Meningitis-retention syndrome: a review and update of an unrecognized clinical condition.

OBJECTIVES: We summarized the clinical and radiological characteristics of meningitis-retention syndrome (MRS), its therapeutic options, and urological outcome, to better understand the pathogenesis of this syndrome and to evaluate the effectiveness of corticosteroids in reducing the period of urinary retention. METHODS: We reported a new case of MRS in a male adolescent. We also reviewed the previously 28 reported cases of MRS, collected from inception up to September 2022. RESULTS: MRS is characterized by aseptic meningitis and urinary retention. The mean length of the interval between the onset of the neurological signs and the urinary retention was 6.4 days. In most cases, no pathogens were isolated in cerebrospinal fluid, except for 6 cases in which Herpesviruses were detected. The urodynamic study resulted in a detrusor underactivity, with a mean period for urination recovery of 4.5 weeks, regardless of therapies. DISCUSSION: Neurophysiological studies and electromyographic examination are not pathological, distinguishing MRS from polyneuropathies. Although there are no encephalitic symptoms or signs, and the magnetic resonance is often normal, MRS may represent a mild form of acute disseminated encephalomyelitis, without radiological detectable medullary involvement, due to the prompt use of steroids. It is believed that MRS is a self-limited disease, and no evidence suggests the effectiveness of steroids, antibiotics, and antiviral treatment in its clinical course.

Intrapartum use of zidovudine in a large cohort of pregnant women living with HIV in Italy.

BACKGROUND: Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy. METHODS: Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT. RESULTS: A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group. CONCLUSIONS: In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.

Imported malaria in children: A 13 years retrospective study.

Malaria is not endemic in Italy, however every year about 600-700 imported cases are detected in people born or living in Italy who return from a stay in their country of origin (visiting friends and relatives - VFR). Children account for 20% of this population and they have an higher risk of severe disease. Socio-economic problems and deficiencies in the doctor-patient relationship often lead to a lack of awareness of the importance of prophylaxis, making the category of VFRs at increased risk of disease. The aim of this study is to analyze the characteristics of pediatric imported malaria, with a specific focus on prevention and risk factors for severe malaria. All malaria cases diagnosed from 2007 to 2019 in Ospedale Infantile Regina Margherita in Turin were retrospectively observed. Epidemiological and clinical data were described. A total of 72 patients were reported: 98.6% had African origins and 73.6% traveled as VFRs. Plasmodium falciparum was the species most commonly isolated (94.4%). Twenty-four patients (33.3%) underwent chemoprophylaxis and never appropriately. Patients not undergoing prophylaxis and those undergoing incomplete prophylaxis showed not statistically significant difference in term of disease severity (p = 0.26). Nineteen cases were considered severe, including 3 with cerebral malaria. High levels of parasitemia were statistically significantly correlated with severe anemia (p = 0.049) and severe thrombocytopenia (p = 0.036). In 25% of cases the first diagnosis was incorrect. The therapeutic use of artemisinin derivatives has resulted in a significant shortening of the parasitemia clearance time compared to the use of other drugs (p < 0.001). Families have to be educated about the serious implications of a malaria infection and the importance of a correct and complete prophylaxis. Clinicians should always consider malaria in the differential diagnoses in patients with fever and a history of a recent travel to an endemic area. Prompt diagnosis and use of appropriate drugs, according to the latest guidelines, could guarantee a better outcome for patients.

MIS-C Treatment: Is IVIG Always Necessary?

Background: MIS-C is a potentially severe inflammatory syndrome associated with SARS-CoV-2 exposure. Intravenous immunoglobulin (IVIG) is considered the first-tier therapy, but it implies infusion of large fluid volumes that may worsen cardiac function. Patients and Methods: Since April 2020, we have developed a treatment protocol that avoids the infusion of IVIG as first-line therapy in the early phase of MIS-C. In this study, we retrospectively analyzed a cohort of consecutive patients treated according to this protocol between 01/04/2020 and 01/04/2021. Results: In the last year, 31 patients have been treated according to the protocol: 25 with high-dose pulse MP (10 mg/kg) and 6 with 2 mg/kg. 67.7% of the patients responded to the initial treatment, while the others needed a step-up, either with Anakinra (25.8%) or with MP dose increase (6.5%). IVIG was administered in four patients. Overall, only one patient (3.2%) needed ICU admission and inotropic support; one patient developed a small coronary artery aneurysm. Conclusions: Timely start of MP therapy and careful fluid management might improve the outcomes of MIS-C patients.

COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases.

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

Corrigendum: MIS-C Treatment: Is IVIG Always Necessary?

[This corrects the article DOI: 10.3389/fped.2021.753123.].

SARS-COV-2-associated coagulopathy and thromboembolism prophylaxis in children: A single-center observational study.

BACKGROUND: Multiple investigators have described an increased incidence of thromboembolic events in SARS-CoV-2-infected individuals. Data concerning hemostatic complications in children hospitalized for COVID-19/multisystem inflammatory syndrome in children (MIS-C) are scant. OBJECTIVES: To share our experience in managing SARS-CoV-2-associated pro-coagulant state in hospitalized children. METHODS: D-dimer values were recorded at diagnosis in children hospitalized for SARS-CoV-2-related manifestations. In moderately to critically ill patients and MIS-C cases, coagulation and inflammatory markers were checked at multiple time points and median results were compared. Pro-thrombotic risk factors were appraised for each child and thromboprophylaxis was started in selected cases. RESULTS: Thirty-five patients were prospectively enrolled. D-dimer values did not discriminate COVID-19 of differing severity, whereas were markedly different between the COVID-19 and the MIS-C cohorts. In both cohorts, D-dimer and C-reactive protein levels increased upon clinical worsening but were not accompanied by decreased fibrinogen or platelet values, with all parameters returning to normal upon disease resolution. Six patients had multiple thrombotic risk factors and were started on pharmacological thromboprophylaxis. No deaths or thrombotic or bleeding complications occurred. CONCLUSIONS: COVID-19 pediatric patients show mildly altered coagulation and inflammatory parameters; on the other hand, MIS-C cases showed laboratory signs of an inflammatory driven pro-coagulant status. Universal anticoagulant prophylaxis in hospitalized children with SARS-CoV-2-related manifestations is not warranted, but may be offered to patients with other pro-thrombotic risk factors in the context of a multi-modal therapeutic approach.

Sequelae of COVID-19 in Hospitalized Children: A 4-Months Follow-Up.

Little is known about the sequelae of SARS-CoV-2 infection in children. In a COVID-19 dedicated clinic, we followed-up for 4 months 25 children previously hospitalized for COVID-19, performing clinical, laboratory, and lung ultrasound evaluation. Mid-term sequelae were rarely observed in our COVID-19 children's cohort.

Diagnosis and management of deep neck infections in children: the experience of an Italian paediatric centre.

Deep neck infection (DNI) is a severe occurrence in children. We've examined the presenting signs and symptoms, the value of single diagnostic procedures, the rate of complications and the impact of the therapeutic options on the final outcome, in children with a DNI. We retrospectively evaluated patients, aged 0-18 years, who were admitted for a DNI, from January 2006 through December 2012, at Regina Margherita Children's Hospital, Turin, Italy. We subdivided them on the basis of type of treatment: pharmacological treatment alone or antimicrobial treatment plus surgery. An univariate analysis has been performed to examine the differences between the two groups. Sixty patients (32 males, 28 females) with diagnosis of DNI were enrolled; 33 children only received medical treatment (group 1), whereas 27 patients underwent also surgical interventions (group 2). The mean abscess size was significantly higher in group 2 than in group 1 (p = 0.01). The predominant organisms were Streptococcus sp. (11 cases, 52.4%, mostly Streptococcus pyogenes). The most frequent antibiotic regimen was a ß lactam alone (either III generation cephalosporin or amoxicillin/clavulanate). The duration of intravenous antibiotic varied between the two groups, without statistical significance (p = 0.052); whereas the oral antibiotic administration was significantly shorter in group 1 than in group 2 (p = 0.0003). Three patients (5%) developed complications. This research confirms that the medical approach, with high doses of intravenous antibiotics for a minimum of 5 days, could be a tolerable and safe option for the treatment of patients with stable condition and/or small DNIs.

Natural history of vertically acquired HCV infection and associated autoimmune phenomena.

UNLABELLED: The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9-15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria. CONCLUSIONS: Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.

An uncommon cause of seizures in children living in developed countries: neurocysticercosis--a case report.

Neurocysticercosis represents an important cause of seizures in children in endemic countries, such as Latin America, Asia and sub-Saharan Africa, while in Europe, especially in Italy, the cases of neurocysticercosis are anectodal. We report the case of a 6 year old boy, born and lived for four years in Cameroon, who presented a right emiconvulsion. The diagnosis was neurocysticercosis. This case accentuates the need to consider neurocysticercosis in a child presenting with non febrile seizures, mainly if he emigrated from an area of high prevalence or if he had long-term stay in endemic regions.

Two pediatric cases of multidrug-resistant tuberculosis treated with linezolid and moxifloxacin.

We report here 2 pediatric cases of multidrug-resistant (MDR) tuberculosis (TB) that were observed in Italy. Both families came from an Eastern European country, which is notably an area with a high prevalence of MDR TB. An increase of new cases of MDR TB in developed countries is expected over the next years because of migratory flow, and specific measures and strategies need to be taken to prevent the propagation and dissemination of MDR TB. An efficacious treatment including linezolid and moxifloxacin was administered for 13 months in 1 case. No adverse reactions were detected during close child monitoring. Linezolid and newer fluoroquinolones such as moxifloxacin have been reported to be effective for MDR-TB treatment in adults. On the contrary, there is limited available evidence regarding the effectiveness and safety of these drugs in infants and children with MDR TB. The use of second-line drugs not approved for use in children may be necessary to treat a life-threatening disease such as MDR TB, but it requires careful monitoring to quickly recognize the occurrence of dose- and duration-dependent adverse drug reactions.

Antiretroviral therapy and bone mineral measurements in HIV-infected youths.

Reduced bone mass measurements are often found in HIV-infected youths. Both in vitro and human studies demonstrated a role of antiretroviral treatment in determining bone mass alteration. Nevertheless, the data regarding the responsibility of different antiretroviral drugs on bone health in children and adolescents are highly controversial. The purpose of the current study was to relate antiretroviral treatment to bone mass measurements in a large cohort of HIV-infected children and adolescents. Bone mineral content (BMC) was measured in 86 HIV-infected youths (aged 4.8-22.1 years), and in 194 healthy controls (aged 4.9-21.9 years). Fifteen patients were naive to antiretroviral treatment, 11 were receiving a dual nucleoside reverse transcriptase inhibitor (NRTIs) combination, 32 a protease inhibitor (PI)-based antiretroviral treatment, and 28 a non-nucleoside reverse transcriptase inhibitor (NNRTIs)-based regimen. Comparisons between healthy and HIV-infected children and adolescents have been performed by multiple regression analyses to correct for differences in age, sex, and anthropometric measurements. Patients receiving a PI-based treatment had lumbar spine and whole body BMC values significantly lower than healthy children (P<0.05). BMC measurements of patients on other therapeutic regimens or naive to antiretroviral treatment did not differ significantly from those of healthy children. Among patients receiving a PI-based regimen, those receiving full dose Ritonavir had significantly lower lumbar spine BMC values compared to other patients. Lumbar spine and whole body BMC measurements of patients receiving a Stavudine-containing regimen were lower compared to healthy controls, naive patients, and patients on other antiretroviral regimens. Multivariate analyses showed that patients receiving both Stavudine and full dose Ritonavir had significantly lower BMC values both at the lumbar spine (P=0.0033), and in the whole skeleton (P=0.05). In conclusion, antiretroviral treatment may have a detrimental effect on bone health of HIV-infected youths: the use of Ritonavir full dose alone or in combination with Stavudine is associated to lower bone mass measurements. The use of antiretroviral regimens including these drugs should thus be monitored closely in HIV-infected youths.