Clinical and Radiological Features of Pneumocystis jirovecii Pneumonia in Children: A Case Series.

BACKGROUND: Pneumocytis jirovecii pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to present the radiological and clinical pathway of PJP in a pediatric population. DESCRIPTION OF CASES: All PJP cases in non-HIV/AIDS patients diagnosed at Istituto Giannina Gaslini Pediatric Hospital in Genoa (Italy) from January 2012 until October 2022 were retrospectively evaluated. Nine cases were identified (median age: 8.3 years), and of these, 6/9 underwent prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX; five once-a-week schedules and one three times-a-week schedule), while 3/9 did not receive this. PJP was diagnosed by real-time PCR for P. jirovecii-DNA in respiratory specimens in 7/9 cases and two consecutive positive detections of ß-d-glucan (BDG) in the serum in 2/9 cases. Most patients (6/8) had a CT scan with features suggestive of PJP, while one patient did not undergo a scan. All patients were treated with TMP/SMX after a median time from symptoms onset of 3 days. In 7/9 cases, empirical TMP/SMX treatment was initiated after clinical suspicion and radiological evidence and later confirmed by microbiological data. Clinical improvement with the resolution of respiratory failure and 30-day survival included 100% of the study population. DISCUSSION: Due to the difficulty in obtaining biopsy specimens, PJP diagnosis is usually considered probable in most cases. Moreover, the severity of the clinical presentation often leads physicians to start TMP/SMX treatment empirically. BDG proved to be a useful tool for diagnosis, and CT showed good accuracy in identifying typical patterns. In our center, single-day/week prophylaxis was ineffective in high-risk patients; the three-day/week schedule would, therefore, seem preferable and, in any case, should be started promptly in all patients who have an indication of pneumonia.

A Rare Pediatric Case of Allopurinol-Induced Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Successfully Treated With Intravenous Immunoglobulins.

Allopurinol-induced drug reaction syndrome with eosinophilia and systemic symptoms (A-DRESS) is a well-described condition in adults, whereas it is uncommon among children. We describe a case of A-DRESS in a 16-year-old male with steroid-dependent nephrotic syndrome. He presented a life-threatening clinical course with persisting fever, skin rash, eosinophilia, lymphadenopathy, distributive shock, and herpesvirus 6 detection. The withdrawal of allopurinol and a combination of intravenous immunoglobulins (IVIGs) and systemic corticosteroids led to the patient's recovery without sequelae. Drug reaction with eosinophilia and systemic symptoms (DRESS) in pediatrics is rare and can present in a severe form. Early diagnosis and timely treatment are critical for prognostic purposes. This report suggests the potentially crucial role of IVIG in the treatment of patients with A-DRESS.

Experience of an Italian Pediatric Third Level Emergency Department during the 2022-2023 Bronchiolitis Epidemic: A Focus on Discharged Patients and Revisits.

The aim of this study was to describe the 2022-2023 bronchiolitis epidemic season (the second after COVID-19 pandemic and the first without social restriction), focusing on patients discharged home from a pediatric emergency department (PED) and on those revisited within 72 h. We performed a retrospective observational study in an Italian tertiary care children's hospital, reviewing PED accesses from 1 October 2022 to 31 March 2023. The number of hospitalizations for bronchiolitis was extracted from hospital discharge forms. A total of 512 patients diagnosed with bronchiolitis were admitted to PED (2.8% of total admissions). Accesses increased sharply from November to January, with a peak in December, in both admissions and hospitalizations. More than half of the patients (55.5%) were safely discharged home, while 38 (13.4%) came back to PED for a revisit. Overall PED accesses and hospitalizations for bronchiolitis increased since the previous epidemic season, and particularly compared to the pandemic and pre-pandemic eras. Empowering the collaboration between all healthcare provisioners is fundamental to suitable management of patients. Monitoring the epidemiology and seasonality of bronchiolitis is a starting point for an effective internal organization of pediatric departments and to further evaluate its socio-economic burden.

Whipple Disease Presenting as Isolated Transverse Myelitis with Permanent Neurological Damage in a Patient with Systemic Lupus Erythematosus: A Case Report of a Difficult Diagnosis with a Literature Review.

We describe an atypical case of Whipple disease exclusively involving the spinal cord in an adolescent receiving immunosuppressive therapy for systemic lupus erythematosus. The diagnosis was particularly difficult since lupus and Whipple disease can present similar clinical features and the patient's prolonged contact with sewage was initially not mentioned. A literature review of the clinical, imaging, diagnostic, and therapeutic challenges of Whipple disease is also performed.

Clinical Course, Laboratory Findings, and Prognosis of SARS-CoV-2 Infection in Infants up to 90 Days of Age: A Single-Center Experience and a Proposal for a Management Pathway.

AIM: To provide a comprehensive description of the clinical features, biochemical characteristics, and outcomes of infants up to 90 days old with COVID-19. Moreover, to assess the severity of the disease and propose an effective management pathway. METHODS: Retrospective single-center study spanning three years. Patient data includes age, sex, symptoms, comorbidities, blood and urine test results, cultures, admission, length of stay, therapies, intensive care unit admission, and mortality. RESULTS: A total of 274 patients were enrolled in the study, comprising 55% males. Among them, 60 patients (22%) were under the age of 29 days, while 214 (78%) fell within the 29 to 90 days age range. The overall incidence of SARS-CoV-2 infections was 0.28 per 10,000 Pediatric Emergency Department admissions. Blood inflammatory markers showed no significant abnormalities, and there were no recorded instances of positive blood cultures. Less than 1% of infants showed urinary tract infections with positive urine cultures, and 1.5% of patients had a concurrent RSV infection. Hospitalization rates were 83% for neonates and 67% for infants, with a median length of stay (LOS) of 48 h for both age groups. None of the patients required admission to the Pediatric or Neonatal Intensive Care Unit, and only one required High Flow Nasal Cannula (HFNC). No secondary serious bacterial infections were observed, and all hospitalized patients were discharged without short-term sequelae. No deaths were reported. DISCUSSION AND CONCLUSIONS: Infants with COVID-19 generally exhibit milder or asymptomatic forms of the disease, making home management a viable option in most cases. Blood tests, indicative of a mild inflammatory response, are recommended primarily for children showing symptoms of illness. Hospitalization precautions for infants without apparent illness or comorbidities are deemed unnecessary. Given the evolving nature of experiences with COVID-19 in infants, maintaining a high level of clinical suspicion remains imperative.

Clinical course and peculiarities of Parechovirus and Enterovirus central nervous system infections in newborns: a single-center experience.

Parechovirus (HpEV) and Enterovirus (EV) infections in children mostly have a mild course but are particularly fearsome in newborns in whom they may cause aseptic meningitis, encephalitis, and myocarditis. Our study aimed to describe the clinical presentations and peculiarities of CNS infection by HpEV and EV in neonates. This is a single-center retrospective study at Istituto Gaslini, Genoa, Italy. Infants aged ≤ 30 days with a CSF RTq-PCR positive for EV or HpEV from January 1, 2022, to December 1, 2023, were enrolled. Each patient's record included demographic data, blood and CSF tests, brain MRI, therapies, length of stay, ICU admission, complications, and mortality. The two groups were compared to identify any differences and similarities. Twenty-five patients (15 EV and 10 HpEV) with a median age of 15 days were included. EV patients had a more frequent history of prematurity/neonatal respiratory distress syndrome (p = 0.021), more respiratory symptoms on admission (p = 0.012), and higher C-reactive protein (CRP) levels (p = 0.027), whereas ferritin values were significantly increased in HpEV patients (p = 0.001). Eight patients had a pathological brain MRI, equally distributed between the two groups. Three EV patients developed myocarditis and one HpEV necrotizing enterocolitis with HLH-like. No deaths occurred.  Conclusion: EV and HpEV CNS infections are not easily distinguishable by clinical features. In both cases, brain MRI abnormalities are not uncommon, and a severe course of the disease is possible. Hyper-ferritinemia may represent an additional diagnostic clue for HpEV infection, and its monitoring is recommended to intercept HLH early and initiate immunomodulatory treatment. Larger studies are needed to confirm our findings. What is Known: • Parechovirus and Enteroviruses are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants. • The clinical course and distinguishing features of Parechovirus and Enterovirus central nervous system infections are not well described. What is New: • Severe disease course, brain MRI abnormalities, and complications are not uncommon in newborns with Parechovirus and Enteroviruses central nervous system infections. • Hyper-ferritinemia may represent an additional diagnostic clue for Parechovirus infection and its monitoring is recommended.

The increase of bronchiolitis severity in the 2022-2023 season in an Italian tertiary children's hospital: An isolated phenomenon or a warning sign?

AIM: Recent literature has shown epidemiological changes in bronchiolitis with an increased incidence in the post-SARS-CoV-2 pandemic period but reports regarding disease severity are conflicting. We aimed to describe the epidemiology, disease severity, and microbiology of bronchiolitis during the 2022-2023 cold season compared to the previous 5 years. METHODS: This single-center retrospective observational study at IRCCS Gaslini, Italy, included all children aged 0-2 years hospitalized for bronchiolitis from 1 September 2017 to 31 August 2023. Findings from the 2022-2023 season were compared to the previous 5 years. RESULTS: We observed a statistically significant increase in the 2022-2023 season in the absolute number of bronchiolitis admissions. Children who required mechanical ventilation (MV) dramatically increased from a total of seven patients in the previous five seasons to 17 in the 2022-2023 season alone (p = .001). All other severity parameters significantly increased: the need for respiratory support (p = .002), the median length of stay (5 days vs. 4 days, p = .001), and the median duration of respiratory support (4 days vs. 3 days, p = .016). CONCLUSIONS: We report a substantial increase in the severity of bronchiolitis in the season 2022-2023 with a remarkable number of previously healthy infants requiring MV. Further studies are needed to confirm whether our findings are an isolated phenomenon or part of a true global trend. Health systems need to be prepared and protective preventive measures should be implemented for all newborns.

Epidemiological and clinical evolution of multisystem inflammatory syndrome in children throughout the SARS-CoV-2 pandemic in a tertiary Italian children's hospital.

Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening disease temporally linked to SARS-CoV-2 whose incidence and clinical presentation may have been altered by the different SARS-CoV-2 variants and by vaccination. METHODS: We retrospectively collected the data of all MIS-C cases admitted to the Gaslini Children's Hospital, the hub for SARS-CoV-2 related diseases in Liguria region, Italy, from 01 October 2020, to 30 November 2022, evaluating the ratio between MIS-C cases and (1) COVID-19 paediatric cases in our region, (2) emergency department admissions and (3) emergency department febrile patients. We also compared MIS-C incidence in pre- post-vaccination periods. RESULTS: We observed a significant global decline in the incidence of MIS-Cover the four variant periods and after the starting of vaccination whereas clinical features, therapeutic management and severity did not significantly vary. CONCLUSIONS: In our setting, we demonstrated a significant decrease of MIS-C incidence according to the predominant variant and including not vaccinated children. Regardless of variant type, the patients showed similar phenotypes and severity throughout the pandemic. SARS-CoV-2 variants as well as immune protection after previous infections and/or vaccination may have interacted by playing different roles and reducing the incidence of MIS-C.

Individual, environmental and demographic factors may play a role in the prognosis of fatal and non-fatal paediatric drowning.

AIM: Drowning is a leading cause of unintentional death. Ongoing efforts are dedicated to preventing these tragic incidents. Our aim was to evaluate whether demographic, environmental and epidemiological characteristics of drowned children influence their prognosis. METHODS: Single-centre retrospective study spanning 12 years. Each patient's record included: age, sex, place of residence, presence of siblings, season of incident, location of event, associated trauma, loss of consciousness, need for cardiopulmonary resuscitation, intubation, admission to intensive care unit, length of stay and mortality. RESULTS: We enrolled 60 patients, with a mean age of 5.9 ± 3.4 years; 63.5% were male. Children who did not reside near the sea were significantly older than those who did (p = 0.01) and faced a higher risk of experiencing sea-related drowning (p = 0.05). No patients died. Loss of consciousness and need for cardiopulmonary resuscitation were recorded in 30 and 19 patients respectively. Seven patients sustained trauma. Only one patient requiring intubation. Pool-related drowning were associated with a higher incidence of needing cardiopulmonary resuscitation (p = 0.02). The need for cardiopulmonary resuscitation (p = 0.05) and the occurrence of trauma (p = 0.02) were identified as risk factors for a longer hospitalisation. CONCLUSION: Prevention and early initiation of cardiopulmonary resuscitation are essential for achieving a favourable prognosis. Identifying demographic and environmental risk factors may help identify other effective preventive measures.

Acute pediatric encephalitis: etiology, course, and outcome of a 12-year single-center immunocompetent cohort.

BACKGROUND: Encephalitis is an uncommon but severe disorder due to an inflammation of the brain parenchyma, usually diagnosed on clinical, laboratory, electroencephalographic, and neuroradiological features. New causes of encephalitis have been reported in recent years, so diagnostic criteria have changed over time. We report on a single-center experience of a pediatric Hospital, the hub of its region, over 12 years (2008-2021), with the evaluation of all children managed for acute encephalitis. METHODS: We retrospectively reviewed clinical, laboratory, neuroradiological, and EEG data from the acute phase and outcome of all immunocompetent patients diagnosed with acute encephalitis. According to the newly proposed criteria for pediatric autoimmune encephalitis, we divided patients into infectious, definite autoimmune, probable autoimmune, and possible autoimmune, and performed a comparison between the different groups. RESULTS: 48 patients (26 females, mean age 4.4 years), 19 with infections, and 29 with autoimmune encephalitis, were included. Herpes simplex virus 1 encephalitis was the most frequently identified etiology followed by anti-NMDA receptor encephalitis. Movement disorders at onset and a longer hospital stay were observed more frequently in autoimmune compared to infectious encephalitis (p p < 0.001 and p = 0.001, respectively). Among the autoimmune group, children who started immunomodulatory treatment earlier (within 7 days from onset) had more frequent complete functional recovery (p = 0.002). CONCLUSIONS: Herpes virus and anti-NMDAR encephalitis are the most frequent etiologies within our cohort. Clinical onset and course are extremely variable. Since early immunomodulatory treatment was associated with a better functional outcome, our data confirm that a timely diagnostic classification in definite, probable, or possible autoimmune encephalitis can help the clinician in a successful therapeutic approach.

Ketamine as advanced second-line treatment in benzodiazepine-refractory convulsive status epilepticus in children.

Status epilepticus (SE) is one of the most common neurological emergencies in children. To date, there is no definitive evidence to guide treatment of SE refractory to benzodiazepines. The main objectives of treatment protocols are to expedite therapeutic decisions and to use fast- and short-acting medications without significant adverse effects. Protocols differ among institutions, and most frequently valproate, phenytoin, and levetiracetam are used as second-line treatment. After failure of first- and second-line medications, admission to the intensive care unit and continuous infusion of anesthetics are usually indicated. Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that has been safely used for the treatment of refractory SE in adults and children. In animal models of SE, ketamine demonstrated antiepileptic and neuroprotective properties and synergistic effects with other antiseizure medications. We reviewed the literature to demonstrate the potential role of ketamine as an advanced second-line agent in the treatment of SE. Pharmacological targets, pathophysiology of SE, and the receptor trafficking hypothesis are reviewed and presented. The pharmacology of ketamine is outlined with related properties, advantages, and side effects. We summarize the most recent and relevant publications on experimental and clinical studies on ketamine in SE. Key expert opinion is also reported. Considering the current knowledge on SE pathophysiology, early sequential polytherapy should include ketamine for its wide range of positive assets. Future research and clinical trials on SE pharmacotherapy should focus on the role of ketamine as second-line medication.

How has the SARS-CoV-2 pandemic changed the epidemiology and management of acute bronchiolitis?

OBJECTIVE: SARS-COV-2 pandemic profoundly impacted acute bronchiolitis epidemiology worldwide, especially respiratory syncytial virus (RSV) diffusion and the burden of disease, with remarkable implications on the management of health resources. We aimed to study the epidemiology and clinical course of bronchiolitis in the past 5 years in our region and to assess the trends that occurred during and after the SARS-COV-2 pandemic. METHODS: We conducted an observational study including all children aged 0-2 years with bronchiolitis admitted to a tertiary children's hospital during the last 5 years. Demographic, clinical, and microbiological data were collected. Comparisons between patient subgroups were carried out. RESULTS: A total of 647 patients admitted for bronchiolitis were included (median age 78 days). Molecular diagnostic tests were performed in 617 patients (95.4%) with RSV detected in 51.5% of patients in prepandemic years and 74.5% in pandemic years. Through the study period, we observed a progressive increase in the number of children requiring respiratory support, RSV infections, and children with a history of prematurity. Conversely, this was not true for mechanical ventilation, duration of respiratory support, intensive care unit admission, and length of stay. CONCLUSIONS: Clinical course and epidemiology of bronchiolitis showed a significant change through the study years with a heavy impact during the 2021-2022 season. The increase in the number of patients requiring respiratory support, although not associated with an increase in mechanical ventilation, may be explained by the higher prevalence of RSV. The change in epidemiology highlights the importance of surveillance systems to monitor RSV circulation, to plan prophylactic strategies, and prepare healthcare systems.

Learning from the COVID-19 pandemic: IMCU as a more efficient model of pediatric critical care organization.

BACKGROUND: A significant proportion of children with SARs-CoV-2-related illnesses have been admitted to the Pediatric intensive care unit (ICU), although often for closer monitoring or concerns related to comorbidities or young age. This may have resulted in inappropriate ICU admissions, waste of resources, ICU overcrowding, and stress for young patients and caregivers. The Pediatric Intermediate Care Unit (IMCU) may represent an appropriate setting for the care of children whose monitoring and treatment needs are beyond the resources of a general pediatric ward, but who do not qualify for critical care. However, research on pediatric IMCUs and data on their performance is very limited. METHODS: We conducted a single-center retrospective study including all patients aged 0-18 with acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C), admitted to a newly established stand-alone 12-bed pediatric IMCU at Gaslini Hospital, Genoa, Italy, between 1 March 2020 and 31 January 2022. Each IMCU room has a multiparameter monitor connected to a control station and can be equipped as an ICU room in case of need for escalation of care, up to ECMO support. IMCU and ICU are adjacent and located on the same floor, allowing a timely escalation from intermediate to critical care in the IMCU, with staff changes without the need for patient transfer. RESULTS: Among 550 patients hospitalized for acute COVID-19 or MIS-C, 106 (19.2%, 80 with acute COVID-19, and 26 MIS-C) were admitted to IMCU. Three of them (2.8%) required escalation to critical care due to the worsening of their conditions. Forty-seven patients (44%) were discharged home from the IMCU, while the remaining 57 (55%) were transferred to low-intensity care units after clinical improvement. CONCLUSIONS: In our study, the need for pediatric ICU admission was low for both acute COVID-19 patients (0.8%) and MIS-C patients (3.1%) compared to the literature data. The IMCU represented an adequate setting for children with COVID-19-related illness who need a higher level of care, but lack strict indications for ICU admission, thus preventing ICU overcrowding and wasting of economic and logistical resources. Further studies are needed to better assess the impact of an IMCU on hospital costs, ICU activity, and long-term psychological sequelae on children and their families.

Protection against MIS-C outweighs the risk of myocarditis after Covid-19 vaccination in children.

From March 2020 to July 2022, in Liguria region (North-West Italy) incidence of MIS-C among pediatric patients infected by SARS-CoV-2 was 38.7/100.000, which is higher than that of myocarditis after COVID-19 vaccination. In our opinion severity of MIS-C-related cardiac disease outweigh the risk of myocarditis after COVID-19 vaccine.

Acute Neurological Presentation in Children With SARS-CoV-2 Infection.

Background: In the pediatric population, the knowledge of the acute presentation of SARS-CoV-2 infection is mainly limited to small series and case reports, particularly when dealing with neurological symptoms. We describe a large cohort of children with acute SARS-CoV-2 infection, focusing on the neurological manifestations and investigating correlations between disease severity and population demographics. Methods: Patients aged 0-18 years with a positive molecular swab were recruited between April 2020 and March 2021 from a tertiary Italian pediatric centre. Clinical data, imaging, and laboratory test results were retrieved from our local dataset and statistically analyzed. Results: A total of 237 patients with a median age of 3.2 years were eligible; thirty-two (13.5%) presented with neurological symptoms, including headache (65.6%), altered awareness (18.8%), ageusia/anosmia (12.5%), seizures (6.3%), and vertigo (6.3%), combined in 7 (21.9%) cases. Respiratory (59.5%) and gastrointestinal (25.3%) symptoms were the most common among the 205 (86.5%) patients without neurological involvement. Neurological symptoms did not significantly influence the severity of the triage access codes. Moreover, pre-existing medical conditions were not higher in the group with neurological manifestations. Overall, fifty-nine patients (25%, 14/59 with neurological symptoms) required treatment, being antibiotics, systemic steroids, and heparin those most prescribed. Conclusion: Our study supports the overall benign course of the SARS-CoV-2 infection in children. Neurological manifestations, except for headache, remain a rare presenting symptom, and disease severity seems unrelated to pre-existing medical conditions.

Longitudinally Extensive Transverse Myelitis (LETM) and Myopericarditis in a 7-Month-Old Child with SARs-CoV-2 Infection.

INTRODUCTION: In the last few months, some pediatric cases with neurological and neuroradiological pictures related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported, often associated with multisystem inflammatory syndrome (MIS-C). The most frequently encountered pediatric neurological complications seem to be postinfectious immune-mediated acute disseminated encephalomyelitis (ADEM)-like changes of the brain, myelitis, neural enhancement, and splenial lesions. Concomitant neurological and cardiac involvement has been reported only in MIS-C, although specific clinical details are often not fully available. METHODS: In this case report, a very young child infected with SARs-CoV-2 and diagnosed as longitudinal extensive transverse myelitis with concomitant myo-pericarditis is presented. RESULTS: A previously healthy 7-month-old girl presented with abrupt onset of generalized weakness with inability to sit up. She had had mild respiratory symptoms 1 week earlier. Spinal magnetic resonance imaging (MRI) showed a T2-hyperintense intramedullary lesion extending from C4 to T2, compatible with acute longitudinally extensive transverse myelitis (LETM). Cerebrospinal fluid analysis was negative.Echocardiography and blood tests were suggestive for myo-pericarditis. Real time polymerase chain reaction for SARS-CoV-2 on nasopharyngeal swab sample tested positive. She was promptly treated with high dose of steroids and immunoglobulin with satisfactory clinical response. CONCLUSION: To the evolving literature of neurological complications of SARs-CoV-2 infection, we add the youngest patient described to date with isolated LETM and concomitant cardiac involvement. Our case suggests that clinicians should be aware of this association, although difficult to recognize in infants. Practitioners are encouraged to consider aggressive first-line immunotherapies with the final aim to prevent permanent disability.