Systemic phenotype of sarcoidosis associated with radiological stages. Analysis of 1230 patients.

BACKGROUND: To analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe. METHODS: The SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al. RESULTS: We analyzed 1230 patients (712 female, mean age 47 yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (n = 98), stage I (n = 395), stage II (n = 500), stage III (n = 195) and stage IV (n = 42). Women were overrepresented in patients presenting with extrathoracic/extrapulmonary disease, while the diagnosis was made at younger ages in patients presenting with BHL, and at older ages in those presenting with pulmonary fibrosis (q values <0.05). Multivariable adjusted analysis showed that patients presenting with pulmonary involvement (especially those with stages II and III) had a lower frequency of concomitant systemic involvement in some specific extrathoracic clusters (cutaneous-adenopathic/musculoskeletal, ENT and neuro-ocular/OCCC) but a higher frequency for others (hepatosplenic), in comparison with patients with extrapulmonary involvement (stages 0 and I). The presence of either BHL or fibrotic lesions did not influence the systemic phenotype of patients with pulmonary involvement. CONCLUSIONS: The key determinant associated with a differentiated systemic phenotype of sarcoidosis at diagnosis was interstitial pulmonary involvement rather than the individual Scadding radiological stage.

HIV/antiretroviral therapy-related lipodystrophy syndrome (HALS) is associated with higher RBP4 and lower omentin in plasma.

Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.

A study of fatty acid binding protein 4 in HIV-1 infection and in combination antiretroviral therapy-related metabolic disturbances and lipodystrophy.

OBJECTIVE: The aim of the study was to determine circulating levels of fatty acid binding protein 4 (FABP-4) in a cohort of HIV-1-infected patients treated with combination antiretroviral therapy (cART) and to investigate the relationships between FABP-4 levels and insulin resistance, dyslipidaemia, lipodystrophy and levels of proinflammatory adipocytokines in these patients. METHODS: A total of 282 HIV-1-infected patients treated with stable cART for at least 1 year (132 with lipodystrophy and 150 without) and 185 uninfected controls (UCs) were included in the study. Anthropometric parameters were determined. Plasma levels of FABP-4, soluble tumour necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2), interleukin-18 (IL-18), IL-6, adiponectin and leptin were also analysed. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous adipose tissue mRNA expression of proinflammatory cytokines was assessed in 38 patients (25 with lipodystrophy and 13 without) by real-time polymerase chain reaction (PCR). RESULTS: The plasma FABP-4 concentration was significantly higher in patients with lipodystrophy than in those without (P=0.012). FABP-4 concentration was positively correlated with body mass index (BMI), HOMA-IR, and the concentrations of insulin, total cholesterol, triglycerides, sTNF-R1, leptin and IL-18, but showed a negative correlation with high-density lipoprotein (HDL) cholesterol and adiponectin concentrations. After adjusting for age, sex and BMI, the odds ratio (OR) for risk of lipodystrophy was found to be significantly increased for those with the highest levels of FABP-4 [OR 0.838, 95% confidence interval (CI) 0.435-1.616 for medium FABP-4 vs. OR 2.281, 95% CI 1.163-4.475 for high FABP-4]. In a stepwise regression model, FABP-4 was independently associated with HOMA-IR after controlling for clinical and inflammatory parameters (P=0.004). Moreover, a positive relationship was observed in patients with lipodystrophy between subcutaneous adipose tissue CD68 expression and FABP-4 plasma levels (r=0.525; P=0.031). CONCLUSIONS: cART-treated HIV-1-infected patients with lipodystrophy have a systemic overproduction of FABP-4, which is closely linked to insulin resistance and inflammatory markers in subcutaneous adipose tissue.

Clinical response to ertapenem in severe community-acquired pneumonia: a retrospective series in an elderly population.

To evaluate in routine hospital practice the clinical response to ertapenem in comparison with other parenteral antibiotics in the treatment of community-acquired pneumonia (CAP), clinical records from patients with severe CAP treated with ertapenem from July 2002 to June 2006 in seven Spanish hospitals were retrospectively reviewed. Patients were classified according to the Pneumonia Severity Index (PSI). Each ertapenem-treated patient was matched with two patients in the same hospital treated with other antibiotics, according to age (difference 76 years). Comorbidities were present in 193 patients (95.5%). No differences were found in median hospital stay (7 days for ertapenem vs. 10 days for comparators, p 0.066). A slightly higher clinical response rate was obtained for ertapenem vs. comparators (88.7% vs. 77.1%; p 0.0465; OR 2.25; 95% CI 0.99-5.12), with significant differences in clinical response in patients coming from nursing homes (95.8% ertapenem vs. 63.8% comparators; p 0.0034) but not in non-institutionalized patients (85.4% ertapenem vs. 84.5% comparators; p 0.929). The higher clinical response to ertapenem vs. comparators in severe CAP was due to its significantly higher efficacy in healthcare-associated CAP in patients coming from nursing homes.

Varón de 76 años con polimialgia y el signo del halo / 76 year old male with polymyalgia and halo sign

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Clinical characterization of breakthrough bacteraemia: a survey of 392 episodes.

BACKGROUND: Few data are available on the clinical features of patients who develop breakthrough bacteraemia, understood as positive blood cultures despite appropriate antibiotic therapy. OBJECTIVES: To determine the clinical significance and outcome of a large series of breakthrough bacteraemia. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: Two university-affiliated hospitals in Catalonia, Spain. SUBJECTS: A total of 392 individuals who suffered an episode of breakthrough bacteraemia recorded between 1997 and 2002. INTERVENTIONS: Demographic characteristics, underlying diseases, origin of infection, sources of infection, microorganisms isolated, McCabe and Jackson prognostic criteria, and mortality were analysed. RESULTS: Breakthrough bacteraemia was detected in 392 of 6324 (6.1%) episodes of bacteraemia. Eighty per cent of episodes were nosocomial. The most frequent source of infection in breakthrough bacteraemia was endovascular (70%). Coagulase-negative staphylococci, Staphylococcus aureus, and Pseudomonas aeruginosa were the most significant microorganisms involved. Nosocomial acquisition together with selected sources (central venous catheter, endocarditis and other endovascular foci), underlying conditions (neutropenia, polytraumatism, allogenic bone marrow and kidney transplantation), and particular microbial aetiologies (S. aureus, P. aeruginosa and polymicrobial) were independently associated with increased risk for developing breakthrough bacteraemia. Crude mortality rate was greater in patients with breakthrough bacteraemia (16% vs. 12.3%; P<0.05), and this condition was an independent predictor of death (OR 1.4, 95% CI, 1-1.9; P=0.04). CONCLUSIONS: In view of a case of breakthrough bacteraemia it is mandatory to search for an endovascular focus. Empiric treatment should be directed to cover S. aureus, coagulase-negative staphylococci and nonfermentative Gram-negative bacilli. Breakthrough bacteraemia is an independent predictor of death.

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Transverse myelitis as a first manifestation of systemic lupus erythematosus: a case report.

Transverse myelitis as a first manifestation of systemic lupus erythematosus (SLE) is very uncommon. No pathognomonic clinical or biochemical characteristics exist, and therefore an early diagnosis is often difficult. Therapy with intravenous pulses of methylprednisolone and cyclophosphamide has been shown to improve the prognosis. However, morbidity and mortality rates in transverse myelitis are still high due to the fact that complications such as opportunistic infections and pulmonary embolism are still frequent causes of death. We report a woman with relapsing transverse myelitis which was the first manifestation of SLE. A good response to pulse methylprednisolone and cyclophosphamide therapy was obtained but she died later as a result of a pulmonary embolism. We conclude that intravenous pulse methylprednisolone and cyclophosphamide therapy improve the prognosis of transverse myelitis associated with SLE but that a careful follow-up is needed to avoid complications due to the illness itself or secondary to the therapy.

Hepatic amyloidosis associated with systemic lupus erythematosus.

The association between amyloidosis and systemic lupus erythematosus has rarely been described. We report a case of a 37-year-old man with a long-standing SLE who developed clinical and laboratory signs of hepatic dysfunction. A liver biopsy revealed secondary amyloidosis.

Malignancy in systemic lupus erythematosus: a report of five cases in a series of 96 patients.

The association of systemic lupus erythematosus (SLE) and malignancy has been reported previously and suggests an increased risk of cancer in this disease. Lymphomas are the most frequent neoplasias reported in these patients and carcinoma of the cervix and breast are also seen. Several factors probably play a role in the aetiology of malignancies associated with SLE including intrinsic disturbances of immunity and concomitant immunosuppressive therapy. We report five solid tumors (one breast carcinoma, one squamous cell carcinoma of the anus, one adenocarcinoma of the rectum, one carcinoma of the cervix and one carcinoma of the gallbladder) among 96 patients with SLE. The most striking finding in this study was the absence of haematological malignancies. The incidence of malignancy in the series, the age of diagnosis of SLE and neoplasia and the time delay between SLE and malignancy diagnosis was similar to other series. We did not find any clinical or immunological feature that predicted the development of neoplasia. In conclusion, patients with SLE may have the same malignancies as the general population after adjustment for age and sex. There are no predictive indicators for malignancy and immunosuppressive therapy may be a contributing factor.

[Intra-abdominal paraganglioma: clinical, functional, structural, and immunohistochemical study of an exceptional case]. / Paraganglioma intraabdominal: estudio clínico, funcional, estructural e inmunohistoquímico de un caso excepcional.

Paragangliomas are tumors, derived from paraganglionary system, able to synthesize and to liberate substances with neuroregulatory activity. They are rare, mainly in the neck located, difficult to anatomo-pathologic diagnose, and of poor prognosis. They may present as space-occupying lesions or as secondary syndromes due to the liberation of biologically active substances. Whenever it is possible, surgical excision is the treatment of choice. Nor chemotherapy, nor immunomodulators, like alpha-2b-interferon, have provided satisfactory results. A 57 year-old man, with a non-surgical paraganglioma characterized by abdominal mass associated with liver and bone metastasis, is presented. The rarity of the intra-abdominal presentation, the image study findings, the histopathological and immunohistochemical examinations, and the evolution after alpha-2b-interferon therapy are analyzed.

Clinical, endoscopic, immunologic, and therapeutic aspects of oropharyngeal and esophageal candidiasis in HIV-infected patients: a survey of 114 cases.

The medical records of 114 consecutive HIV-infected patients with oropharyngeal and esophageal candidiasis, in whom esophagoscopy was performed, were reviewed. Esophageal candidiasis and isolated oral candidiasis were found in 75% and 25% of patients, respectively. Esophageal candidiasis was the AIDS-defining illness in 65 patients and dysphagia was the commonest symptom, but asymptomatic Candida esophagitis was observed in 43% of them. Symptoms were present in six patients with oropharyngeal candidiasis; three of them had a normal esophagoscopy and the other three had acute nonfungal esophagitis. Invasive fungal esophagitis was confirmed by biopsy in 47/74 patients (64%). The patients with esophageal candidiasis had lower CD4+ cell counts (129/microliter) and CD4:CD8 ratios (0.23) than those with oropharyngeal candidiasis (CD4 179/microliter; CD4:CD8 0.35). Thirty-six patients with esophageal candidiasis were treated with fluconazole, 100 mg/daily, for 28 days, and another 34 patients received the same dose for 10 days. A similar efficacy was seen in both regimens, but a higher incidence of oropharyngeal fungal colonization and liver dysfunction was observed in the longer therapy (p < 0.001). We conclude that asymptomatic C. esophagitis is common in HIV-infected patients. Patients with oropharyngeal candidiasis may complain of esophageal symptoms; it could be due to superficial C. infection or another not-identified opportunistic infection. More severe immunologic impairment was required to develop esophageal candidiasis than oropharyngeal candidiasis. A short course of 10 days of fluconazole therapy could be the standard regimen for the treatment of C. esophagitis in AIDS.

[A clinical study of Kaposi's sarcoma associated with the acquired immunodeficiency syndrome]. / Estudio clínico del sarcoma de Kaposi asociado al síndrome de inmunodeficiencia adquirida.

We have retrospectively studied 35 cases of Kaposi's sarcoma in 460 patients with AIDS (incidence of 7.6%) during a period of 10 years. All of them were males, with a mean age of 38 years. 88% of the cases belonged to the homosexual risk group. The tumor was the diagnostic criteria of AIDS in 25 patients. At the moment of the diagnosis, 4 patients were at stage I, 23 at stage II, 1 at stage III and 7 at stage IV, according to the Mitsuyasu's classification; 7 patients had systemic symptoms. The tumor was localized at the skin (34 cases), mucosa (16), digestive tract (7), lung (6) and ganglion (4). The immunological study revealed lymphopenia in 74% of patients, reduction of T4 lymphocytes ( < 0.5 x 10(9)/L) in 93% and inverted T4/T8 ratio in 96%. Sixteen patients received antitumoral treatment (8 with chemotherapy, 7 with interferon and 5 with radiotherapy). The response was stabilization of lesions in 8 cases, partial remission in 2 and progression in 3; in other 3 cases, such response was not assessed. The mortality was 48% and the average survival, 13 months. Opportunistic infections were the cause of death in most patients. Our results confirm the clinical and evolutive characteristics of the Kaposi's sarcoma associated to AIDS; disseminated cutaneous affectation with frequent visceral affectation, poor response to treatment and low survival associated to the presence of opportunistic infections. The lower incidence of tumor observed in our study is related to the different distribution of the risk groups for HIV in our country.

[Azidothymidine in the treatment of patients with human immunodeficiency virus infection and persistent generalized adenopathies]. / La azidotimidina en el tratamiento de los pacientes con infección por el virus de la inmunodeficiencia humana y adenopatías generalizadas persistentes.

The effectiveness and security of azidothymidine (AZT) in the treatment of patients with infection by the human immunodeficiency virus (HIV) and persistent generalized adenopathies (PGA), were assessed. Thirty six patients with HIV infection and PGA participate in the study. Eighteen were treated with AZT and the other 18 were included in the control group, since they did not accept the treatment. Both groups were homogeneous with respect to their clinical, immunological and virological characteristics. A common study protocol was used and the clinical, immunological and virological effectiveness was assessed. Lymphocyte subpopulations were quantified by flow cytometry, viral antigens were determined by sandwich-type ELISA and antibodies against viral proteins (anti-gp120, anti-gp160, anti-gp41, anti-gp24 and anti-p18) were detected by Western blot. Naranjo and Busto's algorithm was used for the causality of adverse effects. We did not observe any significant differences regarding the presence of infection and the evolution of AIDS in both groups. A positive response to thrombocytopenia was observed, more evident in patients under low doses of AZT. The small initial transitory improvement of the immunological parameters was not statistically significant. The viral antigen was not modified by the treatment. With respect to the behaviour of the several antibodies studied, no differences were observed. The initial doses of AZT had to be modified in 44% of patients due to their hematological toxicity, more frequent in the first stages of the treatment. In two patients, the treatment had to be finally discontinued due to severe neutropenia. 25% of patients showed mild to moderate gastrointestinal manifestations.(ABSTRACT TRUNCATED AT 250 WORDS)