Identification of the novel HLA-DPA1*01:130 allele by next-generation sequencing.

The novel HLA-DPA1*01:130 allele differs from HLA-DPA1*01:03:01:03 by one nucleotide substitution in Exon 3.

The new HLA-DQB1*05:304 allele identified in an Italian patient.

DQB1*05:304 allele was identical to DQB1*05:02:01 except for a single nucleotide substitution.

Identification of the novel allele, HLA-A*02:653, in an Italian patient.

HLA-A*02:653 differs from A*02:01:01:01 by a C to T substitution in exon 2.

Characterization of the novel HLA-C*02:106 allele in a hematopoietic stem cell volunteer donor.

HLA-C*02:106 allele differs from C*02:02:02:01 by a C to T substitution in exon 4.

A nucleotide insertion in Exon 2 is responsible for a new HLA-DRB1 null allele, HLA-DRB1*14:166N.

DRB1*14 is identical to DRB1*14:54:01 except for a single nucleotide insertion of A in position 175 in Exon 2.

Influence of the HLA characteristics of Italian patients on donor search outcome in unrelated hematopoietic stem cell transplantation.

The information regarding the probability of finding a matched unrelated donor (MUD) within a relatively short time is crucial for the success of hematopoietic stem cell transplantation (HSCT), particularly in patients with malignancies. In this study, we retrospectively analyzed 315 Italian patients who started a search for a MUD, in order to assess the distribution of human leukocyte antigen (HLA) alleles and haplotypes in this population of patients and to evaluate the probability of finding a donor. Comparing two groups of patients based on whether or not a 10/10 HLA-matched donor was available, we found that patients who had a fully-matched MUD possessed at least one frequent haplotype more often than the others (45.6% vs 14.3%; P = 0.000003). In addition, analysis of data pertaining to the HLA class I alleles distribution showed that, in the first group of patients, less common alleles were under-represented (20.2% vs 40.0%; P = 0.006). Therefore, the presence of less frequent alleles represents a negative factor for the search for a potential compatible donor being successful, whereas the presence of one frequent haplotype represents a positive predictive factor. Antigenic differences between patient and donor observed at C and DQB1 loci, were mostly represented by particular B/C or DRB1/DQB1 allelic associations. Thus, having a particular B or DRB1 allele, linked to multiple C or DQB1 alleles, respectively, might be considered to be associated with a lower probability of a successful search. Taken together, these data may help determine in advance the probability of finding a suitable unrelated donor for an Italian patient.

Prospective assessment of peripheral neuropathy in Duodopa-treated parkinsonian patients.

BACKGROUND: Although peripheral neuropathies (PN) have been described in patients with Parkinson's disease (PD) treated with oral dopaminergic therapies, anecdotal reports of subacute severe PN have been reported during treatment with enteral levodopa/carbidopa infusion (Duodopa). AIM OF THE STUDY: We prospectively assessed clinical and electrophysiological data of 15 consecutive patients with PD treated with Duodopa for a mean follow-up of 9 months. METHODS: Nerve conduction studies and a clinical evaluation with a standardized battery of peripheral neuropathy scales were performed at baseline and after a mean follow-up of 9 months. RESULTS: At baseline, mild signs of PN were observed in three subjects, and vitamin B12 serum levels were found to correlate with the amplitude of sural sensory action potentials. Follow-up data were available for 10/15 subjects: one patient developed a subacute sensory-motor PN and three subjects with pre-existing PN showed a moderate worsening of electrophysiological and clinical features. Subclinical electrophysiological alterations of peripheral nerves were observed in two subjects. No significant changes were observed in vitamin B12, folate, homocysteine and methylmalonic acid levels. CONCLUSIONS: In this consecutive series of patients treated with Duodopa, we observed one subacute sensory-motor PN and few length-dependent alterations of peripheral nerves, similar to those described during oral levodopa treatment.

A new allele, HLA-DQB1*04:09.

The novel allele HLA-DQB1*04:09 differs from DQB1*04:02:01 by three nonsynonymous nucleotide substitutions in exon 2.

[Survey on the prevalence, duration and exclusivity of breastfeeding in the province of Rieti, Italy]. / Indagine su prevalenza, esclusività e durata dell'allattamento al seno nel territorio reatino.

BACKGROUND: The aim of the survey was to estimate the prevalence, duration and exclusivity of breastfeeding (AS) in the province of Rieti, using standardized indicators, for further assessment. METHODS: this is an observational prospective study, through questionnaires self-administered to parents of children receiving the first two vaccinations mandatores. The survey was conducted in the outpatient paediatric vaccine clinics and attended by parents of 198 children born in 2010, who carried out the vaccinations required by law in the first six months of life. The main outcome measures were the prevalence of exclusive breastfeeding (AE), predominant breastfeeding (AP), partial breastfeeding (AC) and with formula feeding only (not AS) after three and six months in postpartum. Have been also studied a number of factors that may affect the ability of the mothers to breastfeed and its continuation. RESULTS: At 3 months of age, the proportion of infants who were being breastfed was 65.5%, (AE 39.7%, AP 11.7%, 14.1% AC), while, after 5 months in postpartum the proportion of any AS was 51.7% ( AE 18.5%, AP 15.6% and 17.9% AC). Based on the regression model, significant associations were observed between AS complete at the 3rd and 5th month, and natural delivery (OR 2.6, respectively, and OR 1.9); having breastfed her son during the first 48 hours of birth was associated with increased prevalence of AS at 3rd month (OR 3.5), but it was not significant associated at the 5th month. Pre-term birth reduces significantly the probability of BF (OR 0.3) at the first vaccination. The use of pacifiers has been associated with reduced prevalence and early discontinuation of BF (respectively, OR 0.2 at 3rd month and OR 0.3 at 5th month). CONCLUSION: The survey confirms the need to assist the new mothers in the postpartum to promote the practice of exclusive breastfeeding and its continuation. The identification of specific risk groups, such as women who have caesarean delivery or who started late lactation, allows health professionals to act with greater awareness and achieve greater efficiency in interventions.

Genotypes and haplotypes in the 3' untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia.

Polymorphisms in the 3' untranslated region (3'UTR) of HLA-G, an important player in immunological tolerance, could be involved in post-transcriptional expression control, and their association with different clinical immune-related conditions including autoimmunity and transplantation is of mounting interest. Most studies have focused on a 14 base pair (bp) insertion/deletion (ins/del), while additional single-nucleotide polymorphisms (SNPs) in the HLA-G 3'UTR have been described but not extensively investigated for their clinical relevance. Here we have comparatively studied the association between 3'UTR haplotypes of HLA-G, or the 14 bp ins/del, with clinical outcome of HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in 147 Middle Eastern beta-thalassemia patients. Sequence based typing of 3'UTR HLA-G polymorphisms in the patients and in 102 healthy Italian blood donors showed strong linkage disequilibrium between the 14 bp ins/del and five 3'UTR SNPs, which together could be arranged into eight distinct haplotypes based on expectation-maximization studies, with four predominant haplotypes (UTRs1-4). After HSCT, we found a moderate though not significant association between the presence of UTR-2 in double dose and protection from acute graft versus host disease (hazard ratio (HR) 0.45, 95% confidence intervals (CI): 0.14-1.45; P = 0.18), an effect that was also seen when the corresponding 14 bp ins/ins genotype was considered alone (HR 0.42, 95% CI: 0.16-1.06; P = 0.07). No association was found with rejection or survival. Taken together, our data show that there is no apparent added value of considering entire 3'UTR HLA-G haplotypes for risk prediction after allogeneic HSCT for beta-thalassemia.

Characterization of the novel HLA-C*07:195 allele in an Italian hematopoietic stem cell volunteer donor, detected by sequence-based typing.

The new allele shows one nucleotide change from C*07:02:01:01 at 351 nt from C to A, resulting in an amino acid change at codon 93 of exon 3 from H to Q.

The novel HLA-C*06:58 allele, identified by sequence-based typing in an Italian family.

The novel HLA-C allele C*06:58 shows one nucleotide change from C*06:02:01:01 at nt 366 from G to A, resulting in an amino acid change at codon 98 of exon 3 from Met to Ile.

Identification of the new HLA-A*31:48 allele in an Italian patient.

Human leukocyte antigen (HLA) class I sequence-based typing (SBT) for hematopoietic unrelated donor searching in an Italian Caucasian patient showed the presence of a novel HLA-A allele defined as A*31:48. HLA-A*31:48 has one nucleotide change from A*31:01:02 at nt 727 from C to T, resulting in an amino acid change at codon 219 of exon 4 from Arg to Trp.

Distribution of HLA alleles and haplotypes in the Maldivian population.

The study of human leukocyte antigen (HLA), allele and haplotype frequencies within populations provides an important source of information for anthropological investigation, organ and hematopoietic stem-cell transplantation purposes as well as disease association studies. As of today, there are no data available in the literature on the HLA structure of the Maldivian population. Altogether 106 families were studied. We used the parents of each family (212 unrelated individuals) to analyze the frequencies of HLA class I and class II allele groups and haplotypes.

Infliximab efficacy in nail psoriasis. A retrospective study in 48 patients.

BACKGROUND: Nail psoriasis occurs in up to half of psoriatic patients and can lead to significant physical impairment and pain. To date, patients and clinicians are actually dissatisfied by current therapeutic approaches. OBJECTIVE: Our main aim is to evaluate Infliximab efficacy in nail psoriasis. METHODS: We performed an open-label and uncontrolled retrospective study considering all psoriatic patients presenting recalcitrant nail involvement and receiving Infliximab in our Department during the period between January 2008 and March 2009. We calculated nail psoriasis severity index (NAPSI) score at 0, 14, 22 and 38 weeks and percentage of patients achieving NAPSI-50,-75,-90 at 14, 22 and 38 weeks. RESULTS: We observed a rapid nail improvement in most cases after 22 weeks of Infliximab therapy, but a complete nail clearing was reached in only five (10.4%) patients. We don't have a follow-up longer than 38 weeks to assess long-term efficacy of this treatment in nail psoriasis. CONCLUSIONS: Infliximab, in our experience, has proved to be effective in reducing nail lesions and, in some cases, even clearing them. Our data demonstrate long-term efficacy of this biological agent in nail psoriasis.

Intense pulsed light in the treatment of non-aesthetic facial and neck vascular lesions: report of 85 cases.

BACKGROUND: Intense pulsed light (IPL) treatment is one of the most effective procedures for patients with non-aesthetic vascular lesions in addition to signs of skin photoageing, and it has been reported as very successful in the treatment of telangiectasias, spider nevi, erythrosis, and above all, rosacea and poikiloderma. Its use is based on the principle of selective photothermolysis, which exploits the haemoglobin absorption peak among its range of wavelengths. OBJECTIVE: The aim of this study is to assess the efficacy and safety of intense pulsed light in treating non-aesthetic vascular skin lesions, especially with regard to poikiloderma of Civatte and rosacea. METHODS: A total of eighty-five patients, 64 women and 21 men, with 63 non-aesthetic vascular lesions (28 Poikiloderma of Civatte and 35 rosacea), 22 pigmented lesions (UV-related hyperpigmentation of solar lentigo-type) and four precancerous lesions (actinic keratosis, AKs), were treated repeatedly with IPL for 2 years. The patients received a mean of five treatments (range 4-6) at 3-weekly intervals. They were evaluated via clinical observations and professional photographs were taken before each treatment and after 2 weeks, 4 weeks, 3 months, 6 months and 12 months. The outcome of the IPL treatments was evaluated by four independent dermatologists, who were not informed about the study protocol, and who assessed the performance of IPL by dividing the results into four categories: no results, slight improvement, moderate improvement and marked improvement. RESULTS: All the patients showed improvements in their overall lesions: 72 lesions (80.9%) achieved a marked improvement, 14 lesions (15.7%) achieved a moderate improvement and three lesions (3.4%) achieved a slight improvement. The results of the 63 non-aesthetic vascular lesions in Rosacea and Poikiloderma of Civatte were: 51 with a marked improvement, 10 with moderate improvement, whereas only two lesions achieved a slight improvement. The improvement of all four actinic keratoses was marked whereas the 22 pigmented lesions obtained a marked improvement in 17 cases, a moderate improvement in four cases and a slight improvement in one case. No undesirable effects were observed. CONCLUSIONS: Our study confirms how by minimizing side-effects, time and costs, IPL can be effective and safe for the treatment of non-aesthetic facial and neck vascular lesions.

La determinación de PTH intraquirúrgica o posquirúrgica por quimioluminiscencia predice la hipocalcemia en el posoperatorio de la tiroidectomía en niños / Determination of PTH during or post surgery for quimioluminiscency can predict hypocalcemy in the post surgery children´s thyroidectomy

Objetivo: Evaluar la eficacia diagnóstica de la determinación de PTH en muestras de plasma tomadas durante la cirugía (intra) y posquirúrgica inmediata para predecir el riesgo de desarrollar hipocalcemia en el postoperatorio de la tiroidectomía total en pacientes pediátricos. Métodos: Se llevó a cabo un estudio de cohortes,prospectivo, longitudinal con 20 pacientes pediátricos en los que se practicó tiroidectomía total. Se determinaron los niveles de PTH preoperatorios, intraoperatorios y en el período posquirúrgico inmediato (basal, 5 y 60 minutos de la remoción de la glándula tiroides) utilizando un ensayo automatizado quimioluminiscente (IMMULITE, Siemens), límite de cuantificación 8 pg/mL, CV intra e interensayos < 5,4%. Para este estudio, la concentración de PTH de cada paciente no fue conocida por el equipo tratante hasta el final del mismo. Además se determinó la concentración en suero de Calcio total (Ca T) y/o Calcio iónico (Cai) regularmente durante las 48 hs posquirúrgicas y se controló la presencia de síntomas o signos de hipocalcemia. Se consideró hipocalcemia Ca T < 8 mg/dl y/o Cai < 0,8 nmol/L. Se realizó un análisis por curva ROC para determinar el nivel de PTH que fuera más eficaz en predecir la aparición de hipocalcemia según su sensibilidad (S), especificidad (E), eficiencia diagnóstica (ED) y Valor Predictivo Positivo (VPP). Resultados: Diez de los 20 pacientes (50%) desarrollaron hipocalcemia y 3 de ellos presentaron síntomas. La presentación de hipocalcemia sucedió: 40% en las primeras 6 hs y 40% a las 24 hs.vel de PTH en la muestra intraoperatoria < 14 pg/ml mostró S: 80%, E: 100%, ED: 90% (IC95%: 73-100) y VPP: 100% para predecir hipocalcemia posquirúrgica. En la muestra posquirúrgica inmediata, la concentración de PTH < 14 pg/ml presentó S: 80%, E: 90%, ED 82% (IC95% 63-100) y VPP 90% para predecir hipocalcemia posquirúrgica. Cuando la PTH intraquirúrgica o posquirúrgica es <14 pg/ml el riesgo relativo de presentar hipocalcemia postiroidectomía es de 9. Conclusiones: La medición de PTH intraquirúrgica y posquirúrgica es una herramienta eficiente para predecir hipocalcemia posquirúrgica por tiroidectomía total en la población pediátrica. Esta detección permite la inmediata decisión sobre el tratamiento suplementario con calcio en los pacientes de riesgo mejorando su evolución y evitando la presentación de tetania y otros síntomas de hipocalcemia. Además, permitiría disminuir los controles en los pacientes que evolucionarán con normocalcemia, reduciendo en ambos grupos de pacientes los costos de internación.