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.

Hematemesis from esophageal varices associated with esophageal perforation: sclerotherapy and endoscopic clipping.

A 46-year-old man was referred to our Unit for hematemesis. The medical history of the patient revealed an HCV-related cirrhosis, a human immunodeficiency virus (HIV) infection and recent and persistent episodes of emesis. An urgent gastroscopy disclosed evidence of active bleeding from varices of the lower third of the esophagus and a concomitant laceration of the esophageal wall due to the emesis. These two conditions have been endoscopically diagnosed and successfully treated by sclerotherapy and endoscopic clipping.

Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.

LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(TFH)-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications.

Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis.

Lamina propria (LP) T cells respond poorly to a proliferative stimulus delivered via TCR/CD3 pathway, but retain considerable ability to respond to a stimulus delivered via CD2 costimulatory or accessory pathway. In the present study, we showed first that unstimulated LP T cells, as compared to unstimulated peripheral blood (PB) T cells, exhibit an increased level of apoptosis which is further increased following CD2 pathway stimulation, but not following via TCR/CD3 pathway stimulation. We next showed that IL-2 had a sparing effect on apoptosis of unstimulated LP T cells in that IL-2 decreased and anti-IL-2 increased apoptosis of these cells; in contrast, IL-2 had no effect on apoptosis of CD2-pathway stimulated cells. Finally, we showed that increased apoptosis of LP T cells induced by CD2-pathway stimulation is inhibited when Fas antigen is blocked by a nonstimulatory anti-Fas antibody. These studies suggest that LP T cells are characterized by increased susceptibility to Fas-mediated apoptosis most due to a downstream change in the Fas signaling pathway. Given that IFN-gamma secretion is significantly increased in LP T cells in which apoptosis is inhibited, this feature of LP T cells may represent a mechanism of regulating detrimental immune responses in the mucosal environment.

[Foreign bodies in the upper gastrointestinal tract. Personal experience]. / Corpi estranei del tratto digestivo superiore. Esperienza personale.

OBJECTIVE: Foreign bodies ingestion is a potentially serious problem. The majority of ingested foreign bodies pass spontaneously, but serious complications, such as bowel perforation and obstruction, can occur. In the present work, we report our experience in the management of ingested foreign bodies. MATERIALS AND METHODS: The study was observational and retrospective. We included in the study the foreign bodies ingestions occurred during urgent endoscopy (examination performed from 1 to 6 h by the call). RESULTS: Records of 696 consecutive EGDS performed in urgency at the Unit of Gastroenterology and Digestive Endoscopy of the Hospital Sandro Pertini of Rome, from 01-02-'04 to 18-01-2006, were analyzed retrospectively. Out of these procedures, 21 (3.01%) were performed for suspected foreign bodies ingestion. CONCLUSIONS: We present the initial report of our working experience. Objects that have passed the duodenum should be managed conservatively by radiographic surveillance and inspection of stool. Endoscopic or surgical approach is indicated when significant symptoms develop or if the object fails to progress through the gastrointestinal tract. The present data are in keeping with previous studies of the literature.

Placement of two overlapping uncovered metallic stents for malignant gastric outlet and duodenal obstruction due to colon cancer.

Malignant obstruction of the gastric outlet and duodenum is frequently due to extrinsic involvement by tumors from contiguous organs, in particular from pancreas and gallbladder. The treatment of malignant gastroduodenal stenoses is difficult. Many patients have advanced malignant disease and are too ill to undergo surgical approach. Surgical gastrojejunostomy has been considered the palliative treatment of choice. Metallic stents can be useful in this condition with adequate palliation obtained in most cases. We report a case in which self-expanding metallic stents were placed for stenoses of the gastric outlet and duodenum due to a colon cancer.

Comparison of two different daily dosages (2.4 vs. 1.2 g) of oral mesalazine in maintenance of remission in ulcerative colitis patients: 1-year follow-up study.

BACKGROUND: Mesalazine as maintenance therapy in ulcerative colitis is used worldwide and has been proven to be effective. However, the optimal dosage remains to be defined. AIM: To establish whether daily treatment with 2.4 g of oral mesalazine is more effective than 1.2 g in preventing disease relapse. METHODS: A total of 156 patients with ulcerative colitis in remission were randomly treated for 1 year with 2.4 (n = 80) or 1.2 (n = 76) g/day of mesalazine. Activity of disease was assessed by periodical clinical, endoscopic and histological examinations. RESULTS: After 12 months, 24 of 80 patients (30%) on 2.4 g and 20 of 76 patients (26%) on 1.2 g were still in remission (P = N.S.). Patients in 2.4 g group remained in remission for a longer time than those in 1.2 g group (P < 0.001). Among clinical variables considered in the study, course of disease prior to enrollment (< or = 3 or > 3 relapses/year) was found to influence response to therapy. CONCLUSIONS: A daily dosage of 2.4 g of oral mesalazine seems to better at preventing and delaying relapses of ulcerative colitis than 1.2 g. The course of disease seems to be crucial in choosing the optimal dosage of mesalazine in a maintenance regimen.

Beta-lactamase inhibition with clavulanic acid supplementing standard amoxycillin-based triple therapy does not increase Helicobacter pylori eradication rate.

BACKGROUND: Antibiotic resistance is the main reason of failure for H. pylori eradication and beta-lactamases produced by resistant H. pylori strains is a possible mechanism underlying ineffectiveness of an amoxycillin-based triple therapy. AIM: To investigate the benefit of using clavulanic acid associated with amoxycillin compared with amoxycillin alone in a standard triple therapy. METHODS: A total 172 H. pylori-positive dyspeptic patients were randomised to a daily treatment with esomeprazole (20 mg bid), clarithromycin (500 mg bid) and either amoxycillin plus clavulanic acid (1 g bid) or amoxycillin (1 g bid) alone for 1 week. H. pylori status was defined by histology and urea breath test at entry and following 8 weeks from the end of therapy by urea breath test and antigen faecal assessment. RESULTS: At intention-to-treat and per-protocol analysis eradication rates achieved by amoxycillin plus clavulanic acid (72 and 78%) were higher, but not significantly, than those achieved by amoxycillin alone triple therapy (62 and 72%). Compliance was good, side-effects mild and with a similar incidence in both regimens. CONCLUSIONS: Clavulanic acid supplemented to amoxycillin-based standard triple therapy does not significantly increase the H. pylori eradication rate with standard triple therapy.

One-week once-daily triple therapy with esomeprazole, levofloxacin and azithromycin compared to a standard therapy for Helicobacter pylori eradication.

BACKGROUND: Primary antibiotic-resistance and poor compliance are the main causes of Helicobacter pylori eradication failure of standard regimens. AIM: To investigate eradication rate, patient compliance and tolerability of a 1-week once-daily levofloxacin plus azithromycin triple therapy versus the standard twice-daily triple therapy. PATIENTS AND METHODS: A total of 164 H. pylori-positive patients were randomised to either esomeprazole 20mg, levofloxacin 500 mg and azithromycin 500 mg once-daily (ELAz) or esomeprazole 20mg, clarithromycin 500 mg and amoxycillin 1g twice-daily (ECA) for 1 week. H. pylori infection was defined at entry by histology and urea breath test; cure of infection was determined both by negative urea breath test and H. pylori stool antigens. RESULTS: H. pylori eradication rates of ELAz and ECA were similar at intention-to-treat (both 65%) and per-protocol analyses (70% versus 76%, respectively). Incidence of poor compliance was lower, although not significantly, in patients randomised to ELAz than to ECA (4% versus 10%); tolerability was significantly higher for ELAz than for ECA (88% versus 70%; P=0.01). CONCLUSIONS: Once-daily levofloxacin plus azithromycin-based triple therapy achieves an H. pylori eradication rate comparable to that of standard twice-daily triple therapy, but is associated with higher patient compliance and might even be better tolerated.

[Celiac disease, laboratory updates]. / Malattia celiaca, diagnostica di laboratorio.

A celiac disease update review and a case report are presented, especially concerning a Clinical Pathology Laboratory approach. Implemented basic research, case finding strategy and information technologies are the key tools for a better understanding of the multi-etiological features of this disease. By these tools it will be achieved appropriateness in diagnosing and monitoring of the related clinical pictures.

Efficacy of mesalazine or beclomethasone dipropionate enema or their combination in patients with distal active ulcerative colitis.

OBJECTIVE: Mesalazine or Beclomethasone dipropionate (BDP) enema have been shown effective in treatment of distal active ulcerative colitis (UC). This study was aimed to determine whether the combination of topical mesalazine and BDP is superior to topical mesalazine or BDP used alone in patients with distal active UC. PATIENTS AND METHODS: One-hundred and twenty patients with clinical, endoscopic and histological diagnosis of distal active UC were randomly assigned to a regimen with mesalazine tablets 2.4 g/day associated to either mesalazine enema 4 g/day (group A, n=40), BDP 3 mg/60 ml every day (group B, n=40) or the combination treatment with the two compounds in a single administration (group C, n=40) for eight weeks. After four weeks of treatment all patients underwent clinical controls but only 109 patients returned back for clinical, endoscopic and histological controls at the end of the treatment period. RESULTS: After eight weeks, complete remission rates were of 52%, 47% and 65% respectively, in group A, B and C. From baseline to 4 and 8 weeks the CAI score decreased significantly in all the three groups (p < 0.0001). CONCLUSIONS: All the three combinations achieved equivalent results in terms of symptoms in inducing symptoms relief and mucosa healing in distally active UC.

Azathioprine or methotrexate in the treatment of patients with steroid-dependent or steroid-resistant ulcerative colitis: results of an open-label study on efficacy and tolerability in inducing and maintaining remission.

BACKGROUND: The role of azathioprine and methotrexate in inducing and maintaining remission in patients with ulcerative colitis is still controversial. AIM: To evaluate the efficacy and tolerability of these two drugs in a series of patients with steroid-dependent or steroid-resistant active ulcerative colitis. METHODS: Forty-two patients were treated with a daily dose of azathioprine (2 mg/kg) and, if intolerant or not responding, with methotrexate (12.5 mg/week intramuscularly), and their efficacy was established by clinical, endoscopic and histological examinations at 6 months. Patients achieving clinical remission continued with treatment and were followed up. RESULTS: Of the 42 patients on azathioprine, 10 experienced early side-effects requiring withdrawal from treatment, 22 (69%) achieved complete remission, six (19%) achieved improvement and four (12%) obtained no substantial benefit. Methotrexate, administered to eight patients intolerant to and two patients resistant to azathioprine, induced complete remission in six patients (60%) and improvement in four (40%). During follow-up, a larger number of patients on azathioprine relapsed in comparison with patients on methotrexate [16/28 (57%) vs. 2/10 (20%), respectively; P < 0.05]. Only minor side-effects were observed on both treatments. CONCLUSIONS: Azathioprine is effective in patients with steroid-dependent or steroid-resistant ulcerative colitis. Methotrexate seems to be a good alternative in patients intolerant to or not responding to azathioprine.

Traumatic internal carotid artery dissection presenting as delayed hemilingual paresis.

A case of internal carotid artery dissection presenting as delayed right hemilingual paresis after blunt craniocervical trauma is presented. Diagnosis is discussed with emphasis on MR and MR angiographic findings. Mechanisms of injury and lower cranial nerve palsy are also briefly discussed.

Diffuse febrile dermatosis in a patient with active ulcerative colitis under treatment with steroids and azathioprine: a case of Sweet's syndrome. Case report and review of literature.

Ulcerative colitis is an inflammatory bowel disease often associated with extra-intestinal manifestations, such as dermatological disorders. Of these, the most frequent are erythema nodosum and pyoderma gangrenosum, the two neutrophilic forms of dermatosis. Another is Sweet' s syndrome, which results in a sudden eruption of tender, raised erythematous or violaceous plaques/papules or nodules, less frequent vesicles, pustules or bullae, involving face, neck, arms and trunk. This skin disorder is frequently observed in patients with leukaemia or connective tissue diseases, while it is very rare in patients with inflammatory bowel disease. The present report deals with the case of a febrile diffuse skin eruption in a 53-year-old patient with moderately active ulcerative colitis after few days' treatment with steroids and azathioprine. At first, the dermatosis was addressed to an idiosyncrasy to azathioprine, which was, therefore, promptly discontinued. Histological examination of skin biopsies revealed the presence of features typical of a Sweet's syndrome. The eruption gradually improved as well as the patient's general condition, until complete regression was achieved following steroid treatment.

Oral and topical 5-aminosalicylic acid (mesalazine) in inducing and maintaining remission in mild-moderate relapse of ulcerative colitis: one-year randomised multicentre trial.

BACKGROUND: The association of oral 5-aminosalicylic acid (mesalazine) and enema is effective in treatment of mild-moderate forms of ulcerative colitis. However no study has been aimed at determining optimal duration of this association in active ulcerative colitis. AIM: To determine whether longer duration of therapy: 1. increases the rate of patients achieving remission, and 2. reduces relapse rate during the maintenance period in patients in remission. PATIENTS AND METHODS: A total of 149 patients, (89 male, 60 female), were randomly assigned to a regimen with 5-aminosalicylic acid tablets 2.4 g/day associated with 5-aminosalycilic enema 2 g/day for a 4-week (n = 73) or 8-week regimen (n = 76). After this acute therapy, patients were submitted to clinical, endoscopic and histological examinations and those in remission were assigned to a follow-up (maintenance) period with oral mesalazine alone at a dosage of 1.2 g/day. A clinical visit, including laboratory tests, at 6 months and an endoscopic-histological control at 12 months were carried out to exclude symptoms and endoscopic-histological signs of activity. Relapse of disease, i.e., presence of clinical symptoms or abnormal laboratory tests, was confirmed by endoscopy and histology. RESULTS: At end of acute phase, clinical, endoscopic and histological remission was comparable in the two groups: 42/76 (55%), in the 4-week, and 47/73 patients (64%), in the 8-week regimen. No difference was found stratifying patients according to extension of disease. Of these 89 patients in remission, 75 (34 from 4-week regimen; 41 from 8-week regimen) completed 12 months' follow-up. At end of follow-up, a similar percentage of patients in the 4-week regimen (50%) and 8-week regimen (51%) were still in remission. No significant difference between cumulative relapse rates of the two groups was found. Stratifying patients according to extension of disease, in the 8-week regimen group, those with left-sided colitis showed a higher remission rate than that of patients with diffuse colitis (66% versus 35%, p < 0.05). All regimens were well tolerated by most patients during the entire study period. CONCLUSIONS: An additional 4 weeks of topical treatment does not increase the remission rate in patients with mild-moderate active ulcerative colitis but seems to reduce the probability of relapse in patients with left-sided colitis.

Sulphasalazine and 5-aminosalicylic acid in long-term treatment of ulcerative colitis: report on tolerance and side-effects.

BACKGROUND: Use of sulphasalazine in ulcerative colitis patients is hampered by a variety of side-effects, including male infertility. 5-aminosalicylic acid is better tolerated and has been increasingly used to treat patients intolerant/allergic to sulphasalazine but it may also be associated with side-effects. AIM: To evaluate tolerance of long-term treatment with sulphasalazine and 5-aminosalicylic acid in ulcerative colitis. METHODS: Side-effects to sulphasalazine (2-3 g/day) and 5-aminosalicylic acid (1.2-2.4 g/day) were recorded in 685 patients: 410 patients received only sulphasalazine, 130 only 5-aminosalicylic acid, and 145 both drugs. In patients with side-effects to sulphasalazine, a desensitisation protocol (rechallenge) was attempted to improve tolerance, and patients still presenting side-effects after desensitisation were switched to 5-aminosalicylic acid. Male fertility was also assessed in 42 males on sulphasalazine and on 5-aminosalicylic acid. RESULTS: Side-effects were observed in 110/555 patients (20%) on sulphasalazine and in 18/275 patients (6.5%) on 5-aminosalicylic acid during a median period of follow-up of 7 and 5 years, respectively. Desensitisation was achieved in 40% of patients intolerant to sulphasalazine. 5-aminosalicylic acid intake induced side-effects in 2/130 patients (1.5%) who had not taken sulphasalazine before versus 4/91 patients (4%) tolerating sulphasalazine and 12/54 patients (22%) intolerant/allergic to sulphasalazine, the difference in incidence of side-effects in the two latter groups being statistically significant (4.4% vs 20.8%, p=0. 001). Fertility was found to be affected in all patients on sulphasalazine but improved when put onto 5-aminosalicylic acid. CONCLUSIONS: 5-aminosalicylic acid should be considered the drug of choice in the treatment of ulcerative colitis bearing in mind that intolerance or allergy may occur in a few patients also on this drug.

An unusual finding in a peripheral blood smear of Plasmodium falciparum malaria.

An attack of hyperpyrexia, in a young Senegalese male resident in Rome on his return from a brief trip to Senegal, was recognized as Plasmodium falciparum malaria. In a Giemsa peripheral blood smear a merozoite cluster and haemozoin pigment were observed into a monocyte, as a phagocytosis outcome. This finding, unexpected in view of the relatively moderate severity of the disease, was likely to be expression of good immune response against the blood stages of P. falciparum.

Stimulation and expansion of a human T-cell subpopulation by a monoclonal antibody to T-cell receptor molecule.

A murine monoclonal antibody (MAb) was obtained that showed unique specificity for the immunizing T-cell line HPB-ALL. This antibody, C37 (an IgG1,K) also reacted with a small (2-5%) population of normal peripheral blood T (PBL-T) cells. These C37-positive (C37+) cells were found in both the T4/Leu3+ and T8/Leu2+ subsets. Like OKT3 antibody, C37 induced T-cell mitogenesis with a peak proliferative response at day 3. In long-term cultures containing irradiated autologous feeder cells and IL-2, C37 antibody caused the selective expansion of C37+ T cells. On HPB-ALL cells C37 induced comodulation of the T3 molecule. C37 precipitated a disulfide-linked dimer characteristic of the T-cell antigen receptor consisting of an alpha-subunit (45-48 kD) and a beta-subunit (38-42 kD) from both C37+ T-cell blasts of a normal individual and HPB-ALL cells that were surface radioiodinated. However, the precipitated molecule isolated from C37 antibody-activated T-cell blasts exhibited a different pI from that isolated from HPB-ALL cells. Our studies indicate that C37 recognizes an epitope on the T-cell receptor molecule that is shared by a subpopulation of human T cells, which raises the possibility that multiple variable-region associated and/or framework-like determinants of the T-cell antigen receptor can be defined serologically and used in functional and molecular studies of T-cell subsets.

[Comparison of the Waaler-Rose reaction and the optimized Singer-Plotz reaction]. / Confronto tra reazione di Waaler Rose e reazione di Singer e Plotz ottimizzata.

The latex reaction according to Singer & Plotz, an optimised version of the same employing heating at 56 degrees C for 24 hr, and the modified Rose-Waaler test were used to determine rheumatoid factor in the serum of 65 subjects, including 33 with rheumatic and joint diseases, 22 with liver diseases, and 10 presumed to be normal. This optimised latex test is put forward as a supplement to high sensitivity of the simple latex test, and the high specificity of the Rose-Waaler test. In the series examined, it gave results whose clinical comparability was at least on a par with that provided by the Rose-Waaler test.