A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection.

BACKGROUND: Acral chilblain-like lesions are being increasingly reported during COVID-19 pandemic. However, only few patients proved positivity for SARS-CoV-2 infection. The relationship between this skin manifestation and COVID-19 infection has not been clarified yet. OBJECTIVE: To thoroughly characterize a prospective group of patients with chilblain-like lesions and to investigate the possible relationship with SARS-CoV-2 infection. METHODS: Following informed consent, patients underwent (i) clinical evaluation, (ii) RT-PCR and serology testing for SARS-CoV-2, (iii) digital videocapillaroscopy of finger and toe nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence and, in selected cases, electron microscopy. RESULTS: Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu-like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillaroscopy showed pericapillary oedema, dilated and abnormal capillaries, and microhaemorrhages both in finger and toe in the majority of patients. Major pathological findings included epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in two cases. Blood examinations were normal. Nasopharyngeal swab for SARS-CoV-2 and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS-CoV-2 spike protein was positive in 6 patients and borderline in 3. CONCLUSIONS: Chilblain-like lesions during COVID-19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS-CoV-2 infection in our patients, history data and the detection of anti-SARS-COV-2 IgA strongly suggest a relationship between skin lesions and COVID-19. Further investigations on the mechanisms of SARS-CoV-2 infection in children and pathogenesis of chilblain-like lesions are warranted.

Strategies to control antibiotic resistance: results from a survey in Italian children's hospitals.

BACKGROUND: Antimicrobial stewardship programs and comprehensive infection control programs represent the main strategies to limit the emergence and transmission of multi-drug resistant bacteria in hospital settings. The purpose of this study was to describe strategies implemented in Italian children's hospitals for controlling antibiotic resistance. STUDY DESIGN: Cross sectional multicenter study. METHODS: Four tertiary care Italian children's hospitals were invited to participate in a survey aimed at collecting information on activities implemented as of December 2015 using a self-administered online questionnaire. The questionnaire was divided in three sections focalizing on: i) policies for prevention and control of hospital-acquired infection, ii) prevention and control of multi-drug resistant bacteria, and iii) antibiotic prescribing policies and Antimicrobial stewardship programs. Questionnaires were compiled between May and July 2016. RESULTS: All hospitals had multidisciplinary infection control committee, procedures on hand hygiene, isolation measures, disinfection/sterilization, waste disposal and prevention on infections associated to invasive procedures. All sites screened patients for multi-drug resistant bacteria colonization in selected units, and adopted contact precautions for colonized patients. Screening during hospitalization, or in case of infections in the same ward were not universally implemented. All hospitals had policies on surgical prophylaxis, while policies on medical prophylaxis and treatment of bacterial infections varied among sites. Two sites recommended to review the appropriateness of antibiotic prescribing after 48-72 hours and one recommended de-escalation therapy. CONCLUSIONS: This study highlighted several areas of improvement, such as actions for screening patients in case of occurrence of multi-drug resistant bacteria, antimicrobial stewardship programs and implementation of policies targeting antibiotic prescriptions for therapeutic purposes and medical prophylaxis.

CPAP by helmet for treatment of acute respiratory failure after pediatric liver transplantation.

ARF after pediatric liver transplantation accounts for high rate of morbidity and mortality associated with this procedure. The role of CPAP in postoperative period is still unknown. The aim of the study was to describe current practice and risk factors associated with the application of helmet CPAP. In this retrospective observational cohort study, 119 recipients were divided into two groups based on indication to CPAP after extubation. Perioperative variables were studied, and determinants of CPAP application were analyzed in a multivariate logistic model. Sixty patients (60/114) developed ARF and were included in the CPAP group. No differences were found between the two groups for primary disease, graft type, and blood product transfused. At multivariate analysis, weight <11 kg (OR = 2.9; 95% CI = 1.1-7.3; P = .026), PaO2 /FiO2 <380 before extubation (OR = 5.4; 95% CI = 2.1-13.6; P < .001), need of vasopressors (OR = 2.6; 95% CI = 1.1-6.4; P = .038), and positive fluid balance >148 mL/kg (OR = 4.0; 95% CI = 1.6-10.1; P = .004) were the main determinants of CPAP application. In the CPAP group, five patients (8.4%) needed reintubation. Pediatric liver recipients with lower weight, higher need of inotropes/vasopressors, higher positive fluid balance after surgery, and lower PaO2 /FiO2 before extubation were at higher odds of developing ARF needing CPAP application.

Incidence of surgical site infections in children: active surveillance in an Italian academic children's hospital.

BACKGROUND: Surgical Site Infections (SSIs) account for 16-34% of all health-care associated infections. This study aimed to assess the incidence rate of SSIs in children who underwent surgical procedures in an academic children's hospital in Italy. STUDY DESIGN: Prospective cohort study. METHODS: We actively followed-up 0-17 year old children at 30 days of surgical procedures without implants conducted during one index week per quarter, from the second quarter of 2014, to the first quarter of 2016 (8 index weeks in total). Follow up data were collected by telephone interview, or derived by clinical records if patients were still hospitalized. SSIs were defined according to case definitions of Centers for Diseases Control, Atlanta, USA. We calculated cumulative incidence of SSIs per 100 surgical procedures, by patient characteristics, procedure characteristics, and quarter. To investigate variables associated with SSIs, we compared characteristics of procedures with SSIs with those of procedures without SSIs. RESULTS: Over the study period, SSI incidence was 1.0% (19 cases/1,830 surgical procedures). SSI incidence was significantly lower after ear, nose and throat procedures compared to all other procedures, and significantly decreased over time. Duration of surgery was a risk factor for SSIs; patients with SSIs had a significantly longer total length of stay (LOS), due to a prolonged post-operative LOS. CONCLUSION: As reported in adults, this study confirms that SSIs are associated with longer hospitalizations in children. Active surveillance of SSIs is an important component of the overall strategy to reduce the incidence of these infections in children.

Epidemiology of pertussis in Italy: disease trends over the last century.

We reviewed the epidemiology of pertussis in Italy over the last 125 years to identify disease trends and factors that could have influenced these trends. We described mortality rates (1888-2012), case fatality rates (1925-2012), cumulative incidence rates (1925-2013) and age-specific incidence rates (1974-2013). We compared data from routine surveillance with data from a paediatric sentinel surveillance system to estimate under-notification. Pertussis mortality decreased from 42.5 per 100,000 population in 1890 to no reported pertussis-related death after 2002. Incidence decreased from 86.3 per 100,000 in 1927 to 1 per 100,000 after 2008. Vaccine coverage increased from 32.8% in 1993 to about 96% after 2006. As for under-notification, mean sentinel/routine surveillance incidence ratio increased with age (from 1.8 in <1 year-olds to 12.9 in 10-14 year-olds). Pertussis mortality decreased before the introduction of immunisation. Incidence has decreased only after the introduction of pertussis vaccine and in particular after the achievement of a high immunisation coverage with acellular vaccines. Routine surveillance does not show an increase in cumulative incidence nor in ≥ 15 year-olds as reported by other countries. Underrecognition because of atypical presentation and the infrequent use of laboratory tests may be responsible for under-notification, and therefore affect incidence reports and management of immunisation programmes.

Microbial tracking of multidrug-resistant Klebsiella pneumoniae isolates in a pediatric hospital setting.

We investigated the clonal relatedness of seven multi-drug-resistant (MDR) Klebsiella pneumoniae isolates, as well as three susceptible K. pneumoniae isolates collected during hospital outbreaks and outbreak-related microbiological surveillance, respectively. The relatedness among K. pneumoniae isolates was assessed by pulsed field gel electrophoresis (PFGE) and automated repetitive-sequence-based PCR (rep-PCR) genotyping and the results were compared to a proteomic phenotyping performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). All typing methods agreed on the generation of three different clusters of K. pneumoniae isogenetic/related MDR strains. After strengthening hospital infection control measures, no other spreading events involving MDR-K. pneumoniae were reported until the end of the observation period. This preliminary investigation suggests that, in a hierarchical approach to bacterial typing, MALDI-TOF MS proteome profiling might offer a fast and valuable preliminary screening tool able to support microbiologists during nosocomial outbreak surveys.

Proactive evaluation of clinical risk: a FMECA analysis in pediatric chemotherapy.

In 2010-2011, we used FMECA to prospectively assess risk-management in chemotherapy of children with cancer, in a third level Italian children's Hospital (Ospedale Pediatrico Bambino Gesù; OPBG). We designed a flow chart representing the entire process; we described potential failure points for each step of the process, as well as their potential underlying causes. We calculated the risk priority number (RPN) of each failure point based on the severity of the failure, the frequency of occurrence, and the likelihood of detecting the failure prior to completion of the process. All FMECA activities were supported by a web-based tool. The highest RPN values were observed for failure points of the paper-based chemotherapy medication orders sent from clinicians to Pharmacy, the transcription of the orders into the Pharmacy paper-based work-sheet for medication preparation, and the selection of medications to be used for chemotherapy preparation. Causes of these failures were mostly related to illegible or incomplete handwriting. As a consequence of these results, the implementation of an electronic ordering process for children's chemotherapy medications was proposed as risk-reducing action.

Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Prolonged in-hospital exposure to an infant with active pulmonary tuberculosis.

Active pulmonary tuberculosis was diagnosed in a 4-month-old infant 16 days after hospitalization; 186 exposed individuals were traced and one conversion detected. Although the risk of tuberculosis transmission in paediatric hospitals is low, paediatricians in low-incidence countries should maintain a high level of alert for timely identification of cases.

Ultrasonographic assessment of mediastinal shift angle (MSA) in isolated left congenital diaphragmatic hernia for the prediction of postnatal survival.

Objectives: To quantify mediastinal shift in isolated congenital diaphragmatic hernia (CDH), by the introduction of a new ultrasonographic (US) marker, defined as mediastinal shift angle (MSA) and to evaluate its ability in predicting postnatal survival at discharge.Methods: Twenty-four consecutive fetuses from singleton pregnancies with isolated left-sided CDH were included in the study group and then subdivided into group A (16 survivors) and group B (8 nonsurvivors). The study group was matched with a control group of 95 fetuses from singleton pregnancies free from structural and/or chromosomal anomalies. On the same US stored images commonly used for lung-to-head ratio (LHR) measurement, a landmark line was drawn from a point on the posterior face of the vertebral body, splitting it into two equal parts, to the mid-posterior surface of the sternum. Another landmark line was then traced from the same point of the vertebral body to touch tangentially the lateral wall of the right atrium. The angle between these two lines was used to quantify mediastinal shift and called "mediastinal shift angle" (MSA).Results: Median MSA was significantly different between group A (34.3° range 29.3-45.9°) and group B (42.7° range 34.1-58.9°) (p < .001) and between study group as a whole and the control group (19° range 13.8-25.9°) (p < .001). Statistical analysis confirmed an inverse correlation between MSA values and survival (p = .004). The best cutoff value for MSA was 43.7°, which demonstrated the highest discriminatory power (sensitivity 63%; specificity 93.75%).Conclusions: In fetuses with isolated CDH, the mediastinal shift may be quantified using mediastinal shift angle (MSA) and this US marker, similarly to the widely accepted and used US prenatal prognostic indicators (LHR and O/E LHR), seems to reliably predict survival.

[Measles and its secondary pulmonary complications: prevention is better than treatment]. / Il morbillo e le sue complicanze polmonari secondarie: prevenire è meglio che curare.

Recent measles outbreaks observed in North America and in several European countries, including Italy, raised the attention about the risks linked to this infection and the need of implementing and maintaining adequate preventive strategies. Measles may cause several respiratory complications such as chronic obstructive lung disease, pneumonia, with subsequent development of chronic suppurative lung disease, giant cells pneumonia or progressive respiratory insufficiency. The current preventive strategies aim to improve vaccination coverage rates with 2 doses of measles-mumps and rubella vaccine, and to catch up individuals who have not been previously vaccinated. The present review analyses pulmonary complications of measles and measles preventive strategies. Elimination of measles is a feasible goal. Since measles complications are preventable by vaccination, improvement in vaccination coverage is highly desirable.

Point prevalence study of antibiotic use in a paediatric hospital in Italy.

A survey aimed to describe the prevalence of antibiotic use in hospitalised children was conducted in June 2007, in Bambino Gesù Children's Hospital in Rome which has the highest annual number of inpatients among paediatric hospitals in Italy. Data were collected by reviewing medical charts of all patients hospitalised for >48 hours. A total of 412 hospitalised children were evaluated; their median age was 42.3 months, and 55.6% were males. Antibiotics were prescribed to 181 of the 412 patients (43.9%). The prevalence was lowest (37.7%) in medical wards, higher (51.1%) in intensive care units and highest (52.2%) in surgical wards. Of the patients treated with antibiotics in surgical wards, 71% received the treatment as prophylaxis. The most frequently prescribed antibiotics were ceftazidime and the combination of amoxicillin and clavulanic acid. The observed prevalence of antibiotic use was within the range recently reported from other paediatric hospitals in Europe; however, it is advisable to collect data from all over the country in order to identify priority areas and design interventions. These results also highlight the need to implement guidelines for surgical prophylaxis in children, and to further investigate reasons for prescription of parenteral antibiotic therapy in paediatric hospitals.

[Survey on computerized immunization registries in Italy]. / Indagine conoscitiva sulle anagrafi vaccinali informatizzate in Italia.

Computerized immunization registries are essential for conducting and monitoring vaccination programs. In fact, they enable to improve vaccine offering to target population, generating needed-immunization lists and assessing levels of vaccination coverage. In 2007, a national survey on immunization registries was conducted in Italy. In February 2007, all the 21 Regional Health Authorities (RHAs) completed and returned an ad hoc questionnaire. In June 2007, RHAs were further contacted by telephone in order to verify and update the information provided in questionnaires. In 9 Italian Regions (42.8%), vaccination registries are computerized in all Local Health Units (LHUs). In five of these Regions, all LHUs use the same software, while in the remaining four Regions, different softwares are in use. In six additional Regions (28.6%), only some LHUs use computerized immunization registries (range 61.5%-95%). In the remaining 6 Regions (28.6%), which are all in Southern Italy, there are no computerised immunization registries at all. In total, computerised immunization registries cover 126/180 Italian LHUs (70%); in 76/126 (60%) of these LUHs, immunization registries are linked with population registries. This survey shows the need to improve the implementation of computerised immunization registries in Italy, especially in Southern Regions.

An Easter outbreak of Salmonella Typhimurium DT 104A associated with traditional pork salami in Italy.

Salmonella enterica is a common cause of gastrointestinal illness in Italy. S. Typhimurium accounts for approximately 40% of isolates, and most of these strains belong to the phage type DT104. We describe the investigation of an outbreak of S. Typhimurium DT104A, a subtype never observed before in Italy, which occurred in Rome during spring 2004.We conducted a matched case control study between 24 July and 9 September 2004. Controls were matched for age and area of residence. Each case had between one and four controls. Odds of exposure to potential risk factors and vehicles for the outbreak were compared between cases and controls. A multivariate analysis was conducted to estimate adjusted Odds Ratios.Sixty-three cases of S. Typhimurium DT 104A infection with onset between 1 April and 5 May 2004 were identified. Sixty-one were residents of Rome and two were residents of a neighbouring region. Twenty-six cases (43%) were enrolled in the study. Their median age was 7.5 years. Fourteen of 26 cases and 16 of 62 controls had eaten pork salami (OR= 25.5; 95% CI 1.6- 416.8). No food samples were available for testing. In northern Italy, two months prior to the outbreak, the veterinary surveillance system identified the first isolation of S. Typhimurium DT104A in a pig isolate. Both human and pig isolates showed indistinguishable PFGE patterns. It was not possible to trace the pig after the sample was taken at slaughter. The epidemiological evidence on the implication of pork salami in this outbreak suggests that pork products can also be a vehicle for salmonella in Italy and underlines the importance of good manufacturing practices for ready-to-eat foods. This investigation highlights the value of laboratory-based surveillance in identifying community-wide outbreaks of uncommon pathogens. It also underlines the need to improve surveillance timeliness, for promptly detecting outbreaks, undergoing field investigation, and implementing control measures. Moreover, our study shows the usefulness of integrated human and animal surveillance in tracing the possible source of infection.

[Rubella epidemiology in Italy in years 1998-2004]. / Epidemiologia della rosolia in Italia negli anni 1998-2004.

In November 2003 the National Plan for the elimination of measles and congenital rubella was approved, with the aim of reducing and maintaining the incidence of congenital rubella syndrome (CRS) at less than 1 case per 100,000 live births by 2007. In order to describe the epidemiology of rubella in Italy, we conducted a serosurvey and evaluated incidence and vaccination coverage data available for the period 1998-2004. In the years considered, national mean coverage of measles-mumps-rubella vaccination within the second year of life, even though still below the 95% threshold, has progressively increased reaching 87%. In addition, previously existing differences in coverage among regions have diminished. In the same period the incidence of rubella has decreased, with a historic minimum of 461 cases notified in 2004. The cyclic pattern typical of rubella persists, but with a prolongation of the interepidemic period and an increased mean age of acquisition of the infection. Although the proportion of immune individuals has increased, the percentage of women of childbearing age susceptible to rubella remains high (11% in the 15-19 year age group and 8% in the 20-39 year age group) and CRS cases continue to occur. Despite the clear results achieved through the implementation of vaccination strategies in children within the second year of life, a continued strong public health commitment is required to increase the proportion of vaccinated individuals and absolute priority must be given to immunising women of childbearing age.

Intra-dialytic blood oxygen saturation (SO2): association with dialysis hypotension (the SOGLIA Study).

BACKGROUND: Intradialytic hypotension (IDH) has a dramatic impact on the main outcomes of dialysis patients. Early warning of hemodynamic worsening during dialysis would enable preventive measures to be taken. Blood oxygen saturation (SO2) is used for hemodynamic monitoring in the critical care setting and may provide useful information about IDH onset. AIM: To evaluate whether short- and medium-term variations in the SO2 signal (ST-SO2var, MT-SO2var,) during dialysis are a predictor of IDH. METHODS: In this 3-month observational cohort study, 51 hypotension-prone chronic hemodialysis (HD) patients, with vascular access by arteriovenous fistula (AVF) or central venous catheter (CVC), were enrolled. Continuous non-invasive blood SO2 was monitored (fc = 0.2 Hz) by an optical sensor on the arterial line of the extracorporeal circulation; blood pressure (every 30 min), symptoms and their time of appearance were noted. Predictive power of IDH was expressed by the area under curve (AUC) sensitivity and specificity based on intradialytic variations in SO2. RESULTS: A total of 1290 HD sessions were analyzed. Overall, off-line ST-SO2var analysis proved able to correctly predict IDH in 67 % of the sessions where IDH occurred. The best predictive performance was found in the presence of highly arterialized AVF (SO2 > 95 %) (75 % sensitivity; AUC 0.825; p < 0.05). On the contrary, in sessions with CVC, IDH prediction proved more efficient by MT-SO2var (AUC 0.575; p = 0.01). CONCLUSIONS: Intradialytic SO2 variability could be a valid parameter to detect in advance the hemodynamic worsening that precedes IDH. Appropriate timely intervention could help prevent IDH onset.

Cluster of measles cases in the Roma/Sinti population, Italy, June-September 2006.

Three clusters of measles cases occurred between June and September 2006, in the Roma/Sinti populations in three different Italian regions: the Bolzano-South Tyrol in northern Italy; Lazio in central Italy; and the island of Sardinia in the southwest.

New horizon in dialysis depuration: Characterization of a polysulfone membrane able to break the 'albumin wall'.

The uremic syndrome is attributed to the progressive retention of a large number of toxins, which under normal conditions are excreted by the healthy kidneys. Standard dialytic membranes do not purify middle-high molecular weight toxins. Haemodiafiltration with endogenous reinfusion coupled with a highly permeable membrane could break the limit of the 'albumin wall' improving the dialytic depuration without loss of important nutrients. The aim of this study was to evaluate the performance of a new polysulfone membrane, Synclear 0.2, to remove uremic molecules. Surface Enhanced Laser Desorption Ionization-Time of Flight was employed to evaluate the proteomic profile of ultrafiltrate and Electrospray Ionization-Quadruple-ToF coupled with on-chip elution was used for proteins identification. A high and specific permeability for middle-high molecular weight molecules was revealed by mass spectrometry for the investigated membrane. The identified proteins are mostly uremic toxins: their relative abundance, estimated in the ultrafiltrate by exponentially modified protein abundance index, showed a high purification efficiency of the new membrane when compared with conventional ones. In conclusion, Synclear 0.2, used as convective membrane in hemodiafiltration with endogenous reinfusion treatment, permits to break the 'albumin wall', clearing middle-high molecular weight uremic toxins, improving the dialytic treatment purification efficiency.