CD30, CD15, CD50, and PAX5 Expressions as Diagnostic Markers for Hodgkin Lymphoma (HL) and Systemic Anaplastic Large Cell Lymphoma (sALCL).

BACKGROUND: the expression of CD30, CD15, CD50, and PAX5 are used to help in confirming diagnosis of HL and sALCL; however data on the proportion of these markers have not been available. The study was aimed to identify the proportion of CD30, CD15, CD50 and PAX5 expressions and characteristics of patients with HL and sALCL at Dharmais National Cancer Center Hospital between 2005 and 2015. METHODS: a retrospective observational study was conducted using data from medical records and histopathological results of HL and sALCL adult patients who sought treatment at the hospital between 2005 and 2015. Immunohistochemistry (IHC) examinations were performed and data on the proportion of positive CD30, CD15, CD50, and PAX5 expressions were analyzed descriptively. RESULTS: a total of 45 patients were recruited in this study, with the majority (42 patients, 93.3%) were HL patients and only 6.7% were sALCL patients. The median age of HL patients was younger than sALCL patients; 35 (18-72 years old) versus 54 (49-61 years old). Moreover, the immunohistochemistry examination demonstrated that the positive CD15, CD30, CD50, and PAX5 expressions were found respectively in 37.5%, 88.9%, 31.2%, and 31.2% patients with HL; while in patients with sALCL, in spite of their small sample size, positive CD30, CD15, CD50 and PAX5 expressions were found in 100%; 66,7%; 50%; and 50%, respectively. Overall, CD15, CD50, and PAX5 positive expressions were found in 39.5%, 32.4%, and 32.4% patients who had HL and sALCL; while positive expression of CD30 was found in 89.5% of them. CONCLUSION: present study shows that almost 90% patients have positive CD30 expression;  while the positive expressions of CD15, CD50, and PAX5 are found in less than 40% patients. It indicates that CD30 is an important diagnostic marker for HL and sALCL and it may improve treatment strategy.

Hospitalization rates of complicated pneumococcal community-acquired pneumonia is increasing in Tuscan children.

To provide epidemiological data on community-acquired pneumonia (CAP) and complicated CAP, a retrospective study was conducted on a partially vaccinated paediatric population. Data from children hospitalized for CAP in Tuscan hospitals between January 1st, 1999 and December 31st, 2009 were analysed. A total of 5,450 children with CAP were hospitalized. Annual hospitalization rates for CAP did not change significantly over the study period (X2 for trend= 0.652; p=0.419). The total annual hospitalization rate for pneumococcal CAP varied according to age (28.04 per 100,000 children aged less than 5 years, 10.06 per 100,000 children aged 6-12 years and 0.98 per 100,000 children aged greater than13years). Hospitalization rates for pneumococcal CAP increased from12.84 (95 percent CI:7.35-18.34) in 2001 to 45.4 (95 percent CI:35.93-54.90) per 100,000 children aged less than 5 years in 2009 (p less than 0.0001). In addition, a significant increase of hospitalization rates for complicated CAP (from 6.07 in 1999 to 13.66 in 2009 per 100,000 children; P less than 0.0001) and pneumococcal complicated CAP (from 0.19 in 1999 to 3.41 in 2009 per 100,000 children) over the study period were highlighted. Our epidemiological data confirm the decision to introduce the PCV13 vaccine, to satisfy the need to prevent a wider group of pneumococcal serotypes.

Macrophage activation syndrome in a child affected by malaria: the choice of steroid.

Macrophage activation syndrome is a potentially fatal clinical syndrome caused by an excessive activation and proliferation of macrophages and T cells, leading to an exaggerated inflammatory reaction. It is well known that it can complicate the course of different conditions, especially autoimmune, lympho-proliferative, infectious diseases and drugs. Many infective pathogens can trigger the syndrome but the association with malaria has rarely been described, especially in children. We report a child with severe malaria complicated by MAS, in whom the clinical appearance of this syndrome could be considered as worsening of malaria itself. Furthermore, the use of steroids as first choice drugs in this complication, but arguable in malaria, has been highlighted. Clinicians should be aware of this syndrome when malaria does not respond to conventional therapy, since early diagnosis and prompt treatment may dramatically reduce the mortality associated with this condition.

Severe necrotizing pneumonia complicating influenza A (H1N1): the role of immunologic interaction.

This report describes the successful management of a documented necrotizing pneumonia due to Streptococcus pneumoniae in a child with pandemic influenza A (H1N1). The importance of early recognition of bacterial superinfection in patients with influenza and the immunologic interactive mechanisms between viruses and bacteria in determining respiratory diseases are highlighted. The role of modern molecular techniques in improving diagnostic microbiology sensitivity and informing consequent clinical care is emphasized.

Vertical hepatitis C virus transmission is not related to mother-child class-1 HLA concordance.

Mother-child human leukocyte antigen (HLA)diversity is protective for vertical transmission of some viruses. The aim of this study is to evaluate the role of mother-child HLA diversity on hepatitis C virus (HCV) vertical transmission. Forty consecutive HCV infected and 46 consecutive control uninfected children born to HCV-RNA positive mothers were evaluated for HLA class-1 type concordance with their mothers. No significant difference in the degree of HLA concordance was found between HCV infected and uninfected children both when A, B, C (p=0.30) and when only A and B alleles were evaluated (p=0.59). Mother-infant HLA concordance does not affect HCV vertical transmission.

Altered natural killer cells subsets distribution in children with hepatitis C following vertical transmission.

BACKGROUND: Natural killer (NK) cells number, phenotypes and function have been evaluated in many studies in adults with hepatitis C as compared with healthy controls or dynamically during interferon-based and interferon-free treatments. Overall, in adults with chronic infection number of circulating NK cells has been reported to be lower when compared to spontaneous resolvers and healthy subjects. Different studies yielded inconsistent findings due to patient and virus heterogeneity. AIM: To evaluate NK cells in children according to the different outcomes of the infection. METHODS: In this cross-sectional study, we examined numbers and phenotypes of circulating NK cells from a homogenous cohort of Italian children with vertically acquired hepatitis C. RESULTS: We compared 31 children who developed chronic infection with nine who presented spontaneous clearance and 13 controls. CD56(+) CD3(-) NK cell numbers were consistently lower in the persistently infected group (P = 0.03 and 0.04). This decrease was due to depletions of CD56(dim) NK cells (P = 0.03 chronic infection vs. spontaneous clearance), while CD56(bright) NK cells were expanded (P = 0.03). No significant difference was found in the frequencies of CD56(+) CD16(+) and CD56(dim) CD16(-) cells. Perforin expression was higher in children with chronic infection (P = 0.03 vs. spontaneous clearance). CONCLUSIONS: Altered NK cells number and phenotypes could impact the outcome of HCV infection in children following vertical transmission. This study suggests for the first time that NK cells cytolytic function, featured by CD56(dim) cells, contributes to the elimination of HCV in children presenting spontaneous clearance.

VIP restores natural killer cell activity depressed by hepatitis B surface antigen.

Vasoactive intestinal peptide (VIP) has recently been shown to bind to human lymphocytes and modulate immune functions. The ability of VIP in restoring natural killer (NK) cell activity depressed by hepatitis B surface antigen (HBsAg) has been investigated in the present research. Human lymphocytes were incubated with HBsAg and, after washing, a 4-hr cytotoxicity assay was performed. VIP was coincubated with lymphocytes during the preincubation with HBsAg or, alternatively, throughout the cytotoxicity assay. The study revealed that VIP, either preincubated or coincubated in the 4-hr assay, strongly restores NK cell activity depressed by viral antigen. This is noteworthy considering that a number of lymphocyte modulators such as interferons fail in restoring viral-dependent NK cell activity depression. In contrast with previous reports, even when coincubated in the 4-hr assay, VIP is a strong activator of NK cell activity. Further studies will be required to understand which mechanisms are involved in the interrelation between VIP and NK cells during viral infections.

Severe abdominal involvement as the initial manifestation of cutaneous polyarteritis nodosa in a young girl.

We report a young girl who developed ingravescent intestinal symptoms as the first manifestation of cutaneous polyarteritis nodosa (PAN) while the typical skin nodules developed later during the disease course. Cutaneous PAN predominantly affects children and presents with crops of painful skin nodules in the medial aspect of the foot, often preceded by sore throat. Visceral manifestations including gut involvement are commonly associated with the classical form of PAN while they are rarely reported in the cutaneous form. In our patient the severity of the abdominal symptoms required a laparoscopy, which revealed diffuse erythematosus swelling of the intestine on the serosal side. The administration of penicillin and steroids was followed by a dramatic improvement in the disease course. Chronic anterior uveitis developed 4 months after the disease onset and responded to local treatment. At a 2-year follow-up the girl is in good condition under prophylaxis with benzathine-penicillin with no recurrence of the illness. Our case confirms that cutaneous PAN is often related to streptococcal infection, and suggests that ASO titers should be determined in children with vasculitides to ensure a timely diagnosis and treatment of the condition if present.

Acute febrile cholestasis as an inaugural manifestation of Kawasaki's disease.

We report a child who developed acute febrile cholestasis with jaundice and pruritus as the inaugural manifestation of Kawasaki's disease (KD). The severe obstructive icterus and hydrops of the gallbladder required cholecystectomy that was not followed by remission of the fever and cholestasis. KD was suspected after the exclusion of all infectious, metabolic and neoplastic conditions responsible for acute cholestasis. The administration of intravenous gammaglobulin (IVGG) promptly induced defervescence and improvement of the patient's general condition. Mucocutaneous alterations, peeling of the digits, right cervical lymph node enlargement and bilateral non-suppurative conjunctivitis supporting the diagnosis of KD developed 14 days after the appearance of jaundice. No coronary abnormalities had developed after 2 years of follow-up. We conclude that this syndrome should be suspected in any child with febrile cholestasis of unknown origin, in order that coronary involvement may be prevented by the administration of IVGG.

Guidelines for the screening and follow-up of infants born to anti-HCV positive mothers.

Hepatitis C virus infection in infancy largely depends on vertical transmission. The transfer of hepatitis C virus from mother to child is almost invariably restricted to children whose mother is viremic, and the rate of transmission seems to be influenced by maternal virus load, although, in the single patient, the levels of viremia cannot be used as predictors of pediatric infection. In fact, the flow-chart for screening children at risk for vertically transmitted hepatitis C virus infection takes into account maternal viremia. In children born to anti-hepatitis C virus antibody positive, hepatitis C virus-RNA negative mothers, alanine aminotransferase and anti-hepatitis C virus should be investigated at 18-24 months of life. If alanine aminotransferase values are normal and anti-hepatitis C virus is undetectable, follow-up should be interrupted. In children born to hepatitis C virus-RNA positive mothers, alanine aminotransferase and hepatitis C virus RNA should be investigated at 3 months of age: (1) hepatitis C virus-RNA positive children should be considered infected if viremia is confirmed by a second assay performed within the 12th month; (2) hepatitis C virus-RNA negative children with abnormal alanine aminotransferase should be tested again for viremia at 6-12 months, and for anti-hepatitis C virus at 18 months; (3) hepatitis C virus-RNA negative children with normal alanine aminotransferase should be tested for anti-hepatitis C virus and alanine aminotransferase at 18-24 months, and should be considered non-infected if alanine aminotransferase is normal and anti-hepatitis C virus undetectable; (4) anti-hepatitis C virus seropositivity beyond the 18th month in a never-viremic child with normal alanine aminotransferase is likely consistent with past hepatitis C virus infection.

Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1. Tuscany Study Group on Hepatitis C Virus Infection.

OBJECTIVE: To determine the risk factors for and timing of vertical transmission of hepatitis C virus in women who are not infected with HIV-1. DESIGN: Follow up for a median of 28 (range 24-38) months of babies born to women with antibodies to hepatitis C virus but not HIV-1. SUBJECTS: 442 mothers and babies, of whom 403 completed the study. MAIN OUTCOME MEASURES: Presence of antibodies to hepatitis C virus and viral RNA and alanine aminotransferase activity in babies. Presence of viral RNA, method of infection with hepatitis C, method of delivery, and type of infant feeding in mothers. RESULTS: 13 of the 403 children had acquired hepatitis C virus infection at the end of follow up. All these children were born to women positive for hepatitis C virus RNA; none of the 128 RNA negative mothers passed on the infection (difference 5%, 95% confidence interval 2% to 7%). 6 children had viral RNA immediately after birth. 111 women had used intravenous drugs and 20 had received blood transfusions. 11 of the infected children were born to these women compared with 2 to the 144 with no known risk factor (difference 7%, 2% to 12%). CONCLUSIONS: This study suggests that in women not infected with HIV only those with hepatitis C virus RNA are at risk of infecting their babies. Transmission does seem to occur in utero, and the rate of transmission is higher in women who have had blood transfusions or used intravenous drugs than in women with no known risk factor for infection.

[Recent acquisitions on viral hepatitis]. / Recenti acquisizioni sulle epatiti virali.

In the last years the research on viral hepatitis let to better understand the biological, molecular, immunological and epidemiologic characteristics of the viruses that are responsible for hepatitis. The first studied virus was hepatitis B virus (HBv). The scientific attention is still, today, focused on that virus since new markers of infectivity and biological importance in early diagnosis and in disease evolution have been found. The most important result in the last years in the field of viral hepatitis has been, however, the identification of agents responsible for Non-A-Non-B hepatitis. Its epidemiology and clinical importance are discussed in the present paper. Virus C is the most important parenteral agent of NANB hepatitis. Its epidemiology in at risk populations and its role in post-transfusional and cryptogenetic hepatitis are here discussed. The research of new markers of HCV infection is today considered a main goal since the role of the only marker now available is still under discussion.

[Unusual reactions to food additives]. / Manifestazioni cliniche "inusuali" da additivi alimentari.

The most important symptoms caused by food additives are urticaria and angioedema, but rhinitis, asthma and gastrointestinal disturbances are also reported. Only seldom food additives have been shown to induce symptoms in other organs such central nervous system or joints and with a sparse objective evidence. In this study, we report two cases of unusual reactions to food additives (tartrazine and benzoates) involving mainly the central nervous system (headache, migraine, overactivity, concentration and learning difficulties, depression) and joints (arthralgias), confirmed with diet and double blind challenge. The possible pathogenetic mechanisms are also discussed.

[Hepatitis B virus: new markers and their immunology]. / Il virus dell'epatite B: i nuovi markers e la loro immunologia.

Hepatitis B virus (HBV) is one of the most important causes of chronic liver disease. HBV is a DNA virus with an external glycoprotein surface and an internal nucleocapsid which contains the viral genome. HBV infection is revealed by the appearance of specific markers. Some of these markers are well known and their presence in serum is important to understand the behaviour of the disease. Among them HBsAg, HBeAg, anti-HBs and anti-HBe are found in serum, so as anti-Core; the HBcAg may be found in hepatic tissue and marks infectivity and virus replication. In the few last years some new antigens and antibodies have been studied and their importance in diagnosis and follow-up of hepatitis has been recognized. HBxAg, Pre-S and DNA-Polymerase (Pol) seem to be specific and early signals of viral replication. More studies showed the trans-activating properties of HBxAg; actually the X protein seems to be involved in replicative cycle of HBV. Many Authors also demonstrated a relationship between the presence of X in serum and/or liver and the progression of disease to cirrhosis and hepatocellular carcinoma. The Pol antigen and its antibody seem to be very common markers of HBV infection in serum of patients with hepatitis. Moreover their presence is the only signal of viral infection in some patients which have no other marker of HBV. More studies are of course needed to exactly establish the significance of these new markers and their importance for diagnosis and prognosis of HBV infection.

[IgG subclasses against bovine alpha-lactalbumin and beta-lactoglobulin in infants fed with a seroprotein hydrolysate]. / Sottoclassi IgG anti-alfa-lattoalbumina e anti-beta-lattoglobulina bovina in lattanti alimentati con un idrolisato di sieroproteine.

Prevention of food allergy in infancy has been the aim of important researches in the last years but many studies have produced conflicting conclusions. The use of hydrolysate formulas seems to be an helpful tool in prevention of cow milk protein allergy but confusion often remains about capability of small hydrolysate molecules to be "allergens" or "antigens". In order to clarify this point IgE, IgG and IgM as well as IgG subclasses against alfa-lactoalbumin (ALA) and beta-lactoglobulin (BLG) have been evaluated in 41 infants at risk for allergy and in 30 controls at the fourth month. The same evaluation has been done on their mothers. The 41 "at risk" children were fed with breast milk or with an hypoallergenic formula (Nidina HA, Nestlè) or both. The control children received an adapted formula. No difference between the two groups of children was found regarding IgM or IgG against ALA while antibodies against BLG were more frequently found in controls than in "at risk" children. Only one child in the group fed with Nidina HA developed specific IgE against whole milk. Therefore hydrolysate formula seems to be as antigenic (not allergenic) as adapted formula in respect of ALA while BLG contained in adapted formula seems to be a stronger immunogen. The pattern of specific IgG subclasses against ALA and BLG is different between the two groups of children because of the absence in "at risk" group of specific IgG2 and IgG3. As for the mothers, the presence in their sera of IgG against ALA or BLG seems to induce in infants a reduced response to the same antigen.

[Biology of human immunodeficiency virus infection]. / Biologia dell'infezione da virus dell'immunodeficienza umana.

This review will describe the current state of basic knowledge on the acquired immune deficiency syndrome (AIDS), which has now spread worldwide becoming an acute public health problem in western countries and in Africa. AIDS is a viral infection, due to a retrovirus designated human immune deficiency virus (HIV), which affects the immune system resulting in a wide array of secondary manifestations which include opportunistic infections, neoplasia, autoimmune phenomena, neurologic disorders, and hematologic abnormalities. AIDS has now been recognized in the pediatric population, and infection occurs by perinatal and blood-borne transmission. As a consequence, pediatricians are no more involved only by a theoretical point of view (AIDS is a perfect model of interaction of virus with the immune system), but also by an operative point of view. Knowledges on immunological modifications in AIDS and on the underlaying features of the HIV are essential for the clinical approach. This goal may be difficult, if one considers that the pace of research in AIDS and the progress attained to date are unprecedent. However, clinicians must be aware that the ultimate solution of clinical problems in AIDS exclusively depends on sound basic research.

[Subclasses of IgG: biological aspects and functional behavior in response to vaccination]. / Le sottoclassi delle IgG: aspetti biologici e comportamento funzionale in risposta alle vaccinazioni.

The IgG subclasses are known to have different structure and functions. The IgG1 and IgG3 bind to monocyte and neutrophils and activate the complement more easily then IgG2 and IgG4. The levels of IgG subclasses found in newborns are mainly determined by the transplacental passage since the synthesis, in the first time of life, is very low. The levels found in adults are reached only during the adolescence. The immune response to a protein antigen is mainly in the IgG1 subclass, on the contrary the response to polysaccharide antigens is mainly IgG2. For that reason children, who produce very few IgG2 till they are 2 years old, cannot be vaccinated with carbohydrate vaccines unless a protein conjugate vaccine is used. In addition, the route of subministration, the dose of antigen, the age of vaccinated people and genetic factors can modify the subclass pattern obtained in response to vaccinations. For these reasons, probably, the immune response studied after a vaccination or in individuals who recovered from a natural disease is not always the same. Since the role of the different subclasses is not yet completely clarified, the interpretation of the importance of a selective "choice" of a subclass instead of another after vaccination is still difficult.

[Active and passive immunoprevention of hepatitis B in newborn infants with HBsAg-positive mothers]. / L'immunoprofilassi attiva e passiva dell'epatite da virus B nel neonato da madre HBsAg-positiva.

Infants born to HBsAg-positive mothers are at high risk of contracting perinatal hepatitis B infection. The prevention is based on active as well as passive immunoprophylaxis. We have used hepatitis vaccine in 18 newborns of as many HBsAg-positive mothers. Some haematologic and immunologic parameters are here reported. No alterations were observed as to liver function. Immunoglobulin values were normal for age. Auto-antibodies and rheumatoid factor were constantly absent. Immunecomplexes were present in the serum of some infants. The study of T cell subsets and of natural killer cells activity did not reveal any important changes, whereas minor modifications were present in polymorphonuclear leucocyte function. In all infants submitted to vaccination serum conversion was observed a with different antibody levels.

[Reduced natural killer function in children with recurrent respiratory tract infections]. / Ridotta funzionalità natural killer in bambini con infezioni respiratorie ricorrenti.

Respiratory infections are the major cause of disease in childhood in the industrialized areas of the world. This essentially depends on two factors: immunological immaturity and immunological naivety. In most cases a virus has been considered the causative agent in respiratory infection. A defect in immune responses has been described in children with recurrent respiratory infections and in particular a decrease in CD4/CD8 T lymphocyte ratio or in IL-2 and IFN-gamma production. Our results show that Natural Killer (NK) cell activity is defective in children with recurrent respiratory infections. That is particularly noteworthy since NK cells play an important role in host defense against viral infections. At present it is difficult to understand whether the NK defect is a primary defect or it is secondary to viral infections. Further studies will help to clarify whether NK decreased activity depends on a cell damage directly caused by virus or it depends on the decreased levels of cytokines.

[Gastroesophageal reflux and respiratory pathology]. / Reflusso gastroesofageo e patologia respiratoria.

The prevalence of gastroesophageal reflux (GER) in 86 children with respiratory disease (recurrent pneumonia, chronic cough, bronchial asthma) has been evaluated by mean of prolonged (22-24 hours) esophageal pH-monitoring. The following parameters were evaluated: the total percentage of time pH < 4 and the percent time the esophageal pH was < 4 while sleeping. None of the children had gastrointestinal symptoms suggesting GER and no neurological disorder was noted in any of the studied patients. The mean age was 68.98 +/- 46.46 months (range 14-189); 53 (61.6%) males and 33 (38.4%) females were considered in the study. Atopy was evidenced in 42/86 (48.8%) children (total IgE > 2SD in 42/86 and prick tests positiveness in 32/86. A pH-metry indicating pathological GER was present in 52/86 (60.5%) children: 39/62 (62.9%) patients with bronchial asthma, 5/10 (50%) subjects with chronic cough and 8/14 (57.2%) children with recurrent pneumonia. No significant difference in the diagnosis of GER was recorded between atopic or non-atopic patients. The children with abnormal pH-metric recording were also evaluated by upper gastrointestinal series and/or endoscopy. A conventional barium radiology was performed in 44/52 patients and confirmed GER in 19/44 (43.2%). Esophagitis was evidenced in 21/46 (45.7%) studied patients. The presence of esophagitis was significantly (p = 0.032) related to the total percentage of time pH < 4, but the most significant (p = 0.002) association was with the percent time the esophageal pH was < 4 during sleep.(ABSTRACT TRUNCATED AT 250 WORDS)