Occult HBV infection may negatively impact on drug survival in patients with rheumatoid arthritis on treatment with a first biologic drug. An appraisal from the Biologic Apulian Registry (BIOPURE).

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

Influence of TNF-α inhibition on oxidative stress of rheumatoid arthritis patients.

The aim of this study was to assess circulating levels of reactive oxygen metabolites (ROMs) as a marker of oxidative stress in rheumatoid arthritis (RA) patients during an anti-tumor necrosis factor alpha (TNF-α) treatment. We enrolled 40 patients with RA (36 females; age 53 ± 13 yrs) treated with different subcutaneously administered TNF-α inhibitors. The oxidative status was determined on the basis of plasma samples taken before, at 24 and 52 weeks of the anti-TNF-α treatment. Hydroperoxide levels were measured using the d-ROMs test, a useful clinically proven oxidative stress marker. During the anti-TNF-α therapy, we observed a significant reduction in serum ROMs levels in RA patients from 33.2 ± 10 mg H2O2/L at baseline to 29.5 ± 7 and 29.3 ± 9 mg H2O2/L, at 24 and 52 weeks, respectively (p<0.05). We also identified a significant correlation between the oxidative stress status and the disease activity score on 28 joints/C-reactive protein and health assessment questionnaire disability index. The results of our study demonstrate that a good control of the disease with anti-TNF-α agents can reduce oxidative stress in RA patients. However, further studies of larger patient cohorts are needed to confirm these preliminary data.

Contrast-enhanced MR imaging in patients with BI-RADS 3-5 microcalcifications.

PURPOSE: The aim of this study was to evaluate the role of magnetic resonance imaging (MRI) in patients with microcalcifications classed as Breast Imaging Reporting and Data Systems (BI-RADS) 3-5. MATERIALS AND METHODS: Fifty-five patients with mammographic microcalcifications classified as BI-RADS categories 3, 4 or 5 underwent MRI and biopsy with stereotactic vacuum-assisted biopsy (VAB). Our gold standard was microhistology in all cases and histology with histological grading in patients who underwent surgery. Patients with a microhistological diagnosis of benign lesions underwent mammographic follow-up for at least 12 months. MRI was performed with a 1.5-Tesla (T) unit, and T1 coronal three-dimensional (3D) fast low-angle shot sequences were acquired before and after injection of paramagnetic contrast agent (0.1 mmol/kg). MRI findings, according to the Fisher score, were classified into BI-RADS classes. In patients with cancer who underwent surgery, we retrospectively compared the extension of the mammographic and MRI findings with histological extension. RESULTS: Histology revealed 26 ductal in situ cancers (DCIS) and ductal microinvasive cancers (DCmic), three atypical ductal hyperplasias (ADH) and 26 benign conditions. Histological grading of the 26 patients with cancer revealed four cases of G1, 11 cases of G2 and 11 cases of G3. If we consider mammographic BI-RADS category 3 as benign and BI-RADS 4 and 5 as malignant, mammography had 77% sensitivity, 59% specificity, 63% positive predictive value (PPV), 74% negative predictive value (NPV) and 67.2% diagnostic accuracy. If we consider MRI BI-RADS categories 1, 2 and 3 as benign and 4 and 5 as malignant, MRI had 73% sensitivity, 76% specificity, 73% PPV, 76% NPV and 74.5% diagnostic accuracy. As regards disease extension, mammography had 45% sensitivity and MRI had 84.6% sensitivity. CONCLUSION: Mammography and stereotactic biopsy still remain the only techniques for characterising microcalcifications. MRI cannot be considered a diagnostic tool for evaluating microcalcifications. It is, however, useful for identifying DCIS with more aggressive histological grades. An important application of MRI in patients with DCIS associated with suspicious microcalcifications could be to evaluate disease extension after a microhistological diagnosis of malignancy, as it allows a more accurate presurgical planning.

Percutaneous cholecystostomy for acute cholecystitis in critically ill patients.

BACKGROUND/AIMS: The aim of this study was to ascertain the therapeutic efficacy of percutaneous cholecystostomy in a selected group of high-risk patients who were physiologically unable to tolerate an open procedure. METHODOLOGY: We reviewed the hospital records of 11 critically ill patients who underwent percutaneous cholecystostomy for acute cholecystitis during the intensive care unit course of major underlying diseases. RESULTS: Percutaneous cholecystostomy was easily performed in all cases (feasibility rate: 100%). No procedure-related death was recorded and minor complications occurred in 2 patients (18%). Percutaneous cholecystostomy led to resolution of the sepsis in all but 1 patient with gangrenous calcolous cholecystitis who required emergent cholecystectomy (success rate: 91%). Percutaneous cholecystostomy was the permanent treatment in all patients with acalcolous cholecystitis. Among patients with calcolous cholecystitis, 4 underwent delayed elective cholecystectomy, 1 required no further treatment, and 2 eventually died from the evolution of their underlying diseases. After a mean follow-up of 25 months (range: 12-32 months), none of the patients managed non-operatively required surgery or re-hospitalization. CONCLUSIONS: Ease of performance, low complication rate, and high success rate make percutaneous cholecystostomy the procedure of choice for critically ill patients with acute cholecystitis. Whenever possible, percutaneous cholecystostomy should be followed by elective cholecystectomy. However, especially in acalcolous cholecystitis, it may constitute the definitive treatment.

Serum and red blood cell magnesium levels in juvenile migraine patients.

Recently an important role for magnesium in establishing the threshold for migraine attacks has become evident. Accordingly, we measured serum and red blood cell magnesium levels in juvenile migraine patients with and without aura interictally. In comparison with normal subjects, migraineurs had significantly lower serum and red blood cell magnesium levels.

Expression of cathepsin D in malignant and in the corresponding non-malignant node-negative laryngeal samples: correlation with receptors for androgen, glucocorticoid, oestrogen and progesterone.

A standard immunoradiometric technique was used to investigate the distribution of the intracellular aspartic proteinase cathepsin D in 33 malignant and in the corresponding histologically-proven non-malignant fragments obtained from lymph node negative patients suffering from larynx cancer. In both tissues the androgen, glucocorticoid, oestrogen and progesterone receptors were also assayed. Our data indicate that cathepsin D was present in both tissues, with level significantly higher (P < 0.0001) in the cancerous fragments (with a mean of 33 +/- 3.4 pmol/mg protein) than in the corresponding non-cancerous specimen (with a mean of 20.8 +/- 2 pmol/mg protein). A significant positive association (P < 0.001) between cathepsin D and PR concentration values in the cancerous larynx was observed; accordingly, tumours expressing PR had significantly (P = 0.0005) higher cathepsin D levels than the tumours which did not contain the receptor. In contrast, such a relationship was absent in the non-malignant specimens. As regards the other steroid receptors, no significant relationship between them and cathepsin D was observed. We conclude that cathepsin D may have a role also in laryngeal carcinoma and that its association with the PR could indicate a possible role of the receptor in the biology of this disease.

Serum and erythrocyte magnesium concentrations in solid tumours: relationship with stage of malignancy.

Magnesaemia is often decreased in solid tumours, but magnesium (Mg) is mainly an intracellular cation and serum levels do not reflect actual body stores. In this study serum Mg (SMg) and erythrocyte Mg (EMg) concentrations were measured in 40 healthy controls and in 108 patients affected by various types of tumour (50 lung cancers, 25 breast cancers, 18 ovarian cancers, and 15 oropharyngeal and hypopharyngeal cancers). EMg was higher (P < 0.05) and SMg lower P < 0.001) in neoplastic patients than in controls. All tumour types behaved in the same way, though in the lung cancer group the increase in EMg did not reach statistical significance in comparison with the control group (P = 0.05). The extent to which EMg was increased and SMg decreased was positively correlated with the advancement in the stage of malignancy. These results suggest that in neoplastic disease Mg requirement is not only increased in tumour tissue, but also in erythrocytes. The increase in EMg may derive from a change in the red blood cell membrane, facilitating intracellular concentration of magnesium for transport to the tumour. The concomitant decrease in SMg may be the consequence of the enhanced erythrocyte uptake of magnesium from the extracellular circulating pool.

Evaluation of bone metabolic markers as indicators of osteopenia in climacteric women.

Lumbar bone mass (LBM) determination by quantitative computerized tomography in pre-, peri- and postmenopausal women was utilized to identify subjects at risk to develop osteoporosis. The results were related to determinations of bone metabolic markers (serum osteocalcin and urinary calcium excretion). Osteocalcin was the only metabolic marker which underwent significative changes. However, we found very poor correlations between LBM and metabolic markers and it is concluded that bone mass determination remains the method of choice to select women for preventive therapy.

Serum and erythrocyte levels of magnesium in microcytosis: comparison between heterozygous beta-thalassemia and sideropenic anemia.

In thalassemia erythrocyte cation permeability is increased, but the increment in ATPase-dependent cation pumps maintains normal concentrations of Ca++, Na+ and K+. In this study we investigated erythrocyte concentrations of Mg++ in heterozygous beta-thalassemia and in microcytic sideropenic anemia. Twenty-five healthy controls, 40 heterozygous beta-thalassemics and 25 patients with sideropenic anemia were studied. Erythrocyte Mg++ was assayed either by atomic absorption or by standard laboratory methods. Erythrocyte Mg++ was significantly lower in the beta-thalassemia group than in the other two groups (p less than 0.001). Serum magnesium was significantly lower in sideropenic anemia patients than in beta-thalassemics and in controls (p less than 0.01), whereas these latter two groups showed similar values. Our results suggest that the increment in ATPase-dependent cation pumps is not sufficient to maintain normal erythrocyte Mg++ concentrations in heterozygous beta-thalassemia. In sideropenic anemia cation permeability is not increased, therefore erythrocyte Mg++ is normal. Low serum Mg++ levels in sideropenic anemia could be explained by a primary Mg++ deficit associated with sideropenia.

Changes in serum, erythrocyte, and urinary magnesium after a single dose of cisplatin combination chemotherapy.

The changes in serum and erythrocyte Mg concentrations and in renal Mg excretion induced by a single dose of cisplatin (100 mg/mq body surface area) were investigated in 16 patients with lung cancer. Magnesuria increased significantly (P less than 0.001) the day after cisplatin administration, returned to basal levels in the following days, and increased again on the 7th day (P less than 0.05). Magnesaemia decreased gradually and after 7 was significantly lower than before treatment (P less than 0.05). Erythrocyte Mg decreased significantly on days 1 (P less than 0.05) and 2 (P less than 0.001) after cisplatin administration, began to increase on day 4, and recovered to pretreatment values on day 7. These results suggest that, besides the well known damage to tubular function with consequent increase in renal Mg wasting, cisplatin may also interfere with Mg metabolism at cellular and subcellular levels. The activity of the drug on nucleic acids and membrane transport systems, where Mg is abundant and exerts important stabilizing functions, could induce Mg mobilization and increased membrane permeability, with a consequent shift of Mg from cells into the blood stream. This would counterbalance the increase in magnesuria, and magnesaemia would decrease significantly only when intracellular Mg returns to pretreatment levels.

Coagulation disorders and tumor markers in the diagnosis of pancreatic cancer.

Twenty patients (42-80 years old of whom 9 women) affected by instrumentally ascertained pancreatic cancer (7 cases were operated on) were studied. In all of them the following coagulation indices (fibrinopeptide A, FpA; beta-thromboglobulin, BTG; platelet factor IV, PF4; fibrinogen degradation products, XDP) and tumor markers (gastrointestinal cancer associated antigen, GICA; tissue polypeptide antigen, TPA; carcinoembryonic antigen, CEA; alpha-fetoprotein, or AFP) were assessed at the time of diagnosis, and 10 and 30 days after diagnosis, to test whether and which of the above parameters are more sensitive for entertaining the underlying affection. In both operated and nonoperated patients FpA was shown to be the most sensitive index. Lesser sensitivity was shown by XDP, GICA, and BTG. AFP proved to be quite useless as its serum levels constantly fell within the normal range.

[Amebic liver abscess: 2 imported cases]. / L'ascesso amebico del fegato: due casi di importazione.

Two imported cases of amebic liver abscess are discussed with regard to laboratory, diagnostic and therapeutic peculiarities. The diagnostic role of ultrasonography and especially of specific serology is stressed, whereas in therapeutic terms, the efficacy of medical approach alone is emphasized even when complications until yesterday surgically treated occur.

Changes of magnesium concentrations in endurance athletes.

Erythrocitary and serum magnesium (Mg) were determined in a group of 11 well-trained athletes before and after a 25-km running race, and in a group of 30 sedentary controls. The significant increase of mean erythrocitary Mg (EMg) concentration observed in the athletes after physical strain (2.58 +/- 0.34 mEq/l before, 3.10 +/- 0.45 mEq/l after the race: significance level = 5%) leads to the assumption that the possible Mg uptake is effected by the red blood cell to enhance some enzymatic reactions. The decrease of mean serum Mg concentration observed in the same subjects after the effort (1.70 +/- 0.14 mEq/l before, 1.64 +/- 0.15 mEq/l after the race) is not significant. The difference between mean Mg concentrations observed in the athletes' group before the race and in the sedentary group (EMg: 2.58 +/- 0.34 mEq/l in athletes, 3.67 +/- 0.38 mEq/l in sedentaries, significance level = 1%; serum Mg: 1.70 +/- 0.14 mEq/l in athletes, 1.96 +/- 0.15 mEq/l in sedentaries, significance level = 1%) suggests that athletes suffer from a Mg deficiency, partially due to physical exercise. The two hypotheses and the possible causes of the observed phenomena are discussed.

Neurological involvement in group iv HIV-positive patients. Neurophysiological and clinical data.

Spinal and cortical SEP responses were recorded during tibial and median nerve stimulation in 58 HIV+ subjects (8 IV/C1, 24 IV/C2 & IV/A, 11 III and 15 II), all asymptomatic from a neurological point of view. The electrophysiological features were compared with clinical assessment and serum HIV markers for purposes of prognosis and therapy. In group IV we observed a slowing of conduction along the afferent pathway in the spinal tracts and afferent ways to the cortex. The major part of the delay occurred in the mid and lower medullary tract. These results agree with neuropathological finding from post-mortem examination in AIDS pts.

[New Campylobacters in human pathology. Current findings and research contributions]. / Nuovi campylobacter in patologia umana. Attuali acquisizioni e contributi di ricerca.

The Authors focused on the new isolates' important role in human infections (particularly pylori, laridis, hyointestinalis and Campylobacters like- organisms) by clinical, microbiological and research data. Recent knowledge about pathogenetic mechanisms of classical Campylobacters is also reported.

Campylobacter laridis bacteraemia in an AIDS patient.

The likely first case of Campylobacter laridis bacteraemia in AIDS is reported. Microbiological, epidemiological and clinical characteristics of C. laridis human infection are also described.

Reduction of erythrocyte magnesium concentration in heterozygote beta-thalassaemic subjects and in normal subjects submitted to physical stress.

Erythrocyte and serum magnesium (Mg) concentrations have been assayed in a group of sedentary heterozygote beta-thalassaemic subjects (beta-thal), in a group of non-thalassaemic well trained runners before and after a 25 km running race, and in a group of sedentary healthy controls. The mean erythrocyte Mg concentration (EMg) found in beta-thal (2.72 mEq/litre) and in runners, both before and after the race (2.58 mEq/litre before, 3.10 after), was significantly lower than the EMg values from the control group (3.69 mEq/litre). We propose various hypotheses to explain the reductions observed.