Early instrumental predictors of long term neurodevelopmental impairment in newborns with perinatal asphyxia treated with therapeutic hypothermia

Background. Hypoxic-ischemic encephalopathy (HIE) is a leading cause of disability in full-term newborns. Long-term consequences of HIE, even when treated by hypothermia, are not easily predictable. Aims. To assess the potential role of electroencephalography and neuroimaging parameters as early predictors of neurodevelopmental outcome in HIE newborns treated with hypothermia. Methods. We retrospectively evaluated 13 HIE patients treated with hypothermia in January 2012-September 2014. We reviewed their amplitude-integrated electroencephalography (a-EEG) at 6, 12 and 24 hours (h), cranial ultrasonography (US) at 12, 72 h and >7 days of life (DOL) and brain magnetic resonance (MRI) performed at 7-28 DOL, according to validated scores. aEEG, US and MRI patterns were correlated to neurodevelopmental outcome at 18- 24 months, considered as negative if one of the following was present: Mental Development Index (MDI)<85, motor, visual or hearing impairment. Results. Te severity of a-EEG, US and MRI alterations at each time point was not diferent according to the outcome. MDI was negatively correlated with aEEG score at 12h (R= -0.571, p=0.04) and with US score at 72h (R= -0.630, p=0.02). A positive correlation was found between aEEG score at 6h and US score at >7DOL (R=0.690, p=0.013). US alterations of the cortical matter at 72h were directly correlated with a-EEG score at 12h (R = 0.606, p=0.028) and 24h (R=0.605, p=0.029). Conclusions. Early instrumental evaluations, in particular aEEG and US, seem to predict neurodevelopmental outcome at 18-24 months in HIE newborns treated with hypothermia

Biliary acids is a critical laboratory value in pregnant women: a case report as an opportunity to improve the quality of care

Biliary acids (BA) levels were found greatly increased to 72.1 µM/l in a pregnant woman. Bambino Gesù Children’s Hospital had not established critical alarm values for BA, so communication of the result was overpassed. After 30 hours, the patient referred to the emergency room of another hospital for the assessment of the pregnancy course and BA re-evaluation, which in turn resulted normal. BA levels in our sample were re-analyzed in both laboratories and high levels were confirmed. We utilized an enzymatic cycling colorimetric method measuring primary, secondary and tertiary BA. The patient was on therapy with ursodeoxycholic acid (UDCA) explaining total BA results difference reported in the two different blood samples. BA accumulation maybe leads to fetal complications or loss and a quick communication of the result to clinician could potentially be life-saving for the baby. We implemented corrective actions to avoid adverse events by the introduction of a note on the report, warning of UDCA therapy interference in BA dosage and recommending the suspension of therapy 24 hours before blood sampling; furthermore, in order to provide high level of health care, we introduced an alarm value for fertile women in our critical values list

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p&lt;0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p&lt;0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p&lt;0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p&lt;0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69&nbsp;%. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24&nbsp;h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3&nbsp;days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30&nbsp;min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Migraine in Systemic Autoimmune Diseases

Background and Objective: Migraine and systemic autoimmune diseases are 2-3-fold more common in women and various studies have reported an association between the two pathologies. Methods: This review takes into account epidemiological studies involving migraine and systemic lupus erythematosus, antiphospholipid syndrome, Sjogren's syndrome, and other diffuse connective tissue diseases. This scientific literature analysis consists of the main articles found in Medline with a search up to April 2017. Results: Many epidemiological studies were carried out on patients suffering from systemic lupus erythematosus. Results showed that headache and migraine are more prevalent in systemic lupus erythematosus patients compared to controls, especially migraine with aura. Patients with Lupus and migraine show a higher lupus activity and association with Raynaud and/or antiphospholipids in these populations are contradictory. There are not enough data to establish an association between antiphospholipid syndrome and migraine. However, data are more consistent between antiphospholipid carrier condition and migraine. Systemic sclerosis is a rare disease, for this reason the amount of available data on this disorder are scanty. However, some studies reported an association between headache, migraine and systemic sclerosis, especially where gliotic brain lesions and Raynaud are coexisting. Finally, large propensity cohort population based studies suggested that systemic autoimmune diseases are more frequent in patients suffering from migraine. Conclusion: An attempt at explaining the possible link between these disorders and migraine is discussed at the end of the review. Several autoimmune alterations are shared by most autoimmune diseases and headache types. Endothelial dysfunction is the only alteration that is common among all these disorders