Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP).

Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.

Outbreak of NDM-1-producing Enterobacteriaceae in northern Italy, July to August 2011.

Between July 2011 and August 2011, the New Delhi metallo-beta-lactamase 1 (NDM-1) gene was detected in Klebsiella pneumoniae and Escherichia coli isolates obtained from six patients hospitalised in four healthcare facilities in northern Italy. The patient who had been hospitalised in New Delhi, India, from February to May 2011 and subsequently in the Bologna area, Italy, from May to July 2011, may have been the source of the outbreak. Our findings suggest ongoing spread of this carbapenem-resistance gene in Italy and highlight the need for intensive surveillance.

The possible utility of steroids in the prevention of relapses of Crohn's disease in remission. A preliminary study.

In Crohn's disease, prednisone is believed to be ineffective for relapse prevention. Because all patients with Crohn's Disease Activity Index lower than 150 and with some altered lab tests (erythrocyte sedimentation rate, C-reactive protein, alpha-1-acid glycoprotein, alpha-1-acid antitrypsin, and white blood cell count) had a clinical relapse in 18 months of follow-up, we tried to ascertain whether methylprednisolone could reduce the risk of clinical relapse in such patients. Eighteen patients were included in a controlled study against placebo. Nine patients were treated with methylprednisolone at a dosage of 0.25 mg/kg daily for a period of 6 months; treatment was discontinued if disease relapsed or if lab tests were normalized. During the steroid treatment, 1 of 9 patients showed a clinical relapse; in 7, the normalization of lab tests was obtained; in 5 of these 7 patients a relapse occurred within 1 month after the suspension of the treatment; in 1 patient, lab tests remained altered. In those 9 patients on placebo, relapses occurred in 7. We conclude that methylprednisolone was effective in the prevention of relapses for patients in clinical remission but with altered lab tests.

Clinical course of Crohn's disease in Italy.

The clinical course of Crohn's disease in 131 patients was studied for a mean period of 4.2 +/- 3.2 years. The clinical activity of the disease, expressed as percentage of patients per year in an active phase, is high in the first year (70.2 percent) and progressively decreases during subsequent years (25 percent after seven years). The percentage of patients who needed steroid treatment is high during the first year (68 percent) and falls to 19 percent after seven years. An operative risk rate of 54 percent was registered, with a probability of reoperation equal to 34 percent. Clinical relapse after the first surgery occurred in 70 percent of cases. The registered mortality was 6.9 percent, with a ratio of 6 to 1 between observed and expected mortality. In conclusion, the disease, while showing a tendency to reduce its activity over the years, is burdened by a risk of surgery and mortality which progressively increases with time.

A laboratory index for predicting relapse in asymptomatic patients with Crohn's disease.

Currently there are no completely reliable methods for predicting an impending relapse in Crohn's disease. As approximately 50% of patients in remission [Crohn's disease activity index (CDAI) less than 150] show some laboratory abnormalities, we inquired whether these alterations might be of value for predicting relapse. We prospectively studied 41 patients with Crohn's disease who had been showing CDAI less than 150 for at least 6 mo before entering the study and who were not receiving any long-term treatment. The 41 patients were studied at the ninth and at the 18th month after inclusion in the study. Disease activity was monitored by CDAI calculation and by measurement of erythrocyte sedimentation rate, white blood cell count, hemoglobin, albumin, alpha 2-globulin, serum iron, C-reactive protein, alpha 1-glycoprotein, and alpha 2-antitrypsin. Seventeen of the 41 patients had a clinical relapse during follow-up. At the beginning of the study the patients who later relapsed showed a remarkable alteration of acid alpha 1-glycoprotein (p less than 0.0001), alpha 2-globulin (p less than 0.0003), and erythrocyte sedimentation rate (p less than 0.0006), in comparison with the patients who remained in remission. by discriminant analysis a prognostic index with these laboratory investigations provided a high percentage (88%) of accuracy according to the outcome at the 18th month.

Importance of laboratory parameters in the evaluation of Crohn's disease activity.

Some laboratory investigations are abnormal during the course of Crohn's disease (CD). We investigated the trend of some of these laboratory tests in a group of patients with CD to study the relationships between an activity index made up of such laboratory parameters only (LCDAI) and the usual Crohn's disease activity index (CDAI). One hundred thirty-one examinations of 63 patients were evaluated. At each investigation, besides calculation of the CDAI, 10 laboratory investigations were carried out. Three gastroenterologists independently gave an overall evaluation of the laboratory activity for each of the 131 examinations on the basis of the results of the blood tests alone. The sum of the evaluations was used as an independent variable on which a laboratory index was developed by multiple regression analysis. C reactive protein, red cell sedimentation rate, acid alpha 1-glycoprotein, alpha 1-antitrypsin, and white blood cells had an important share in the development of this laboratory index. The evaluation of the relationships existing between LCDAI and CDAI showed that in patients with moderate to severe clinical disease activity, LCDAI was constantly altered. The same happened in 55% of cases in clinical remission, which suggests an inflammatory activity that is not clinically evident. These results point to the advisability of supplementing a predominantly clinical index, such as CDAI, with a laboratory index such as LCDAI in the evaluation of CD.

Dietary allergy evaluated by PRIST and RAST in inflammatory bowel disease.

The role of allergic responses to dietary antigens in the pathogenesis of inflammatory Bowel Disease (IBD) remains speculative. We studied 50 patients with Ulcerative Colitis (UC), 50 patients with Crohn's Disease (CD) and 100 healthy controls (HC) matched for sex and age. In these patients total serum IgE and specific IgE to ten selected foods were estimated using Phadebas PRIST and RAST. There was no significant difference in the total serum IgE level between UC, CD and HC. The percentage of positive reaction to specific IgE was significantly lower in HC (score 1-2: 7%; score 2: 3%) compared with UC (score 1-2: 24%, p less than 0.004; score 2: 8%, n.s.) and CD (score 1-2: 16%, n.s.; score 2: 12%, p less than 0.03). In CD with colic or ileocolic involvement, the percentage of patients with a positive response to RAST was significantly greater (score 1-2: 26%; score 2: 21%) than in CD with ileal involvement. The considerable increase in positive results to RAST in IBD may be due to a greater absorption of antigens through the diseased wall.

Effect of colchicine on angiotensin receptors in rabbit aorta.

Colchicine (10(-5) M) significantly depressed the dose-response curve for angiotensin in isolated rabbit aortic strips. A lower maximal response was observed without apparent change in receptor affinity for angiotensin, as can be judged by unchanged ED50 values. Colchicine also diminished the dose-response curve for norepinephrine. The angiotensinase activity in cell membrane fraction and high-speed supernate was significantly inhibited. Colchicine did not change the specific receptor binding of radioactive angiotensin to either cell membrane fraction or supernate. It is concluded that colchicine possibly depresses the response to angiotensin through a mechanism involving a site beyond membrane receptors.

Separation of angiotensin receptor from cell membrane angiotensinase in rabbit aorta.

Deoxycholic acid (0.01%) diminished the tissue response to angiotensin in rabbit aortic strips. A lower maximal response was obtained, but the affinity of angiotensin receptors did not change. Specific angiotensin receptor binding was measured in cell membrane fraction, solubilised fraction and pellet fraction after solubilization. The solubilised fraction showed threefold increase in receptor binding and was devoid of angiotensinase activity. The binding to pellet fraction after solubilization was increased or unchanged and contained the same angiotensinase activity as before solubilization. We conclude that it is possible to separate angiotensin receptor from cell membrane angiotensinase.