HaemoPREF: Further evaluation of patient perception and preference for treatment in a real world setting.

INTRODUCTION: Adherence to haemophilia A (HA) treatment may be influenced by patients' beliefs about their condition and treatment. Furthermore, difficulties administering treatment may lead to poor adherence. New treatment strategies aim to reduce the burden associated with administration and to improve patient perception of treatment, which, in turn, increase adherence levels. AIMS: This study aimed to examine patient perception of HA treatment and related factors using patient-reported outcome (PRO) questionnaires and to confirm the psychometric properties of a recently developed questionnaire, the HaemoPREF. METHODS: A non-interventional, cross-sectional, questionnaire study was conducted with adult HA patients in Spain (n=31), Germany (n=10) and Italy (n=48), who were using ReFacto AF with the FuseNGo administration device. Patients completed the HaemoPREF and other questionnaires measuring related constructs: treatment adherence, satisfaction and well-being, online at two time points. Correlational, regression and psychometric analyses were conducted. RESULTS: PRO scores indicated that patients are satisfied with and adherent to their treatment. Multivariate regression of the HaemoPREF global score identified a number of significant predictors (P≤.05). The HaemoPREF Global Score had a moderate relationship with subscales on the related questionnaires (mean correlation=0.43; range=0.39-0.48). The HaemoPREF demonstrated good test-retest reliability (intraclass correlation coefficient=0.82), internal consistency reliability (Cronbach's alpha range=0.69-0.82) and convergent validity with measures of treatment satisfaction (Spearman correlation coefficient, r=.48) and well-being (r=.41). CONCLUSION: The findings suggest that patients using ReFacto AF with FuseNGo were satisfied with and adherent to their treatment. The HaemoPREF can identify important concepts relating to patient treatment experience in HA.

Epidural anesthesia and non-invasive ventilation for radical retropubic prostatectomy in two obese patients with chronic obstructive pulmonary disease.

We report two cases of anesthesia for radical retropubic prostatectomy (RRP) in obese-chronic obstructive pulmonary disease (COPD) patients using the combination of epidural anesthesia and non-invasive ventilation (NIV). This technique avoided intubation, general anesthesia and perioperative pulmonary complications.

[Applications of noninvasive mechanical ventilation in anesthesiology and postanesthesia recovery care]. / Aplicaciones de la ventilación mecánica no invasiva en anestesiologáa y reanimación.

Noninvasive ventilation (NIV) can be useful to anesthesiologists working in critical care units, postanesthesia recovery units, operating theaters, or other settings. NIV can help in situations of acute respiratory failure or serve as a preventive measure in patients undergoing interventions under local-regional anesthesia or diagnostic or therapeutic procedures requiring sedation. Successful NIV depends on adequately trained health personnel and the proper choice of material (interfaces, respirators, etc.) for each setting where this modality is used.

Employment in a cohort of breast cancer patients.

BACKGROUND: Breast cancer survivors can have problems in returning to work. However, the importance of work to cancer survivors has until recently received little attention. AIMS: To investigate employment- and work-related disability in a cohort of breast cancer patients to identify possible discrimination and other obstacles to remaining in work. METHODS: Questionnaire study of breast cancer patients employed at diagnosis and where diagnosis had been confirmed at least 6 months before the interview. Participants completed a questionnaire concerning cancer-related symptoms and work-related factors and clinical details were obtained from their medical records. RESULTS: The study included 96 consecutive patients with breast cancer aged between 18 and 65 years. In total, 80% of patients were unable to work after diagnosis, but 56% returned to work at the end of treatment. The sequelae of the disease or its treatment and the stage of disease were independently associated with the ability to work after the end of treatment. Only one patient did not tell his/her employers and coworkers about his/her disease. In total, 29% noticed changes in their relation with co-workers and managers, usually in the sense that they tried to be helpful. None reported job discrimination. CONCLUSION: Breast cancer survivors in this study encountered some problems in returning to work, mainly linked to the sequelae of their disease and its treatment rather than to discrimination by employers or colleagues.

[Continuous infusion of baclofen and an antibiotic for treating meningitis related to refilling of an intrathecal infusion pump reservoir]. / Infusión continua de baclofeno con antibiótico para el tratamiento de meningitis asociada a relleno del reservorio de la bomba de perfusión intratecal.

Baclofen via intrathecal infusion pump is a widely used treatment severe spasticity. Complications are rare and usually mild, though they can also be serious. The sudden discontinuation of intrathecal baclofen may have significant adverse effects. We report the case of a 59-year-old man with chronic spasticity and torsion dystonia who developed meningitis due to Staphylococcus epidermidis due to contamination of the intrathecal, infusion pump reservoir during refilling. It was decided to treat the patient by administering vancomycin through the pump, together with the baclofen. We believe that changing the intrathecal perfusion pump is not necessary as the first measure to take in these cases. Combined infusion of baclofen and an antibiotic through the pump makes it possible to maintain antispastic treatment, sterilize the pump reservoir and tubes, and effectively treat infections that develop during use of these systems.

Dissociated primary nerve cell cultures as models for assessment of neurotoxicity.

Exogenous and endogenous neurotoxins may have poisoning effects on living organisms. Neurotoxic signs can result from human intoxication by substances present in natural ecosystems as pollutants, such as inorganic mercury, cadmium, manganese and lead, or by abnormal accumulation of endogenous compounds, as bilirubin. Dissociated primary nerve cell cultures are powerful models that can be used to evaluate the responses of target cells at the cellular and molecular levels to the deleterious effects of neurotoxic substances. Primary cultures of nerve cells are prepared from either fetal (neurons) or 2-day-old (macroglia and microglia) rat brains, cultured with specific media. Cells can then be used to evaluate the neurotoxic effects of a particular substance. By using cells with different days-in-culture it is possible to mimic and evaluate developmental-related modifications. These modifications can comprise morphological changes, cell death by necrosis (release of lactate dehydrogenase, LDH) and apoptosis (nuclear fragmentation), altered neurotransmission (impaired uptake or increased release of glutamate), neuroinflammation (enhanced cytokine production) and the generation of oxidative damage (formation of reactive oxygen species and disruption of glutathione metabolism). Here we describe the methods for nerve cell cultures, as well as some of the procedures that can be used to assess neuronal and glial cytotoxicity induced by different neurotoxins.

Mitral Valve Surgery for Rheumatic Lesions in Young Patients.

BACKGROUND: The appropriateness of rheumatic mitral valve repair remains controversial due to the risks of recurrent mitral dysfunction and need for reoperation. The aims of this study were to determine the overall short- and long-term outcomes of pediatric rheumatic mitral valve surgery in our center. METHODS: Single-center, observational, retrospective study that analyzed the results of rheumatic mitral valve surgery in young patients, consecutively operated by the same team, between 1999 and 2014. RESULTS: We included 116 patients (mean age = 12.6 ± 3.5 years), of which 66 (57%) were females. A total of 116 primary surgical interventions and 22 reoperations were performed. Primary valve repair was possible in 86 (74%) patients and valve replacement occurred in 30 (26%). Sixty percent of the patients were followed up beyond three months after surgery (median follow-up time = 9.2 months [minimum = 10 days; maximum = 15 years]). Long-term clinical outcomes were favorable, with most patients in New York Heart Association functional class I (89.6%) and in sinus rhythm (85%). Freedom from reoperation for primary valve repair at six months, five years, and ten years was 96.4% ± 0.25%, 72% ± 0.72%, and 44.7% ± 1.34%, respectively. Freedom from reoperation for primary valve replacement at six months, five years, and ten years was 100%, 91.7% ± 0.86%, and 91.7% ± 0.86%, respectively. Mitral stenosis as the primary lesion dictated early reintervention. CONCLUSIONS: Despite the greater rate of reoperation, especially when the primary lesion was mitral stenosis, rheumatic mitral valve repair provides similar clinical outcomes as compared with replacement, with the advantage of avoiding anticoagulation.

[Non-invasive mechanical ventilation with a facial interface during sedation for a percutaneous endoscopic gastrostomy in a patient with amyotrophic lateral sclerosis]. / Ventilación mecánica no invasiva con interfase facial durante la sedación para una gastrostomía endoscópica percutánea en un paciente con esclerosis lateral amiotrófica.

Amyotrophic lateral sclerosis is a chronic neurodegenerative disease of the central nervous system which affects the motor neurons and produces a progressive muscle weakness, leading to atrophy and muscle paralysis, and ultimately death. Performing a percutaneous endoscopic gastrostomy with sedation in patients with amyotrophic lateral sclerosis can be a challenge for the anesthesiologist. The case is presented of a 76-year-old patient who suffered from advanced stage amyotrophic lateral sclerosis, ASA III, in which a percutaneous endoscopic gastrostomy was performed with deep sedation, for which non-invasive ventilation was used as a respiratory support to prevent hypoventilation and postoperative respiratory complications.

Biliary tract cancers: SEOM clinical guidelines.

Biliary tract cancer (BTC) is an uncommon and highly fatal malignancy. It is composed of three main different entities; Gall bladder carcinoma (GBC), intrahepatic cholangiocarcinoma (iCC) and extrahepatic cholangiocarcinoma (eCC) sharing different genetic, risk factors and clinical presentation. Multidetector-row computed tomography (MDCT) and magnetic resonance cholangio-pancreatography (MRCP) are the more important diagnostic techniques. Surgery is the only potentially curative therapy but disease recurrence is frequent. Treatment with chemotherapy, radiotherapy or both has not demonstrated survival benefit in the adjuvant setting. Cisplatin plus gemcitabine constitutes the gold standard in metastatic disease. New ongoing studies mainly in the adjuvant and neoadjuvant setting along with molecular research will hopefully help to improve survival and quality of life of this disease.

Pregnancy in a breast cancer patient treated with a LHRH analogue at ablative doses.

A 36-year-old female diagnosed of breast cancer was treated with surgery, chemotherapy, radiotherapy and goserelin. After 17 months of uninterrupted therapy with this LHRH analogue at hormone suppressive doses, a 16-week gestation foetus was detected and the treatment was withdrawn. Although the drug was administered throughout the first 4 months of pregnancy it resulted in the term delivery of a healthy infant, and no foetal adverse effects were detected. A review of the influence of hormonal treatment for breast cancer on fertility and birth defects has been performed.

Activation of development in mammals: is there a role for a sperm cytosolic factor?

In mammalian oocytes, fertilization-associated calcium [Ca2+]i oscillations are responsible for the activation of development. The mechanism(s) by which the sperm triggers the initial [Ca2+]i rise and supports long-lasting oscillations is not resolved. It has been proposed that the sperm may interact with receptors in the oocyte's plasma membrane and engage intracellular signaling pathways that result in Ca2+ release. A different line of investigation suggests that upon sperm-oocyte fusion, a sperm cytosolic factor is released into the oocyte which interacts with unknown cytosolic targets, and generates [Ca2+]i oscillations. We will discuss the most recent evidence for both lines of thought and demonstrate that injections of sperm crude extracts (SF) into mammalian oocytes trigger [Ca2+]i oscillations that support in vitro parthenogenetic development to the blastocyst stage.

Oral cabergoline. Single-dose inhibition of puerperal lactation.

Cabergoline, a new dopaminergic drug with a long-lasting prolactin inhibitory effect, was investigated at different single oral doses administered to puerperas who wished to inhibit their lactation. The study was prospective, randomized and double blind and included 140 puerperas divided into three groups of 40 women each treated with cabergoline and one group of 20 women who received a placebo. The tested doses were 1.0, 0.75 and 0.5 mg, administered orally within 24 hours after delivery. Prolactin levels were measured immediately before drug administration and then after 6 and 12 hours as well as on days 2, 3, 4, 5 and 14 after delivery. At those times the subjects were examined for milk secretion, breast engorgement, pain and possible side effects. In cases of symptoms requiring treatment, an additional 1 mg of cabergoline was administered. Complete inhibition of lactation up to day 14 was obtained in 90.2% of the women given 1 mg, 62.5% of those given 0.75 mg, 45% of those given 0.5 mg and 20% of those given a placebo. Four subjects experienced mild and transient side effects.

Circulating cancer cells in peripheral blood. A case report.

BACKGROUND: Carcinocythemia, the presence of circulating cancer cells in peripheral blood, is a rare complication of solid neoplasms. When the number of such cells is very high, they can be detected during routine laboratory tests. They are associated with a dismal prognosis. CASE REPORT: Carcinocythemia occurred in a patient with disseminated breast cancer. Eighteen cases were identified from a review of the literature. The most common neoplasms associated with circulating cancer cells in peripheral blood were breast adenocarcinoma, small cell lung carcinoma and rhabdomyosarcoma. All the patients had stage IV disease at the time of diagnosis, and all had involvement of the reticuloendothelial system. Patients survived for an average of a few days or weeks. CONCLUSION: Circulating cancer cells in peripheral blood are an unusual manifestation of disseminated neoplasms that occurs as a terminal event.

[Primary intestinal T lymphoma: a report of two cases and a review of the literature]. / Linfoma T primario intestinal: a propósito de dos casos con revisión de la literatura.

Lymphomas of the gastrointestinal tract are the most common type of primary extranodal lymphomas and about 15-20% of these are primary intestinal lymphomas. They may be or B or T- cell. Intestinal T-cell lymphomas are much less common and they can be enteropathy-associated. This disease occurs in adults with abdominal pain often associated with intestinal perforation. The course is aggressive. The major problem is to distinguish this disease from a benign ulcer. Two cases with differents clinical and pathologic features are reported with a review in the literature of this uncommon entity.

[Superior vena cava syndrome: presentation of six cases]. / Síndrome de vena cava superior: presentación de seis casos.

Superior vena cava syndrome is a devastating complication of obstructive lesions compromising the superior vena cava an its branches. Most cases today are caused by malignant tumors. The most frequent are lung carcinoma. The clinical presentation is dyspnea, vuvular enlargement, collateral circulation. Imaging techniques and histological confirmation are used for diagnosis. Early diagnosis and treatment is needed. The following report deals with six patients with superior vena cava syndrome. All entered our hospital through Emergency Department. The description of the principal symptoms and sings, the early diagnosis and the treatment.

Biological risks for neurological abnormalities associated with hyperbilirubinemia.

Unconjugated bilirubin (UCB) injury to glial cells leads to the secretion of glutamate and elicits a typical inflammatory response. Release of pro-inflammatory cytokines may influence gliogenesis and neurogenesis, and lead to deficits in learning and memory. Glutamate metabolism dysregulation and overexpression of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta are consistent with schizophrenia neuropathology. Recently, an increased prevalence of schizophrenia was reported in individuals with Gilbert's syndrome and among those who have had elevated levels of UCB in the neonatal life. In this review, we explore the reactivity of astrocytes, neurons and microglia to UCB, the cascade of events implicated in the immunostimulant effects of UCB, as well as the role of each nerve cell type and maturation state in the neuropathology of UCB. Identification of the signaling events promoted by UCB will be relevant for developing novel therapies that might reduce the risk of brain injury and disabilities.

Descriptive analysis of clinical factors affecting terminally ill cancer patients.

GOALS OF WORK: To make a descriptive analysis of clinical and laboratories parameters in advanced neoplastic patients. MATERIALS AND METHODS: We interviewed 406 terminally ill cancer patients to study demographic and neoplastic data, 24 graded symptoms, 21 analytical parameters and scales to evaluate general condition, quality of life and independence in daily activities. MAIN RESULTS: An average of 9.3 symptoms per patient were detected and median survival was 26.5 days. Most frequent symptoms were asthenia (96.8%), anorexia (94.8%), weight loss (88.1%) and pain (80.5%). Principal laboratory abnormalities were high blood sedimentation rate (96%), high cytolysis and cholestasis enzyme levels (50-77%), anemia (81.5%), low protein (66%) and low albumin levels (67%). Symptom prevalence was different according to age, gender, primary tumour, location of metastasis, laboratory parameters, performance status, quality of life or independence in daily-living activities. CONCLUSIONS: We should know more frequent symptoms affecting terminal cancer patients and any factor contributing to it to provide more comfort in the final phases of life.

Injection of sperm cytosolic factor into mouse metaphase II oocytes induces different developmental fates according to the frequency of [Ca(2+)](i) oscillations and oocyte age.

Intracellular calcium ([Ca(2+)](i)) rises are a hallmark of mammalian fertilization and are associated with normal activation of embryonic development. Injection of mammalian sperm cytosolic factor (SCF) into oocytes has been shown to trigger [Ca(2+)](i) rises similar to those observed during fertilization, and to initiate normal embryonic development. However, Ca(2+) release has also been shown to be associated with cell death, but the mechanisms of the detrimental effects of Ca(2+) stimulation on development have not yet been investigated. Thus, studies were undertaken using SCF to test the effects of [Ca(2+)](i) oscillations on oocyte activation in freshly ovulated and aged oocytes. Injections of 1 mg/ml SCF into freshly ovulated mouse metaphase II oocytes, which evoked Ca(2+) responses with low frequency and short duration, induced normal activation and cleavage to the two-cell stage. Conversely, injection of 15 mg/ml SCF, which triggered high-frequency and persistent Ca(2+) responses, induced abnormal activation that was characterized by abnormal chromatin configurations, inhibition of DNA synthesis, and lack of first mitotic spindle assembly. More importantly, fertilization-like Ca(2+) responses induced by injection of 1 mg/ml SCF triggered cell death, rather than activation, in in vitro-aged oocytes. These oocytes exhibited extensive cytoplasmic and DNA fragmentation that was accompanied by activation of protein caspases, all of which are signs of apoptotic cell death. Fewer similarly aged oocytes that were either unstimulated or activated with 7% ethanol underwent fragmentation. Together, these results suggest that [Ca(2+)](i) oscillations are required to activate freshly ovulated oocytes, but if initiated at abnormally high frequency and duration or if induced in aged oocytes, the [Ca(2+)](i) oscillations may trigger premature termination of embryonic development.

Mitogen activated protein kinase plays a significant role in metaphase II arrest, spindle morphology, and maintenance of maturation promoting factor activity in bovine oocytes.

Mammalian oocytes are arrested at the G2/M transition of the first meiotic division from which, after reaching full size and subsequent to an LH surge, they undergo final maturation. Oocyte maturation, which involves germinal vesicle breakdown, progression through metaphase I (MI), and arrest at MII, is triggered and regulated by the coordinated action of two kinases, maturation promoting factor (MPF) and mitogen activated protein kinase (MAPK). The importance of the role of MPF in mammalian oocyte maturation is well established, while the role of MAPK, although well understood in mouse oocytes, has not been fully elucidated in oocytes of large domestic species, especially bovine oocytes. Here we show that injection of MKP-1 mRNA, which encodes a dual specificity MAPK phosphatase, into germinal vesicle stage bovine oocytes prevents the activation of MAPK during maturation. Despite the lack of MAPK activity, MKP-1-injected oocytes resume and progress through meiosis, although they are unable to arrest at MII stage and, by 22-26-hour post-maturation, exhibit decondensed pronucleus-like chromatin, a clear sign of parthenogenetic activation. MKP-1-injected bovine oocytes exhibit normal activation of MPF activity; however, by 18-hour post-maturation, MPF activity starts to decline and by 22-26 hr MPF activity is absent. MKP-1-injected oocytes also show disorganized MII spindles with poorly aligned chromosomes. In summary, our results demonstrate that in bovine oocytes MAPK activity is required for MII arrest, maintenance of MPF activity, and spindle organization.