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Toxoplasma gondii is one of the most common protozoan parasites and is widely present in all warm-blooded animals. Although clinical disease is uncommon, some species, including ring-tailed lemurs (Lemur catta), have been found to develop acute and lethal toxoplasmosis. The aim of this study was to describe the pathologic, immunohistochemical, serological, and molecular findings of an outbreak of fatal toxoplasmosis in three captive ring-tailed lemurs in Central Italy in 2009. The animals died acutely within few days. The necropsy was immediately performed; necrotic lesions in the spleen, liver, and kidney, as well as interstitial pneumonia, were found histologically. All animals had high titers of anti–T. gondii-specific antibodies (1:1280 IgM and 1:640 IgG) according to a modified agglutination test (MAT) and immunohistochemistry showed scattered tachyzoites in the target organs. Diagnosis was confirmed by PCR and clonal type II was identified. In addition, the seven co-habiting lemurs were seronegative. This paper reports the first outbreak of acute disseminated toxoplasmosis in captive ring-tailed lemurs in Italy. These findings confirm the high susceptibility of this endangered species to toxoplasma infection, which may be considered a further threat to captive population viability. [ABSTRACT FROM AUTHOR]

Since the inception of industrial plasma fractionation during the Second World War, a succession of protein therapies isolated from plasma have determined the volume of plasma requiring collection, and have also shaped the economics of the industry. These so-called plasma drivers have successively included albumin, coagulation Factor VIII (FVIII) and, for the past thirty years, intravenously (IV) and subcutaneously (SC) administered immunoglobulin (IG) solutions. The sale of IG underpins the profitability of the industry and has experienced continuous growth over the past decades, as the result of growing clinical demand. Modelling this demand using decision analysis indicates that supplying the evidence-based indications for IG therapies will generate a need for IG which exceeds the current plasma collection capacity of most countries. A notable exception to this situation is the United States (US) of America, whose population of compensated plasma donors generates two thirds of the global supply of plasma for fractionation. The US is also the leading consumer of IG, and its health care providers pay the highest price for the product globally. Shortages of IG occur whenever the demand for the product outstrips the supply. Current shortages, following other historical periods of shortage, threaten the well-being of patients dependant on these products and incur heavy costs on health systems. In Italy, the national blood system, which is based on voluntary unpaid donors, reflects a policy of national self-sufficiency in blood-derived therapies (a strategic objective of the national blood system itself), based on solidarity as an ethical principle. This system has increased the collection of plasma for fractionation by 3.8% per annum over 2008-2017, in accordance to a plan for plasma procurement targeting a collection rate of 14.1 L of plasma per thousand (10 3 ) population by 2020. Over the same period, IG usage has increased by 8.5/per annum, to 89.2 g IG/10 3 population. In this paper, we review the factors which, increasingly, are causing an imbalance between the global supply and demand for IG, and we assess Italy's capacity to ensure that increasing this level of independence is no longer simply an ethical, but also an economic imperative, with implications for the security of Italy's health system.

Background: Equine piroplasmosis is caused by two tick-borne protozoan parasites, Theileria equi and Babesia caballi,, which are clinically relevant in susceptible horses, donkeys, and mules. Moreover, equine piroplasmosis significantly constrains international trading and equestrian events. Rapidly diagnosing both parasites in carrier animals is essential for implementing effective control measures. Here, a rapid immunochromatographic test for the simultaneous detection of antibodies to T. equi and B. caballi was evaluated using samples from horses and donkeys collected in Greece, Israel, and Italy. The results were compared with an improved competitive enzyme-linked immunosorbent assay (cELISA) for detecting antibodies to both parasites using the same panel of samples. Methods: Blood samples were collected from 255 horses and donkeys. The panel consisted of 129 horses sampled at four locations in northern Greece, 105 donkeys sampled at four locations in Sicily, and 21 horses sampled at two locations in Israel. The rapid test and the cELISA were performed according to the manufacturer's instructions, and the results were subjected to a statistical analysis to determine the sensitivity and specificity of both tests and their association. Results: The immunochromatographic test provided a result within 15 min and can be performed in the field, detecting both pathogens simultaneously. The overall coincidence rate between the rapid test and the cELISA for detecting antibodies against T. equi was 93% and 92.9% for B. caballi. The rapid test's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for T. equi were above 91.5%. Sixteen samples were positive for both parasites in the rapid test and eight in the cELISA. Either test had no significant association between T. equi and B. caballi detection. The detection rates of both parasites were significantly higher in Italy than in Greece or Israel and in donkeys than in horses. The agreement for T. equi between the results of both tests was high in Greece (93.8%) and Italy (95.2%) and moderate in Israel (76.2%). For B. caballi, the specificity and NPV of the rapid test were high (94.2% and 98.3%, respectively), although the sensitivity and PPV were moderate (69.2% and 39.1%, respectively) due to the small sample size. However, for B. caballi, the sensitivity was higher with the rapid test. Conclusions: The rapid test detected T. equi and B. caballi simultaneously in the field, potentially replacing laborious cELISA testing and is recommended for import/export purposes. The test can also be helpful for the differential diagnosis of clinical cases, since seropositivity may rule out equine piroplasmosis since it does not indicate current or active infection. [ABSTRACT FROM AUTHOR]

Background: Chronic Fatigue Syndrome (CFS) is a distinctive syndrome characterized by specific symptoms cluster. CFS mostly affects women and often results in severe functional limitation. Its prevalence varies from 0.4 to 2.5% in the general population. In our prior studies on the clinical features of 205 CFS patients we founded immunological and brain abnormalities. In this paper we illustrate our caseload on CFS treatment., Patients and Methods: From January 2000 to December 2005, we evaluated all the patients admitted at the CFS Unit of the Aviano National Cancer Institute, for staging procedures and treatments. Patients not meeting the Fukuda diagnostic criteria were excluded., Results: 250 male and 491 female (median age 35.5 and 39.3 years, respectively) were enrolled and treated for CFS. As expected, CFS resulted from previous infectious disease in all patients. Female patients showed to be more affected by symptoms than male patients. The treatment schedules followed by the patients included nutritional supplements alone, corticosteroids, antidepressant/sedative drugs, and antiviral/immunoglobulin drugs. Antiviral/ immunoglobulin drugs achieved the best response (15.3% positive responses vs. 8.3% negative responses; OR 0.44, CI 0.26-0.74, p = 0.002). The carrying out of 4 or more treatments showed a protective effect (OR 0.46, CI 0.28-0.77, p = 0.003). This finding was confirmed in the multivariate analysis, adjusted by type of drugs (OR 0.49, CI 0.28-0.84, p = 0.009) and number of treatments carried out (OR 0.51, CI 0.30-0.86, p = 0.01); these two variables were independent., Conclusions: These findings show that the antiviral/immunoglobulin approach has a longer positive disease free survival in comparison with other approaches. However, CSF still remains a difficult disease to be effectively treated.

Background: Monoclonal antibodies directed against the epidermal growth factor receptor (EGFR) have been approved for the treatment of patients with metastatic colorectal carcinoma (mCRC) that do not carry KRAS mutations. Therefore, KRAS testing has become mandatory to chose the most appropriate therapy for these patients. Methodology/Principal Findings: In order to guarantee the possibility for mCRC patients to receive an high quality KRAS testing in every Italian region, the Italian Association of Medical Oncology (AIOM) and the Italian Society of Pathology and Cytopathology -Italian division of the International Academy of Pathology (SIAPEC-IAP) started a program to improve KRAS testing. AIOM and SIAPEC identified a large panel of Italian medical oncologists, pathologists and molecular biologists that outlined guidelines for KRAS testing in mCRC patients. These guidelines include specific information on the target patient population, the biological material for molecular analysis, the extraction of DNA, and the methods for the mutational analysis that are summarized in this paper. Following the publication of the guidelines, the scientific societies started an external quality assessment scheme for KRAS testing. Five CRC specimens with known KRAS mutation status were sent to the 59 centers that participated to the program. The samples were validated by three referral laboratories. The participating laboratories were allowed to use their own preferred method for DNA extraction and mutational analysis and were asked to report the results within 4 weeks. The limit to pass the quality assessment was set at 100% of true responses. In the first round, only two centers did not pass (3%). The two centers were offered to participate to a second round and both centers failed again to pass. Conclusions: The results of this first Italian quality assessment for KRAS testing suggest that KRAS mutational analysis is performed with good quality in the majority of Italian centers. [ABSTRACT FROM AUTHOR]

Simkania negevensis, a recently found Chlamydia-like organism, has been associated with respiratory infections in children and adults with pneumonia, but S. negevensis findings have been common also without any infection. The aims of the present paper were to evaluate S. negevensis in the aetiology of paediatric community-acquired pneumonia (CAP), its seroprevalence in north Italian children, and whether there is cross-reactivity between S. negevensis and Chlamydia pneumoniae serology. Antibodies to S. negevensis were measured by microimmunofluorescence (MIF) in 101 frozen paired sera obtained from children with CAP. Serological evidence (>/=4-fold increase or decrease in IgM or IgG) of acute S. negevensis infection was achieved in 5 (5%) cases. Two were mixed infections with Mycoplasma pneumoniae and 1 with respiratory syncytial virus. In total, 20-30% of the children had measurable antibodies to S. negevensis, with no association with age. No cross-reactivity was observed between antibodies to S. negevensis and C. pneumoniae. S. negevensis appears to be a real, though rare, cause of CAP in children. [ABSTRACT FROM AUTHOR]

Keywords: diagnosis; heparin-induced thrombocytopenia; vaccine-induced immune thrombotic thrombocytopenia (VITT) EN diagnosis heparin-induced thrombocytopenia vaccine-induced immune thrombotic thrombocytopenia (VITT) e91 e95 5 04/25/23 20230515 NES 230515 To the Editor, Although relatively rare, heparin-induced thrombocytopenia (HIT) is a potentially ominous side effect of heparin treatment and must be promptly recognized to prevent serious consequences [[1]]. However the period analyzed was relatively short and no notable changes in the operative setting of laboratories performing HIT diagnostics were reported, with the exception that a few additional laboratories established the functional assay after VITT emergence. Moreover, the rise in anti-PF4 testing in the period after the VITT uprise (total tests/year=4,790) lies above the 95% CIs of the projected progressive increase of testing based on the trend in the previous three year (n=3,364) (Supplementary Figure 2). [Extracted from the article]

The advent of vaccines against SARS-CoV-2 has drastically reduced the level of hospitalization with severe COVID-19 disease in infected individuals. However, the diffusion of variants of concern still challenge the protection conferred by vaccines raised against the wild-type form of the virus. Here, we have characterized the antibody response to the BNT162b2 (Comirnaty) mRNA vaccine in patients infected with the Omicron variant. We analyzed a population of 4354 vaccinated healthcare workers (HCW) from 7 different hospitals in Italy and monitored infection with SARS-CoV-2 Omicron. We correlated infection with the antibody response after vaccination. We found that a lower level of IgG, younger age, and the presence of allergies correlate with increased infection during the Omicron wave, and that infections correlate with wild-type spike protein antibody titers below 350 BAU/mL. These results support the necessity of a fourth booster dose, particularly for individuals with lower levels of antibodies. [ABSTRACT FROM AUTHOR]

Background: US Food and Drug Administration has issued Emergency Use Authorizations for hundreds of serological assays to support Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) diagnosis. The aim of this study is to evaluate, for the first time in children, the performance of three widely utilized SARS-CoV-2 serology commercial assays, Diesse Diagnostics (IgG, IgA, IgM) and Roche Diagnostics, both Roche Nucleocapsid (N) IgG and Roche Spike (S) IgG assays. Methods: Sensitivity and 95% confidence intervals (CIs) were estimated for each of the three different serological tests and mixed and direct comparison were performed. Univariate and multivariate Poisson regression models were fitted to calculate incidence rate ratios and 95% CIs as estimate of the effects of age, gender, time on the serology title. A p-value < 0.05 indicated statistical significance. Results: Overall, 149 children were enrolled in the study. A low sensitivity was found for Diesse IgA, IgM and IgG. Compare to Diesse, Roche S had a higher sensitivity at 15–28 days from infection (0.94, 95%CI: 0.73–1.0) and Roche N at 28–84 days (0.78, 95%CI: 0.58–0.91). When a direct comparison of IgG tests sensitivity was feasible for patients with pairwise information, Roche S and Roche N showed a statistically significant higher sensitivity compared to Diesse in all the study periods, whereas there was no difference between the two Roche tests. Conclusion: Roche S and Roche N serology tests seem to better perform in children. Large prospective studies are needed to better define the characteristics of those tests. [ABSTRACT FROM AUTHOR]

Background: Acute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. Epstein-Barr virus (EBV)-associated acute pancreatitis is a rare condition and it may occur in children and adults. Case presentation: A 3-year-old female was admitted to the "G. Di Cristina" Children's Hospital in Palermo for vomiting and abdominal pain. Laboratory investigations revealed elevated amylase and lipase, with normal liver function tests. Abdominal ultrasound demonstrated an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. Infectious disease serology was positive for the presence of EBV VCA IgM and IgG. A diagnosis of EBV-associated acute pancreatitis was made. The patient was treated conservatively and recovered. Conclusions: Acute pancreatitis is rarely associated with EBV infection; a review of the English literature revealed only 10 pediatric and 6 adult cases. Patients with pancreatitis should always be evaluated for EBV serology, even in the absence of the typical clinical and hematological features of infectious mononucleosis. For these patients, good prognosis is generally expected. [ABSTRACT FROM AUTHOR]

Background The spread of severe acute respiratory coronavirus 2 (SARS-CoV-2) among active workers is poor known. The aim of our study was to evaluate the seroprevalence of immunoglobulin G (IgG) among a convenience sample of workers and to identify high-risk job sectors during the first pandemic way. Methods We conducted a cross-sectional study among workers tested for SARS-CoV-2 between 28 March and 7 August 2020, recorded by a private healthcare center located in North-West Italy. Association among seroprevalence and demographic and occupational variables was evaluated using chi square test and the seroprevalence and 95% confidence intervals (CI) were calculated. Results We collected the results for 23568 serological tests from a sample of 22708 workers from about 1000 companies. Median age was 45 years and about 60% of subjects were male. The overall seroprevalence was 4.97% [95%CI 4.69–5.25]. No statistical difference was found among gender while seroprevalence was associated with subjects' age, geographical location, and occupational sector. Significantly higher values of positivity were observed for the logistics sector (31.3%), weaving factory (12.6%), nursing homes (9.8%), and chemical industry (6.9%) workers. However, we observed some clusters of cases in single companies independently from the sector. Then, a detailed focus on 940 food workers shown a seroprevalence of 5.21% [95%CI 3.79–6.63] and subjects who self-reported COVID-19 symptoms and who worked during lockdown had a higher probability of being infected (p < 0.001). Conclusions Data obtained might be useful for future public health decision; more than occupation sector, it seems that failure on prevention system in single companies increase the SARS-CoV-2 transmission. [ABSTRACT FROM AUTHOR]

Adequate follow-up in celiac disease is important to improve dietary compliance and treat disease-related symptoms and possible complications. However, data on the follow-up of celiac children is scarce. We aimed to assess current pediatric celiac follow-up practices across Europe. Pediatricians and pediatric gastroenterologists from 35 countries in Europe, Israel, Turkey, and Russia completed an anonymous survey which comprised a 52-item questionnaire developed by the ESPGHAN Special Interest Group on Celiac Disease. A total of 911 physicians, the majority of whom exclusively worked in pediatric care (83%) and academic institutions (60%), completed the questionnaire. Mean age and mean experience with celiac care were 48.7 years (± 10.6) and 15.7 years (± 9.9), respectively. The vast majority (≥ 92%) always assessed anthropometry, dietary adherence, and tissue-transglutaminase IgA-antibodies at every visit, with the first visit being between 3 and 6 months after diagnosis. Other parameters (% always tested) were as follows: complete blood count (60%), iron status (48%), liver enzymes (42%), thyroid function (38%), and vitamin D (26%). Quality of life was never assessed by 35% of the responding physicians. Transition to adult care was mostly completed via a written transition report (37%) or no formal transition at all (27%). Conclusions: Follow-up of celiac children and adolescents in Europe may be improved, especially regarding a more rational use of (laboratory) tests, dietary and QoL assessment, and transition to adult care. Evidence-based advice from international scientific societies is needed. What is Known: • Follow-up in celiac disease is important to treat disease-related symptoms, improve dietary compliance, and prevent possible complications. • There is a lack of consensus about the appropriate follow-up. What is New: • Almost all European physicians assess anthropometry, tissue-transglutaminase IgA-antibodies, and dietary adherence at every visit, but there are large variations in other follow-up aspects. • Follow-up could be improved by a more rational use of (laboratory) tests, increased intention to dietary compliance, and quality of life together with transition programs to adult care. [ABSTRACT FROM AUTHOR]

Abstract: Meningococcal disease is particularly severe. The case-fatality rate is 7.78% in Europe and 10–14% in the USA. This paper reports the results of a sero-epidemiological study in Italy on meningitis due to Meningococcus C before the introduction of the monovalent conjugate vaccine. In 2003–2004, a total of 577 sera were collected in 17 of the 20 Italian Regions. Serum Bactericidal Assay (SBA) was performed by using rabbit complement serum according to standardized SBA. The results showed that the percentages of protected subjects decreased from 6 to 12 months of age, increased from 1 to 4 years, decreased again until the age of 8 years and from 13 to 16 years, and were particularly high in 9- and 17-year-old subjects. The geometric mean titre of bactericidal antibodies (SBAbs GMT) was low in subjects under 1 year of age, significantly increased in 1–9-year-old children and decreased in adolescents and young adults. Finally, in each one-year age-group, low levels of antibodies were observed in subjects under 1 year of age, in 10-year-old subjects and in 14–16-year-old adolescents. High titres were observed in 3-, 8-, 9- and 17-year-old subjects. Our results therefore indicate that meningococcus C has the highest probability of spreading among 1–4, 8–10 and 14–17-year-old subjects in Italy. [Copyright &y& Elsevier]

Background Despite efforts to increase coverage by two doses of measles vaccine in Italy, measles continues to circulate, with over 13 000 cases of disease since 2013. This study aimed to evaluate immunity to measles in Italian children and adolescents. Methods A total of 378 serum samples from subjects aged 9 months–18 years were collected in Northern, Central and Southern regions of Italy between 2012 and 2016. Specific IgG antibodies against measles were measured by a commercial ELISA kit. Results The frequency of IgG-positive samples ranged from 10.5% in infants under 1 year to 98.3% in children aged 6–7 years. The frequency of IgG was 72.2% in subjects aged 1–2 years, 85.6% in those aged 3–5 years and 88.3 and 86.8% in those aged 8–10 and 11–18 years, respectively. In Northern Italy, IgG prevalence was consistent with data on vaccination coverage, whereas some differences were observed in samples from subjects aged more than 8 years in Central and Southern Italy. Conclusions Our findings confirm that a large proportion of children and adolescents in Italy are still susceptible to measles. While data on first- and second-dose measles vaccination are essential, they are not sufficient to identify susceptible population cohorts to be targeted by vaccination. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status. Methods: A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab). Results: According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population). Conclusions: There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii infects millions of individuals worldwide. This protozoan is food and water-borne transmitted but blood transfusion and organ transplantation constitute alternative forms for transmission. However, the influence of IgG anti- T. gondii antibodies in molecular analysis carried out in peripheral blood still remain unclear. This study aimed to investigate the serum IgG anti- T. gondii antibody concentrations correlate Nested PCR results in blood donors. Methods: 750 blood donors were enrolled. IgM and IgG anti- T. gondii antibodies were assessed by ELISA (DiaSorin, Italy). Nested PCR was performed with primers JW62/JW63 (288 bp) and B22/B23 (115 bp) of the T. gondii B1 gene. The mean values of IgG concentration were compared for PCR positive and PCR Negative blood donors using the t -test or Mann-Whitney according to the normal distribution (p -value ≤ 0.05). Results: 361 (48.1%) blood donors presented positive serology as follow: IgM+/IgG−: 5 (0.6%); IgM+/IgG+: 21 (2.8%); IgM−/IgG+: 335 (44.7%) and 389 (51.9%), negative serology. From 353 blood donors with positive serology tested, the Nested PCR was positive in 38 (10.8%) and negative in 315 (89.2%). There were no differences statistically significant between the mean values of serum IgG anti- T. gondii antibody concentrations and the Nested PCR results. Conclusions: In conclusion, our data show that variations in the serum IgG anti- T. gondii antibody concentrations do not correlate T. gondii parasitemia detected by Nested PCR in chronically infected healthy blood donors. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the presence of total IgA and anti-gliadin antibodies (AGA) in BM from CD mothers who follow a gluten-free diet (GFD) and from mothers on a normal gluten-containing diet (ND).Methods: 218 samples of mature milk were obtained at different months of lactation (1-6) from 83 mothers (2 or more samples per mother) from Italy (Naples), The Netherlands (Leiden) and Spain (Madrid, Valencia and Reus): 42 CD mothers on GFD for more than 2 years and 41 non-CD mothers on a ND. Whey samples were analyzed for AGA-IgA by an indirect homemade ELISA and for total IgA (g/L) by a commercial ELISA kit.Results: AGA-IgA was detected in BM, both in mothers on a GFD and mothers on a ND. AGA-IgA levels in both groups of mothers, CD and non-CD, show the same trend towards decreasing slightly along the months of lactation (p = 0.91). A different trend is observed for total IgA levels, decreasing markedly in CD mothers from the first month of lactation onwards but remaining stable in non-CD mothers (p = 0.048). A statistically significant association was found between the means of total IgA and AGA-IgA (p < 0.001).Conclusion: AGA-IgA is present in BM from mothers on a ND as well as in BM from mothers who had been on a GFD for years. This reflects the existence of a long-lasting immunological memory independent of the mother’s diet. If the presence of these antibodies has any role in promoting the acquisition of gluten tolerance in the infant, our study shows that children of CD mothers would be on equal conditions as children of non-CD mothers. [ABSTRACT FROM AUTHOR]

Background: Prevalence of allergy has steeply increased during the past few decades, particularly in high-income countries. The development of atopy could present different characteristics in internationally adopted children with regard to incidence, specific patterns of allergies and timing of occurrence. We aimed to investigate the occurrence of allergic diseases among adopted children in Italy. Methods: We collected demographic information, preadoption immunization data, infectious diseases screening results, immunological status, and performed hematological and biochemical tests according to a standardized protocol in 108 adopted children. Results: At initial visit (mean age was 5.7 ± 3.2 years), 48 children displayed elevated total serum IgE levels with a prevalence of 56.5% (95%CI: 0.45; 0.67). The prevalences of children screened positive for one or more food allergens and inhalants were 30.1% (95%CI: 19.9%; 42.0%) and 34.3% (95%CI: 23.3%; 46.6%) respectively, only 9 children exhibited abnormal absolute eosinophil counts, 23 (21.3%) had a parasitic infection and 60 (55.6%) had received at least one dose of vaccine. Conclusions: Children without medical records or with a past medical history suggestive of atopy should perform a thorough allergy evaluation at the time of adoption. Our study offers also a glimpse at the vaccination status and immune-allergic profiles of recent migrant children in Italy. [ABSTRACT FROM AUTHOR]

Background: Measles virus, member of the genus Morbillivirus in the family Paramyxoviridae, is a highly contagious human pathogen. An effective live-attenuated vaccine is available and its use has the potential to eradicate the disease from the human population. Although the vaccine was introduced in national vaccination schedules, several measles outbreaks have occurred because of insufficient vaccination coverage. Since early January 2017, a new outbreak of measles in Italy has been observed. Methods: We analyzed all the patients admitted to the Emergency Department of Bambino Gesù Children Hospital of Rome from the 1st of January 2017 to the end of May 2017 and discharged with diagnosis of suspected or confirmed measles or admitted to the Pediatric and Infectious Disease Unit. For each confirmed case, demographic data, vaccination history, exposure to source case, clinical presentation, date of onset of symptoms, hospitalization, laboratory test results, complications and therapy were collected. Results: From the 1st of January 2017 to the 31st of May 2017, we enrolled 139 patients who were conducted to the Emergency Department of Bambino Gesù Children's Hospital because of measles: 33 patients were discharged with the diagnosis of suspected measles by clinical manifestations; 33 discharged with the diagnosis of confirmed measles by laboratory tests and 73 were admitted to the Pediatric and Infectious Disease Unit. Seven patients, who were exposed to mothers with measles, were admitted to receive treatment with Measles Immune Globulin intravenously. Among the 66 patients admitted to the hospital with measles, 31 cases (47%) occurred in unvaccinated individuals who were age-eligible for measles vaccination; 29 (44%) were infants too young to be vaccinated; only five patients (8%) received one dose of measles-containing vaccine. Out of the 66 patients, 35 (53%) developed complications. Acute respiratory failure was the most reported complications (20%). Death, due to multiorgan failure by measles, occurred in one 9-girl-year-age patient with genetic disorders who was unvaccinated. Conclusions: Measles still represents a serious public health problem worldwide. Vaccination against measles is safe, effective, and cost-effective. High vaccination coverage (>95%) with two doses of measles vaccine is crucial to elimination. Health care professionals play an important role in vaccination uptake and prevention of measles spread during an outbreak. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the prevalence of CECR1 mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study.Methods: Direct sequencing of CECR1 was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor.Results: Biallelic homozygous or compound heterozygous CECR1 mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without CECR1 mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect.Conclusions: DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes. [ABSTRACT FROM AUTHOR]

Background: The basophil activation test (BAT), has been proposed as a possible assay for the diagnosis of immediate-type allergy to beta-lactams (BLs). The aim of this study was to assess the utility of BAT in the diagnosis of amoxicillin (AMX) or AMX-clavulanate (AMX-C) IgE-mediated hypersensitivity in children and adults. Material and methods: Eighteen children and 21 adults, with clinical history of immediate reactions to AMX or AMX-C, were referred to Anna Meyer Children's Hospital and San Giovanni di Dio Hospital, respectively. They underwent in vivo tests (skin prick test and intradermal test). Moreover, BAT with AMX or AMX-C was performed within 6 months from the reaction. Results: In the pediatric group, the concordance between the skin tests (ST) and BAT results was 83.3%. Upon comparing the symptom grades and ST results to the BAT results, we found that the reaction severity and ST positivity did not correlate with BAT results in children. In the adult group, the concordance between the ST and BAT results was 61.9%. Upon comparing patients with severe reactions and patients with mild reactions in terms of BAT results, we found a BAT sensitivity of 38.5% and a specificity of 100%. When comparing the symptom grades to the BAT results, we found that no patients with mild symptoms had a positive BAT result, whereas 38.5% of patients with severe symptoms had a positive BAT result. Conclusions: BAT does not seem to be a useful tool to increase the sensitivity of an allergy work-up to diagnose immediate hypersensitivity to AMX or AMX-C. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy (AIT) is currently recognized as a clinically effective treatment for allergic diseases, with a unique disease-modifying effect. AIT was introduced in clinical practice one century ago, and performed in the early years with allergenic extracts of poor quality and definition. After the mechanism of allergic reaction were recognized, the practice of AIT was refined, leading to remarkable improvement in the efficacy and safety profile of the treatment. Currently AIT is accepted and routinely prescribed worldwide for respiratory allergies and hymenoptera venom allergy. Both the subcutaneous (SCIT) and sublingual (SLIT) routes of administration are used in the pediatric population. AIT is recommended in allergic rhinitis/conjunctivitis with/without allergic asthma, with an evidence of specific IgE-sensitization towards clinically relevant inhalant allergens. Long-term studies provided evidence that AIT can also prevent the onset of asthma and of new sensitizations. The favorable response to AIT is strictly linked to adherence to treatment, that lasts 3-5 years. Therefore, several factors should be carefully evaluated before starting this intervention, including the severity of symptoms, pharmacotherapy requirements and children and caregivers' preference and compliance. In recent years, there have been increasing interest in the role of AIT for the treatment of IgE-associated food allergy and extrinsic atopic dermatitis. A growing body of evidence shows that oral immunotherapy represents a promising treatment option for IgE-associated food allergy. On the contrary, there are still controversies on the effectiveness of AIT for patients with atopic dermatitis. This consensus document was promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP) to provide evidence-based recommendations on AIT in order to implement and optimize current prescription practices of this treatment for allergic children. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to evaluate immunoglobulin M indirect-fluorescent antibody test (IgM IFAT) for the diagnosis of acute or chronic Toxoplasma infection in pregnancy. Methods Pregnant women with suspected acute toxoplasmosis referred to the Tuscany Reference Center for Infectious Diseases in Pregnancy during the period 1998-2012 were retrospectively enrolled. All women were tested with a panel of serological tests, including enzyme-linked immunosorbent assay for IgG avidity and IgM IFAT. On the basis of anamnestic, clinical, and serological criteria, pregnant women were classified into three groups: recently infected (RI), latently infected (LI), and doubtful latently infected (DLI). Patients classified as DLI were excluded from the analysis. The association between IgM IFAT (positive or negative) and the diagnosis of infection (acute or chronic) was assessed. Positive predictive value and negative predictive value of the IgM IFAT were calculated. Results A total of 810 pregnant women were enrolled in the study: 302 in the RI group and 508 in the LI group. Fifty-two women classified as DLI were excluded. IgM IFAT was positive in 172 out of 302 (56.9%) pregnant women in the RI group and in 29 out of 508 (5.7%) in the LI group. The positive predictive value and negative predictive value of IgM IFAT in predicting RI was 85.6% and 78.6%, respectively. Conclusion IgM IFAT has reasonable sensitivity and specificity in diagnosing recent infection and, mostly in case of borderline avidity test, could be considered as a further aid for an accurate diagnosis of acute toxoplasmosis in pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association of hepatitis B virus (HBV) genotypes, basal core promoter (BCP)/precore (PC) and S gene mutations with the clinical-epidemiological characteristics of acute hepatitis B (AHB) in Italy. Methods: During July 2005-January 2007, 103 symptomatic AHB patients were enrolled and prospectively followed up at 15 national hospitals. HBV genotypes, BCP/PC and S gene variants were determined by nested-PCR and direct sequence analysis. Results: Genotype D, A and F were detected in 49, 45 and 6 % of patients, respectively. BCP, PC, and BCP plus PC variants were found in 3.1, 11.3 and 7.2 % of patients, respectively. At enrollment, 68.3 % of patients were hepatitis B e antigen (HBeAg)-positive and 31.7 % HBeAg-negative. BCP/PC mutations were more common in HBeAg-negative than in HBeAg-positive patients ( p < 0.0001). Compared to genotype D patients, those harboring non-D genotypes were more frequently males ( p = 0.023), HBeAg-positive ( p < 0.001), had higher bilirubin ( p = 0.014) and viremia ( p = 0.034) levels and less frequently carried BCP/PC mutations ( p < 0.001). Non-D genotype patients more often were from Central Italy ( p = 0.001) and reported risky sexual exposure ( p = 0.021). Two patients had received vaccination before AHB: one harbored genotype F; the other showed a S gene mutation. Four patients developed fulminant AHB; mutations were found in 2 of 3 patients who underwent BCP/PC sequencing. After a 6-month follow-up, only 2 (2.8 %) patients developed persistent infection. Conclusion: AHB by non-D genotypes is increasing in Italy and is associated with risky sexual exposure. The ability of some genotypes to cause persistent and/or severe infection in Italy warrants larger studies for clarification. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease and can be the first step of the atopic march. Objective In this retrospective study, we analysed the immunological and clinical patterns of AD in a group of children affected by the disease since their first years of life, in order to evaluate if and how these patterns can change over time, and to identify biomarkers that can possibly correlate with the clinical phenotype. Methods We enrolled Caucasian children with diagnosis of AD performed by a specialist on the basis of Hanifin and Rajka's criteria and with a first clinical and laboratory evaluation before 5 years of age. Patients were divided in 2 groups: IgE-associated AD (with or without allergic respiratory diseases) and non-IgE-associated AD. Results Among 184 patients enrolled in this study, at the beginning 30/184 were classified as having non-IgE-associated AD, but during follow-up, at the median age of 36 months, 15 patients became allergic. All 15 patients who switched from the non-IgE to the IgE-associated form had a significantly earlier onset of AD than those who did not switch. Dust mite sensitization seem to be the best biomarker (OR 2.86) to predict the appearance of allergic respiratory diseases. Conclusion IgE-associated AD is more frequent in childhood than non-IgE-associated AD. These two phenotypes are different in the age of onset and in the remission patterns. In the first years of life, it is important to distinguish the different phenotypes in order to evaluate possible allergic related conditions. [ABSTRACT FROM AUTHOR]

Background: This study looks at the impact of inflammation during the rehabilitation stage of strokes and its effect on neuro-functional recovery. Methods: This study investigated 94 patients suffering from strokes and admitted to rehabilitation. Anthropometric characteristics, serum proteins and inflammatory markers, plasma amino acids and neurofunction were all assessed. Results: 55.3% patients had an inflammatory status (Interleukin-6 = 19.24 ± 23.01 pg ml−1 vs. 4.1 ± 1.6 pg ml−1 for non-inflamed subjects ( p < 0.001). Inflammation was positively linked to positive proteins (alpha-1 globulin, p < 0.02) and negatively linked to negative proteins (albumin, p < 0.02; prealbumin, p < 0.01; transferrin, p < 0.05) of the acute-phase response. Inflammation was associated with low plasma concentrations of total amino acids. For the multiple logistic regression analysis, albumin ( p < 0.001) and body weight maintenance ( p < 0.001) were independent predictors of patient functional independence. Inflammation in dysphagic stroke (31.9%) patients was associated with more accentuated disability compared to non-inflamed dysphagics. The serum positive reactant alpha 1 globulin was the most powerful predictor of dysphagia severity ( p < 0.001). At discharge, dysphagia improvement was associated with improved acute-phase negative proteins. Conclusions: An inflammatory status may persist for most patients with strokes during the rehabiliation stage of the disease, its prevalence being higher in dysphagic compared to non-dysphagic subjects. The improvement in circulating albumin and body weight maintenance are predictors of neuro-function, even in dysphagic subjects. [ABSTRACT FROM AUTHOR]

Kabuki syndrome (also called Niikawa-Kuroki syndrome) is a rare genetic disease described for the first time in Japan, characterised by anomalies in multiple organ systems and often associated with autoimmune disorders and impaired immune response. We herein report the clinical history, the therapeutic approach and the outcome of two children with Kabuki syndrome who developed autoimmune haematological disorders (haemolytic anaemia and immune thrombocytopenia). Factors regarding differential diagnosis and interventions in better management of this syndrome and its complications are discussed. This is the first report of Italian children with autoimmune haematological disorders complicating Kabuki syndrome. [ABSTRACT FROM AUTHOR]

Data on the effective burden of the SARS-CoV-2 pandemic in the pediatric population are limited. We aimed at assessing the prevalence of SARS-CoV-2 IgG antibodies in children at three subsequent time-points. The study was conducted between January 2021 and July 2021 among children referring to the Research Institute for Maternal and Child Health "Burlo Garofolo" in Trieste, a referral regional hospital in Friuli Venezia Giulia, Italy. A multivariate analysis was conducted to assess factors independently associated with seroconversion. A total of 594 children were included. Anti-SARS-CoV-2 trimeric Spike protein IgG antibodies were found in 32 (15.4%) children tested in April-May and in 20 (11.8%) in June–July 2021, compared with 24 (11.1%) of those tested in January–February 2021 (p = 0.37, Armitage exact test for trend over time p = 0.76). A subgroup analysis and a multivariate logistic regression analysis were performed considering sociodemographic, clinical, and historical variables. Three categories of children showed statistically significant increased odds of positive anti-SARS-CoV-2 IgG antibodies: children previously positive to a nasopharyngeal swab (AdjOR 15.41, 95%CI 3.44–69.04, p < 0.001), cohabitant with a person with an history of a previous positive nasopharyngeal swab (AdjOR 9.95, 95%CI 5.35–18.52, p < 0.001), and children with a foreign citizenship (AdjOR 2.4, 95%CI 1.05–5.70, p = 0.002). The study suggests that seroprevalence studies may be of limited help in estimating the prevalence of the COVID-19 pandemic in children. Further studies are needed to identify other markers of previous SARS-CoV-2 infection in children, such as CD4+ T cells or memory B-cells. [ABSTRACT FROM AUTHOR]

Oral Diseases (2012) 19, 92-99 Objective: Radicular cysts occur as a result of the immunological response to continuous antigenic stimulation from root canals. We correlated the immunophenotypical composition of the lymphoid infiltrate to the microvessel density expressed by the count of CD34 reactive endothelial cells in radicular cysts. Subjects and methods: Thirty-four cases of radicular cysts were evaluated by immunohistochemistry, using antibodies against B- and T-cell antigens (CD20, CD3, CD4, CD8) and against the endothelial cell marker CD34. Statistical analysis was performed. Results: In the epithelium, we observed a low amount of lymphoid infiltrate in all 34 radicular cysts, and a strong significant negative correlation between T and B lymphocytes and between T-helper and T-cytotoxic/suppressor lymphocytes. In the cyst capsule, we observed a significant positive correlation between B and T lymphocytes, B and T-cytotoxic/suppressor lymphocytes, T and T-helper lymphocytes and between the number of CD34+ blood vessels and T and T-helper lymphocytes, respectively. We observed a statistically significant correlation between percentage of CD34+ vessels and inflammatory infiltrate grade. Conclusions: Both humoral and cellular immune reactions and neovascularization are likely to occur in the complex events of tissue destruction. The inflammatory infiltrate has an important role in neoangiogenesis and consequently in radicular cysts development and growth. [ABSTRACT FROM AUTHOR]

Conclusions: Our data confirm the induction of specific and nonspecific immune responses of the upper respiratory tract mucosa and the consequent improvement of its physiology, through an oral ribosomal therapy in patients with pharyngolaryngeal reflux disease (PLRD). Objectives: The aim of this study was to investigate the efficiency and applicability of oral ribosomal immunotherapy in adult patients with PLRD. Methods: One hundred adult patients with PLRD were enrolled. The patients were equally divided, at random, into two groups (A and B): group A patients underwent ribosomal prophylaxis with Immucytal® (one tablet daily, 8 days a month for 3 months), while group B received a placebo (same dosage for the same period). At the beginning, at the end, and 6 months after the beginning of the therapy, all patients underwent medical history, ENT examination, nasal-pharynx-laryngoscopy with optic fiber, plasma levels of immunoglobulins class E, A, G, M, subjective assessment of symptoms on a 10 cm visual analog scale (VAS), reflux symptoms index, and reflux finding score. Results: At the end and 6 months after the beginning of the treatment, all the patients in group A presented a significant ( p < 0.05) improvement of almost all the different items analyzed. [ABSTRACT FROM AUTHOR]

Objective. To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry.Methods. Nine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10 000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted.Results. In both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR) = 2.069, 95% asymptotic CIs (CI95) 1.486, 2.881; P < 0.001] and in Spanish patients (OR = 6.707, CI95 3.974, 11.319; P < 0.001) as well as in anti-topo-positive patients: Italy (OR = 2.642, CI95 1.78, 3.924; P < 0.001) and Spain (OR = 20.625, CI95 11.536, 36.876; P < 0.001). In both the populations we also identified an additional risk allele (HLA-DQB1*03) and a protective allele (HLA-DQB1*0501) in anti-topo-positive patients. The meta-analysis showed different statistically significant associations, the most interesting being the differential association between HLA-DRB1*01 alleles and ACAs (OR = 1.724, CI95 1.482, 2.005; P < 0.001) or topo I antibodies (OR = 0.5, CI95 0.384, 0.651; P < 0.001).Conclusions. We describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc. [ABSTRACT FROM PUBLISHER]

Background: Clinical surveillance may have underestimated the real extent of the spread of the new strain of influenza A/ H1N1, which surfaced in April 2009 originating the first influenza pandemic of the 21st century. Here we report a serological investigation on an influenza A/H1N1pdm outbreak in an Italian military ship while cruising in the Mediterranean Sea (May 24-September 6, 2009). Methods: The contemporary presence of HAI and CF antibodies was used to retrospectively estimate the extent of influenza A/H1N1pdm spread across the crew members (median age: 29 years). Findings: During the cruise, 2 crew members fulfilled the surveillance case definition for influenza, but only one was laboratory confirmed by influenza A/H1N1pdm-specific RT-PCR; 52 reported acute respiratory illness (ARI) episodes, and 183 reported no ARI episodes. Overall, among the 211 crew member for whom a valid serological result was available, 39.3% tested seropositive for influenza A/H1N1pdm. The proportion of seropositives was significantly associated with more crowded living quarters and tended to be higher in those aged <40 and in those reporting ARI or suspected/confirmed influenza A/H1N1pdm compared to the asymptomatic individuals. No association was found with previous seasonal influenza vaccination. Conclusions: These findings underline the risk for rapid spread of novel strains of influenza A in confined environment, such as military ships, where crowding, rigorous working environment, physiologic stress occur. The high proportion of asymptomatic infections in this ship-borne outbreak supports the concept that serological surveillance in such semi-closed communities is essential to appreciate the real extent of influenza A/H1N1pdm spread and can constitute, since the early stage of a pandemic, an useful model to predict the public health impact of pandemic influenza and to establish proportionate and effective countermeasures. [ABSTRACT FROM AUTHOR]

The atopy patch test (APT) was recently defined as an important tool in diagnosis of atopic dermatitis (AD) and also of rhinitis and asthma caused by hypersensitivity to the house dust mites. We evaluated 465 children (279 males and 186 females) aged 0.4-17.6 years (mean 6.6 +/- 3.8 years), by dividing them into four groups: group A, current AD (40 patients); group B, current AD with respiratory symptoms (156 patients); group C, past AD with respiratory symptoms (203 patients); and the control group, respiratory symptoms with no history of AD (66 patients). The APT was significantly more frequently positive in groups with current AD (groups A and B) or past AD (group C) than in the control group, while skin prick test (SPT) and radioallergosorbent test (RAST) were significantly more frequently positive in the control group. With multivariate analysis, for APT, significant differences were found in the comparison between group A vs group B (odds ratio (OR) 1.55) and between group A vs group C (OR 1.81). The mean age was significantly lower in group A than in groups B, C, and the control group and with less significance in groups C vs D. Children sensitized to mites with current or past AD, with or without respiratory symptoms, have a different response to diagnostic tests, which is characterized by a highly significantly more frequent positive APT in comparison with subjects who have respiratory symptoms but a negative history for AD, who show the common response to SPT and RAST. [ABSTRACT FROM AUTHOR]

Background: Genital mucosae play a key role in protection from STD and HIV infection, due to their involvement in both horizontal and vertical disease transmission. High variability of published observations concerning IgA isolation and quantification underlies the strong requirement of specific methods able to maximize investigation on HIV-specific IgA. Methodology: Genital fluids from 109 subjects, including male and female cohorts from Italy and Cambodia, were collected, aliquoted and processed with different techniques, to assess optimal conditions maximizing mucosal antibody recovery. Three sampling techniques, up to sixteen preservation conditions, six ELISA methods and four purifications protocols were compared. Principal Findings: The optimal method here described took advantage of Weck-Cel sampling of female mucosal fluids. Immediate processing of genital fluids, with the addition of antibiotics and EDTA, improved recovery of vaginal IgA, while the triple addition of EDTA, antibiotics and protease inhibitors provided the highest amount of seminal IgA. Due to low amount of IgA in mucosal fluids, a high sensitive sandwich ELISA assay was set; sensitivity was enhanced by milk-based overcoating buffer and by a two-step biotin-streptavidin signal amplification. Indeed, commercial antisera to detect human immunoglobulins showed weak cross-reactivity to different antibody types. Three-step affinity purification provided reproducible immunoglobulin recovery from genital specimens, while conventional immuno-affinity IgA purification was found poorly manageable. Affinity columns were suitable to isolate mucosal IgA, which are ten-fold less concentrated than IgG in genital specimens, and provided effective separation of IgA monomers, dimers, and J-chains. Jacalin-bound resin successfully separated IgA1 from IgA2 subfraction. Conclusions/Significance: Specific, effective and reliable methods to study local immunity are key items in understanding host mucosal response. The sequence of methods here described is effective and reliable in analysing humoral local responses, and may provide a solid advance to identify and measure the effective mucosal responses to HIV. [ABSTRACT FROM AUTHOR]

A fraction of chronic lymphocytic leukaemia (CLL) cases carry highly homologous B-cell receptors (BCR), i.e. characterized by non-random combinations of immunoglobulin heavy-chain variable ( IGHV) genes and heavy-chain complementarity determining region-3 (HCDR3), often associated with a restricted selection of IGVK/L light chains. Such ‘stereotyped’ BCR occur more frequently in CLL with unmutated (UM) than mutated (M) IGHV genes. We analysed 1426 IG rearrangements (from 1398 CLL cases) by a clustering driven by HCDR3 similarities. Molecular findings were correlated to time-to-treatment (TTT) and presence of known prognosticators. Sixty-nine clusters (319 IG-rearrangements, 22·4%) with stereotyped BCR were identified. Among 30 confirmed clusters (≥3 IG-rearrangements/cluster), we found 14 novel clusters, of which 11 had M IG rearrangements (M clusters) and predominantly (8/11) used IGHV3 subgroup genes. Recurrent cluster-biased amino acid changes were found throughout IGHV sequences of these ‘M clusters’. Regarding clinical outcome: (i) UM CLL from the IGHV1-2/1-3/1-18/1-46/7-4-1/IGKV1-39 cluster had poorer prognosis than UM/M cases, or UM cases using the same IGHV genes but not in clusters; (ii) M CLL from the IGHV3-21/IGLV3-21 cluster had TTT similar to UM CLL, and shorter than M CLL expressing IGHV3-21 but not in cluster. Altogether, our analysis identified additional molecular and clinical features for CLL expressing stereotyped BCR. [ABSTRACT FROM AUTHOR]

As for a consolidated tradition, the 5th annual meeting of the Italian Network for Cancer Biotherapy took place in the Certosa of Pontignano, a Tuscan monastery, on September 20-22, 2007. The congress gathered more than 40 Italian leading groups representing academia, biotechnology and pharmaceutical industry. Aim of the meeting was to share new advances in cancer bioimmunotherapy and to promote their swift translation from pre-clinical research to clinical applications. Several topics were covered including: a) molecular and cellular mechanisms of tumor escape; b) therapeutic antibodies and recombinant constructs; c) clinical trials up-date and new programs; d) National Cooperative Networks and their potential interactions; e) old and new times in cancer immunology, an "amarcord". Here, we report the main issues discussed during the meeting. [ABSTRACT FROM AUTHOR]

Background: We previously reported a high prevalence (22.3%) of gestational diabetes mellitus (GDM) in a large group of Sardinian women, in contrast with the prevalence of Type 2 diabetes. Sardinia has an unusual distribution of haplotypes and genotypes, with the highest population frequency of HLA DR3 in the world, and after Finland, the highest prevalence of Type 1 diabetes and Autoimmune-related Diseases. In this study we preliminarily tested the prevalence of serological markers of Type 1 diabetes in a group of Sardinian GDM patients. Methods: We determined glutamic decarboxylase antibodies (anti-GAD65), protein tyrosine phosphatase ICA 512 (IA2) antibodies (anti-IA2), and IAA in 62 GDM patients, and in 56 controls with matching age, gestational age and parity. Results: We found a high prevalence and very unusual distribution of antibodies in GDM patients (38.8%), the anti-IA2 being the most frequent antibody. Out of all our GDM patients, 38.8% (24 of 62) were positive for at least one antibody. Anti-IA2 was present in 29.0 % (18 out of 62) vs. 7.1% (4 out of 56) in the controls (P < 0.001). IAA was present in 14.5% (9 out of 62) of our GDM patients, and absent in the control subjects (P < 0.001). Anti-GAD65 was also present in GDM patients, with a prevalence of 3.2% (2 out of 62) while it was absent in the control group (P = NS). Pre-gestational weight was significantly lower (57.78 ± 9.8 vs 65.9 ± 17.3 P = 0.04) in auto-antibodies-positive GDM patients. Conclusion: These results are in contrast with the very low prevalence of all antibodies reported in Italy. If confirmed, they could indicate that a large proportion of GDM patients in Sardinia have an autoimmune origin, in accordance with the high prevalence of Type 1 diabetes. [ABSTRACT FROM AUTHOR]

The article presents abstracts on the molecular aspects of antibodies to be discussed at the Human Antibodies & Hybridomas conference in Milan, Italy on October 29, 2007, which include the ability of minimalist synthetic antibodies to recognize proteins, the use of CD32B Fc receptors in enhancing antibody therapeutics and the use of human antibodies selected by phage display as potent and selective protease inhibitors.

The article presents abstracts on antibodies to be discussed at the Human Antibodies & Hybridomas conference in Milan, Italy from October 29 to 31, 2007, which include the effectiveness of EMAB-6 anti-CD20, a human B cell, monoclonal antibody in the treatment of B-chronic lymphocyctic leukemia, the use of monoclonal antibodies in the diagnosis of peste des petits ruminants (PPR) virus infection and the efficacy of chemiluminescence in the screening of tail/heart bleeds and hybridomas in the development of monoclonal antibodies.

Background: A study was undertaken to investigate the effect of gas cooking on the lung function of adolescents while considering serum IgE level as a possible effect modifier.Method: The cross sectional study was performed in 702 subjects aged 11-13 years from primary and secondary schools in Civitavecchia and Viterbo ( Latium region in Central Italy), categorised according to how often they were in the kitchen while the mother cooked (never, sometimes, often). Data were collected by questionnaire and lung function was measured by spirometric tests. Bronchial hyperresponsiveness was evaluated by the methacholine test, atopic status by a skin prick test, and a blood sample was collected to determine serum IgE levels. The results were analysed separately for boys and girls. Multiple regression analysis was performed, taking functional parameters (FEV(1), FEV(1)/FVC, FEF(25-75), FEF(50), FEF(75)) as the dependent variables and age, height, parental smoking, and father's education as independent variables.Results: There was no association between time spent in the kitchen and lung function level in boys, but a reduction in lung function was detected in girls which was statistically significant for FEF(75) (sometimes -10.3%, often -11.1%). After stratifying boys and girls into four groups on the basis of the IgE serum level (below and above the median value of IgE), the reduction in lung function was significant in girls with a high IgE value whereas no significant deleterious effects were evident in girls with a low IgE value or in boys with either a low or high IgE. The results remained substantially unchanged after excluding girls with a response to methacholine below the concentration of 4 mg/ml, asthmatic patients, and those with positive skin prick tests.Conclusion: Gas cooking has a harmful effect on the lung function of girls with a high serum level of IgE. We do not know whether serum IgE, a marker of allergic susceptibility, is a simple indicator that an inflammatory process is in progress or whether it is involved in the pathogenesis of injury leading to bronchial obstruction. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary ovarian mesothelioma is a rare and aggressive neoplastic disease with a poor prognosis. The rarity of this entity and the challenging differential diagnosis with other ovarian and peritoneal neoplasms may lead to frequent misdiagnosis and some concerns about its histogenesis. This case series describes four histologically and ultrastructurally documented primary ovarian mesotheliomas in exposed patients, as reported in the medical history. Because of the few cases described, we reviewed the English literature on ovarian mesothelioma and on its possible risk factors, already known and recognized for pleural, pericardial, peritoneal, tunica vaginalis mesothelioma. Describing such rare cases and summarizing the knowledge so far is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions on its origin. Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either ovarian carcinoma or peritoneal mesothelioma may lead to frequent misdiagnoses and may raise some concerns about its histogenesis. Thus, reporting such rare cases is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions. Herein, we described four cases of histological diagnoses of ovarian mesothelioma extrapolated by the regional mesothelioma register of Apulia (southern Italy). In all cases, a detailed medical history was collected according to national mesothelioma register guidelines. A broad panel of antibodies was used for immunohistochemistry to confirm the diagnoses. Moreover, ovarian tissue samples were also examined by transmission and scanning electron microscopy, detecting asbestos fibers and talc crystals in two cases. Because of the few cases described, we reviewed the English literature in the Medline database, focusing on articles about ovarian mesothelioma "misclassification", "misdiagnosis", "diagnostic challenge" or "diagnostic pitfall" and on unsolved questions about its histogenesis and possible risk factors. [ABSTRACT FROM AUTHOR]

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Simple Summary: Since the beginning of the COVID-19 outbreak, Cancer Centers adopted specific procedures to protect patients as well as to monitor the possible spread of SARS-CoV-2 among healthcare personnel. In April 2020, we implemented a prospective longitudinal study aimed at monitoring the serological response to SARS-Cov-2 in the healthcare personnel of a Comprehensive Cancer Center identified by the Lombardy region (the Italian region most affected by the COVID-19 pandemic) as one of the three oncologic hubs where the Regional Health Authorities referred all the cancer patients in the region. We identified a fraction of healthcare personnel with long-term anti-SARS-CoV-2 antibody response, though negative for viral RNA, who could safely approach fragile cancer patients. Since the beginning of the COVID-19 outbreak, Cancer Centers adopted specific procedures both to protect patients and to monitor the possible spread of SARS-CoV-2 among healthcare personnel (HCP). In April 2020 at Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, one of the three oncologic hubs in Lombardy where the Health Regional Authorities referred all the cancer patients of the region, we implemented a prospective longitudinal study aimed at monitoring the serological response to SARS-Cov-2 in HCP. One hundred and ten HCP answered a questionnaire and were screened by nasopharyngeal swabs as well as for IgM/IgG levels; seropositive HCPs were further screened every 40–45 days using SARS-CoV-2-specific serology. We identified a fraction of HCP with long-term anti-SARS-CoV-2 antibody responses, though negative for viral RNA, and thus probably able to safely approach fragile cancer patients. Monitoring asymptomatic HCP might provide useful information to organize the healthcare service in a Cancer Center, while waiting for the effectiveness of the active immunization by SARS-CoV-2 vaccines, which will provide protection from infection. [ABSTRACT FROM AUTHOR]

Simple Summary: The COVID-19 or SARS-CoV-2 pandemic has been spreading in our country since the beginning of 2020. Despite the emergency patients with head and neck cancer could not wait for treatment. Surgery in head and neck tumors, which consists of resection and reconstruction, must be timely, considering crucial further adjuvant treatments. Furthermore, the therapeutic results and morbidity depend on the size and progression of the disease. The management protocol included: telephone triage, nasopharyngeal swab tested for SARS-CoV-2 RNA before hospitalization, application of infection prevention and control (IPC) policies. This preliminary study reports our experience in managing oncological patients during the COVID-19 pandemic, evaluating the efficacy of the safety and containment measures implemented in our unit for the protection of the whole staff as well. In our opinion, even though restrictions have to be developed first and foremost for the patient's safety, medical and paramedical staff need to be protected as well. The COVID-19 pandemic has significantly affected the surgical units, especially those operating on the airways. This study evaluates the series of patients with tumors of the head and neck treated by our unit during Phase-1 of the pandemic and the efficacy of the preventive measures implemented for protecting both the patients and staff. A screening program was administered to all the patients who had to undergo surgery. None of the patients tested and operated during Phase 1, between 10 March and 18 May 2020, were positive for COVID-19. A significant portion of the patients was suffering from tumors in advanced stages (T3 and T4). Two patients developed respiratory symptoms during their stay at the unit, so they were put in precautionary isolation and tested, but resulted negative for COVID-19. All the surgical department staff followed the Italian Ministry of Health's prevention protocol and underwent serological testing. IgG and IgM were negative in everyone, thus confirming that nobody had been exposed to the virus. This study highlights the commitment to efficiently treating patients suffering from tumors of the head and neck region and confirms the effectiveness of the safety measures used to protect our patients and staff's health. [ABSTRACT FROM AUTHOR]

Background: Leishmania infantum is a vector-borne pathogen endemic in countries in the Mediterranean basin, including Italy. Dogs act as the primary reservoir for this parasite, but other animal species may also be infected. Low-to-moderate seroprevalence levels of infection have been reported in apparent healthy equine populations in southern Europe, reinforcing the importance of exploring those species, including horses, that act as a food source for vectors and may thus participate in the epizoological scenario of canine leishmaniosis (CanL) and zoonotic visceral leishmaniosis (ZVL). Since little is known regarding the exposure to L. infantum in horses in Italy, we assessed the seroprevalence in healthy equine populations from different CanL endemic areas. Methods: The survey was conducted on 660 apparently healthy horses distributed throughout central and northern regions of Italy between 2016 and 2019. Blood samples were collected and the presence of anti-Leishmania antibodies (IgG) was investigated by the immunofluorescence antibody test. Information on the location and altitude of the stables, along with the horses' breed, age, sex, and reproductive status was obtained by filling in a questionnaire. This was then used for statistical analysis by generalized linear models to explore risk factors associated with seroreactivity to L. infantum. Results: An average seroprevalence of 13.9% was detected for L. infantum in the equine populations investigated, with statistically significant associations between seroprevalence, geographical variables (northern vs central Italy, origin and altitude) and individual factors (i.e. age and breed morphotype). Conclusions: Our results highlight that horses are frequently exposed to L. infantum. Further prevalence surveys in horses, also using direct methods (e.g. PCR), are warranted to clarify the role of these hosts in the epidemiology of Leishmania in Italy. [ABSTRACT FROM AUTHOR]

The article determines the prevalence of antibodies to pestiviruses in Alpine ibexes from the Italian Alps and in the Iberian ibexes from Spain. It says that although the species, which belong to the subfamily Caprinae, are not listed under the International Union for Conservation of Nature, there is concern on their genetic diversity and the survival of their population. It offers information on their reproductive disorders that affect the conservation and management of the species.

The article highlights a study which examined Borna disease virus (BDV) infection in children with psychiatric disorders. The study involved children from Rome, Italy who have either psychiatric diseases or participated in an epidemiological study and their sera were tested for BDV infection by a triple enzyme-linked immunosorbent assay (ELISA). No significant differences were found between the antibodies, antigens and circulating immune complexes (CIC) in the two groups.