Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Association of extrahepatic manifestations with HLA class II alleles and with virus genotype in HCV infected patients.

It has been postulated that host factors, such as the human leucocyte antigen (HLA) system, may play a predominant role in the pathogenesis of HCV-related extra-hepatic manifestations. This study was performed to investigate the role of HLA- DR and DQ alleles in a group of Italian patients, with HCV infection and associated extrahepatic manifestations and to test whether an association between HCV genotype, HLA locus and clinical or serological manifestations can be demonstrated. Thirty unrelated patients affected by HCV infection with extra-hepatic manifestations were consecutively included in the study. One hundred and sixty-three HCV patients without extrahepatic manifestations were tested as controls for the prevalence of HCV genotypes, and 283 healthy donors were used as controls for HLA class II alleles distribution. HCV-RNA was quantified by an reverse transcription-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay on B lymphocyte purified. HCV 2c genotype was found in 53.3% compared to 18.4% of controls (p=0.00001; OR=5.1). Cryoglobulins were detected in 72.7% DR6+ patients and in 31.6% DR6- patients (p=0.05; OR=3.21). Rheumatoid factor was found in 90.9% of DR6+ patients and in 42.1% DR6- patients (p=0.018; OR 13.7). Only two DR5+ patients (20%) had cryoglobulinemia, while 6 patients (30%) in the DR5- group had cryoglobulinemia (p=0.02; OR=0.07). Associations were found between DR7 and ANA (OR=1.74) and between DQ2 and ANA (OR=1.97). According to our findings HLA-DR6 might play an important role in developing extra-hepatic manifestations and genotype 2c could be considered as a risk factor for their onset.

Pulmonary hypertension in primary Sjögren's syndrome: report of a case and review of the literature.

A 61-year-old female with a history of vaginal dryness, Raynaud's phenomenon, xerostomia and xerophthalmia presented with exertional dyspnoea and weakness. Laboratory and instrumental examinations enabled us to make the diagnosis of primary Sjögren's syndrome, while cardiologic and imaging investigations evidenced isolated pulmonary hypertension and ruled out pulmonary fibrosis. Oral anticoagulant and furosemide therapy induced a partial improvement of exertional dyspnoea and weakness.

[Chromosome aberrations, valued as frequency of spontaneous micronuclei, in subjects with suspected presclerodermic Raynaud's phenomenon]. / Anomalie cromosomiche, valutate come frequenza di micronuclei spontanei, in soggetti con fenomeno di Raynaud sospetto presclerodermico.

OBJECTIVE: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with suspected presclerodermic Raynaud's phenomenon (RP), by means of molecular cytogenetic analysis. METHODS: We studied 20 suspected presclerodermic RP, 20 idiopathic RP and 25 healthy subjects. As marker of chromosome alteration we used the micronucleus assay. All subjects were also classified as ANA-, ACA+ or Scl70+. To identify the mechanism of MN formation, a MN fluorescence in situ hybridisation (FISH) analysis using a pancentromeric DNA probe was also performed. RESULTS: Suspected presclerodermic RP subjects, showed significantly higher MN frequencies than idiopathic RP and controls (39+/-15.2 vs 10+/-2.1 and 9.8+/-3.5 respectively p<0.0001). Interestingly, subjects with idiopathic RP displayed MN frequency comparable to that of controls. Furthermore, ACA+ subjects showed the highest MN frequencies (44+/-8.1) as compared to subjects with different antibody pattern (26+/-7.1). CONCLUSIONS: Our results show the presence of higher levels of chromosomal damage in circulating lymphocytes of suspected presclerodermic RP. They also would suggest a key role of anti-centromere antibody in determining the observed cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contribute to the formation of MN observed in suspected presclerodermic RP.

[The high frequency of spontaneous micronuclei observed in lymphocytes of systemic sclerosis patients: preliminary results]. / Alta frequenza di micronuclei spontanei osservati in linfociti di pazienti con sclerosi sistemica: risultati preliminari.

OBJECTIVE: Aim of the study is to assess the presence of spontaneous chromosome damage in patients affected by limited (lSSc) or diffuse (dSSc) Systemic Slerosis, using the micronucleus (MN) assay. METHODS: We evaluated MN frequency in cultured peripheral lymphocytes of 18 SSc and in a group of 20 healthy controls. Patients were also classified as ACA+, Scl70+, FAN+ according to the presence of the specific anti-nuclear antibodies. We also explored the hypothesis that the extent of cytogenetic alteration might be related to the severity of the pathological condition and/or to the immunological profile. RESULTS: Compared to controls, the patient group as a whole showed significantly higher MN frequencies (10.8+/-4.5 vs. 27.8+/-13.7, p<0.001). No correlation was found between spontaneous chromosome damage and severity of the disease, being MN frequency 33.1+/-17.0 and 19.8+/-2.7 in lSSc and dSSc, respectively. Interestingly, ACA+ subjects displayed the highest MN frequency (36.9+/-15.0), as compared to patients with different antibody pattern (Scl70+, FAN+; 19.7+/-8.2). CONCLUSIONS: Our results confirm the presence of chromosomal damage in circulating lymphocytes of SSc patients and would suggest a key role of antibodies to the centromere in determining the observed cytogenetic anomalies.

Scintigraphic findings on 99mTc-MDP, 99mTc-sestamibi and 99mTc-HMPAO images in Gaucher's disease.

Gaucher s disease is an autosomal recessive lysosomal storage disease characterized by the specific deficiency of glucocerebrosidase that leads to accumulation of insoluble glucocerebroside in the reticuloendothelial system, particularly the bone marrow, liver, spleen and lymph nodes. Direct scintigraphic visualization of lipid deposits in Gaucher s disease has recently been described, based on the use of the lipid-soluble xenon-133. We report here on the use of the lipophilic cationic complex technetium-99m sestamibi (99mTc-MIBI), employed as an indicator of increased cellular density and metabolic activity, to evaluate Gaucher cell infiltrates in the bone marrow; 99mTc-hexametazime (99mTc-HMPAO) was also employed, as a pure indicator of lipidic infiltration in the bone marrow. A 67-year-old patient with known type 1 Gaucher s disease presented with a painful left hip and knee and difficulty in gait subsequent to traumatic fracture of the left femoral neck that had required implant of a fixation screw-plaque. Bone scan with 99mTc-methylene diphosphonate revealed reduced uptake at the distal metaphyseal-epiphyseal femoral region. In addition, whole-body maps and spot-view acquisitions of the thighs and legs were recorded at both 30 min and 2.5 h after the injection of 99mTc-MIBI: the scintigraphic pattern clearly showed increased uptake at several sites involved by Gaucher deposits in the bone marrow (both knees, with variable intensity in different areas), matching the bone changes detected by conventional x-ray. The target to non-target ratios slowly decreased with time, from an average value of 2.25 in the early scan to an average value of 2 in the delayed scan. The lipid-soluble agent 99mTc-HMPAO exhibited a superimposable scintigraphic pattern of accumulation at the involved sites, though with lower target to non-target ratios (1.27-1.48). The results obtained in this patient suggest a potential role of 99mTc-MIBI in the scintigraphic evaluation of Gaucher s lipid deposits in the bone marrow. If the results are confirmed in other patients, this radiopharmaceutical would offer clear advantages over 133Xe because of its wider availability and greater practicality (i.v. administration of 99mTc-MIBI versus inhalation of 133Xe, and use of a single gamma camera instead of two as with 133Xe).

Bone involvement in Gaucher's disease: 'bone crisis' or disease complication?

Bone involvement can represent the inaugural symptom of Gaucher's disease (GD). Here, we report the case of a 68-year old man diagnosed as having GD since 1963. In June 1994 the patient was referred to our Rheumatology Unit because of a long-lasting coxalgia on the left hip and progressive walking impairment following traumatic fracture of the left femur. Multicystic osseous changes at standard X-ray and hyper-gamma-globulinemia with an elevated ESR (122 mm, 1st hour) suggested the diagnosis of either osteonecrosis of the femoral head or multiple myeloma. On bone marrow biopsy examination, Gaucher's cell infiltrates were detected and an increased uptake in the distal left femur and proximal tibia were demonstrated by lipophilic tracer scan (99mTc-Sestamibi). Subsequently, the patient suffered another femoral fracture at a site of Gaucher's infiltrates previously documented by bone scan. We conclude that in patients with GD, 99mTc-Sestamibi bone scan can selectively evaluate the presence of bone lipid deposits, and could indirectly differentiate this bone condition from other serious skeletal complications of the disease.

Multiple and reversible osteolytic lesions: an unusual manifestation of behcet's disease.

We describe a patient with Behcet's disease (BD) who developed multiple and reversible osteolytic lesions during the course of disease. The possible relationships between BD and this very unusual manifestation are discussed.