Transplantation to save the life, TSH screening to save the brain: A report and brief literature review of autoimmune thyroid disease after HSCT for severe combined immunodeficiency.

Autoimmune thyroid disease has been described as a complication of HSCT for different indications and as a manifestation of inborn errors of immunity, like SCID. A 1-month female was diagnosed with RAG1-mutated SCID and received allogenic HSCT. She developed autoimmune hypothyroidism 5 months after transplantation and was treated with levo-thyroxine with a good response. Autoimmune thyroid disease can develop after HSCT during the immune reconstitution phase, leading to potentially severe neurological and growth impairment, particularly in SCID patients, often transplanted during the first year of life. Recommendations regarding early and frequent vigilance for thyroid function are needed in these patients.

A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation.

We analyzed the use of isavuconazole (ISA) as treatment or prophylaxis for invasive fungal disease (IFD) in children with hemato-oncologic diseases. A multicentric retrospective analysis was performed among centers belonging to the Italian Association for Pediatric Hematology and Oncology (AIEOP). Pharmacokinetic (PK) monitoring was applied by a high-performance liquid chromatography-tandem mass spectrometry (HLPC-MS/MS) assay. Twenty-nine patients were studied: 10 during chemotherapy and 19 after allogeneic hematopoietic stem cell transplantation (HSCT). The patients consisted of 20 males and 9 females with a median age of 14.5 years (age range, 3 to 18 years) and a median body weight of 47 kg (body weight range, 15 to 80 kg). ISA was used as prophylaxis in 5 patients and as treatment in 24 cases (20 after therapeutic failure, 4 as first-line therapy). According to European Organization for Research and Treatment of Cancer (EORTC) criteria, we registered 5 patients with proven IFD, 9 patients with probable IFD, and 10 patients with possible IFD. Patients with a body weight of <30 kg received half the ISA dose; the others received ISA on the adult schedule (a 200-mg loading dose every 8 h on days 1 and 2 and a 200-mg/day maintenance dose); for all but 10 patients, the route of administration switched from the intravenous route to the oral route during treatment. ISA was administered for a median of 75.5 days (range, 6 to 523 days). The overall response rate was 70.8%; 12 patients with IFD achieved complete remission, 5 achieved partial remission, 5 achieved progression, and 3 achieved stable IFD. No breakthrough infections were registered. PK monitoring of 17 patients revealed a median ISA steady-state trough concentration of 4.91 mg/liter (range, 2.15 to 8.54 mg/liter) and a concentration/dose (in kilograms) ratio of 1.13 (range, 0.47 to 3.42). Determination of the 12-h PK profile was performed in 6 cases. The median area under the concentration-time curve from 0 to 12 h was 153.16 mg·h/liter (range, 86.31 to 169.45 mg·h/liter). Common Terminology Criteria for Adverse Events grade 1 to 3 toxicity (increased transaminase and/or creatinine levels) was observed in 6 patients, with no drug-drug interactions being seen in patients receiving immunosuppressants. Isavuconazole may be useful and safe in children with hemato-oncologic diseases, even in the HSCT setting. Prospective studies are warranted.

Contact investigation based on serial interferon-gamma release assays (IGRA) in children from the hematology-oncology ward after exposure to a patient with pulmonary tuberculosis.

BACKGROUND: Interferon-gamma release assays (IGRAs) have high specificity and sensitivity for the diagnosis of tuberculosis (TB) infection. However, their role as a screening tool in children with immunodeficiency disorders is still unclear. In the present study, we performed a contact investigation using serial IGRAs on children with immunodeficiency conditions exposed to a contagious TB patient. METHODS: Children who were exposed to a contagious TB case underwent serial QuantiFERON(®) TB Gold In-Tube (QFT-GIT) and T-SPOT(®).TB (T-SPOT) testing. RESULTS: Eighteen children were tested. At the first testing, only two children (11 %) were positive to T-SPOT. Indeterminate results were more frequent with QFT-GIT (35 %) than with T-SPOT (12 %). In the multivariable analysis, a statistically significant association of lymphocyte count <500 cells/mm(3) (p < 0.00005) and low age (p = 0.03) with indeterminate results for the QFT-GIT test but not for T-SPOT (p = 0.10 and p = 0.88, respectively) was found. At the end of October 2012, 15 of the 18 children were alive and none developed active TB disease. CONCLUSION: T-SPOT provided more determinate results and was less influenced by low age and lymphocytopenia than QFT-GIT in this population of immunodeficient children. These findings suggest that T-SPOT is a more accurate test for the identification of TB infection in young children with lymphocytopenia and should be preferred to QFT-GIT under such specific conditions.

Stem cell transplantation for primary immunodeficiencies.

BMT is curative in almost 75% of children affected by severe primary immunodeficiencies (PIDs). Recently, the chance of cure has increased thanks to the availability of matched unrelated donors (MUDs). Nevertheless, besides the conventional indications to BMT (profound or absent T-cell function, profound or absent natural killer function, known syndromes with T-cell deficiencies), indications to BMT for PIDs affecting the quality of life or having an expectation of life that does not exceed the third-fourth decade remain unclear. Infact, if it is evident that the survival rate in an infant grafted for a PID with a MUD is expected to be more than 80%, alternative treatments such as gene therapy are now available.

[Perinatal risk factors for infection in the newborn. Multicenter clinico-epidemiologic investigation]. / Fattori perinatali di rischio d'infezione nel neonato. Indagine multicentrica clinico epidemiologica.

UNLABELLED: The neonate, in particular if preterm, has a specific immunological system that makes him/her more susceptible to infections which are still a major cause of mortality and morbidity. The early onset infective patterns are often vertically transmitted from the mother to the fetus in the perinatal period. Some mother conditions like genitourinary infections, pre-delivery fever, PROM, pPROM, preterm delivery, abortions, fetal demise are important neonatal risk factors. The role of these factors as causes of early onset neonatal infections was evaluated by an Italian multicentric epidemiologic investigation supported by the MIUR. Mothers admitted to obstetrician hospitals for parturition were studied in a case control retrospective analysis. Mothers presenting with the selected risk factors were the cohort of cases while the admissions without risk factors next to each case represented the controls. The following risk factors were considered for analysis: 2nd trimester abortion, PROM, pPROM, preterm delivery and fetal demise. Eight hospitals entered the multicentric research and 29610 patients have been analyzed: 2466 PROM, 478 pPROM, 946 preterm delivery, 244 abortions, 133 fetal demise. Every woman received a microbiological screening by cervico-vaginal and rectal swab and/or urine culture. As much as 3892 cases from the University Hospitals of Parma and Torino concern, the cervicovaginal swab was positive in 76.5% pPROM, in 50.6% PROM and 50.5% preterm deliveries. The positivity of the swabs showed statistical relevance in cases compared to controls. In cases presenting with abortion the frequency of positive cultures (44.1%) was higher than the controls, but it did not reach statistical relevance. Conversely, positivity of cultures was lower in cases with fetal demise than control group but without statistical difference. In the cohort of 675 women selected from our Institute (University of Parma) the overall rate of positivity of cervico-vaginal swabs was about 44% and only one germ was isolated in 94.6% cases: 49,8% Gram positive and negative, 14.1% Streptococcus hemolyticus B group, 34.7% Candida. The rate of cultural tests performed before delivery was statistically higher in cases than controls (74.3% vs 23.2%, p < 0.001). Furthermore 14.3% newborns from mothers in the case group and 2.3% newborns from mothers in the control group were admitted to the neonatal care unit. Among them 8.4% and 1.2% respectively needed antibiotics while 0.4% and 0.2% respectively presented with early onset infection. Ear swabs were performed in 48,8% of infants born to mothers from the case group and in 26.9% of infants born to mothers from the control group, in 6.5% and in 2.9% respectively were the skin swabs performed as well. No statistical difference was met. The choice to perform cultural examinations was statistically higher in cases than controls, but the positivity rate was similar in both groups, perhaps because of a more specific choice in the control group. CONCLUSION: our data confirm the relationship between infections and preterm delivery, PROM, pPROM and support the hypothesis that infections might be the cause of these conditions and not simply an association. A prompt maternal microbiological control during pregnancy and delivery, especially in women presenting with known risk factors, gives the possibility to do early diagnostic-therapeutic interventions and to minimize the frequency and severity of early sepsis in newborns.

[Intraepithelial cervical carcinoma and HIV. Prevalence, risk factors and prevention strategies]. / Carcinoma cervicale intraepiteliale ed HIV. Prevalenza, fattori di rischio e strategie di prevenzione.

BACKGROUND: The present study analyses cervical dysplastic lesions associated with HIV infection by means of cytological, colposcopic and histologic examinations, and the diagnostic accuracy of the Pap test. METHODS: Cross-sectional study. We have studied colposcopic and histologic findings of 115 HIV-positive women. In 86 patients a cytological examination was also carried out. The results were compared with those of a control group consisting of 127 HIV-negative women in pre-menopause age. RESULTS: The prevalence of cervical dysplastic lesions present at colposcopic/bioptic examination was 3.2 times greater in HIV+ women than in HIV- women (38% vs 12%, p<0.001) and that of lesions of a higher degree 7 times greater. Compared to non-HIV+ women, patients who were positive presented more severe dysplastic lesions, a higher frequency of HPV-derived lesions and inflammatory pictures. There was also a correlation between high incidence of dysplastic cervical lesions and advanced stage of immunodepression. The negative predictive value of the Pap test was higher in the seronegatives (95%) than in the seropositives (83%, p<0.01). The overall agreement between cytology and colposcopy/histology was greater in the seronegati-ves than in the seropositives (87% vs 74%, p<0.05). CONCLUSIONS: Cervical dysplastic lesions in seropositive patients are more frequent and aggressive than in HIV negatives and are related both to the degree of immunodepression and to the HPV infection. Further, the diagnostic value of the Pap test in association with HIV is reduced. These results suggest that in HIV+ patients careful combined cytological-colposcopic screening should be adopted, together with an attentive cyto-colposcopic follow-up in treated patients.