Multisystem inflammatory syndrome in children (MIS-C): A nationwide collaborative study in the Greek population.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition that may occur following SARS-CoV-2 infection. This retrospective, descriptive study of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) in 12 tertiary care centers from 3/11/2020 to 12/31/2021. Demographics, clinical and laboratory characteristics, treatment and outcomes are described. Among 145 patients (95 males, median age 8.2 years) included, 123 met the WHO criteria for MIS-C, while 112 (77%) had serological evidence of SARS-CoV-2 infection. Fever was present in 99%, gastrointestinal symptoms in 77%, mucocutaneous involvement in 68% and respiratory symptoms in 28%. Fifty-five patients (38%) developed myocarditis, 29 (20%) pericarditis and 19 (13%) coronary aneurysms. Among the above cases 11/55 (20%), 1/29 (3.4%) and 5/19 (26.3%), respectively, cardiac complications had not fully resolved at discharge. Underlying comorbidities were reported in 18%. Median CRP value was 155 mg/l, ferritin 535 ng/ml, PCT 1.6 ng/ml and WBC 14.2 × 109/mm3. Most patients had elevated troponin (41.3%) and/or NT-pro-BNP (49.6%). Intravenous immunoglobulin plus corticosteroids were used in 117/145 (80.6%), monotherapy with IVIG alone in 13/145 (8.9%) and with corticosteroids alone in 2/145 (1.3%). Anti-IL1 treatment was added in 15 patients (10.3%). Thirty-three patients (23%) were admitted to the PICU, 14% developed shock and 1 required ECMO. Mortality rate was 0.68%. The incidence of MIS-C was estimated at 0.69/1000 SARS-CoV-2 infections. Patients who presented with shock had higher levels of NT-pro-BNP compared to those who did not (p < 0.001). Acute kidney injury and/or myocarditis were associated with higher risk of developing shock. CONCLUSION: MIS-C is a novel, infrequent but serious disease entity. Cardiac manifestations included myocarditis and pericarditis, which resolved in most patients before discharge. Timely initiation of immunomodulatory therapy was shown to be effective. NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. Further research is required to elucidate the pathogenesis, risk factors and optimal management, and long-term outcomes of this clinical entity. WHAT IS KNOWN: • MIS-C is an infrequent but serious disease entity. • Patients with MIS-C present with multi-organ dysfunction, primarily involving the gastrointestinal and cardiovascular systems. WHAT IS NEW: • NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. • Acute kidney injury and/or myocarditis were associated with higher risk of developing shock.

First case report of a successful delivery of a healthy boy by preimplantation genetic testing for Beckwith-Wiedemann syndrome.

PURPOSE: To showcase the successful use of ICSI with PGT-M to overcome Beckwith-Wiedemann syndrome (BWS)-related reproductive challenges, resulting in the birth of a healthy baby boy. By targeting the maternally inherited CDKN1C pathogenic gene variant, this report highlights the genetic interventions in BWS reproductive risk management. METHODS: This case report describes a 41-year-old woman seeking fertility assistance after a previous pregnancy revealed a fetal anomaly related to BWS. Families with BWS recurrence face challenges, as maternally inherited CDKN1C pathogenic variants contribute to approximately 40% of genetic alterations, with a potential recurrence risk as high as 50%. Genetic analysis identified a pathogenic variant in the CDKN1C gene of the fetus that was maternally inherited. The pregnancy was terminated due to the fetal anomalies. The couple underwent intra-cytoplasmic sperm injection (ICSI) combined with preimplantation genetic testing for monogenic diseases (PGT-M) and preimplantation genetic testing for aneuploidy (PGT-A). RESULTS: Two embryos from IVF with low-risk PGT-M and euploid status. One transferred via frozen embryo transfer (FET) in February 2023 resulted in the successful birth of a healthy baby boy. This study reports the first successful delivery of a healthy boy after PGT-M for the CDKN1C gene variant c.79_100delinsGTGACC, contributing to the limited literature on successful outcomes for BWS. CONCLUSION: Utilizing PGT-M in combination with IVF can lead to favorable outcomes in managing BWS-associated reproductive challenges, offering insights into potential genetic interventions and successful birth.

The importance of heart and brain imaging in children and adolescents with Multisystem Inflammatory Syndrome in Children (MIS-C).

Multisystem Inflammatory Syndrome in Children (MIS-C) recently reported in a minority of children affected by SARS-CoV-2, mimics Kawasaki disease (KD), a medium vessel vasculitis of unknown cause. In contrast to acute COVID-19 infection, which is usually mild in children, 68% of patients with MIS-C will need intensive care unit. Myocarditis and coronary artery ectasia/aneurysm are included between the main cardiovascular complications in MIS-C. Therefore, close clinical assessment is need it both at diagnosis and during follow-up. Echocardiography is the cornerstone modality for myocardial function and coronary artery evaluation in the acute phase. Cardiovascular magnetic resonance (CMR) detects diffuse myocardial inflammation including oedema/fibrosis, myocardial perfusion and coronary arteries anatomy during the convalescence and in adolescents, where echocardiography may provide inadequate images. Brain involvement in MIS-C is less frequent compared to cardiovascular disease. However, it is not unusual and should be monitored by clinical evaluation and brain magnetic resonance (MRI), as we still do not know its effect in brain development. Brain MRI in MIS-C shows T2-hyperintense lesions associated with restricted diffusion and bilateral thalamic lesions. To conclude, MIS-C is a multisystem disease affecting many vital organs, such as heart and brain. Clinical awareness, application of innovative, high technology imaging modalities and advanced treatment protocols including supportive and anti-inflammatory medication will help physicians to prevent the dreadful complications of MIS-C.

Sperm Preparation with Microfluidic Sperm Sorting Chip May Improve Intracytoplasmic Sperm Injection Outcomes Compared to Density Gradient Centrifugation.

Does sperm preparation using the FERTILE PLUS™ Sperm Sorting Chip improve fertilization rates, blastocyst formation, utilization, and euploidy rates in patients undergoing intracytoplasmic sperm injection (ICSI), compared with density gradient centrifugation (DGC)? A single-cohort, retrospective data review including data from 53 couples who underwent ICSI cycles within a 12-month period. For each couple, the two closest, consecutive cycles were identified, where one used the standard technique of sperm preparation (DGC) and the subsequent used FERTILE PLUS™, therefore, couples acted as their own controls. Paired samples t-test was used to compare means for the outcomes (fertilization, blastocyst formation, utilization, and euploidy rates). Binary logistic regression analysis assessed the relationship between female age, the presence of male factor infertility, and euploidy rates. Blastocyst, utilization, and euploidy rates were significantly higher for cycles using FERTILE PLUS™ compared to DGC (76% vs 56%, p = 0.002; 60% vs 41%, p = 0.005, and 40% vs 20%, p = 0.001, respectively). Although there was an increase in fertilization rates for cycles using FERTILE PLUS™, this was not significant (72% vs 68%, p = 0.449). The euploidy rates of females ≤ 35 years were significantly increased when the FERTILE PLUS™ sperm preparation method was used, compared to the older age group (OR 2.31, p = 0.007). No significant association was found between the presence or absence of male factor infertility and euploidy rates between the two cycles. This study provides tentative evidence that the FERTILE PLUS™ microfluidic sorting device for sperm selection can improve blastocyst formation, utilization, and euploidy rates following ICSI in comparison to the DGC method.

Effect of clarithromycin on acute asthma exacerbations in children: an open randomized study.

BACKGROUND: Asthma exacerbations are major contributors to asthma morbidity and rather difficult to treat. There is inconclusive evidence that macrolide antibiotics may have an effect on asthma exacerbations through their antibacterial and/or anti-inflammatory properties. The aim of the study was to evaluate the efficacy of clarithromycin on medium-term asthma activity when given as an add-on therapy in children with acute asthma. METHODS: This pilot, open-labeled, randomized, prospective study included 40 school-aged children, with intermittent or mild persistent asthma, presenting with an acute exacerbation. Children were randomized to receive 15 mg/kg of clarithromycin for 3 wk, in addition to their regular (GINA-guided) exacerbation treatment. The microbial trigger of exacerbations was assessed by serology and PCR. Children were followed up with diary cards for 12 wk; lung function was assessed at entry, 3, and 12 wk after the exacerbation. RESULTS: Children in the clarithromycin group had significantly more symptom-free days (78 ± 2 vs. 69 ± 6 days, p < 0.00001) and less total number of periods with loss of control (9 vs. 19, respectively, p = 0.013) during the follow-up period, compared to controls. Moreover, treated children presented reduced duration of the index episode (5.0 ± 1 vs. 7.5 ± 1 days, p < 0.00001). Lung function did not differ between groups. CONCLUSIONS: When added to regular treatment, a 3-wk course of clarithromycin was associated with an increase in the number of symptom-free days, reductions in the number and severity of days with loss of control following index episode, and a decrease in the duration of the initial asthma exacerbation.

Risk factors and psychosocial characteristics of potential problematic and problematic internet use among adolescents: a cross-sectional study.

BACKGROUND: Problematic internet use (PIU) is associated with a plethora of psychosocial adversities. The study objectives were to assess the determinants and psychosocial implications associated with potential PIU and PIU among adolescents. METHODS: A cross-sectional study design was applied among a random sample (n = 866) of Greek adolescents (mean age: 14.7 years). Self-completed questionnaires, including internet use characteristics, Young Internet Addiction Test, and Strengths and Difficulties Questionnaire, were utilized to examine the study objectives. RESULTS: Among the study population, the prevalence rates of potential PIU and PIU were 19.4% and 1.5%, respectively. Multinomial logistic regression indicated that male gender (Odds Ratio, OR: 2.01; 95% Confidence Interval, 95% CI: 1.35-3.00), as well as utilizing the internet for retrieving sexual information (OR: 2.52; 95% CI: 1.53-4.12), interactive game playing (OR: 1.85; 95% CI: 1.21-2.82), and socialization, including chat-room use (OR: 1.97; 95% CI: 1.36-2.86) and email (OR: 1.53; 95% CI: 1.05-2.24), were independently associated with potential PIU and PIU. Adolescents with potential PIU had an increased likelihood of concomitantly presenting with hyperactivity (OR: 4.39; 95% CI: 2.03-9.52) and conduct (OR: 2.56; 95% CI: 1.46-4.50) problems. Moreover, adolescent PIU was significantly associated with hyperactivity (OR: 9.96; 95% CI: 1.76-56.20) and conduct (OR: 8.39; 95% CI: 2.04-34.56) problems, as well as comprehensive psychosocial maladjustment (OR: 8.08; 95% CI: 1.44-45.34). CONCLUSIONS: The determinants of potential PIU and PIU include accessing the internet for the purposes of retrieving sexual information, game playing, and socialization. Furthermore, both potential PIU and PIU are adversely associated with notable behavioral and social maladjustment among adolescents.

Evaluation of potential medical and economic benefits of universal rotavirus vaccination in Greece.

AIM: To evaluate the potential benefits of introducing universal rotavirus (RV) vaccination in Greece. METHODS: A decision analytic model was developed to compare the burden and cost of rotavirus gastroenteritis (RVGE) with and without a universal RV vaccination (88% vaccination coverage) for a cohort of children followed from birth until the age of five. RESULTS: Universal RV vaccination would substantially decrease the RVGE burden on the National Health System by reducing RVGE-related hospitalizations/emergency visits and medical consultations by 83% and 75%, respectively. Total RVGE-related costs was estimated at about 7.6 M€ and would be reduced by 5.9 M€ (-78%) if RV vaccination was introduced. A rapid effect is expected with 76% of cases and 84% of costs avoided would be averted within 2 years postvaccine introduction. The societal benefit would also be significant: total annual number of RVGE cases and parent's lost work days would be reduced by 67% and 78%, respectively. Including indirect costs, the total disease cost reduction would be 9 M€. CONCLUSION: Introduction of universal RV vaccination in Greece could offer considerable medical and economic benefits for the National Health System and society. Potential herd immunity would improve results in favour of vaccination.

Association between internet gambling and problematic internet use among adolescents.

The study objectives were to evaluate the correlates and psychosocial implications of internet gambling among adolescents, as well as the association between internet gambling and problematic internet use. A cross-sectional study design was applied among a random sample (N = 484) of adolescents (71.2% boys; 28.8% girls; mean age ± standard deviation, SD = 14.88 ± 0.55 years). Self-completed questionnaires, including internet gambling practices, internet use characteristics, Young Internet Addiction Test, and Strengths and Difficulties Questionnaire were utilized. The prevalence of internet gambling was 15.1%. Internet gambling was associated with psychosocial maladjustment, including Abnormal Conduct Problems (gender adjusted odds ratio, AOR = 3.83; 95% confidence interval, 95% CI: 1.86-7.92) and Borderline Peer Problems (AOR = 2.04; 95% CI: 1.09-3.85). The likelihood of concomitant problematic internet use was significantly higher among internet gamblers (AOR = 1.81; 95% CI: 1.03-3.19). Multivariate regression analyses indicated that among all characteristics of internet use assessed, utilizing the internet for the purposes of gambling practices was independently associated with problematic internet use among adolescents (AOR = 3.43; 95% CI: 1.40-8.39). Thus, the study findings suggest that adolescents who participate in internet gambling practices are more likely to concomitantly present with problematic internet use.

Determinants of Internet addiction among adolescents: a case-control study.

Internet Addiction (IA) is associated with adverse psychosocial development and mental disorders. The study aims were to evaluate the psychosocial profiles and psychiatric comorbidities associated with IA among adolescents. A case-control study was conducted among 129 adolescents in the outpatient setting of the Adolescent Health Unit of the Second University Department of Pediatrics in Athens, Greece. The case group consisted of 86 adolescents with IA as evaluated following psychiatric interview with two independent examiners. The control group consisted of 43 adolescents without IA, frequency matched for age and gender with case group participants. The study findings indicated that adolescents with IA were significantly more likely to have divorced parents (p = 0.012) and/or dysfunctional familial relationships (p < 0.0001). The proportion of adolescents with poor academic performance (p < 0.0001) and unexcused school absences (p = 0.004) was greater among those with IA. Moreover, approximately two-thirds of the adolescents with IA were engaged in high-risk behaviors (p < 0.0001). Finally, adolescents with IA were 3.89 times more likely to present with comorbid psychiatric conditions (CI 95%: 1.19-12.70), including depression (10.5 vs. 0%; p = 0.022). Adolescent IA is associated with deterred familial functions, poor academic performance, engagement in high-risk behaviors, and an augmented likelihood for depression.

Comparison of the ultrasonic scalpel to CO(2) laser in cervical conization.

The aim of the present study was to compare the efficacy of CO(2) laser with that of ultrasonic scalpel in cervical conization in terms of intraoperative and postoperative outcome. One-hundred and two patients were submitted to cervical conization by ultrasonically activated scalpel, while 97 patients were submitted to cervical conization by use of CO(2) laser. Comparison of mean estimated blood loss, mean operative time and mean cone volume between the two groups was performed with Student t test. Postoperative complications were compared by x(2) test. There was no statistical significance regarding the mean operating time, mean blood loss, mean cone volume and postoperative complications in the two methods. However, thermal artifacts at the cone margins were minimal in the harmonic group (2/102 cones, 1.96%), while in the laser group they were considerably more (18/97 cones, 18.5%) (p < 0.05). Conization using the harmonic scalpel is as safe and effective as the CO(2) laser procedure. It is cheaper, produces less smoke, better visual field and less thermal artifacts in the cone margins. It is a reliable method that overcomes most problems associated with the CO(2) laser, as well as the other conventional conization procedures.

Adenovirus genome in the placenta: association with histological chorioamnionitis and preterm birth.

Adenovirus is isolated frequently from the amniotic fluid and has been implicated in severe neonatal infections. A case control study was carried out to examine the association of detection of adenovirus in placentas with preterm birth and histological chorioamnionitis. Placentas from preterm and full term deliveries were collected prospectively. Preterm cases were divided into three subgroups according to the gestational age. PCR was carried out on placental tissues for the detection of adenovirus genome. Placentas were evaluated histologically for the presence of chorioamnionitis. Chi-square and odds ratios (OR) were used to determine if detection of adenovirus is associated with preterm birth and histological evidence of inflammation. Seventy-one preterm and 122 full term placentas were studied. Adenovirus genome was detected in 29 (40.8%) of preterm cases and in 25 (20.5%) of the full term controls (OR = 2.6; 95% CI, 1.4-5.1; P = 0.002). Detection of adenovirus in preterm placentas was significantly higher compared to full term particularly in the lower gestational age. Detection of adenovirus in placenta followed the seasonal variation of adenovirus infections. Thirty-seven preterm and 21 full term placentas were also selected for paraffin inclusion and histological examination. Chorioamnionitis was present more frequently in preterm adenovirus-positive placentas compared to preterm adenovirus-negative placentas (75% vs. 36%; P = 0.026) as well as compared to term adenovirus-positive placentas (75% vs. 19%; P = 0.003). This study demonstrates that adenovirus infection of the placenta is associated strongly with histological chorioamnionitis and preterm birth.

Cognitive and psychosocial development of HIV pediatric patients receiving highly active anti-retroviral therapy: a case-control study.

BACKGROUND: The psychosocial development of pediatric HIV patients has not been extensively evaluated. The study objectives were to evaluate whether emotional and social functions are differentially associated with HIV-related complications. METHODS: A matched case-control study design was conducted. The case group (n = 20) consisted of vertically infected children with HIV (aged 3-18 years) receiving HAART in Greece. Each case was matched with two randomly selected healthy controls from a school-based population. CNS imaging and clinical findings were used to identify patients with HIV-related neuroimaging abnormalities. The Wechsler Intelligence Scale III and Griffiths Mental Abilities Scales were applied to assess cognitive abilities. The age specific Strengths and Difficulties Questionnaire was used to evaluate emotional adjustment and social skills. The Fisher's exact test, student's t-test, and Wilcoxon rank sum test were used to compare categorical, continuous, and ordinal scores, respectively, of the above scales between groups. RESULTS: HIV patients without neuroimaging abnormalities did not differ from patients with neuroimaging abnormalities with respect to either age at HAART initiation (p = 0.306) or months of HAART treatment (p = 0.964). While HIV patients without neuroimaging abnormalities had similar cognitive development with their healthy peers, patients with neuroimaging abnormalities had lower mean General (p = 0.027) and Practical (p = 0.042) Intelligence Quotient scores. HIV patients without neuroimaging abnormalities had an increased likelihood of both Abnormal Emotional Symptoms (p = 0.047) and Hyperactivity scores (p = 0.0009). In contrast, HIV patients with neuroimaging abnormalities had an increased likelihood of presenting with Abnormal Peer Problems (p = 0.033). CONCLUSIONS: HIV patients without neuroimaging abnormalities are more likely to experience maladjustment with respect to their emotional and activity spheres, while HIV patients with neuroimaging abnormalities are more likely to present with compromised social skills. Due to the limited sample size and age distribution of the study population, further studies should investigate the psychosocial development of pediatric HIV patients following the disclosure of their condition.

Assessment of the feasibility of bipolar coagulation use to reduce hemorrhage in myomectomy performed by minilaparotomy.

The major problem with myomectomy is excessive bleeding from increased uterine blood supply, and this can be a life-threatening condition and prolong postoperative stay. The aim of our study was to evaluate our experience in symptomatic myoma excision with bipolar electrode by mini-laparotomy; we compared 67 procedures with bipolar electrode, in normal saline as distension fluid, to 42 cases performed with unipolar electrode. All participants were pre-menopausal women who had symptomatic myomas

Risk factors for nasopharyngeal carriage of drug-resistant Streptococcus pneumoniae: data from a nation-wide surveillance study in Greece.

BACKGROUND: A nation-wide surveillance study was conducted in Greece in order to provide a representative depiction of pneumococcal carriage in the pre-vaccination era and to evaluate potential risk factors for carriage of resistant strains in healthy preschool children attending daycare centers. METHODS: A study group was organized with the responsibility to collect nasopharyngeal samples from children. Questionnaires provided demographic data, data on antibiotic consumption, family and household data, and medical history data. Pneumococcal isolates were tested for their susceptibility to various antimicrobial agents and resistant strains were serotyped. RESULTS: Between February and May 2004, from a total population of 2536 healthy children, a yield of 746 pneumococci was isolated (carriage rate 29.41%). Resistance rates differed among geographic regions. Recent antibiotic use in the last month was strongly associated with the isolation of resistant pneumococci to a single or multiple antibiotics. Serotypes 19F, 14, 9V, 23F and 6B formed 70.6% of the total number of resistant strains serotyped. CONCLUSION: Recent antibiotic use is a significant risk factor for the colonization of otherwise healthy children's nasopharynx by resistant strains of S pneumoniae. The heptavalent pneumococcal conjugate vaccine could provide coverage for a significant proportion of resistant strains in the Greek community. A combined strategy of vaccination and prudent antibiotic use could provide a means for combating pneumococcal resistance.

Internet use and misuse: a multivariate regression analysis of the predictive factors of internet use among Greek adolescents.

The internet is an integral tool for information, communication, and entertainment among adolescents. As adolescents devote increasing amounts of time to utilizing the internet, the risk for adopting excessive and pathological internet use is inherent. The study objectives include assessing the characteristics and predictors of excessive internet use and evaluating the prevalence of pathological internet use among Greek adolescents. A cross-sectional study design was applied to this effect. The study population (n = 897) consisted of a random sample of adolescents residing in Athens, Greece. Self-completed questionnaires, pertaining to internet access characteristics and Young's Internet Addiction Scale (YIAS) score, were applied in order to investigate the study objectives. The multivariate regression analysis indicated that the most significant predictors of overall internet use included accessing the internet via one's own home portal and for the purpose of social interaction. Internet access via the school environment was a significant deterrent among low (1-3 h/week) internet users, while access via internet cafés was a significant predictor for high (11-20 h/week) internet users. Moreover, accessing the internet for the purposes of game playing was the most significant predictor for excessive (>20 h/week) internet use. The prevalence of borderline internet use among the study population was 12.8%, while 1.00% reported addictive internet use. Also, 10.4% of male excessive internet users reported addictive internet use (p < 0.0001). In conclusion, excessive internet use is predicted solely by the location of internet access (own home portal) and the scope of internet use (i.e., sites relating to socialization and game playing) and may lead to internet addiction, particularly among male adolescents.

Detection of cytomegalovirus, parvovirus B19 and herpes simplex viruses in cases of intrauterine fetal death: association with pathological findings.

There are previous indications that transplacental transmission of cytomegalovirus (CMV), parvovirus B19 (PB19) and herpes simplex virus types 1 and 2 (HSV-1/2) cause fetal infections, which may lead to fetal death. In a prospective case-control study we examined the incidence of these viruses in intrauterine fetal death and their association with fetal and placenta pathological findings. Molecular assays were performed on placenta tissue extracts of 62 fetal deaths and 35 controls for the detection of CMV, PB19 and HSV-1/2 genomes. Formalin-fixed, paraffin-embedded liver, spleen and placenta tissues of fetal death cases were evaluated histologically. Thirty-four percent of placental specimens taken from intrauterine fetal deaths were positive for any of the three viruses (16%, 13%, and 5% positive for CMV, PB19, and HSV-1/2, respectively), whereas only 6% of those taken from full term newborns were positive (P = 0.0017). No dual infection was observed. This difference was also observed when fetal deaths with a gestational age <20 weeks or a gestational age >20 weeks were compared with the controls (P = 0.025 and P = 0.0012, respectively). Intrauterine death and the control groups differed in the detection rate of CMV DNA (16% and 3%, respectively; P = 0.047), which was more pronounced in a gestational age >20 weeks (P = 0.03). Examination of the pathological findings among the PCR-positive and PCR-negative fetal deaths revealed that hydrops fetalis and chronic villitis were more common among the former group (P = 0.0003 and P = 0.0005, respectively). In conclusion, an association was detected between viral infection and fetal death, which was more pronounced in the advanced gestational age. Fetal hydrops and chronic villitis were evidently associated with viral DNA detection in cases of intrauterine death.

Tuberculosis in neonates and infants: epidemiology, pathogenesis, clinical manifestations, diagnosis, and management issues.

Tuberculosis is one of the leading infectious causes of death and as such represents a major global health problem. Infants may develop congenital tuberculosis from an infectious mother or, most commonly, they may acquire postnatal disease by contact with an infectious adult source. Important epidemiologic, pathogenetic, and clinical data regarding the management of infantile disease are reviewed. Diagnostic evaluation includes tuberculin skin tests, chest radiography and other imaging studies, smears and cultures, examination of the cerebrospinal fluid, and polymerase chain reaction, as well as the more recent interferon-gamma assay. Pregnant women with a positive Mantoux skin test but normal chest x-ray should either start chemoprophylaxis during gestation or after delivery depending on the likelihood of being recently infected, their risk of progression to disease, as well as their clinical evidence of disease. Pregnant women with a positive Mantoux skin test and chest x-ray or symptoms indicative of active disease should be treated with non-teratogenic agents during gestation; all household contacts should also be screened. When tuberculosis is suspected around delivery, the mother should be assessed by chest x-ray and sputum smear; separation of mother and offspring is indicated only if the mother is non-adherent to medical treatment, needs to be hospitalized, or when drug-resistant tuberculosis is involved. According to the American Academy of Pediatrics, treatment of latent infection is highly effective with isoniazid administration for 9 months. This regimen may be extended to 12 months for immunocompromised patients. When drug resistance is suspected, combination therapies, which usually consist of isoniazid with rifampin (rifampicin), are administered until the results of susceptibility tests become available. Organisms resistant to isoniazid only may be treated with rifampin alone for a total of 6-9 months. All infants with tuberculosis disease should be started on four agents (isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) until drug susceptibility is assessed. For susceptible intrathoracic tuberculosis, isoniazid, rifampin, and pyrazinamide are administered for a total of 2 months, at which point pyrazinamide is withdrawn and the other two agents are continued for another 4-10 months depending on the severity of the disease. The same regimen may be applied in extrapulmonary tuberculosis with the exception of skeletal, miliary, and CNS disease, which require daily administration of isoniazid, rifampin, pyrazinamide, and streptomycin for 1-2 months, followed by isoniazid and rifampin daily or twice weekly for another 10 months. When drug-resistant tuberculosis is suspected, a regimen of isoniazid, rifampin, and pyrazinamide plus either streptomycin or ethambutol should be initially prescribed, until the results of susceptibility tests become available. HIV-seropositive infants with pulmonary tuberculosis should receive isoniazid, rifampin, pyrazinamide, and ethambutol or an aminoglycoside for 2 months, followed by isoniazid and rifampin for a total of at least 12 months. Apart from conventional antimycobacterial agents, novel therapeutic modalities, which stimulate the host immune system such as interleukin-2 (IL-2), IL-12, interferon-gamma, and tumor necrosis factor antagonists have been tested with promising results.

Human Metapneumovirus as a causative agent of acute bronchiolitis in infants.

BACKGROUND: Human Metapneumovirus (hMPV), has been recently isolated from children with acute respiratory tract infections (RTIs), including bronchiolitis, and classified in the Pneumovirinae subfamily within the Paramyxoviridae family. OBJECTIVES: Since most bronchiolitis studies fail to detect any viral pathogen in part of the samples, we sought for the presence of hMPV in a well characterized bronchiolitis cohort. STUDY DESIGN: Nasal washes were obtained from 56 children admitted to the hospital for acute bronchiolitis. RNA extraction and subsequent RT-PCR were used to detect hMPV, and correlated the presence of the virus with clinical characteristics of the disease. RESULTS AND CONCLUSIONS: PCR revealed the presence of hMPV in 16% of bronchiolitis cases, whereas respiratory syncytial virus (RSV; 67.9%) was the most frequently encountered viral pathogen. hMPV was identified either as a unique viral pathogen or co-existed with RSV, with whom they shared a similar seasonal distribution. There were no differences in disease characteristics, either clinical or laboratory, between bronchiolitis cases where hMPV was present and those caused by RSV or other viral pathogens. These findings suggest that hMPV is a common and important causative agent in infants with bronchiolitis, with clinical characteristics similar to that of RSV.

Does respiratory syncytial virus subtype influences the severity of acute bronchiolitis in hospitalized infants?

Respiratory syncytial virus (RSV) subtypes A and B are present either simultaneously or alternate during yearly epidemics. It is still not clear whether clinical severity of acute bronchiolitis differs between the two subtypes. Reverse transcription polymerase chain reaction was used to subtype RSV in previously healthy infants hospitalized with RSV bronchiolitis during a winter epidemic. A severity index based on heart rate, respiratory rate, wheezing, difficulty in feeding and oxygen saturation was calculated upon admission. Infants infected with RSV subtype-A were found to have a significantly higher (more severe) clinical score than those infected with RSV-B. There was no statistically significant difference in duration of hospitalization or need of intensive care. Boys and infants younger than 3 months of age were also more severely affected than girls or older infants, respectively. These results support the notion that RSV-A-induced bronchiolitis is more severe than RSV-B-induced one, in agreement with the majority of previously published studies.

Enteral L-arginine supplementation for prevention of necrotizing enterocolitis in very low birth weight neonates: a double-blind randomized pilot study of efficacy and safety.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal disease in premature infants and has high mortality and morbidity. Endothelial nitric oxide is an important regulator of vascular perfusion and is synthetized from the amino acid L-arginine. Hypoargininemia is frequently observed in preterm neonates and may predispose them to NEC. Our objective was to determine the effect of enteral L-arginine supplementation on the incidence and severity of NEC in very low birth weight (VLBW) neonates. MATERIALS AND METHODS: We conducted a parallel blind randomized pilot study, comprising VLBW neonates with birth weight ≤1500 g and gestational age ≤34 weeks. VLBW neonates were randomly assigned to receive enteral L-arginine supplementation (1.5 mmol/kg/d bid) between the 3rd and 28th day of life or placebo. Diagnosis and classification of NEC were done according to modified Bell's criteria. RESULTS: Eighty-three neonates were randomized to the arginine (n = 40) or placebo (n = 43) group. No adverse effects were observed in neonates receiving L-arginine supplementation. The incidence of NEC stage III was significantly lower in the arginine-supplemented group (2.5% vs 18.6%, P = .030). CONCLUSIONS: Enteral L-arginine supplementation of 1.5 mmol/kg/d bid can be safely administered in VLBW neonates from the 3rd to the 28th day of life. Enteral L-arginine supplementation appears to reduce the incidence of stage III NEC in VLBW infants. Larger studies are needed to further evaluate the effect of L-arginine supplementation in preventing NEC in VLBW infants.