Once versus twice daily enoxaparin for the initial treatment of acute venous thromboembolism.

Essentials In venous thromboembolism (VTE), it is uncertain if enoxaparin should be given twice or once daily. We compared the 15- and 30-day outcomes in VTE patients on enoxaparin twice vs. once daily. Patients on enoxaparin once daily had fewer major bleeds and deaths than those on twice daily. The rate of VTE recurrences was similar in both subgroups. SUMMARY: Background In patients with acute venous thromboembolism (VTE), it is uncertain whether enoxaparin should be administered twice or once daily. Methods We used the RIETE Registry data to compare the 15- and 30-day rates of VTE recurrence, major bleeding and death between patients receiving enoxaparin twice daily and those receiving it once daily. We used propensity score matching to adjust for confounding variables. Results The study included 4730 patients: 3786 (80%) received enoxaparin twice daily and 944 once daily. During the first 15 days, patients on enoxaparin once daily had a trend towards more VTE recurrences (odds ratio [OR], 1.79; 95% confidence interval [CI], 0.55-5.88), fewer major bleeds (OR, 0.42; 95% CI, 0.17-1.08) and fewer deaths (OR, 0.32; 95% CI, 0.13-0.78) than those on enoxaparin twice daily. At day 30, patients on enoxaparin once daily had more VTE recurrences (OR, 2.5; 95% CI, 1.03-5.88), fewer major bleeds (OR, 0.40; 95% CI, 0.17-0.94) and fewer deaths (OR, 0.58; 95% CI, 0.33-1.00). On propensity analysis, patients on enoxaparin once daily had fewer major bleeds at 15 (hazard ratio [HR], 0.30; 95% CI, 0.10-0.88) and at 30 days (HR, 0.16; 95% CI, 0.04-0.68) and also fewer deaths at 15 (HR, 0.37; 95% CI, 0.14-0.99) and at 30 days (HR, 0.19; 95% CI, 0.07-0.54) than those on enoxaparin twice daily. Conclusions Our findings confirm that enoxaparin prescribed once daily results in fewer major bleeds than enoxaparin twice daily, as suggested in a meta-analysis of controlled clinical trials.

Differences in cardiovascular mortality in smokers, past-smokers and non-smokers: findings from the FRENA registry.

BACKGROUND: The influence of smoking on outcome in patients with coronary artery disease (CAD) is controversial. Even less is known about its influence in patients with cerebrovascular (CVD), or peripheral artery (PAD) disease. PATIENTS AND METHODS: FRENA is an ongoing, observational registry of consecutive outpatients with symptomatic CAD, CVD, or PAD. We reviewed their cardiovascular mortality according to smoking status. RESULTS: As of May 2008, 2501 patients had been enrolled in FRENA. Of these, 439 (18%) were current smokers, 1086 (43%) past-smokers, 976 (39%) had never smoked. Current- and past-smokers were 10 years younger, more often males, and more likely to have chronic lung disease, but had diabetes, hypertension, heart failure, or renal insufficiency less often than non-smokers. Over a mean follow-up of 14 months, 123 patients died (cardiovascular death, 68). On univariate analysis, current smokers had a significantly lower rate of cardiovascular death: 1.1 (95% CI: 0.4-2.4) per 100 patient-years in current smokers; 1.9 (95% CI: 1.2-2.8) in past-smokers; 3.5 (95% CI: 2.5-4.7) in non-smokers, with no differences between patients with CAD, CVD or PAD. Mean age at cardiovascular death was 82+/-6.4; 70+/-9.9 and 67+/-15 years, respectively. On multivariate analysis, smoking status was not independently associated with a lower risk for cardiovascular death. CONCLUSIONS: Current and past-smokers with CAD, CVD or PAD had a less than half cardiovascular mortality than those who never smoked, but this may be explained by the confounding effect of additional variables. They died over 10 years younger than non-smokers.

Prognostic factors in the diagnostic work-up of cancer patients in an internal medicine department: does age matter?

INTRODUCTION: Increasing life expectancy in the general population has led to a rise in the incidence of cancer and new challenges with regard to the diagnosis, therapy and prognosis of this disease. AIM: To assess prognostic factors in the initial work-up of patients ultimately diagnosed with cancer in an Internal Medicine Service, particularly those related with age. PATIENTS AND METHODS: A prospective study was undertaken with 224 patients ultimately diagnosed with cancer, as confirmed by histological or cytological study. The neoplasms included respiratory, gastrointestinal, genitourinary, metastatic adenocarcinoma of unknown origin, gynaecological, hepatobiliary and others. Before reaching the diagnosis, the following factors were investigated in all patients: functional status [Karnofsky Performance Status (KPS)], comorbidity (Charlson scale), body mass index (BMI), serum cholesterol and albumin concentrations, cognitive level (Mini-mental test), quality of life (Short Form 36 questionnaire), and extension of the disease according to established criteria. Survival at 1 year was analysed. Statistical analyses were done with spss 11.0 for Windows, using a forward stepwise (likelihood ratio) method to construct the model and a Cox multivariate model for the survival analysis. RESULTS: A total of 224 patients, 167 men (74.5%) and 57 women (25.5%), with a mean age of 66.1 +/- 12.3 years were studied. KPS was >or= 70 in 84% and comorbidity was zero or one in 74%. BMI was 24.25 +/- 4.3, cholesterol 180.7 +/- 4.3, albumin 3.32 +/- 0.5 and Mini-mental score 25.4 +/- 3.7. Metastasis was seen in 131 patients (58.5%) and local disease in 93 cases (41.5%). One-year survival was 38.8% (87 patients) with a mean of 203.8 +/- 143 days. In the Cox analysis, the independent predictive factors for survival were KPS [hazard ratio (HR) = 0.951; 95% CI = 0.930-0.974; p < 0.01], metastatic dissemination (HR = 2.422; 95% CI = 1.643-3.571; p < 0.01), physical quality of life (HR = 0.978; 95% CI = 0.962-0.995; p < 0.01) and albumin (HR = 0.653; 95% CI = 0.455-0.936; p < 0.01). CONCLUSIONS: In the initial work-up of patients ultimately diagnosed with cancer in an Internal Medicine Service, functional status, dissemination, the physical component in the quality of life scale and serum albumin levels were independent prognostic factors for survival. Age was not an independent prognostic factor and should not be used as a basis for adopting diagnostic or therapeutic decisions in these patients.

Mioclonías en el curso de una meningitis tuberculosa / Tuberculous meningitis and myoclonis

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Diagnostic accuracy of pleural fluid polymorphonuclear elastase in the differentiation between pyogenic bacterial infectious and non-infectious pleural effusions.

BACKGROUND AND OBJECTIVES: To establish the diagnostic accuracy of the markers of neutrophil activity (elastase and lysozyme) determined in pleural fluid, for differentiating between pyogenic bacterial infectious and non-infectious pleural effusions. PATIENTS AND METHODS: At our tertiary referral teaching hospital, 160 patients over 14 years with pleural effusion (PE), classified as pyogenic bacterial infectious (41 parapneumonic complicated, 32 parapneumonic non-complicated) and non-infectious (32 neoplasm and 55 undiagnosed pleural exudates) were examined in a prospective study. Polymorphonuclear elastase (PMN-E) was determined by an immunoactivation method and lysozyme by a turbidimetric method. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. RESULTS: Pleural fluid PMN-E was the biochemical marker that best differentiated between pyogenic bacterial infectious and non-infectious PE. The ROC area under the curve (AUC) for PMN-E was 0.8276. A PMN-E value over 230 microg/l diagnosed infectious PE with a specificity of 0.81 and a sensitivity of 0.74. The ROC AUC for proteins plus lactate dehydrogenase was 0. 7430. Differences between the two ROC curves were significant (p = 0. 032). After excluding purulent parapneumonic complicated PE, the sensitivity of a pleural fluid PMN-E value equal to or greater than 230 microg/l was 0.64 and the specificity 0.81. CONCLUSIONS: Pleural fluid PMN-E was the marker that best differentiated infectious from non-infectious PE, and PMN-E values lower than 230 microg/l suggest non-infectious PE.

Prospective clinical and microbiological study of pleural effusions.

A prospective clinical microbiological study of pleural fluid samples was conducted to investigate the etiology of pleural effusions and to evaluate two different methods for transport and culture of these samples. A total of 245 pleural fluid specimens were inoculated into a transport vial, an aerobic and an anaerobic blood culture vial, and a sterile tube. One hundred nine samples were from infectious patients and 128 from noninfectious patients. Gram stain had a sensitivity of 48% and a specificity of 100% as compared to culture. Of the total, 15.5% of the samples were positive for microorganisms, and 60% of the positive samples were nonpurulent pleural fluid. Single-organism growth was found in 23 samples (60.5%). Sixty-three microorganisms were isolated: 25 (39.7%) aerobic, 22 (35%) anaerobic, 13 (20.6%) mycobacteria, and three (4.7%) fungi. Of the 25 positive samples, excluding those samples that grew mycobacteria, nine (36%) were positive exclusively in the blood culture vials. Twelve organisms were isolated, only one of which did not grow in the anaerobic vial. Two (8%) samples were positive by conventional culture only, and 14 (56%) were positive by both methods. The microorganism isolation rate obtained with use of blood culture vials was significantly greater than that obtained with the conventional method of transport and culture. Sixty-three percent of the empyema patients had an associated underlying pathology, pneumonia being the most frequent. In conclusion, for microbiological study of pleural fluid, it seems appropriate to inoculate all samples, including nonpurulent samples, into both a sterile tube and an anaerobic blood culture vial.

Interleukin-8 and markers of neutrophil degranulation in pleural effusions.

In order to know the degree of interleukin-8 (IL-8) production in the pleural space and its relationship to neutrophil activation, IL-8, neutrophil elastase (NE), and myeloperoxidase (MPO) were assessed in blood and pleural fluid (PF) of 219 patients with pleural effusions. Correlations between blood and PF IL-8, NE, and MPO were either absent or weak, except for IL-8 in transudates (r = 0.6745, p < 0.001). PF IL-8, NE, and MPO concentrations in cases of empyema were higher than in cases of effusion of other causes (p < 0.001). No significant differences in inflammatory markers were observed between parapneumonic and tuberculous fluids. IL-8, NE, and MPO levels in malignant, nonspecific, and transudative effusions were lower than in those due to infection, the lowest levels corresponding to transudates. No significant correlation was observed between PF IL-8 and neutrophil count in any group; in contrast, IL-8 was associated with NE and MPO in empyema (r = 0.7545, and r = 0.7283; p < 0.001), tuberculosis (r = 0.4016, p = 0.008 and r = 0.6545, p < 0.001), and nonspecific effusions (r = 0.3748, p = 0.007 and r = 0.3085, p = 0.028). Our results indicate that local production of markers of the nonspecific inflammatory response is high in both chronic and acute pleural infection, and suggest a role for IL-8 in the release of NE and MPO.

[Study of 86 cases of Mediterranean boutonneuse fever hospitalized at a university hospital]. / Estudio de 86 casos de fiebre botonosa mediterránea que ingresaron en un hospital universitario.

OBJECTIVES: To study the clinical manifestations of 86 patients with Mediterranean Boutonneuse Fever who were admitted in a University General Hospital. PATIENTS AND METHODS: Between 1986 and 1994 we studied retrospectively the clinical manifestations, evolution and complications of 86 patients with Mediterranean Boutonneuse Fever. Diagnosis was based on clinical and serological findings. RESULTS: We studied a total of 86 patients (64 males; 22 females) with a mean age of 55 years. 88% of cases were diagnosed between June and September, and 89% of them had contact with dogs. 53% of patients had an underlying disease. All patients presented with fever and a generalized erythematous rash. 60% of patients had a initial lesion (tache noire) especially in legs. All patients were treated with doxicycline during one week. 22% of patients had complications such as renal failure, respiratory failure, gastrointestinal bleeding and stroke. Old patients and those with underlying disease had severe complications with a higher significant frequency. No patients died. CONCLUSIONS: 22% of patients with Mediterranean Boutonneuse Fever, especially those with advanced age or underlying disease, who were admitted in the Hospital had severe complications.

Determination of D-lactate by enzymatic methods in biological fluids: study of interferences.

Analysis of nondeproteinized samples with an enzymatic method to determine D-lactate indicated interferences. The presence of L-lactate dehydrogenase (LD) and L-lactate in the sample led to underestimation of D-lactate content when a sample blank was processed and overestimation when it was omitted. We proved that this interference is not due to lack of D-LD stereospecificity. Moreover, assessment of D-LD and L-LD KM for NAD+ allowed us to rule out the different affinities for this coenzyme as a cause of the interference. Our results underline the importance of deproteinizing samples for D-lactate analysis when enzymatic methods are used. The ultrafiltration procedure we propose is convenient and shows acceptable mean recovery (108%) and good imprecision (within-run CV = 4.2% and 3.0% for D-lactate at 31 and 107 mumol/L, respectively; between-run CVs were 7.3% at 49 mumol/L D-lactate and 3.1% at 115 mumol/L D-lactate).

[Cutaneous vasculitis during primary myelofibrosis]. / Vasculitis cutánea en el curso de una mielofibrosis primaria.

A leukocytoclastic cutaneous vasculitis in the course of an idiopathic myelofibrosis is reported. The cutaneous lesions that might appear in this hematological disease are discussed, including cutaneous infections, myeloid metaplasia and cutaneous infiltration due to the myeloproliferative process. We point out the rarity of cutaneous vasculitis during the course of primary myelofibrosis.

[Esophageal candidiasis in patients without cellular immunity changes. Report of 7 cases]. / Candidiasis esofágica en pacientes sin alteraciones en la inmunidad celular. A propósito de siete casos.

OBJECTIVE: To study the clinical and immunological features of esophageal candidiasis in patients with no changes in cellular immunity. PATIENTS AND METHODS: Seven patients with the endoscopic diagnosis of esophageal candidiasis were studied and in no patient were changes in cellular immunity detected. An investigation was carried out of the presence of antibodies to the human immunodeficiency virus antigen, lymphocyte populations, complement, and immunoglobulins. RESULTS: Seven male patients with a mean age of 57 years (range: 43-67 years) and no underlying diseases were studied. The symptom at presentation in all cases was dysphagia and odynophagia of several days; two patients had also retro-sternal pain and one of them upper digestive hemorrhage. The digestive endoscopy showed white confluent patches highly suggestive of esophageal candidiasis. Therapy with intravenous fluconazole was started and both the clinical course and endoscopic lesions had a favorable outcome. Antibodies and antigen of human immunodeficiency virus were negative. Lymphocyte populations, complement, and immunoglobulins were normal in all patients but one, in whom a severe IgG hypogammaglobulinemia was detected. COMMENT: Esophageal candidiasis, though rare, is an entity to be considered in immunocompetent patients or with no changes in cellular immunity.

[Severe weight loss at the beginning of mesenteric panniculitis]. / Severa pérdida de peso en el debut de una paniculitis mesentérica.

We report a case of mesenteric panniculitis that presented with a severe lost of weight. We stress the difficulty that entails the diagnosis of this unusual entity, and also the excellent response to corticoid therapy in our patient. The clinical, pathological and therapeutic features of mesenteric panniculitis are reviewed.

[Neurologic manifestations of varicella herpes zoster infection]. / Manifestaciones neurológicas en la infección por el virus de la varicela herpes zoster.

BACKGROUND: The aim of the present study was to analyze the clinical characteristics and fluid alterations in neurologic infection by varicella herpes zoster virus in hospitalized patients. METHODS: A retrospective study of the cases with neurologic involvement by the varicella herpes zoster virus in patients admitted in the authors' hospital from March 1991 to March 1993 was carried out. RESULTS: Our of the 14 patients studied with neurologic involvement by the varicella herpes zoster virus, 10 were males (71%) with a mean age of 38 years (range: 13-83 years). Only 4 patients (28%) presented a base disease (diabetes mellitus in 2 cases and HIV infection in another 2). In 10 cases (71%) the appearance of cutaneous lesions was prior to neurologic manifestations (between 1 and 30 days before neurologic clinical manifestations). All the patients presented hyperthermia at some time. The most common symptoms were: headache, vomiting, confusion and/or neck stiffness, with meningitis, encephalitis and neurologic foci and mixed pictures. In 4 cases (28%) the cephalorhachidian fluid did not present analytical changes suggestive of viral meningitis. All the patients underwent i.v. acyclovir treatment at a dosis of 10-15 mg/kg/8 h with good evolution, with no deaths being observed. In 3 out of the 6 cases presenting neurologic foci the evolution was slow with sequelae following treatment completion. CONCLUSIONS: Neurologic involvement by the varicella herpes zoster virus does not clinically defer from other neutrotropic virus. Fluid alterations were compatible with benign lymphocytary meningitis although some cases of encephalitis showed normal LCR. Taking into account that none of the patients herein reported died and considering the mortality associated with meningitis or encephalitis by varicella herpes zoster referred in the literature in untreated patients, the authors believe that the use of acyclovir is obligatory in these cases.