Prevalence, risk factors, and type of sleep apnea in patients with paroxysmal atrial fibrillation.

BACKGROUND: Recent studies have suggested an association between sleep apnea (SA) and atrial fibrillation (AF). We aimed to study the prevalence, characteristics, risk factors and type of sleep apnea (SA) in ablation candidates with paroxysmal AF. METHODS/RESULTS: We prospectively studied 579 patients with paroxysmal AF, including 157 women (27.1%) and 422 men (72.9%). Mean age was 59.9 ± 9.6 years and mean body mass index (BMI) 28.5 ± 4.5 kg/m2. SA was diagnosed using polygraphy for two nights at home. The Epworth Sleepiness Scale (ESS), STOP-Bang Questionnaire, and Berlin Questionnaire (BQ) assessed the degree of SA symptoms. A total of 479 (82.7%) patients had an apnea-hypopnea index (AHI) ≥ 5, whereas moderate-severe SA (AHI ≥ 15) was diagnosed in 244 patients (42.1%). The type of SA was predominantly obstructive, with a median AHI of 12.1 (6.7-20.6) (range 0.4-85.8). The median central apnea index was 0.3 (0.1-0.7). AHI increased with age, BMI, waist and neck circumference, body and visceral fat. Using the Atrial Fibrillation Severity Scale and the SF-36, patients with more severe SA had a higher AF burden, severity and symptom score and a lower Physical-Component Summary score. Age, male gender, BMI, duration of AF, and habitual snoring were independent risk factors in multivariate analysis (AHI ≥ 15). We found no association between ESS and AHI (R2 = 0.003, p = 0.367). CONCLUSIONS: In our AF population, SA was highly prevalent and predominantly obstructive. The high prevalence of SA detected in this study may indicate that SA is under-recognized in patients with AF. None of the screening questionnaires predicted SA reliably.

Safety and preliminary efficacy of electrostatic precipitation during pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable carcinomatosis.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was recently introduced to treat unresectable peritoneal metastases. Adding an electrostatic field may enhance charged droplet precipitation and tissue penetration, resulting in improved anticancer efficacy. We report for the first time its safety and preliminary efficacy. MATERIALS AND METHODS: Patients underwent PIPAC combined with an electrostatic field, using the Ultravision™ apparatus. Adverse events were scored with the Common Terminology Criteria. Treatment response was assessed after more than one PIPAC, using clinical symptoms, tumor markers, CT imaging and histological regression. RESULTS: Forty-eight patients (median age, 61 y) with diverse primary tumors underwent 135 procedures (median per patient, 3). Most (65.2%) were treated as outpatient. Twenty-eight (58.3%) patients received concomitant chemotherapy. The most frequent treatment-related toxicities were anemia (grade 1 to 3, 13 [9.6%]), ileus (grade 1 to 3, 5 [3.7%]), anorexia (grade 1 to 3, 6 [4.4%]), nausea (grade 1 to 3, 5 [3.7%]) and vomiting (grade 1 to 3, 7 [5.2%]). There was no grade 4 or 5 morbidity. Twenty (41.7%) patients did not complete three treatments, mainly because of disease progression (n = 13). After two procedures, there were one responder and 8 non-responders. After three treatments, we observed 11 responders, two patients with stable disease, and 15 non-responders. All but one patient with therapy response received simultaneous chemotherapy. CONCLUSION: Electrostatic precipitation during PIPAC is well tolerated and safe. After three procedures and concomitant chemotherapy, response or stable disease is achieved in approximately half of cases. These findings warrant prospective trials in homogeneous patient cohorts.

Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study.

BACKGROUND: To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up. PATIENTS AND METHODS: A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT. RESULTS: Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months. CONCLUSION: Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.

Prospective randomised phase II study of docetaxel versus paclitaxel administered weekly in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.

BACKGROUND: Docetaxel and paclitaxel have activity in the second-line treatment of non-small-cell lung cancer (NSCLC), and can be administered as weekly schedules. This phase II randomised study was designed to test the efficacy and toxicity of both taxanes in patients with NSCLC previously treated with platinum-based chemotherapy. PATIENTS AND METHODS: Patients (n = 71) with documented NSCLC were randomised to receive docetaxel (n = 35 patients; 36 mg/m(2)) or paclitaxel (n = 36 patients; 80 mg/m(2)) as a 1 h weekly infusion for 6 weeks followed by a 2-week rest. The cycles were repeated until disease progression or non-acceptable toxicities occurred. RESULTS: Treatment achieved partial response of one versus five patients, median time-to-progression of 74 versus 68 days, and overall survival of 184 versus 105 days, with docetaxel and paclitaxel, respectively. The most common non-haematological toxicities were (docetaxel versus paclitaxel): grade 3/4 pulmonary toxicity in seven versus one patient; grade 2/3 diarrhoea in nine versus five; and grade 3/4 haematological toxicities occurred in two versus four patients. There were no treatment-related deaths. CONCLUSIONS: Docetaxel and paclitaxel administered weekly have discrete efficacy in patients with NSCLC previously treated with platinum-based chemotherapy. The higher non-haematological toxicity of docetaxel, particularly pulmonary toxicity and diarrhoea, is of concern and warrants further investigation.

Cost-minimisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain.

The study consisted of a cost-minimisation analysis since the findings from a multicentre randomised phase III trial showed that pegylated liposomal doxorubicin hydrochloride was at least as efficacious as topotecan. An economic model from the Spanish hospitals perspective was constructed to compare the costs derived from the treatment using both drugs in patients with recurrent epithelial ovarian cancer who failed a first-line platinum-containing regimen. The cost evaluation included direct medical costs: drug, drug administration and costs of managing adverse events. Estimation of resources used in managing adverse events was made retrospectively through an expert panel. Results obtained per patient were: cost of drug and administration, 8647.70 euros for pegylated liposomal doxorubicin hydrochloride and 8519.94 euros for topotecan, while cost of managing adverse events was 967.02 euros in the pegylated liposomal doxorubicin hydrochloride arm and 3304.75 euros for topotecan. The total cost per patient was therefore estimated to be 9614.72 euros for pegylated liposomal doxorubicin hydrochloride and 11 824.69 euros for topotecan, showing that pegylated liposomal doxorubicin hydrochloride produces a cost saving of 2209.97 euros per patient in comparison to topotecan. Sensitivity analyses verified the robustness of the results. These findings suggest that pegylated liposomal doxorubicin hydrochloride is an efficient therapy and can be used as a cost-saving option for treatment of patients with recurrent epithelial ovarian cancer who have failed a first-line platinum-containing regimen.

Estudio fase II de doxorubicina liposomal pegilada (Caelyx®) en carcinoma de ovario avanzado: análisis de eficacia y toxicidad / Phase II study of pegylated liposomal doxorubicin (Caelix®) in advanced ovarian cancer: analysis of efficacy and toxocity

La doxorubicina liposomal pegilada (Caelyx®) es una nueva formulación con un perfil diferente de toxicidad y actividad demostrada en cáncer de ovario avanzado. Nuestro grupo diseñó un estudio fase II de la administración de Caelyx® en pacientes con carcinoma de ovario avanzado recidivadas a platino/paclitaxel. Se administró Caelyx® 50 mg/m2 IV (1 hs.) en ciclos repetidos cada 4 semanas. Fueron incluidas 53 pacientes con adecuada función hematológica, renal y hepática. La mediana de edad fue 60 años (rango 40-78 años), Karnosfky 100 por ciento= 15, 90 por ciento= 29, 80 por ciento= 9 y 76 por ciento de las pacientes habían recibido 2 o más líneas de quimioterapia previa. La mediana de ciclos administradas fue 5 (rango: 1-17) con una intensidad del 87 por ciento de la dosis teórica. En un total de 223 ciclos administrados fueron necesarios 8 por ciento de reducciones y 16 por ciento de retrasos de tratamiento. La principal toxicidad fue no hematológica con eritrodisestesia palmo-plantar grado 1-2: 23 por ciento y grado 3-4: 6 por ciento; mucositis grado 3-4: 3 por ciento y 2 episodios de reacción de hipersensibilidad a la infusión. La toxicidad hematológica fue moderada con neutropenia grado 3-4 en 18 ciclos (8 por ciento) y 3 episodios de neutropenia febril (2 con sepsis a Gram -). La tasa de respuesta global fue 23,5 por ciento con 2 RC y 9 RP. Después de una mediana de seguimiento de 15 meses, la mediana de intervalo libre de progresión y de supervivencia global fueron 5,8 meses (95 por ciento CI: 4,5-7,3) y 14,7 meses (95 por ciento CI: 11,2-18,3), respectivamente. Estos resultados confirman la actividad de Caelyx® en cancer de ovario altamente pretratado y progresadas a la combinación platino-paclitaxel, con una buena tolerancia y excelente manejo terapéutico. (AU)

Effect of musculoskeletal disorders on prehension strength.

The purpose of this study was to compare the maximum and job simulated hand grip strength in both healthy workers and those suffering from mild and severe stages of musculoskeletal disorders. Three groups of 10 female industrial workers each were recruited after a detailed screening for musculoskeletal disorders: one group of 10 healthy workers (GI) and two other groups (GII and GIII) consisting of workers suffering from mild and severe upper limbs disorders, respectively. A special device was built to reproduce a similar prehension pattern (open palmar) to that used on the job. This was calibrated against a Jamar dynamometer. Job simulated and maximum prehension strength were tested in three consecutive trials. Pearson's correlation coefficient was calculated for the calibration procedure. Descriptive analysis of the musculoskeletal data was computed. ANOVA and Duncan post hoc multiple comparisons were conducted to test the main effects on muscular strength and interactions. Significant differences between types of strength (p<0.00001) and groups of subject (p<0.0001) were identified. The maximum strength decreased progressively from groups I to III. Although job simulated strength also decreased as disorder severity increased, this trend was weaker than the one observed for the maximum strength. These results suggest that a re-allocation of workers suffering from musculoskeletal disorders be considered.

Síndrome dolorosa miofascial: artigo de revisäo / Myofascial pain syndrome: review article

O objetivo deste artigo foi apresentar aspectos da síndrome dolorosa miofascial encontrados na literatura. Além dos conhecidos distúrbios dos tecidos moles, que incluem os efeitos de traumas, as inflamaçöes, fraqueza, tensäo e espasmos musculares, há uma entidade fisiopatológica descrita a alguns anos, que também atinge estes tecidos e é conhecida como síndrome dolorosa miofascial. Esta síndrome é descrita como sendo uma disfunçäo neuromuscular regional caracterizada pela presença de locais sensíveis em bandas musculares contraturadas/tensas que produzem dor referida em áreas distantes ou adjacentes. Inúmeros tratamentos têm sido propostos visando à remissäo do quadro clínico, entre eles: agulhamento seco, uso do spray de cloreto de etila ou fluormetano seguido por alongamento, injeçäo do ponto-gatilho com anestésicos ou soluçäo fisiológica salina também seguida por alongamento, compressäo isquêmica, técnicas de fricçäo profunda miofascial, TENS (estimulaçäo elétrica nervosa transcutânea), ultra-som, iontoforese, calor (seco e úmido), medicamentos analgésicos, antiinflamatórios ou relaxantes musculares, biofeedback. O objetivo desses tratamentos é a iliminaçäo do ponto gatilho, restauraçäo da amplitude de movimento e força muscular normais e sem dor. Além disso, é necessária uma educaçäo para o paciente prevenir e lidar com as recorrências e também bloquear os fatores precipitantes e/ou perpetuantes. Mas ainda há muitas divergências nos resultados de diferentes estudos, o que sugere uma análise crítica dos mesmos e uma maior preocupaçäo com as metodologias empregadas.

In vitro and ex vivo 13C-NMR spectroscopy studies of pyruvate recycling in brain.

Pyruvate recycling is a well established pathway in the liver, but in the brain, the cellular localization of pyruvate recycling remains controversial and its physiological significance is unknown. In cultured cortical astrocytes, pyruvate formed from [U-13C]glutamate was shown to re-enter the TCA cycle after conversion to acetyl-CoA, as demonstrated by the labelling patterns in aspartate C-2 and C-3, lactate C-2, and glutamate C-4, which provides evidence for pyruvate recycling in astrocytes. This finding is in agreement with previous studies of astrocytic cultures, in which pyruvate recycling has been described from [U-13C]glutamine, in the presence of glutamate, and from [U-13C]aspartate. Pyruvate recycling in brain was studied in fasted rats receiving either an intraperitoneal or a subcutaneous injection of [1,2-13C]acetate followed by decapitation 30 min later. Extracts of cortical tissue were analysed with 13C-NMR spectroscopy and total amounts of amino acids quantified by HPLC. Plasma extracts were analysed with 1H- and 13C-NMR spectroscopy, and showed a significantly larger amount of [1, 2-13C]acetate in the intraperitoneal group compared to the subcutaneous group. Furthermore, a small amount of label was detected in glucose in both groups. In the subcutaneously injected rats, [4-13C]glutamate and [2-13C]GABA were less enriched than plasma glucose, which might have been the precursor. In the intraperitoneally injected rats, however, pyruvate formation from [1, 2-13C]acetate, and re-entry of this pyruvate into the TCA cycle was demonstrated by the presence of greater 13C enrichment in [4-13C]glutamate and [4-13C]glutamine compared to the subcutaneous group, probably resulting from the significantly higher [1, 2-13C]acetate concentration in brain and plasma.

Alpha-ketoisocaproate alters the production of both lactate and aspartate from [U-13C]glutamate in astrocytes: a 13C NMR study.

The present study determined the metabolic fate of [U-13C]glutamate in primary cultures of cerebral cortical astrocytes from rat brain and also in cultures incubated in the presence of 1 or 5 mM alpha-ketoisocaproate (alpha-KIC). When astrocytes were incubated with 0.2 mM [U-13C]glutamate, 64.1% of the 13C metabolized was converted to glutamine, and the remainder was metabolized via the tricarboxylic acid (TCA) cycle. The formation of [1,2,3-(13)C3]glutamate demonstrated metabolism of the labeled glutamate via the TCA cycle. In control astrocytes, 8.0% of the [13C]glutamate metabolized was incorporated into intracellular aspartate, and 17.2% was incorporated into lactate that was released into the medium. In contrast, there was no detectable incorporation of [13C]glutamate into aspartate in astrocytes incubated in the presence of alpha-KIC. In addition, the intracellular aspartate concentration was decreased 50% in these cells. However, there was increased incorporation of [13C]glutamate into the 1,2,3-(13)C3-isotopomer of lactate in cells incubated in the presence of alpha-KIC versus controls, with formation of lactate accounting for 34.8% of the glutamate metabolized in astrocytes incubated in the presence of alpha-KIC. Altogether more of the [13C]glutamate was metabolized via the TCA cycle, and less was converted to glutamine in astrocytes incubated in the presence of alpha-KIC than in control cells. Overall, the results demonstrate that the presence of alpha-KIC profoundly influences the metabolic disposition of glutamate by astrocytes and leads to altered concentrations of other metabolites, including aspartate, lactate, and leucine. The decrease in formation of aspartate from glutamate and in total concentration of aspartate may impair the activity of the malate-aspartate shuttle and the ability of astrocytes to transfer reducing equivalents into the mitochondria and thus compromise overall energy metabolism in astrocytes.

[Left ventricular structure and (systolic and diastolic) function in hypertensive patients without atherosclerotic coronaropathy]. / Estructura y función (sistólica y diastólica) ventricular izquierda en hipertensos sin coronariopatía aterosclerosa.

INTRODUCTION AND OBJECTIVES: Electrocardiographic (ECG) ST-T segment abnormalities in hypertensive patients are traditionally associated with hypertrophy and/or ischaemia and a higher cardiovascular risk. Hypertensive patients with typical or non-typical chest discomfort and a normal coronarographic study underwent an echocardiographic and Doppler study in order to assess left ventricular structure and (systolic and diastolic) function. MATERIAL AND METHODS: Hypertensive patients with ST-T changes were classified as follows: Control group (CG) was made up of 12 hypertensive patients (6 women, 6 men, mean age 59.6 +/- 7.4 years) with normal ECG; Group A (GA), 10 patients (6 women, 4 men, mean age 63.1 +/- 6.8 years) with ECG image of strain; Group B (GB) (9 women and 8 men, mean age 61.3 +/- 10.1 years) with other ST-T alterations. We assessed by echocardiographic and transmitral flow Doppler study left ventricular structure and (systolic and diastolic) function. RESULTS: Interventricular septum thickness, left ventricular posterior wall thickness, left ventricular mass and mass index were significantly higher in the GA and GB than in the CG, without differences between GA and GB groups. No differences in left ventricular systolic function parameters were observed between the groups. In comparison with the CG, the GA and GB showed significant differences in E wave deceleration velocity and deceleration time, A wave deceleration time and isovolumetric relaxation time. Between GA and GB differences were observed in A wave deceleration time and isovolumetric relaxation time. CONCLUSIONS: In hypertensive patients without atherosclerotic coronaropathy, ST-T changes identify a group with greater left ventricular mass and worse left ventricular diastolic function. The patients with a ST-T strain pattern showed the impaired diastolic function.

Leukocyte count as a predictor of the severity ischaemic heart disease as evaluated by coronary angiography.

Increased white blood cell count has been reported associated with increase risk of coronary heart disease. We studied the relationship of white blood cell count to the 5 year incidence of coronary heart disease mortality in 152 men, without myocardial infarction or infection in the 6 months prior to the study. The coronary heart disease was determined by coronary arteriography study in all patients. None was treated by revascularization procedures (surgical or percutaneous transluminal coronary angioplasty). The severity of coronary heart disease was assessed by Gensini's Score and number of main coronary arteries with significant stenosis. The white blood cell count showed a positive correlation with Gensini's Score (r = 0.45, p < 0.01), and was significantly higher in the patients with three vessels disease (one vessel = 7084 +/- 1679 leukocytes/mm3; two vessels = 7768 +/- 1860 leukocytes/mm3; three vessels = 8174 +/- 2016 leukocytes/mm3; p < 0.05). The patients who died differed significantly from the survivors as regards total leukocyte count (8309 +/- 2271 against 7548 +/- 1702 cells/mm3; p < 0.05). Multivariate analysis, using a stepwise logistic regression, identified the white blood cell count as the more strong independent predictive variable for Gensini's Score (r = 0.42, p < 0.001). We conclude that, in our experience, increased white blood cell count may contribute to the initiation and progression of the coronary heart disease, and was associated with a shorter subsequent survival time.

Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial.

Fifty-six patients with measurable or evaluable advanced gastric cancer were treated with cisplatin, 100 mg/m2 in continuous infusion of 24 hours, and 5-fluorouracil, 1000 mg/m2/day (by continuous 5-day infusion) every 4 weeks. Three patients were found ineligible for the study. A response rate of 41% (22/53) was obtained (95% confidence interval: 28%-54%), with a median duration of remission of 10.2 months and an overall median survival time of 10.6 months. Leukopenia and thrombocytopenia were mild. Nausea and vomiting were common, and 23.5% of the patients had grade 3 stomatitis. Peripheral neuropathy and renal insufficiency increased with the number of cycles, representing the cumulative dose-limiting toxicity. This study indicates that the combination of cisplatin plus 5-fluorouracil is synergistic or at least has additive antitumor activity. We think that this association of 2 drugs should be considered for further phase III clinical trials.

[Hemoptysis: a prospective study of 108 cases in an emergency service]. / Hemoptisis: estudio prospectivo de 108 casos en un servicio de Urgencias.

A prospective study is performed in 108 patients presenting hemoptysis who were attended in the emergency department. Final diagnosis was achieved in 89 cases (82.4%), being lung infections of tuberculous origin or not, neoplasias, and chronic obstructive lung emphysema the main observed etiologies. A low percentage of severe hemoptysis is found (5.6%). Diagnosis was obtained in 79.6% of patients by clinical history, physical exam, chest x-ray and ORL exam. Only 13.6% of patients who were not diagnosed in the Emergency department were later diagnosed by follow up and performance of complementary tests. Similarly, the lack of an initial etiological diagnosis had no repercussion, by itself, in a worse prognosis. Therefore, it is recommended to perform a single strict evolution control in patients with hemoptysis of unknown origin who present risk factors of lung neoplasia (male sex, age greater than 40 years, smoking greater than 45 packs/year).

[Hypoglycemia: a prospective study in an emergency service]. / Hipoglucemia: estudio prospectivo en un servicio de urgencias.

Hypoglycemia is a frequent clinical situation of particular interest in an emergency department because of its potential gravity and the need for quick and effective treatment. We present a prospective study of 50 patients with hypoglycemia detected in the emergency department. These being 0.17% of all the consultations in this period. The administration of an incorrect doses of insulin was the most frequent cause of hypoglycemia. We observed a good correlation between the BM-test and posterior glycemia. The patients who had initial neurologic symptoms had the lowest levels of glycemia, required more time for recovering and needed more glucose. 20 patients had high levels of glycemia 11.14 mmol/L. This fact was correlated with the amount of glucose administered. The authors suggest 50 g of glucose as the limit for administration, with the possible exception of patients with neurological symptoms.

Percutaneous transluminal coronary angioplasty for coronary stenosis following radiotherapy.

A 50-year-old woman who developed severe angina pectoris 67 months following radiation therapy of the left side of the chest for adenocarcinoma of the left breast is reported. Angiographic studies showed an isolated severe stenosis in the left anterior descending coronary artery. Successful percutaneous transluminal coronary angioplasty was performed.