital aponeurosis, the distal biceps brachii tendon and the external bicipital aponeurosis (also known as lacertus fibrosus). MATERIALS AND METHODS: Fifty cryopreserved cadaver body donor elbows were dissected to obtain morphometric reference values and to establish reliable landmarks for the US examination. Then, a systematic US technique was designed and validated by a one-to-one US/dissection analysis of 11 cryopreserved cadaver body donor elbows. Finally, the systematic US technique was carried out in 44 healthy volunteers and morphometric parameters were compared to those obtained in the first part of the study. RESULTS: Mean dissection reference values: internal bicipital aponeurosis width 39.61 mm (10.02 SD) and thickness 0.75 mm (0.24 SD), distal biceps brachii tendon width 8.38 mm (1.87 SD) and thickness 2.73 mm (0.69 SD), external bicipital aponeurosis width 11.17 mm (5.84 SD) and thickness 0.85 mm (0.28 SD). One-to-one US/dissection correlation was overall good (intraclass correlation coefficient 0.876, p < 0.0001). When comparing volunteer US/dissection measurements, significant differences were encountered in all measures except for internal bicipital aponeurosis width. However, the overall magnitude of such significant differences was < 0.7 mm. CONCLUSIONS: Using the systematics hereby proposed, high-resolution US is reliable for the morphometric assessment of the distal biceps brachii tendinous complex. The external bicipital aponeurosis is morphometrically the most variable structure.

A CMOS application-specified-integrated-circuit for 40 GHz high-electron-mobility-transistors automatic biasing.

This paper presents the design and the experimental results of a CMOS Automatic Control System (ACS) for the biasing of High-Electron-Mobility-Transistors (HEMT). The ACS is the first low-power mixed-signal Application-Specified-Integrated-Circuit (ASIC) able to automatically set and regulate the operating point of an off-chip 6 HEMT Low-Noise-Amplifiers (LNAs), hence it composes a two-chip system (the ACS+LNAs) to be used in the Large Scale Polarization Explorer (LSPE) stratospheric balloon for Cosmic Microwave Background (CMB) signal observation. The hereby presented ACS ASIC provides a reliable instrumentation for gradual and very stable LNAs characterization, switching-on, and operating point (<4 mV accuracy). Moreover, it simplifies the electronic instrumentation needed for biasing the LNAs, since it replaces several off-the-shelf and digital programmable device components. The ASIC prototype has been implemented in a CMOS 0.35 µm technology (12 mm2 area occupancy). It operates at 4 kHz clock frequency. The power consumption of one-channel ASIC (biasing one LNA) is 3.6 mW, whereas 30 mW are consumed by a single LNA device.

High HCV subtype heterogeneity in a chronically infected general population revealed by high-resolution hepatitis C virus subtyping.

OBJECTIVES: This study aimed to characterize the chronically infected general hepatitis C virus (HCV) population in Barcelona using a highly sensitive subtyping method that can identify the 67 recognized HCV subtypes and diagnose mixed infection by various genotypes/subtypes in a single individual. The resulting information has implications for selecting optimal direct-acting antiviral (DAA) treatment for each patient and establishing public healthcare policies in our setting. METHODS: Consecutive HCV patients (treatment-naïve or interferon-based failures) attending Vall d'Hebron Hospital outpatient clinics from February 2015 to May 2016 (N=1473) were included in the study. Patient samples were characterized using HCV subtyping by next-generation ultra-deep pyrosequencing. RESULTS: The following genotypes (G) were found: G1 (1126/1473 (76.4%)), G4 (145/1473 (9.8%)), G3 (135/1473 (9.2%)), G2 (51/1473 (3.5%)), and G5 (1/1473 (0.1%)). Twenty-two subtypes were seen: 1b (790/1473 (53.6%)), 1a (332/1473 (22.5%)), 3a (133/1473 (9.0%)), 4d (105/1473 (7.1%)), 4a (29/1473 (2.0%)), and 2c (25/1473 (1.7%)), with 16 low-prevalence subtypes accounting for the remaining 3.0% (44/1473). There was a worrisome 1.0% (15/1473) of mixed infections. G2 (51/1473 (3.5%)) showed a high level of heterogeneity. Analyses by age groups showed a predominance of G1b over G1a (428/506 (84.6%) vs. 24/506 (4.7%)) in patients born before 1950 (N=506/1473), and similar percentages of these subtypes in those born between 1951 and 1975 (N=834/1473) (315/834, 37.8% vs. 266/834, 31.9%) and after 1976 (N=133/1473) (47/133, 35.3% vs. 42/133, 31.6%). CONCLUSIONS: Subtype distribution showed a higher level of heterogeneity than was expected, particularly for G2. Prevalence of mixed infections was around 1%. HCV subtype distribution related to patient age group suggested that patients born from 1936 to 1975 in our setting should undergo screening for the infection. Next-generation sequencing enabled better classification of candidates for DAA-based treatment.

Mapping elements distribution in carapace of Caretta caretta: A strategy for biomonitoring contamination in sea turtles?

This study analyzed the carapace distribution of Ca, Cd, Cr, Cu, Mg, Mn, Pb, Sb, U, V and Zn by GF-AAS and ICP-AES in one specimen of Caretta caretta from Mediterranean Sea. Calcium, Mg, Mn, Pb, U, Zn were mainly distributed in the central area while Cd, Cr, Cu, Sb, V in lateral areas. Cadmium, Cr, Mg, Mn, Sb, U and V were different between lateral areas. The different distribution may be related to several exposures during lifetime and/or the shell ossification during growth. Carapace may be a suitable matrix for metal biomonitoring, however, further studies are required to confirm these findings.

A PUBS Case in a Palliative Care Unit Experience.

Purple urine bag syndrome (PUBS) is a rare condition in which purple discoloration of the collecting bag and its associated tubing occurs. It is considered a benign condition. PUBS is usually associated with urinary tract infection occurring in elderly bedridden women, with chronic urinary catheterization. This syndrome is usually reported to occur in alkaline urine, but here we describe a rare case of PUBS involving acidic urine.

HBV whole-genome mutation profile in HIV-1/HBV coinfected patients in a long-term follow-up study.

PURPOSE: Human immunodeficiency virus (HIV-1)-infected patients frequently harbour hepatitis B and C viruses (HBV and HCV, respectively). Possible modifications of the natural history of hepatitis B may occur. The aim of this study was to characterise HBV diversity and evolutionary and mutational viral genome profiles in HIV-1/HBV coinfections. METHODS: HIV-1 and HBV markers determinations (Roche, FRG; Abbott, USA) and HBV genome-length retrospective analysis were performed in follow-up isolates from patients who were either stably HBsAg-negative with a low level of HBV DNA (occult hepatitis B infection, OBI) or HBsAg-positive with a high level of HBV DNA. Phylogenetic analysis (maximum likelihood method, MEGA5), statistical analysis and evolutionary rates calculation (d S/d N) were applied. RESULTS: Positive selection pressures in the PreS/S region and a significantly higher number of mutations in this region including the major hydrophilic region (MHR) and the "a" determinant were shown in HBsAg-negative (possibly OBI) compared to stably HBsAg-positive HIV-1/HBV subgenotypes D3/A2 coinfected patients. Mutants previously described in HIV-1/HBV coinfected patients were found. Known mutants Y100C, P127T and P120A associated to Y134H and S143T and new S mutants, which may potentially affect HBsAg expression and secretion and anti-HBs binding, were detected in baseline sera persisting up to the end of 9 years follow-up. Known mutations of BCP, Pre-C, C and X regions were also characterised. Natural mutants strictly known as being involved in diagnostic failure were not detected; however, numerous corresponding sites showed amino acid variations. CONCLUSIONS: Evolutionary and genotypic differences observed, particularly in the PreS/S region, between HBsAg-negative (OBI) and HBsAg-positive HIV-1/HBV coinfected patients, may contribute, in association with mutations of other genomic regions, to the HBsAg-negative phenotype.

National surveillance capacity of water-related diseases in the WHO European region.

Water-related diseases continue to cause a high burden of mortality and morbidity in the countries of the European Region. Parties to the Protocol on Water and Health are committed to the sustainable use of water resources, the provision of safe drinking water and adequate sanitation to all people of the European Region, and to the reduction of the burden of water-related diseases. A specialized Task Force is implementing a work plan aimed at strengthening the capacity for water-related disease surveillance, outbreak detection and contingency planning. Parties to the Protocol are obliged to set targets, and report on progress on water-related disease surveillance. The present paper aims to provide a baseline assessment of national capacities for water-related disease surveillance on the basis of the replies to a questionnaire. This was prepared in English and Russian and administered to 53 countries, 15 of which replied. The results confirm the heterogeneity in surveillance systems, the weakness of many countries to adequately survey emerging water-related diseases, and the need for specific remedial action. The findings of the exercise will form the basis for future action under the Protocol on Water and Health.

The occurrence of chemical elements and POPs in loggerhead turtles (Caretta caretta): an overview.

Chemical elements and persistent organic pollutants (POPs) are globally present in aquatic systems and their potential transfer to loggerhead marine turtles (Caretta caretta) has become a serious threat for their health status. The environmental fate of these xenobiotics may be traced by the analysis of turtles' tissues and blood. Generally, loggerhead turtles exhibited a higher metal load than other turtle species, this could be explained by differences in diet habits being food the main source of exposure. Literature shows that muscle, liver and kidney are most considered for the quantification of chemical elements, while, organic compounds are typically investigated in liver and fat. This paper is an overview of the international studies carried out on the quantification of chemical elements, polychlorinated biphenyls (PCBs), organochlorines (OCs) and perfluorinated compounds (PFCs), in tissues, organs and fluids of C. caretta from the Mediterranean Sea, the Atlantic and the Pacific Oceans.

Genetic diversity and admixture analysis of Sanfratellano and three other Italian horse breeds assessed by microsatellite markers.

Sanfratellano is a native Sicilian horse breed, mainly reared in the north east of the Island, developed in the 19th century from local dams and sires with a restricted introgression of Oriental, African and, more recently, Maremmano stallions. In this study, the genetic relationships and admixture among Sanfratellano, the other two Sicilian autochthonous breeds and Maremmano breed were assessed using a set of microsatellites. The main goals were to infer the impact of Maremmano breed in the current Sanfratellano horse and to provide genetic information useful to improve the selection strategies of the Sanfratellano horse. The whole sample included 384 horses (238 Sanfratellano, 50 Sicilian Oriental Purebred, 30 Sicilian Indigenous and 66 Maremmano), chosen avoiding closely related animals. A total of 111 alleles from 11 microsatellite loci were detected, from four at HTG7 to 15 at ASB2 locus. The mean number of alleles was the lowest in Oriental Purebred (6.7), the highest in Sanfratellano (8.3). All the breeds showed a high level of gene diversity (He) ranging from 0.71 ± 0.04 in Sicilian Oriental Purebred to 0.81 ± 0.02 in Sicilian Indigenous. The genetic differentiation index was low; only about 6% of the diversity was found among breeds. Nei's standards (DS) and Reynolds' (DR) genetic distances reproduced the same population ranking. Individual genetic distances and admixture analysis revealed that: (a) nowadays Maremmano breed does not significantly influence the current Sanfratellano breed; (b) within Sanfratellano breed, it is possible to distinguish two well-defined groups with different proportions of Indigenous blood.

An international parentage and identification panel for the domestic cat (Felis catus).

Seventeen commercial and research laboratories participated in two comparison tests under the auspices of the International Society for Animal Genetics to develop an internationally tested, microsatellite-based parentage and identification panel for the domestic cat (Felis catus). Genetic marker selection was based on the polymorphism information content and allele ranges from seven random-bred populations (n = 261) from the USA, Europe and Brazil and eight breeds (n = 200) from the USA. Nineteen microsatellite markers were included in the comparison test and genotyped across the samples. Based on robustness and efficiency, nine autosomal microsatellite markers were ultimately selected as a single multiplex 'core' panel for cat identification and parentage testing. Most markers contained dinucleotide repeats. In addition to the autosomal markers, the panel included two gender-specific markers, amelogenin and zinc-finger XY, which produced genotypes for both the X and Y chromosomes. This international cat parentage and identification panel has a power of exclusion comparable to panels used in other species, ranging from 90.08% to 99.79% across breeds and 99.47% to 99.87% in random-bred cat populations.

MRI evaluation of myocardial viability.

Cardiac magnetic resonance imaging (MRI) has become an accurate noninvasive imaging procedure for the study of postischaemic residual cardiac function, thanks to the evolution of MRI machines, postprocessing software and, above all, sequences. After infarction, and in chronic myocardial ischaemia, the degree of contractile dysfunction is one of the main determinants of longterm survival. The identification and quantification of viable dysfunctional myocardium and the possibility of improving its contractility after revascularisation improves patient prognosis and quality of life. In current clinical practice, myocardial viability is evaluated with stress echocardiography and nuclear methods. Thanks to its intrinsic characteristics and to the delayed-enhancement technique (DE-MRI), MRI has recently emerged as the only noninvasive modality able to provide a three-dimensional (3D) evaluation of cardiac viability with a multiparametric approach.

Emergency gastric ulcer complications in elderly. Factors affecting the morbidity and mortality in relation to therapeutic approaches.

AIM: In elderly the incidence of the emergency gastric ulcer complications, perforation and bleeding are increasing, with a difficult management of these patients for their concomitant diseases. The aim of this work is to analyze the therapeutical approach of emergency gastric ulcer complications in elderly patients, in order to establish the factors affecting the morbidity and mortality. METHODS: Patients older than 70 years, presenting gastric ulcer, observed in a tertiary University Hospital from 1995 to 2003, have been considered for the present study. Two groups of diseases have been examined: ulcer perforation and bleeding ulcer. Age, sex, risk factors, comorbidity, methods of diagnosis, ulcer characteristics, treatment, morbidity, mortality, hospitalization time and follow-up have been considered in each group. RESULTS: Thirteen elderly patients with perforated gastric ulcer have been observed: 9 (69.2%) females and 4 (30.8%) males with a mean age of 80.5 years (range 70-90). Four patients were hospitalized in suburban hospital with an average time between the diagnosis and the surgery of 36 h, while the remnants were hospitalized directly in our Department with a medium waiting time of about 2 h. The surgical procedures were: simple closure with omentum patch in 11 cases (84.6%), and antrectomy in 2 cases (15.4%), in which the antrum was multiply perforated. Two patients presented an ulcer larger than 2 cm treated with simple suture and omental patch without morbidity and mortality. Three patients (23%) died postoperatively, due to septic shock, ventricular fibrillation and intraoperative massive haemorrhage, 2 of these patients came from other hospitals. Twenty-eight elderly patients with bleeding gastric ulcer have been observed during the same period: 13 (46.4%) females and 15 (53.6%) males with a mean age of 79.6 years (range 71-91). Except 2 patients submitted to endoscopic treatment both with adrenaline injection, all the remnant patients were managed with medical therapy (H2-receptor antagonist or proton pump inhibitors and in 7 patients [24.1%] antihaemorrhage drugs), and clinical observation, with a endoscopic control 3-4 days after from the first endoscopy. One of the 2 patients endoscopically treated developed a ulcer perforation after 11 days, and the other one rebled, without possibility of any kind of treatment due to his instable condition of health. Three patients (10.7%) died during their hospital stay not for causes strictly due to the gastric haemorrhage. CONCLUSIONS: Our results suggest that the early diagnoses and early treatment are 2 basic factor on the prognosis of elderly patients with perforated gastric ulcer. The choice between simple closure, with or without vagotomy, or gastrectomy depends from preoperative and operative health conditions of the patient. In patients with ulcer larger than 2 cm, Graham's technique can be performed safely if the preoperative and intraoperative conditions are favourable. Elderly patients with gastric ulcer bleeding show an high risk of morbidity and mortality, related to the risk factors like non steroid anti-inflammatory drugs (NSAIDs) intake or smoke. Repeated endoscopy and antiulcer drugs can manage the high stage patients of Forrest's classification with a low rate of morbidity and mortality. According to literature surgical treatment should be reserved after the second failure of endoscopic treatment.

Imaging of post-traumatic cardiac rhabdomyolysis with normal coronary arteries.

Numerous cases of acute myocardial infarction (AMI) have been reported in the literature following closed chest injuries, due to post-traumatic dissection or thrombosis of a coronary artery. In the follow-up of AMI, wall thickness during diastole and systole provides important information on heart viability. Multidetector computed tomography (MDCT) is currently the only noninvasive instrumental investigation which provides an appreciable assessment of the coronary arteries, as well as heart wall thickness measurements. We describe and discuss the clinical and imaging findings, especially of MDCT, in a case of post-traumatic regional myocardial necrosis with normal coronary arteries.

Identification of a molecular signature for leukemic promyelocytes and their normal counterparts: Focus on DNA repair genes.

Acute promyelocytic leukemia (APL) is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. Gene expression profiles of APL cells obtained from 16 patients were compared to eight samples of CD34+-derived normal promyelocytes. Malignant promyelocytes showed widespread changes in transcription in comparison to their normal counterpart and 1020 differentially expressed genes were identified. Discriminating genes include transcriptional regulators (FOS, JUN and HOX genes) and genes involved in cell cycle and DNA repair. The strong upregulation in APL of some transcripts (FLT3, CD33, CD44 and HGF) was also confirmed at protein level. Interestingly, a trend toward a transcriptional repression of genes involved in different DNA repair pathways was found in APL and confirmed by real-time polymerase chain reactor (PCR) in a new set of nine APLs. Our results suggest that both inefficient base excision repair and recombinational repair might play a role in APLs development. To investigate the expression pathways underlying the development of APL occurring as a second malignancy (sAPL), we included in our study eight cases of sAPL. Although both secondary and de novo APL were characterized by a strong homogeneity in expression profiling, we identified a small set of differentially expressed genes that discriminate sAPL from de novo cases.

Necrotic uveal melanoma with orbital inflammation.

PURPOSE: Extraocular extension of uveal melanoma can be accompanied by proptosis and signs of orbital inflammation but this clinical presentation is an uncommon feature if the tumor is solely intraocular. METHODS: Case report. RESULTS: The authors describe a patient with a medium-sized necrotic uveal melanoma, without extraocular spread, presenting with the clinical picture of orbital cellulitis. CONCLUSIONS: The ophthalmologist needs to be aware of this uncommon presentation of uveal melanoma, and not assume the presence of proptosis and orbital inflammation as signs of extraocular extension.

Primary cardiac Burkett's type lymphoma: transthoracic echocardiography, multidetector computed tomography and magnetic resonance findings.

Although primary cardiac lymphoma is an extremely rare disease and is associated with high mortality, it is treatable when diagnosed appropriately. We describe the transthoracic echocardiography, 16-row multidetector computed tomography (16-MDCT) and magnetic resonance findings of primary cardiac lymphoma in an immunocompromised patient and review of the literature.

Escherichia coli endophthalmitis after trans-scleral resection of uveal melanoma.

PURPOSE: To report a case of Escherichia coli endophthalmitis after trans-scleral resection of an uveal melanoma. METHODS: A large ciliary body melanoma was treated by trans-scleral resection and full-thickness sclerectomy because of epibulbar tumor extrusion, followed by adjuvant ruthenium plaque therapy. RESULTS: Two months after treatment the patient developed wound dehiscence and consecutive endophthalmitis. Cultures of the involved sclera yielded Escherichia coil. The infection resolved after systemic intravenous ciprofloxacin and ceftriaxone, with aggressive topical ciprofloxacin and tobramycin. Final visual acuity was light perception. CONCLUSIONS: We assume that the ruthenium plaque placed over the scleral patch was responsible for the delay in scleral healing, with consequent wound dehiscence and E. coli endophthalmitis.