Reliability of the Brazilian version of the Functional Assessment of Cancer Therapy-Lung (FACT-L) and the FACT-Lung Symptom Index (FLSI)

OBJECTIVES:

The purpose of this study was to assess the reliability of the Brazilian version of the Functional Assessment of Cancer Therapy‐Lung (FACT‐L) with the FACT‐Lung Symptom Index (FLSI) questionnaire.

INTRODUCTION:

The assessment of quality of life in patients with lung cancer has become an important evaluative endpoint in current clinical trials. For lung cancer patients, one of the most common quality of life tools available is the FACT‐L. Despite the amount of data available regarding this questionnaire, there are no data on its performance in Brazilian lung cancer patients.

METHODS:

The FACT‐L with the FLSI questionnaire was prospectively administered to 30 consecutive, stable, lung cancer outpatients at baseline and at 2 weeks.

RESULTS:

The intraclass correlation coefficient between test and retest for the FACT‐L ranged from 0.79 to 0.96 and for the FLSI was 0.87. There was no correlation between these questionnaire dimensions and clinical or functional parameters.

CONCLUSIONS:

The Brazilian version of the FACT‐L with FLSI questionnaire is reliable and is quick and simple to apply. This instrument can now be used to properly evaluate the quality of life of Brazilian lung cancer patients.     

Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing

Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.     

The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF‐α

The P2×7 receptor (P2×7r) is expressed in innate immune cells (e.g. monocyte/macrophages), playing a key role in IL‐1β release. Since innate immune activation and IL‐1β release seem to be implicated in Behçet's disease (BD), a systemic immune‐inflammatory disorder of unknown origin, we hypothesized that P2×7r is involved in the pathogenesis of the disease. Monocytes were isolated from 18 BD patients and 17 healthy matched controls. In BD monocytes, an increased P2×7r expression and Ca²⁺ permeability induced by the selective P2×7r agonist 2′‐3′‐O‐(4‐benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL‐1β release from LPS‐primed monocytes stimulated with BzATP was markedly higher in BD patients than in controls. TNF‐α‐incubated monocytes from healthy subjects almost reproduced the findings observed in BD patients, as demonstrated by the increase in P2×7r expression and BzATP‐induced Ca²⁺ intake. Our results provide evidence that in BD monocytes both the expression and function of the P2×7r are increased compared with healthy controls, as the possible result, at least in part, of a positive modulating effect of TNF‐α on the receptor. These data indicate P2×7r as a new potential therapeutic target for the control of BD, further supporting the rationale for the use of anti‐TNF‐α drugs in the treatment of the disease.     

Replication of the effect of SLC2A9 genetic variation on serum uric acid levels in American Indians

Increased serum uric acid (SUA) or hyperuricemia, a risk factor for gout, renal and cardiovascular diseases, is caused by either increased production or decreased excretion of uric acid or a mix of both. The solute carrier protein 2 family, member 9 (SLC2A9) gene encodes a transporter that mediates urate flux across the renal proximal tubule. Genome-wide association studies have consistently shown the association of single-nucleotide polymorphisms in this gene with SUA in majority populations. American Indian participants of the Strong Heart Family Study, belonging to multigenerational families, have high prevalence of hyperuricemia. We conducted measured genotype analyses, based on variance components decomposition method and accounting for family relationships, to assess whether the association between SUA and SLC2A9 gene polymorphisms generalized to American Indians (n=3604) of this study. Seven polymorphisms were selected for genotyping based on their association with SUA levels in other populations. A strong association was found between SLC2A9 gene polymorphisms and SUA in all centers combined (P-values: 1.3 × 10⁻³¹–5.1 × 10⁻²³) and also when stratified by recruitment center; P-values: 1.2 × 10⁻¹⁴–1.0 × 10⁻⁵. These polymorphisms were also associated with the estimated glomerular filtration rate and serum creatinine but not albumin–creatinine ratio. In summary, the association of polymorphisms in the uric acid transporter gene with SUA levels extends to a new population of American Indians.     

Searching for a marker of REM sleep behavior disorder: submentalis muscle EMG amplitude analysis during sleep in patients with narcolepsy/cataplexy

STUDY OBJECTIVES: To evaluate the amplitude of submentalis muscle EMG activity during sleep in patients with narcolepsy/cataplexy with or without REM sleep behavior disorder (RBD). DESIGN: Observational study with consecutive recruitment. SETTINGS: Sleep laboratory. PATIENTS: Thirty-four patients with narcolepsy/cataplexy and 35 age-matched normal controls. MEASUREMENTS AND RESULTS: Half the patients (17 subjects) had a clinical and video polysomnographic diagnosis of RBD. The average amplitude of the rectified submentalis muscle EMG signal was used to assess muscle atonia, and the new REM sleep Atonia Index was computed. Chin muscle activations were detected and their duration and interval analyzed. REM sleep Atonia Index was lower in both patient groups (with narcolepsy patients with RBD showing the lowest values) with respect to controls, and it did not correlate with age as it did in controls. The total number of chin EMG activations was significantly higher in both patient groups than controls. No significant differences were found between the two groups of patients, although more chin EMG activations were noted in narcolepsy patients with RBD than those without. CONCLUSIONS: Elevated muscle activity during REM sleep is the only polysomnographic marker of RBD. This study shows that polysomnographically evident RBD is present in many patients with narcolepsy/ cataplexy. This condition might be specific to narcolepsy/cataplexy, reflecting a peculiar form of REM sleep related motor dyscontrol (i.e., status dissociatus), paving the way to enacting dream behaviors, and correlated with the specific neurochemical and neuropathological substrate of narcolepsy/cataplexy.     

Kisspeptin and the Preovulatory Gonadotrophin‐Releasing Hormone/Luteinising Hormone Surge in the Ewe: Basic Aspects and Potential Applications in the Control of Ovulation

The identification of the neural mechanisms controlling ovulation in mammals has long been a ‘holy grail’ over recent decades, although the recent discovery of the kisspeptin systems has totally changed our views on this subject. Kisspeptin cells are the major link between gonadal steroids and gonadotrophin‐releasing hormone (GnRH) neurones. In the female rodent, kisspeptin cells of the preoptic area are involved in the positive‐feedback action of oestrogen on GnRH secretion, although the picture appears more complicated in the ewe. As in rodents, activation of preoptic kisspeptin neurones accompanies the GnRH surge in the ewe but an active role for arcuate kisspeptin neurones has also been proposed. Experimentally, kisspeptin is able to restore reproductive function when the hypothalamic‐hypophyseal ovarian axis is quiescent. For example, i.v. infusion of a low dose of peptide in anoestrous ewes induces an immediate and sustained release of gonadotrophin, which subsides and then provokes a luteinising hormone (LH) surge a few hours later. This pharmacological intervention induces the same hormonal changes normally observed during the follicular phase of the oestrous cycle, including the secretion of oestrogen and its negative‐ and positive‐feedback actions on the secretion of LH and follicle‐stimulating hormone. Accordingly, a high percentage of kisspeptin‐infused animals ovulated. Although the multiple facets of how the kisspeptin systems modulate GnRH secretion are not totally understood, the demonstration that exogenous kisspeptin administration can induce ovulation in anovulatory animals paves the way for future therapeutic applications aiming to control reproduction.     

Pharmacological studies on tiadenol in type IV patients Evidence for a mechanism of action different from other lipid-lowering drugs

Tiadenol [bis(hydrosyethylthio) 1–10 decane], a new absorbable hypolipidemic agent differing in chemical structure from clofibrate and related compounds, was tested in hypertriglyceridemic patients, both responsive and non-responsive to dietary treatment. Tiadenol administration was remarkably effective in inhibiting fructose induced hypertriglyceridemia in diet responsive type IV patients; it was ineffective in patients with stable, diet refractory, hypertriglyceridemia. The significant reduction of plasma triglycerides (−42%) in sensitive patients, was not accompanied in this study, by the activation of plasma lipoprotein and hepatic lipases. In a second, longer term investigation of stable type IV patients, tiadenol administration resulted in significant triglyceride decreases in the very low density lipoproteins (VLDL) (−45%), as well as in the low and high density lipoproteins (LDL and HDL) (both −250). The cholesterol content of LDL and HDL was not modified. In VLDL a significant reduction of apoprotein E was observed (from 15.2 ± 4.9 to 11.9 ± 5.9% of VLDL proteins). The reported observations are consistent with a difference in the mode of action of tiadenol from that of other lipid lowering agents, particularly of the clofibrate type.     

Results obtained with level II oncoplastic surgery spanning 20 years of breast cancer treatment: Do we really need further demonstration of reliability?

Oncoplastic surgery (OPS) has demonstrated its superiority above traditional breast conserving surgery, but is still struggling to consolidate its role in breast cancer therapeutic protocols mainly because of contrasting scientific evidences and reduced follow‐up results available. The objective of our contribution is to analyze results obtained with 381 patients consecutively treated in our Multidisciplinary Breast Center by means of level II OPS between January 1998 and January 2018 for unilateral, primary breast cancer. Surgical endpoints were mean specimen weight and volume, mean diameter of main lesion (MLD), rates of positive margins (PMR), re‐excision (RR), conversion to mastectomy (CMR), complications (CR) and oncological endpoints as overall survival (OS), disease‐free survival (DFS), and local recurrence rate (LR). About 29.1% were treated for multifocal/multicentric disease, and 29.1% previously underwent neo‐adjuvant chemotherapy (NACT). Regarding surgical techniques, 53.0% of patients received “inverted T” and 30.1% “J” mammoplasties, whereas 13.6% underwent “round block,” 2.3% “Grisotti,” and 1% “batwing” techniques. Regarding surgical outcomes, mean specimen weight was 215 g (50‐2157) and volume 345 mm³ (21‐7980). MLD 23 mm, PMR 7.6%, RR 3.6%, CMR 1.6%, and CR 5.8%. With a mean follow‐up of 118 months, oncological outcomes were: OS 93.7%, DFS 82.3%, LR 4.4%. In conclusion, our analysis confirmed level II OPS reliability even for longer follow‐up timing and in difficult situations as multifocal disease or after NACT.     

Relationship between major adverse cardiac events and angiographic findings in dialysis patients

Background  

In dialysis patients, coronary angiography (CA) predicts major adverse coronary events (MACE) better than non-invasive tests. The aim of this study was to investigate in such patients the relationship between coronary atherosclerotic damage shown by angiography and MACE, during an average follow-up period of more than 5 years.     

Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro

Schwann cells, the myelin-forming cells of the PNS, are attractive candidates for remyelination therapy as they can remyelinate CNS axons. Yet their integration in CNS tissue appears hampered, at least in part, by their limited motility in the CNS environment. As the polysialylated (PSA) form of NCAM regulates migration of neural precursors in the CNS and is not expressed by developing Schwann cells, we investigated whether conferring sustained expression of PSA to Schwann cells derived from postnatal rats enhances their motility. Cells were transduced with a retrovirus encoding polysialyl-transferase STX, an enzyme that synthesizes PSA on NCAM. Migration of wild type and transduced cells expressing STX or the marker gene alkaline phosphatase was examined using a gap bridging assay in dissociated cells and by grafting cells in slice cultures of postnatal brain. Migration of PSA expressing cells was significantly increased in both models, as compared to control cells, and this effect was abolished by endoneuraminidase-N stripping of PSA. PSA-positive Schwann cells retained the ability to differentiate in vitro and expressed the Krox20 and P zero myelination markers. When grafted in neonatal cerebellar slices, STX-transduced cells started to myelinate Purkinje cell axons like control cells and make myelin internodes after 2 to 3 weeks. PSA was redistributed on the cell membrane and downregulated during differentiation in pure Schwann cell cultures and slice co-cultures. Thus, migratory properties of PNS myelin-forming cells within the CNS can be enhanced without altering their differentiation program. This finding may be beneficial for the development of remyelination therapies.