Alfons López-Soto

Association between strong inflammatory response and low risk of developing visual loss and other cranial ischemic complications in giant cell (temporal) arteritis

OBJECTIVE To identify clinical and biochemical parameters that have good predictive value for identifying giant cell (temporal) arteritis (GCA) patients who are at high or low risk of developing cranial ischemic events. METHODS In this multicenter study, records of patients at 3 university hospitals in Barcelona were reviewed retrospectively. Two hundred consecutive patients with biopsy-proven GCA were studied. RESULTS Thirty-two patients developed irreversible cranial ischemic complications. The duration of clinical symptoms before diagnosis was similar in patients with and those without ischemic events. Patients with ischemic complications less frequently had fever (18.8% versus 56.9%) and weight loss (21.9% versus 62%) and more frequently had amaurosis fugax (32.3% versus 6%) and transient diplopia (15.6% versus 3.6%). Patients with ischemic events had lower erythrocyte sedimentation rates (ESR) (82.7 mm/hour versus 104.4 mm/hour) and higher concentrations of hemoglobin (12.2 gm/dl versus 10.9 gm/dl) and albumin (37.4 gm/liter versus 32.7 gm/liter). Clinical inflammatory status and biologic inflammatory status were defined empirically (clinical: fever and weight loss; biologic: ESR > or =85 mm/hour and hemoglobin < 11.0 gm/dl). Patients not showing a clinical and biologic inflammatory response were at high risk of developing ischemic events (odds ratio [OR] 5, 95% confidence interval [95% CI] 2.05-12.2). The risk was greatly reduced among patients with either a clinical (OR 0.177, 95% CI 0.052-0.605) or a biologic (OR 0.226, 95% CI 0.076-0.675) inflammatory reaction. No patient with both a clinical and a biologic response developed ischemic events. CONCLUSION The presence of a strong acute-phase response defines a subgroup of patients at very low risk of developing cranial ischemic complications. Our findings provide a rationale for testing less aggressive treatment schedules in these individuals. Conversely, a low inflammatory response and the presence of transient cranial ischemic events provide a high risk of developing irreversible ischemic complications and require a prompt therapeutic intervention.

Vascular involvement in Behçet’s disease: relation with thrombophilic factors, coagulation activation, and thrombomodulin

PURPOSE Thrombosis, usually venous, occurs in 10% to 25% of patients with Behçets disease, but its pathogenesis is poorly understood. We evaluated parameters of hemostasis and their relation with thrombosis in a series of patients with Behçets disease. SUBJECTS AND METHODS We studied 38 patients with Behçets disease (13 with venous thrombosis), 38 patients with venous thrombosis without thrombophilia, and 100 control subjects. Levels or presence of protein C, protein S, antithrombin, methylenetetrahydrofolate reductase C677T, factor V Leiden, prothrombin gene G20210A, antiphospholipid antibodies, plasminogen, tissue-type plasminogen activator (tPA), type-1 tPA inhibitor (PAI-1), PAI-1 4G/5G polymorphism, prothrombin fragment 1+2, plasmin/alpha(2)-antiplasmin complexes, thrombomodulin, and activated factors VII and XII were determined. RESULTS There were no deficiencies in protein C, protein S, antithrombin, or factor V Leiden in the patients with Behçets disease, nor was there evidence of most other thrombotic abnormalities. Compared with control subjects, however, the Behçets disease group had elevated mean (+/- SD) levels of prothrombin fragment 1+2 (2091 +/- 1323 pmol/L vs. 804 +/- 398 pmol/L, P <0.001), plasmin/alpha2-antiplasmin complexes (410 +/- 220 microg/L vs. 214 +/- 92 microg/L, P <0.001), and thrombomodulin (37 +/- 24 ng/mL vs. 27 +/- 10 ng/mL, P <0.001). These levels did not differ between patients with or without thrombosis. CONCLUSIONS Thrombophilic factors do not seem to explain most thromboses in Behçets disease. There is increased thrombin generation, fibrinolysis, and thrombomodulin in Behçets disease, but these abnormalities are not related to thrombosis.

Treatment of Polymyalgia Rheumatica: A Systematic Review

BACKGROUND Polymyalgia rheumatica (PMR) treatment is based on low-dose glucocorticoids. Glucocorticoid-sparing agents have also been tested. Our objective was to systematically examine the peer-reviewed literature on PMR therapy, particularly the optimal glucocorticoid type, starting doses, and subsequent reduction regimens as well as glucocorticoid-sparing medications. METHODS We searched Cochrane Databases and MEDLINE (1957 through December 2008) for English-language articles on PMR treatment (randomized trials, prospective cohorts, case-control trials, and case series) that included 20 or more patients. All data on study design, PMR definition criteria, medical therapy, and disease outcomes were collected using a standardized protocol. RESULTS Thirty studies (13 randomized trials and 17 observational studies) were analyzed. No meta-analyses or systematic reviews were found. The PMR definition criteria, treatment protocols, and outcome measures differed widely among the trials. Starting prednisone doses higher than 10 mg/d were associated with fewer relapses and shorter therapy than were lower doses; starting prednisone doses of 15 mg/d or lower were associated with lower cumulative glucocorticoid doses than were higher starting prednisone doses; and starting prednisone doses higher than 15 mg/d were associated with more glucocorticoid-related adverse effects. Slow prednisone dose tapering (<1 mg/mo) was associated with fewer relapses and more frequent glucocorticoid treatment cessation than faster tapering regimens. Initial addition of oral or intramuscular methotrexate provided efficacy at doses of 10 mg/wk or higher. Infliximab was ineffective as initial cotreatment. CONCLUSIONS The scarcity of randomized trials and the high level of heterogeneity of studies on PMR therapy do not allow firm conclusions to be drawn. However, PMR remission seems to be achieved with prednisone treatment at a dose of 15 mg/d in most patients, and reductions below 10 mg/d should preferably follow a tapering rate of less than 1 mg/mo. Methotrexate seems to exert glucocorticoid-sparing properties.

Mortality and Morbidity in Nonagenarian Patients following Hip Fracture Surgery

Background: The number of people living more than 90 years is increasing, and this population shows a high incidence of hip fractures. Objective: To study prospectively the mortality and morbidity following hip fracture surgery in nonagenarian patients. Methods and Subjects: 106 nonagenarian patients were admitted for femoral neck fracture and treated surgically in the traumatology and geriatric departments of two university hospitals. All patients received comprehensive geriatric assessment. 75 patients were followed up after a 3-month control period. Mortality and functional status were assessed using the Barthel index (BI) and mobility, dependency on walking aids, residential status, and degree of residual pain were the items assessed for morbidity. Results: In-hospital mortality was 10%; the 3-month accumulate mortality was 20%. The mean BI of the 75 patients who survived was 53 showing a persistent decrease compared with their BI previous to the hip fracture (79; p < 0.003). The decline in BI after 3 months persisted in 91% of patients. Before injury, 11% patients were housebound, while 45% were housebound 3 months later. 54% were independent before the fracture occurred, and only 16% 3 months later. Only 12% of patients who survived were unable to return to their pre-admission dwelling. Conclusions: Findings of low perioperative mortality and acceptable morbidity support the view that surgery followed by rehabilitation is indicated in selected nonagenarian patients.

Dying in hospital of terminal heart failure or severe dementia: the circumstances associated with death and the opinions of caregivers

Background: Improving the care provided to elderly patients affected by end-stage chronic diseases dying in acute hospitals is a health priority. We evaluated the circumstances related to death in end-stage non-cancer patients dying in two acute care hospitals, and their caregiver’s opinions about the death. Methods: Some 102 patients, over 64 years of age, with end-stage dementia (37%) or congestive heart failure (64%), were included in the study. Caregiver’s opinions on the circumstances of death were obtained using a questionnaire. In addition, we collected data regarding written instructions on several items, including do not resuscitate (DNR) orders, decisions about care in terms of the level or intensity of interventions, information provided to relatives about the prognosis, total withdrawal of normal drug therapy, and provision of palliative care. Results: Caregivers stated that the clinical information was accurate in 67.6% of cases, and the control of symptoms was good in 55%. However, the perception of pain persisted in 14% and uncontrolled dyspnoea in 45%. The end-of-life care was assessed as: excellent 30.5%, good 36%, fairly good 25.5%, bad 6%, and very bad 2%. DNR orders were specified in 89% of patients, decisions concerning the intensity of care in 64%, and 80% of relatives were aware of the prognosis. Drug therapy was withdrawn in 64% of cases, and terminal palliative care was initiated in 79.5%. Conclusion: Our results suggest that some aspects of the palliative care provided to elderly patients with end-stage chronic diseases, admitted to acute care hospitals, could be improved. Such aspects include the clinical information provided and the successful control of specific symptoms.

Aspiration pneumonia in old patients with dementia. Prognostic factors of mortality.

BACKGROUND Prognostic factors of mortality in elderly patients with dementia with aspiration pneumonia (AP) are scarcely known. We determined the mortality rate and prognostic factors in old patients with dementia hospitalized due to AP. METHODS We prospectively studied 120 consecutive patients aged ≥ 75 years with dementia admitted with AP to two tertiary university hospitals. We collected data on demographic and clinical variables and comorbidities. Oropharyngeal swallowing was assessed by the water swallow test. RESULTS Sixty-one (50.8%) patients were female, and mean age was 86 ± 9 years. The swallow test was performed in 68 patients, revealing aspiration in 92.6%. Patients with repeat AP (28.3%) were more-frequently taking thickeners (61.8% vs.11.6%, p<0.0001) and were less-frequently prescribed angiotensin-converting-enzyme (ACE) inhibitors (8.8% vs. 27.9%, p<0.001) than patients with a first episode. Hospital mortality was 33.3%; these patients had lower lymphocyte counts and higher percentage of multilobar involvement. In the multivariate model, involvement of ≥ 2 pulmonary lobes was associated with hospital mortality (OR 3.051, 95% CI 1.248 to 7.458, p<0.01). Six-month mortality was 50.8%; these patients were older and had worse functional capacity and laboratory data indicative of malnutrition. In the multivariate model, lower albumin levels were associated with six-month mortality (OR 1.129, 95% CI 1.008 to 1.265, p<0.03). CONCLUSION In-hospital and 6-month mortality were high (one-third and one-half patients, respectively). Multilobar involvement and lower lymphocyte counts were associated with hospital mortality, and older age, greater dependence and malnutrition with six-month mortality.

Hospital Deaths of People Aged 90 and Over: End-of-Life Palliative Care Management

Background: In developed countries, hospital deaths at very advanced age are increasingly common.Few studies have addressed end-of-life care in very elderly patients with non-cancer chronic diseases. Objective: To evaluate the circumstances related to end-stage death of non-cancer nonagenarians in an acute care hospital. The results were compared with those from a sample of younger patients. Methods: We conducted a prospective assessment in two teaching hospitals of the written instructions for the following actions: do not resuscitate (DNR) orders, the graduation of therapeutic decisions, information provided to relatives about prognosis, total withdrawal of normal drug therapy and provision of palliative care. Results: 80 patients over 89 years of age with end-stage congestive heart failure (57.5%) or dementia (42.5%) were included. The control group comprised 52 younger patients (65–74 years). DNR orders were specified in 56% of cases, graduation of therapeutic decisions in 35%, and knowledge of relatives regarding the prognosis in 61%. Drug therapy was withdrawn in 66% of cases and terminal palliative care was initiated in 69%. In the nonagenarians who died, we detected a predominance of females (p = 0.001), a higher percentage of DNR orders (p = 0.02) and a higher percentage of graduation of therapeutic measures (p = 0.02) in comparison with younger patients. Conclusion: Our results indicate that there are marked differences according the palliative care provided to oldest-old patients with end-stage non-cancer chronic diseases admitted to an acute care hospital. In any case, care should be improved for both age groups.

Connecting Cerebral White Matter Lesions and Hypertensive Target Organ Damage

Chronic hypertension leads to concomitant remodeling of the cardiac and vascular systems and various organs, especially the brain, kidney, and retina. The brain is an early target of organ damage due to high blood pressure, which is the major modifiable risk factor for stroke and small vessel disease. Stroke is the second leading cause of death and the number one cause of disability worldwide and over 80% of strokes occur in the elderly. Preclinical hypertensive lesions in most target organs are clearly identified: left ventricular hypertrophy for the heart, microalbuminuria for the kidney, fundus abnormalities for the eye, and intima-media thickness and pulse wave velocity for the vessels. However, early hypertensive brain damage is not fully studied due to difficulties in access and the expense of techniques. After age, hypertension is the most-important risk factor for cerebral white matter lesions, which are an important prognostic factor for stroke, cognitive impairment, dementia, and death. Studies have shown an association between white matter lesions and a number of extracranial systems affected by high BP and also suggest that correct antihypertensive treatment could slow white matter lesions progression. There is strong evidence that cerebral white matter lesions in hypertensive patients should be considered a silent early marker of brain damage.

ANTIBODIES TO THROMBOPLASTIN IN SYSTEMIC LUPUS ERYTHEMATOSUS: ISOTYPE DISTRIBUTION AND CLINICAL SIGNIFICANCE IN A SERIES OF 92 PATIENTS

We determined the prevalence and relationship with clinical manifestations of antibodies to thromboplastin (aTP) in 92 patients with systemic lupus erythematosus (SLE). Thirty-two (35%) patients had aTP: 13 (14%) were positive for IgG aTP, 13 (14%) for IgM aTP, and 6 (7%) for both. Patients with aTP had an increased incidence of thrombosis (p = 0.01), thrombocytopenia (p < 0.001), hemolytic anemia (p < 0.001), and fetal losses (p = 0.03). When the IgG and IgM aTP isotypes were analysed separately, the IgG aTP were found to be associated with thrombosis (p < 0.001), thrombocytopenia (p < 0.001), and fetal losses (p = 0.02). The IgM aTP were associated with hemolytic anemia (p < 0.001). A correlation was found between the titers of aTP and those of anticardiolipin antibodies, in both IgG (p < 0.01, r = 0.6) and IgM (p < 0.01, r = 0.64) isotypes, and between the titers of IgG aTP and the diluted Russells viper venom time used to detect the lupus anticoagulant (p < 0.001, r = 0.42). This test is a reliable, reproducible and sensitive assay for the detection of antiphospholipid antibodies, specially in those patients under anticoagulant therapy.

Lack of relationship between human immunodeficiency virus infection and systemic lupus erythematosus

The objective of this work was to determine whether HIV-1 and HIV-2 could be involved in the pathogenesis of systemic lupus erythematosus (SLE). Seventy-five consecutive Caucasian patients with SLE presenting at one institution over a 2-year period were studied. Serum samples were surveyed for anti-HIV-1 antibodies by a commercial ELISA coated with HIV-1-p24. For confirmation, conventional immunoblots were performed with the following antigens: HIV-1-gp41, p31, p24 and p17 (recombinant) and HIV-2-gp36 (synthetic peptide). Additionally, Western blots with HIV-1-gp160, gp120, gp41, p65, p51, p24 and p18 bands were applied. Seventeen (23%) patients exhibited reactivity with HIV-1-p24 in the ELISA, but in the immunoblots and Western blots these sera samples were negative. Patients with SLE may exhibit a reactivity with HIV-1-p24 in the ELISA for HIV infection screening but not in the confirmatory blots. This false-positive reactivity is probably due to molecular mimicry between autoantigens and retroviruses or a contaminant or artefacts in the antigen preparation procedure.