[News on venous thromboembolic disease]. / Novedades en la enfermedad tromboembólica venosa.

This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery.

[Leptomeningeal dissemination in an intestinal-type sinonasal adenocarcinoma: an uncommon presentation]. / Diseminación leptomeníngea en un carcinoma nasosinusal de tipo intestinal: una forma de presentación inusual.

We present the case of a patient with a 30-year history of exposure to sawdust who was diagnosed with mucinous intestinal-type sinonasal adenocarcinoma after histological examination. The patient presented with neurological symptoms; moreover, intra- and extra-cranial leptomeningeal involvement, which is exceedingly rare in this type of tumors, was observed at the time of diagnosis.

Globular glial tauopathy caused by MAPT P301T mutation: clinical and neuropathological findings.

OBJECTIVE: To describe the clinical, biochemical, and neuropathological findings of an autosomal dominant globular glial tauopathy caused by the P301T mutation at the MAPT gene. METHODS: Five patients from two unrelated pedigrees underwent clinical evaluation. Genetic analysis, brain pathological examination, and biochemical analysis of tau were performed. RESULTS: The patients studied were 3 men and 2 women with a mean age at onset of 52.2 years and mean disease duration of 5.2 years. Three patients presented a corticobasal syndrome, one patient an asymmetric pyramidal syndrome compatible with primary lateral sclerosis, and one patient a frontotemporal dementia. In both pedigrees (4 patients) Sanger sequencing showed the p.P301T mutation in exon 10 of the MAPT gene. Neuropathological findings consisted of atrophy of frontal and temporal lobes with marked spongiosis and astrogliosis, and abundant phosphorylated tau protein deposits in the frontal and temporal cortex, limbic area, basal ganglia, and brain stem. The most striking finding was the presence of oligodendroglial 4R phospho-tau globular positive inclusions in the white matter and cortex. Globose-type neurofibrillary neuronal tangles, and in particular astrocytic globular inclusions and coarse tufts, were present in the grey matter. Biochemical analysis of sarkosyl-insoluble fractions revealed two tau bands of 64 and 68 kDa and case-dependent bands of lower molecular weight. CONCLUSION: This is the first pathological and biochemical study of the MAPT p.P301T mutation showing variable clinical manifestation and neuropathological phenotype of globular glial tauopathy not only among different families but also within families.

Prevalence and concordance between the clinical and the post-mortem diagnosis of dementia in a psychogeriatric clinic. / Prevalencia y concordancia entre diagnóstico clínico y anatomopatológico de demencia en una clínica psicogeriátrica.

INTRODUCTION: The aim of our study is to describe the types of dementia found in a series of patients and to estimate the level of agreement between the clinical diagnosis and post-mortem diagnosis. MATERIAL AND METHODS: We conducted a descriptive analysis of the prevalence of the types of dementia found in our series and we established the level of concordance between the clinical and the post-mortem diagnoses. The diagnosis was made based on current diagnostic criteria. RESULTS: 114 cases were included. The most common clinical diagnoses both at a clinical and autopsy level were Alzheimer disease and mixed dementia but the prevalence was quite different. While at a clinical level, prevalence was 39% for Alzheimer disease and 18% for mixed dementia, in the autopsy level, prevalence was 22% and 34%, respectively. The agreement between the clinical and the autopsy diagnoses was 62% (95% CI 53-72%). CONCLUSIONS: Almost a third of our patients were not correctly diagnosed in vivo. The most common mistake was the underdiagnosis of cerebrovascular pathology.

The influence of extreme body weight on clinical outcome of patients with venous thromboembolism: findings from a prospective registry (RIETE).

BACKGROUND: Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in either underweight or obese patients with venous thromboembolism (VTE) are limited. Thus, recommendations based on evidence from clinical trials might not be suitable for patients with extreme body weight. PATIENTS AND METHODS: Patients with objectively confirmed, symptomatic acute VTE are consecutively enrolled into the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. For this analysis, data from patients in the following ranges of body weight were examined: <50, 50-100, and >100 kg. Patient characteristics, underlying conditions, treatment schedules and clinical outcomes during the first 15 days of treatment were compared. RESULTS: As of August 2004, 8845 patients with acute VTE were enrolled from 94 participating centers. Of these, 169 (1.9%) weighed <50 kg, 8382 (95%) weighed 50-100 kg and 294 (3.3%) weighed >100 kg. Patients weighing <50 kg were more commonly females, were taking non-steriodal antiinflammatory drugs (NSAIDs), and had severe underlying diseases more often than patients weighing 50-100 kg. Their incidence of overall bleeding complications was significantly higher than in patients weighing 50-100 kg (odds ratio 2.2; 95% CI: 1.2-4.0). Patients weighing >100 kg were younger, most commonly males, and had cancer less often than those weighing 50-100 kg. Incidences of recurrent VTE, fatal pulmonary embolism or major bleeding complications were similar in both groups. CONCLUSIONS: Patients with VTE weighing <50 kg have a significantly higher rate of bleeding complications. The clinical outcome of patients weighing over 100 kg was not significantly different from that in patients weighing 50-100 kg.

Impact of initial FDG PET/CT in the management plan of patients with locally advanced head and neck cancer.

OBJECTIVE: To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). MATERIALS AND METHODS: We retrospectively reviewed the records of 72 consecutive patients (2007-2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. RESULTS: FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. CONCLUSIONS: Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.

Peripheral neuropathy in essential mixed cryoglobulinemia.

Sixteen patients with essential mixed cryoglobulinemia were studied and followed up clinically and electrophysiologically for 4.2 years. Peripheral neuropathy was diagnosed in seven cases. Five of these patients had distal symmetrical sensorimotor polyneuropathy. Nerve conduction velocities were normal and therefore indicative of pure axonal neuropathy. Sural nerve biopsy showed moderate loss of myelinated axons in two patients and severe loss in one. This patient also had necrotizing arteritis. The remaining two had both clinical and electrophysiologic signs of overlapping mononeuritis multiplex with severe denervation in the territory of the involved nerves, but normal conduction velocities. Sural nerve biopsy in one of these two patients showed marked loss of myelinated fibers and signs of vasculitis. Two types of neuropathy were noted: (1) a mild distal neuropathy with relatively minor neurologic deficit, probably due to vasa nervorum microcirculation occlusion caused by intravascular deposits of cryoglobulins and (2) a severe distal symmetrical sensorimotor neuropathy or overlapping mononeuritis multiplex, associated with necrotizing vasculitis.

Efficacy and safety of oral and early-switch therapy for community-acquired pneumonia: a randomized controlled trial.

PURPOSE: We sought to determine the safety, efficacy, and cost of oral therapy for patients with community-acquired pneumonia. In patients with nonsevere pneumonia, conventional (parenteral) treatment was compared with the oral route; in patients with severe pneumonia, conventional treatment was compared with early switch from parenteral to oral therapy. SUBJECTS AND METHODS: We randomly assigned 85 hospitalized patients with nonsevere pneumonia to one of two groups: 41 received oral antimicrobials from admission, and 44 received parenteral antimicrobials until they had been afebrile for 72 hours before switching to oral treatment. We randomly assigned 103 patients with severe pneumonia who had initially been treated with parenteral antimicrobials to one of two groups: 48 were switched to oral therapy after 48 hours of treatment (early switch), and 55 received a full 10-day course of parenteral antibiotics. RESULTS: Among patients with nonsevere pneumonia, there were no deaths in the oral treatment group, and one death (2%) in the parenteral treatment group (95% confidence interval [CI] for between-group [oral minus parenteral] difference: -7% to 2%, P = 0.3). The time to resolution of morbidity was < or =5 days in 34 (83%) patients in the oral treatment group and 39 (88%) patients in the parenteral treatment group (P = 0.5); there were treatment failures in 4 (10%) patients in the oral treatment group and 14 (32%) patients in the parenteral treatment group (P = 0.02). Among patients with severe pneumonia, there was one (2%) death in the early-switch group and no deaths in the full course of parenteral antibiotics groups (95% CI for between-group [early switch vs. full course] difference: -2% to 6%, P = 0.5). The time to resolution of morbidity was < or =5 days in 38 (79%) patients in the early-switch group and 41 (75%) in the full-course group (P = 0.3). There were 12 (25%) treatment failures in the early-switch group and 13 (24%) in the full-course group (P = 0.9). There were fewer adverse events in the oral and early-switch groups, primarily due to lower rates of infusion-related phlebitis. Significant cost savings, mainly due to a shorter hospitalization, occurred among patients with severe pneumonia in the early-switch group. CONCLUSION: Inpatients with nonsevere community-acquired pneumonia can be effectively and safely treated with oral antimicrobials from the time of admission, whereas those with severe pneumonia can be treated with early-switch therapy.

Muscle biopsy findings in systemic capillary leak syndrome.

Two patients with systemic capillary leak syndrome (SCLS) were followed up clinically for 5 and 2 years, respectively. Muscle biopsy was performed 1 week after the end of an acute crisis in one patient, and after 3 years in the other. In both cases, muscle capillary basement membranes were extremely thick--more than 15 times thicker than normal. Capillary basement membrane enlargement appears to be a permanent lesion, probably limited to muscle vessels. This finding has not been previously reported in SCLS, and would appear to indicate a relationship with the pathogenesis and severity of the crisis.

Successful treatment of peripheral neuropathy with chemotherapy in osteosclerotic myeloma.

A patient with a severe polyneuropathy in association with osteosclerotic myeloma improved after melphalan and prednisone treatment. Aggressive treatment with chemotherapy is appropriate in this type of patient.

Chronic alcoholism decreases neuronal nuclear size in the human entorhinal cortex.

The effect of chronic alcoholism in the neuronal nuclear area (karyometry) of the lateral entorhinal cortex at three rostro-caudal levels (rostral, intermediate and caudal) has been studied in 19 alcoholic subjects and in 15 aged-matched controls. Cases were distributed into three groups according to their age (29-44, 45-60 and 61-70 years of age). In the second group (45-60 years), the nuclear size in layers II and III of the caudal entorhinal cortex showed a very significant decrease compared to controls. The first group (29-44 years) also showed a significant reduction in size, while the third group presented the smallest differences. The presence of cirrhosis in the alcoholic group did not vary the observed results. Thus, chronic alcoholism significantly decreases the nuclear size in layers II and III of the lateral entorhinal cortex, and thus the entorhinal output to the hippocampus may be altered in alcoholism.

Pulmonary amyloidosis and unusual lung involvement in SLE.

The association of systemic lupus erythematosus (SLE) with amyloidosis is exceptional. We present a 37-year-old patient who was diagnosed five months earlier for SLE. She developed an acute episode of chest pain, cough and dyspnoea. Hypoxemia and obstructive changes in respiratory tests were present. The chest X-ray was repeatedly normal. Open lung biopsy revealed lupus pneumonitis with positive stain for immunoglobulins and complement, bronchiolitis obliterans, and pulmonary amyloidosis.

[The toxic shock syndrome versus the adult Kawasaki syndrome. The diagnostic difficulties]. / Síndrome del shock tóxico frente a síndrome de Kawasaki del adulto. Dificultades diagnósticas.

The case of a 18-year-old woman with the toxic shock syndrome (TSS) associated to a staphylococcal infection in the maxillary sinus is presented. The initial course of the disease was clinically superposed to a Kawasaki syndrome (KS). Both entities, of purely clinical diagnosis, possess many common elements occasionally making differentiation extremely difficult. The clinical data that may orient diagnosis to one of the processes was analyzed. Finally, it is emphasized that the paranasal sinus must be considered as an occult foci in those cases of TSS in which there is no apparent foci of infection.

[Absence of antiDNA antibodies in the cryoglobulins of a case with sicca syndrome (author's transl)]. / Ausencia de anticuerpos antiDNA en las crioglobulinas de un sicca syndrome.

Cryoglobulins are serum immunoglobulins (immunocomplexes) that precipitate in the cold and redissolve on warming. Cryoglobulins from patients with several diseases showed the presence of antiDNA antibodies when previously underwent incubation in acid buffer. The possibility that antiDNA antibodies might constitute the immunocomplexes found in patients with systemic lupus erythematosus and with other connective tissue diseases is suggested. Negative findings in relation to the presence of antiDNA antibodies in cryoglobulins of a case with sicca syndrome are reported.

[Mixed essential cryoglobulinemia. Report of five cases (author's transl)]. / Crioglobulinemia mixta esencial. Communicación de cinco casos.

Cryoglobulins are serum immunoglobulins which precipitate in the cold and redissolve on warming at 37 degrees C. According to its immunochemical composition three different types have been described. Cryoglobulins have been reported associated with hematologic disorders, systemic diseases, infectious conditions, and diseases of the liver and kidneys. There is also an idiopathic variant called essential cryoglobulinemia. Five patients (four males) with mixed essential cryoglobulinemia are reported. Common clinical manifestations included fever, articular symptoms, purpura, glomerulonephritis, Raynaud's phenomenon, erythematomacular cutaneous eruption, polyneuritis and abdominal pain. Serum activity of rheumatoid factor has been detected in three cases; in other three decreased levels of serum complement have been found. Serum HBsAg was negative in four cases (passive hemagglutination technique). It is possible that all cases of mixed essential cryoglobulinemia may correspond to bacterial, viral or fungal occult infections.

[Cryoglobulins in systemic and rheumatological diseases. Report of 70 cases (author's transl)]. / Crioglobulinas en enfermedades sistémicas y reumatológicas. Estudio en 70 casos.

Cryoglobulins are immunoglobulins characterized by precipitating when serum is cooled and redissolving when serum is heated. There is strong evidence to consider mixed cryoglobulins as circulating immunocomplexes. Cryoglobulins have been demonstrated in association to hematologic, hepatic, lymphoproliferative, autoimmune and infectious conditions. There is also an essential or idiopathic variant. The present report studies a series of 70 patients with several rheumatic and systemic diseases, and a group of ten patients with cutaneous vasculitis. Significant levels of cryoglobulins have been detected in nine cases (overall incidence 12.8 percent). The diagnoses corresponding to these patients were as follows: systemic lupus erythematosus in three cases, dermatopolymyositis in three cases, Sjögren's syndrome in two cases, and Wegener's granulomatosis in one case. Cryoglobulins could not be demonstrated in patients with rheumatoid artritis, sclerodermia, periarteritis nodosa, cutaneous vasculitis, Reiter's syndrome, ankylosing spondilitis and acute articular rheumatism. Among patients with systemic lupus erythematosus a good correlation has been observed between the presence of serum cryoglobulins, the activity and severity of the diseases and the decrease of serum complement levels.

[Wine as a source of lead contamination: study in the southern region of Sevilla]. / El vino como fuente contaminante de plomo: estudio en el área sur de Sevilla.

To assess whether the wines from the south of Sevilla constitute a source of lead intoxication we have prospectively studied the blood levels of lead in 100 healthy controls, 100 patients with alcoholic and nonalcoholic hepatopathy and at the same time the lead content in 135 samples of water and in 176 samples of alcoholic drinks consumed by the above patients. The results demonstrate: 1) presence of normal amounts of lead (mean +/- SD = 62 +/- 5 micrograms/l) in 97 of wines analyzed; 2) a higher content of lead in wines from areas close to the highway A-4 (100 +/- 10 micrograms/l) than in those from more remote zones (42 +/- 3 micrograms/l, p less than 0.005); and 3) although the blood levels of lead in alcohol consumers are not at the toxic range (22.9 +/- 8.9 micrograms/l) are, however, significantly higher (p less than 0.0007) than in patients with no alcohol intake (16.8 +/- 9.9 micrograms/l) or in healthy persons (17.1 +/- 7.4 micrograms/l, p less than 0.0008). Blood levels of lead correlate with the condition of "usual drinker" but not with the amount of alcohol consumed, number of cigarettes, lead content of water and wine, nor with the existence of severe hepatopathy among the studied factors. Our results suggest that alcohol influences the lead metabolism and that the usual drinkers constitute a risk population for saturnism.

[Multi-infarct dementia in giant cell arteritis (temporal arteritis)]. / Demencia multiinfarto en la arteritis de células gigantes (arteritis de la temporal).

Dementia is an infrequent and little known manifestation of giant cell arteritis or temporal arteritis (GCA-TA). The cases of 2 women with histologically proven GCA-TA are presented in which, together with the most classical symptoms, they presented a brusque mental deterioration on initiation of the disease. One patient developed a severe irreversible dementia which coincided with a rapid reduction in the doses of corticoids; while the other patient demonstrated improvement in cognitive function with steroid treatment and control of the disease. Magnetic resonance studies revealed multiple areas of infarction in both hemispheres in the two patients. The importance of treating multi-infarct dementia is underlined in the context of GCA-TA with high doses of corticoids. It is also emphasized that GCA-TA should be considered in the evaluation of older patients with mental alterations.

[Muscular dystrophy due to a mutation in the gene of alpha-sarcoglycan subunit of dystrophin associated protein complex]. / Distrofia muscular por déficit de la subunidad alfa-sarcoglucano del complejo de proteínas relacionadas con la distrofina.

Linkage studies have confirmed the existence of clinical an genetic heterogeneity among the muscular dystrophies due to adhalin deficiency. We present the clinical, histological and genetic characteristics in a case of primary adhalinopathy (deficiency of the 50 kD subunit or alpha-sarcoglycan). It was a 19 years-old woman, born of non consanguineous parents, who shows a long evolution myopathy with onset before age 7, a severe evolution and becoming wheelchair bound at 10 years. She showed evident calf pseudohypertrophy and serum creatinkinase (CK) levels were elevated (40-180 times the standard level). The histological pattern showed a destructed fascicular architecture in agreement with severe muscular dystrophy, normal staining with anti-dystrophin monoclonal antibodies and abnormal staining pattern with anti-adhalin antibodies. The molecular study evidenced an homozygous point mutation (Arg-->Cys) at position 77 of exon 3 of the gene coding for the 50 kD subunit of the alpha-sarcoglycan complex localised in chromosome 17. In the light of this case, we suggest a revision of the diagnostic orientation in the muscular dystrophies and we review the new taxonomy of the limb-girdle muscular dystrophies, remarking the clinical signs which could indicate a given genetic locus.