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Objective: We aimed to evaluate epidemiology, seizure type, EEG, and etiology of neonatal seizures (NS) in a tertiary neonatal intensive care unit., Methods: Data on infants with a neurophysiological confirmation of NS were collected between 2009 and 2022. Seizure types and epileptic syndromes were classified by the ILAE classification and EEG by the Italian Neonatal Seizure Collaborative Network (INNESCO) score., Results: Out of 91,253 neonates, 145 presented with NS; 69.7 % were born at term and 30.3 % were preterm infants. The incidence of NS in neonates born at our center was 1.2 per 1,000 live newborns (96/80697 neonates) while in the entire neonatal population admitted to our center it was 1.6 per 1,000 live births, increasing with lower preterm age. Compared to previous studies, we found a lower proportion of hypoxic-ischemic encephalopathy (HIE) (23.4 %) and a higher rate of genetic contribution (26.2 %). The infection rate was higher in preterm (31.8 %) than in full term (9.9 %) infants. Electrographic seizures were associated with acute provoked seizures (35.9 %), preterm age (52.3 %), and HIE (52.9 %). Vascular etiology was associated with focal clonic seizures (56.8 %). Non-structural neonatal genetic epilepsy was associated with sequential seizures (68.2 %), particularly KCNQ2 and SCN2A epilepsy. Background EEG was abnormal in all HIE, infections (85.7 %) and metabolic NS (83.3 %). In genetic epilepsy, background EEG depended on the epileptic syndrome: normal in 80 % of self-limited neonatal epilepsy and abnormal in 77.8 % of developmental and epileptic encephalopathy. Electroclinical seizures were associated with focal onset, while electrographic seizures correlated with a multifocal onset., Conclusions: A low incidence of HIE and a high incidence of genetic etiology were observed in our cohort of NS. Seizure type and EEG features are fundamental to address etiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone's resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly., Methods: Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D)., Results: Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho -0.44; p = 0.034), without significant associations with BMD (p = 0.151), age (p = 0.500), BMI (p = 0.957), serum IGF-I (p = 0.889), duration of active disease (p = 0.434) and sex (p = 0.563)., Conclusions: Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Non-polio enteroviruses (EV) and human parechoviruses (HPeV) are known etiological agents of meningoencephalitis in neonates. However, reports of neuroradiological findings and neurodevelopmental outcomes in this population are scarce., Objectives: to describe clinical characteristics, neuroradiological findings and, in a subset of patients, neurodevelopmental outcomes in a cohort of infants with EV or HPeV meningoencephalitis within 60 days of life., Study Design: clinical/laboratory data, neuroradiological findings (cranial ultrasound, cUS, brain magnetic resonance imaging, MRI), and neurodevelopmental outcomes assessed by Ages and Stages Questionnaires - third edition were prospectively collected., Results: overall, 32 infants with EV (21, 67.8 %) or HPeV (11, 28.2 %) meningoencephalitis were enrolled. Infants with HPeV (73 %: type 3 HPeV) presented more frequently with seizures (18.2 % vs. 0, p value=0.03), lymphopenia (1120 vs. 2170 cells/mm 3 , p = 0.02), focal anomalies at electroencephalography (EEG) (63.6 vs. 23.8 %, p = 0.03), and pathological findings at MRI (72.7 % vs. 15.8 %, p value=0.004) compared to those affected by EV. cUS was not significantly altered in any of the enrolled infants. All infants with EV meningoencephalitis evaluated at 12-24 months and at 30-48 months were normal. Two out of the 7 infants with HPeV meningoencephalitis showed some concerns in gross motor (1/7, 14.3 %) or in problem solving (1/7, 14.3 %) function at 30-48 months of age., Conclusions: In our cohort, neonates infected by HPeV had more severe clinical manifestations, more alterations at brain MRI, and some signs of long-term neurodevelopmental delay. Our data highlight the heterogeneity of manifestations in infants with EV or HPeV meningoencephalitis, and the need for long-term follow-up of those infected by HPeV in the neonatal period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs)., Methods: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors., Results: The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment., Conclusion: I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination., Competing Interests: Competing interests: BF does not report conflicts of interest. SL-T does not report conflicts of interest. KLH reports non-personal speaker's fees from AbbVie and grant income from BMS and Pfizer, all unrelated to this manuscript; and her institute was supported by EULAR for COVAX database management. LG reports research grants from Amgen, Galapagos, Lilly, Pfizer and Sandoz; and consulting fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB, all unrelated to this manuscript. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as Galapagos, Pfizer, Lilly, MSD, Novartis, Roche, Sanofi Aventis, BMS and Sandoz; she also reports safety board participation, not paid personally. AS reports personal fees from lectures for AbbVie, Galapagos, Lilly, Pfizer and Takeda. EFM does not report conflicts of interest. MS does not report conflicts of interest. AR does not report conflicts of interest. EH does not report conflicts of interest. JAG-P does not report conflicts of interest. MM reports having received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, all unrelated to this manuscript. PD reports speaker's fees from AbbVie, Lilly, Galapagos, Janssen and Biogen, all unrelated to this manuscript. LT does not report conflicts of interest. TG does not report conflicts of interest. MC does not report conflicts of interest. ES reports receiving grants from AbbVie; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, AbbVie, Pfizer, Eli Lilly, UCB, Sobi, Roche, Sanofi, Boehringer-Ingelheim, Viatris, Sandoz, Mylan, MSD, Amgen and Janssen-Johnson & Johnson; support for attending meetings and/or travel from AbbVie and Janssen-Johnson & Johnson; participation in a data safety monitoring board or advisory board from AbbVie, Eli Lilly, UCB, Sobi, Boehringer-Ingelheim and Janssen-Johnson & Johnson; and is a committee member of Slovak Society of Rheumatology, all unrelated to this manuscript. IB reports receiving speaker's fees from AbbVie, Pfizer, Boehringer Ingelheim and Janssen; and has received support for attending meetings and/or travel from AbbVie, all unrelated to this manuscript. ES does not report conflicts of interest. JZ reports consulting fees from AbbVie, Janssen, Novartis and Boehringer-Ingelheim; speaker's fees from AbbVie, Janssen, Novartis, Boehringer Ingelheim Latvia and UAB Viasana; receiving support for attending meetings and/or travel from AbbVie, UAB Viasana and Johnson & Johnson; and is a board member of Latvian Society of Adult Rheumatology; all unrelated to this manuscript. NR has nothing to disclose. OB has nothing to disclose. EV has nothing to disclose. BR has nothing to disclose. GRB has nothing to disclose. XM reports personal consultant fees from BMS, Galapagos, GSK, Novartis and Pfizer; and having received support for attending meetings and/or travel from Novartis, all unrelated to this manuscript. PMM has received consulting/speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: Exercise is recommended for patients with chronic heart failure (CHF) and its intensity is usually set as a percentage of the maximal work rate (MWR) during cardiopulmonary exercise testing (CPX) or a symptom-limited incremental test (SLIT). As these tests are not always available in cardiac rehabilitation due to logistic/cost constraints, we aimed to develop a predictive model to estimate MWR at CPX (estMWR@CPX) in CHF patients using anthropometric and clinical measures and the 6-min walk test (6 MWT), the most widely used exercise field test., Methods: This is a multicentre cross-sectional retrospective study in a cardiac rehabilitation setting. Six hundred patients with HF in New York Heart Association (NYHA) functional class I-III underwent both CPX and 6 MWT and, t hrough multivariable linear regression analysis, we defined several predictive models to define estMWR@CPX., Results: The best model included 6 MWT, sex, age, weight, NYHA class, left ventricular ejection fraction (LVEF), smoking status and chronic obstructive pulmonary disease COPD (adjusted R 2  = 0.55; 95% LoA -39 to 33 W). When LVEF was excluded as a predictor, the resulting model performed only slightly worse (adjusted R 2  = 0.54; 95% LoA -42 to 34 W). Only in 34% of cases was the percentage difference between estMWR@CPX and real MWR@CPX <10% in absolute value. EstMWR@CPX tended to overestimate low values and underestimate high values of true MWR@CPX., Conclusions: Our results showed a lack of accuracy in the predictive model evaluated; therefore, for an accurate prescription of cycle-ergometer exercise training, it is necessary to assess MWR by CPX or SLIT., Competing Interests: All Authors declare no conflict of interest relevant to the research, analysis, or interpretation presented in the manuscript., (© 2024 The Authors.)

Significance: Critically ill newborns are at risk of brain damage from cerebrovascular disturbances. A cerebral hemodynamic monitoring system would have the potential role to guide targeted intervention., Aim: To obtain, in a population of newborn infants, simultaneous near-infrared spectroscopy (NIRS)-based estimates of cerebral tissue oxygen saturation ( StO 2 ) and blood flow during variations of carbon dioxide tension ( pCO 2 ) levels within physiologic values up to moderate permissive hypercapnia, and to examine if the derived estimate of metabolic rate of oxygen would stay constant, during the same variations., Approach: We enrolled clinically stable mechanically ventilated newborns at postnatal age > 24    h without brain abnormalities at ultrasound. StO 2 and blood flow index were measured using a non-invasive device (BabyLux), which combine time-resolved NIRS and diffuse-correlation spectroscopy. The effect of changes in transcutaneous pCO 2 on StO 2 , cerebral blood flow (CBF), and cerebral metabolic rate of oxygen index ( tCMRO 2 i ) were estimated., Results: Ten babies were enrolled and three were excluded. Median GA at enrollment was 39 weeks and median weight 2720 g. StO 2 increased 0.58% (95% CI 0.55; 0.61, p < 0.001 ), CBF 2% (1.9; 2.3, p < 0.001 ), and tCMRO 2 0.3% (0.05; 0.46, p = 0.017 ) per mmHg increase in pCO 2 ., Conclusions: BabyLux device detected pCO 2 -induced changes in cerebral StO 2 and CBF, as expected. The small statistically significant positive relationship between pCO 2 and tCMRO 2 i variation is not considered clinically relevant and we are inclined to consider it as an artifact., (© 2023 The Authors.)

Background: Several studies suggested that SARS-CoV-2 was already spreading worldwide during the last months of 2019 before the first outbreak was detected in Wuhan, China. Lombardy (Northern Italy) was the first European region with sustained SARS-CoV-2 transmission and recent investigations detected SARS-CoV-2-RNA-positive patients in Lombardy since late 2019., Methods: We tested for anti-SARS-CoV-2 IgG all serum samples available in our laboratory (N = 235, collected between March 2017 and March 2022) that we received within the framework of measles/rubella surveillance from measles and rubella virus-negative patients., Results: Thirteen of 235 samples (5.5%) were IgG-positive. The positivity rate increased starting in 2019 and was significantly different from the expected false positive rate from 2019 onwards. Additionally, in 2019 the percentage of IgG-positive patients was significantly lower among SARS-CoV-2 RNA-negative patients (3/92) compared to SARS-CoV-2 RNA-positive patients (2/7, p = 0.04). The highest percentage of IgG positivity in the pre-pandemic period was recorded during the second half of 2019. This coincided with an increase in negativity for measles and a widening of the peak of the number of measles discarded cases per 100,000 inhabitants, indicating a higher-than-normal number of measles-negative patients experiencing fever and rash. This also coincided with the first patient positive for SARS-CoV-2 RNA (September 12th, 2019); this patient was also positive for anti-SARS-CoV-2 IgG and IgM., Conclusions: Although the number of samples was low and one cannot conclusively establish that the virus started circulating in Lombardy around September 2019, our findings should stimulate similar research investigating the possibility of undetected SARS-CoV-2 pre-pandemic circulation., (© 2023. The Author(s).)

This article provides an overview of the reasons to attend the 2023 ERS Congress, including a summary of the ECM session and the NEXT programme. https://bit.ly/46ghP4g., Competing Interests: Conflict of interest: A. Farr is a current employee of the European Respiratory Society. T. Gille reports personal fees from Roche S.A.S., other from Oxyvie (oxygen provider), other from VIVISOL France (oxygen provider), other from Menaniri France; all disclosures made outside the submitted work. H. Pinnock reports receiving speaker fees from Teva Pharmaceuticals and Sandoz, outside the submitted work. M.R. Bonsignore reports participation on an Advisory board for Bioprojet, outside the submitted work. N. Roche reports receiving grants paid to his institution from Boehringer Ingelheim, Novartis, GSK and Pfizer; consulting fees from Boehringer Ingelheim, GSK, AstraZeneca, Sanofi, Chiesi, Pfizer, Novartis, Teva, Bayer, Austral and Biosency; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim, GSK, AstraZeneca, Sanofi, Chiesi, Pfizer, Novartis, Teva, Zambon, MSD and Menarini; and support for attending meetings and/or travel from Chiesi, AstraZeneca, and GSK; all disclosures made outside the submitted work. P. Laveneziana reports payment or honoraria from CHIESI France and GlaxoSmithKline; support for attending meetings and/or travel from Chiesi France; and participation on a data safety monitoring board or advisory board for CHIESI France; all disclosures made outside the submitted work. R.W. Costello reports grants or contracts from GSK; consulting fees from BioNTech, GSK, AstraZeneca and PMD; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BioNTech, GSK, AstraZeneca and PMD; support for attending meetings and/or travel from AstraZeneca; patents planned, issued or pending on detection of exacerbation, and quantifying adherence; and is the Education Chair of ERS; all disclosures made outside the submitted work. S. Harari reports receiving a research grant from Boehringer Ingelheim; consulting fees from Roche; participation on a data safety monitoring board or advisory board for a French study on IPF IIS; is a fellow of the American Thoracic Society; and his department received an unrestricted grant for acquiring PFT equipment from AstraZeneca; all disclosures made outside the submitted work. S. Meiners reports receiving payment from the European Respiratory Society for editorial work, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©ERS 2023.)

It is well known that regulatory T-cells (Tregs) are required to prevent autoimmunity, but they may also have some less-well understood immune-stimulatory effects. In particular, in CD8 + T-cell responses Tregs select high-affinity clones upon priming and promote memory by inhibiting inflammation-dependent generation of short-lived effector cells. In the current issue of the European Journal of Immunology [Eur. J. Immunol. 2023. 53: 2149400], Madi et al. report the surprising finding that human and murine FOXP3 + Tregs are a physiologically relevant source of IL-15, a homeostatic cytokine that promotes antigen-independent maintenance of CD8 + memory T-cells. In mice that lack IL-15 selectively in FOXP3 + Tregs the authors show that the composition of the CD8 + T-cell memory pool is altered in the absence of Treg-derived IL-15, since a subset of terminally effector memory cells is drastically reduced. Otherwise Treg-derived IL-15 is dispensable for antiviral immune responses and the generation of anti-viral CD8 + memory T-cells. These findings add to our understanding of the multifaceted role of Tregs in immune responses, and how IL-15 derived from different cellular sources maintains anti-viral T-cell memory., (© 2022 Wiley-VCH GmbH.)

Background: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O 2 ; V.O 2 AT) has been reported as an absolute value (V.O 2 ATabs), as a percentage of predicted peak V.O 2 (V.O 2 AT%peak&#95;pred), or as a percentage of observed peak V.O 2 (V.O 2 AT%peak&#95;obs). A direct comparison of the prognostic power among these different ways to report AT is missing., Research Question: What is the prognostic power of these different ways to report AT?, Study Design and Methods: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer., Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O 2 ATabs (mean ± SD, 823 ± 305 mL/min) and V.O 2 AT%peak&#95;pred (mean ± SD, 39.6 ± 13.9%), but not V.O 2 AT%peak&#95;obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O 2 ATabs (0.680) and V.O 2 AT%peak&#95;pred (0.688) performed similarly, whereas V.O 2 AT%peak&#95;obs (0.538) was significantly weaker (P < .001). Moreover, the V.O 2 AT%peak&#95;pred AUC value was the only one performing as well as the AUC based on peak V.O 2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O 2  < 12 mL/min/kg). Finally, the combination of V.O 2 AT%peak&#95;pred with peak V.O 2 and V. per CO 2 production shows the highest prognostic power., Interpretation: In HF, V.O 2 AT%peak&#95;pred is the best way to report V.O 2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O 2 and, remarkably, in patients with severe HF., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The current data on climate change and environmental degradation are dramatic. The consequences of these changes are already having a significant impact on people's health. Physicians - as advocates of the patients, but also as citizens - have an ethical obligation to be involved in efforts to stop these changes. The European Federation of Internal Medicine (EFIM) strongly encourages the Internal Medicine societies and internists across Europe to play an active role in matters related to climate change and environmental degradation. At a national level, this includes advocating the adoption of measures that reduce greenhouse gas (GHG) emissions and environmental degradation and contributing to policy decisions related to these issues. At a hospital level and in clinical practice, supporting actions by the health sector to reduce its ecological footprint is vital. At the level of EFIM and its associated internal societies, promoting educational activities and developing a toolkit to prepare internists to better care for citizens who suffer from the consequences of climate change. In addition to advocating and implementing effective actions to reduce the ecological footprint of the health industry, recommending the introduction of these themes in scientific programs of Internal Medicine meetings and congresses and the pre- and postgraduate medical training. At a personal level, internists must be active agents in advocating sustainable practices for the environment, increasing the awareness of the community about the health risks of climate change and environmental degradation, and being role models in the adoption of environmentally friendly behaviour., Competing Interests: Declaration of Competing Interest The authors declare they have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Infants born preterm are at high risk of presenting neurodevelopmental delay. The Neurofunctional Assessment (NFA) describes infants' neurodevelopment through the evaluation of six different domains. This study aimed to evaluate how, in a cohort of preterm infants, each NFA domain assessed at 3 months of corrected age (CA) was associated with neurodevelopment at 2 years of CA using the Griffiths Mental Developmental Scales Extended Revised (GMDS-ER). In addition, by introducing the NFA complexity score (CS), the study aimed to define a threshold that can help clinicians discriminate infants at higher risk of later neurodevelopmental delay. We conducted an observational, longitudinal study including 211 preterm infants. At 3 months of CA, infants who had normal scores in each domain showed a significantly higher GMDS-ER global quotient (GQ) at 2 years of CA. In addition, linear model results showed a significant negative relationship between the NFA CS and 2-year GMDS-ER GQ (estimate: - 0.27; 95% CI - 0.35, - 0.20; p value < 0.001). Each 10-point increase in the NFA CS was associated with an average 2.7-point decrease in the GMDS GQ. These results highlight how the NFA domains and NFA CS are compelling instruments for the early identification of children at risk for long-term adverse outcomes., (© 2022. The Author(s).)

Background: Delayed puberty is a possible complication of Epidermolysis Bullosa (EB), though the actual incidence is still unknown. In chronic illnesses delayed puberty should be correctly managed since, if untreated, can have detrimental effects on adult height attainment, peak bone mass achievement and psychological health., Aims and Methods: This is a single-centre study on pubertal development, growth and bone status in EB. Auxological, densitometric (areal Bone Mineral Density-aBMD Z-score, Bone Mineral Apparent Density-BMAD Z-score, Trabecular Bone Score-TBS and Bone Strain Index-BSI at Lumbar spine) and body composition data (Total Body DXA scans) were collected. Disease severity was defined according to Birmingham Epidermolysis Bullosa Severity (BEBS) score., Results: Twenty-one patients (12 Recessive Dystrophic EB-RDEB, 3 Dominant Dystrophic EB, 3 Junctional EB-JEB, 2 EB Simplex and one Kindler EB) aged 13 years (females) or 14 years (males) and above were enrolled (age 16.2±2.5 years, M/F 11/10). Short stature was highly prevalent (57%, mean height -2.12±2.05 SDS) with 55% patients with height <-2SD their mid-parental height. 7/21 patients (33%, 6 RDEB and 1 JEB) had delayed puberty with a median BEBS of 50 (range 29 to 63), a height SDS of -2.59 SDS (range -5.95 to -2.22) and a median lumbar BMAD Z-score of -4.0 SDS (range -5.42 to -0.63 SDS). Pubertal status was negatively associated with BEBS, skin involvement, inflammatory state and positively with height SDS and BMI SDS., Conclusions: Pubertal delay is highly prevalent in EB, especially in patients with RDEB and JEB, high severity score and inflammatory state. Moreover, pubertal delay worsens growth impairment and bone health. A study on pubertal induction is ongoing to enlighten possible beneficial effects on adult height attainment and peak bone mass accrual., Competing Interests: The authors have no competing interest to declare.

Objectives: The primary aim of this study was to compare the immunological profiles of children affected by recurrent acute otitis media (rAOM) with and without spontaneous tympanic membrane perforation (STMP). The secondary aim was to compare immunological features of children without parameters outside the normal range and affected by either rAOM or recurrent respiratory tract infections (rRTI)., Methods: In this study, otherwise healthy children (<10 years of age) with rAOM or rRTI were included. Data on perinatal history, vaccination status, presence of risk factors for rAOM or rRTI (including personal or family history of allergy) and number of infectious episodes in the previous 12 months were retrospectively obtained. Furthermore, data on immunological profile (blood cell count, circulating IgA, IgG, IgM and total IgE, IgG subclasses and lymphocyte subpopulations) were collected. The immune profile of children affected by rAOM with and without STMP were compared. Among children with parameters within normal range, we compared the levels of the immunological parameters of children affected by rAOM (with and without STMP) and rRTI., Results: The study involved a total of 751 children: 566 (75.3%) with rAOM and 185 (24.7%) with rRTI. Among the 566 children with rAOM, 39.7% had uncomplicated rAOM and 60.3% had rAOM with STMP. The mean age of the study population was 34.9 (SD 20.5) months. The frequency of children with parameters outside the normal range was similar among children with rAOM with (4.9%) and without STMP (6.1%). Among subjects without parameters outside the normal range, children with uncomplicated rAOM had significantly lower serum IgG, lymphocyte CD8 + and CD19 + and significantly higher IgG2 levels than children affected by rAOM with STMP. Finally, children with rAOM had lower levels of IgA, IgM and IgG2 and higher levels of IgG, lymphocyte CD19 + and CD16/56+ compared to children with rRTI., Conclusions: A low (<6.5%) percentage of children with rAOM with or without STMP present parameters outside the normal range. Among subjects without parameters outside the normal range, children with uncomplicated rAOM have a different immune profile as compared to those with STMP and rRTI. New prospective studies are needed to further explore the immune features of children affected by rAOM with and without STMP., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The magnitude of mother-to-infant transfer of anti-SARS-CoV-2 antibodies through breast milk (BM) after maternal vaccination during breastfeeding, in the absence of transplacental transfer of IgG, remains unclear. Here, we quantified anti-S and anti-RBD IgG, IgA, IgA1, and IgA2 in maternal serum, maternal saliva, BM, infant buccal swabs, and infant feces up to 90 days after the second maternal vaccine dose. BNT162b2 vaccine induced long-lasting IgG in maternal serum, but weaker mucosal antibody production, with anti-SARS-CoV-2 IgG and IgA amounts in BM between 10- and 150-fold lower compared to serum. BM IgA were exclusively of the IgA1 isotype, with no production of the mucosal-specific and protease-resistant IgA2. Accordingly, only traces of antibodies were retrieved from the feces of breastfed infants, and no IgG nor IgA were retrieved from infants' buccal swabs. Newly engineered anti-SARS-CoV-2 vaccines may be needed to stimulate the antibody production at mucosal sites such as breast milk., (© 2022. The Author(s).)

Objective: primary empty sella (PES) represents a frequent finding, but data on hormonal alterations are heterogeneous, and its natural history is still unclear. Our aim was to evaluate the pituitary function of patients with PES over a long follow-up., Design: multicenter retrospective cohort study enrolling patients referred between 1984-2020 to five Pituitary Units, with neuroradiological confirmed PES and a complete hormonal assessment., Methods: we analyzed hormonal (including basal and dynamic evaluations), clinical and neuroradiological data collected at diagnosis and at the last visit (at least 6 months of follow-up)., Results: we recruited 402 patients (females=63%, mean age=51.5 ± 16 years) with PES (partial, total, undefined in 66%, 13% and 21%, respectively). Hypopituitarism was present in 40.5% (hypogonadism=20.4%, hypoadrenalism=14.7%, growth hormone deficiency=14.7%, hypothyroidism=10.2%, diabetes insipidus=1.5%; multiple deficiencies=11.4%) and hypeprolactinemia in 6.5%. Interestingly, hormonal alterations were diagnosed in 29% of incidental PES. Hypopituitarism was associated with male sex ( p =0.02), suspected endocrinopathy ( p <0.001), traumatic brain injury ( p =0.003) and not with age, BMI, number of pregnancies and neuroradiological grade. A longitudinal assessment was possible in 166/402 (median follow-up=58 months). In 5/166 (3%), new deficiencies occurred, whereas 14/166 (8.4%) showed a hormonal recovery. A progression from partial to total PES, which was found in 6/98 patients assessed with a second imaging, was the only parameter significantly related to the hormonal deterioration ( p =0.006)., Conclusions: this is the largest cohort of patients with PES reported. Hypopituitarism is frequent (40%) but hormonal deterioration seems uncommon (3%). Patients need to be carefully evaluated at diagnosis, even if PES is incidentally discovered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carosi, Brunetti, Mangone, Baldelli, Tresoldi, Del Sindaco, Lavezzi, Sala, Mungari, Fatti, Galazzi, Ferrante, Indirli, Biamonte, Arosio, Cozzi, Lania, Mazziotti and Mantovani.)

Background: Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is the presence of hypothalamic hamartomas, which may manifest with seizures, panhypopituitarism and visual impairment. In Pallister-Hall syndrome, dysplastic histogenetic processes responsible for hypothalamic hamartomas are thought to disrupt early craniofacial development. The clinical presentation of Pallister-Hall syndrome may include: characteristic facies (low-set and posteriorly angulated ears, short nose with flat nasal bridge), cleft palate and uvula, bifid epiglottis and laryngotracheal cleft, limb anomalies (e.g., polysyndactyly, short limbs and nail dysplasia), anal atresia, genitourinary abnormalities and congenital heart defects., Case Presentation: We report the case of two monochorionic diamniotic twins diagnosed with Pallister-Hall syndrome during the neonatal period, after the identification of a hypothalamic hamartoma on day 1 by cerebral ultrasound scan, later confirmed by brain magnetic resonance imaging. Cerebral ultrasound and magnetic resonance imaging presentations were identical in both twins., Discussion and Conclusions: We review previously published cases (four reports) of hypothalamic hamartomas identified via cerebral ultrasound and compare reported ultrasonographic features. Main differential diagnoses based on cerebral ultrasound findings are discussed. Full description of typical magnetic resonance imaging appearance is also provided. This is the first case reported in the literature of monochorionic diamniotic twins affected by genetically confirmed Pallister-Hall syndrome with identical hypothalamic hamartomas at cerebral ultrasound and magnetic resonance imaging. Moreover, this paper adds to the existing literature on the sonographic appearance of hypothalamic hamartomas. Considering the consistency in hypothalamic hamartomas' sonographic appearance, we support the use of cerebral ultrasound as a first-line neuroimaging modality in case of clinical suspicion of Pallister-Hall syndrome., (© 2022. The Author(s).)

Congenital dacryocystocele is a rare clinical condition, more commonly unilateral, secondary to the defective canalization of the nasolacrimal duct. In case of failure of conservative treatment, surgical marsupialization is recommended. We describe the case of a 40-day-old male newborn treated by means of microdebrider marsupialization., Competing Interests: Authors have no conflicts of interest to declare., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

The pharmacological treatment of pituitary tumours is based on the use of stable analogues of somatostatin and dopamine. The analogues bind to somatostatin receptor types 2 and 5 (SST2 and SST5) and dopamine receptor type 2 (DRD2), respectively, and generate signal transduction cascades in cancerous pituitary cells that culminate in the inhibition of hormone secretion, cell growth and invasion. Drug resistance occurs in a subset of patients and can involve different steps at different stages, such as following receptor activation by the agonist or during the final biological responses. Although the expression of somatostatin and dopamine receptors in cancer cells is a prerequisite for these drugs to reach a biological effect, their presence does not guarantee the success of the therapy. Successful therapy also requires the proper functioning of the machinery of signal transduction and the finely tuned regulation of receptor desensitization, internalization and intracellular trafficking. The present Review provides an updated overview of the molecular factors underlying the pharmacological resistance of pituitary tumours. The Review discusses the experimental evidence that supports a role for receptors and intracellular proteins in the function of SSTs and DRD2 and their clinical importance., (© 2021. Springer Nature Limited.)

Introduction: Lenvatinib (LEN) is a multitarget tyrosine kinase inhibitor currently used for advanced, radioiodine refractory differentiated thyroid cancer (RAI-R DTC). Among adverse events (AEs), nausea, vomiting, and decreased appetite have been frequently described. We aimed to evaluate the prevalence, the clinical presentation, and the effectiveness of conservative treatment of gallbladder disorders in a consecutive series of patient treated with LEN., Methods: Patients with RAI-R DTC experiencing clinical symptoms suggestive for gallbladder disorders during LEN treatment were evaluated with laboratory investigations and contrast-enhanced abdominal computed tomography (CT) and ultrasound scan (US)., Results: After a median time of 2 months from the start of treatment, 5/13 patients (38.4%) complained of gastrointestinal symptoms, with increased biliary enzymes levels, especially γGT, and CT/US suggestive of acute cholecystitis (AC). The onset of symptoms and the peak of γGT levels frequently corresponded to the highest reduction in body weight during the first months of treatment. All patients were treated with supportive care and, when appropriate, with ursodeoxycholic acid; in 4 patients, LEN dose reduction or short interruption was needed, too., Conclusions: In patients with RAI-R DTC treated with LEN, a high prevalence of AC in the first months of treatment was documented. Mainly due to the low specificity of symptoms such as anorexia, nausea, and vomiting, this AE is likely to be frequently misdiagnosed. The onset of the disease was associated to the weight loss observed during the first months of treatment and contributes to further decrease in body weight. Therefore, particularly during the first months of treatment, or at any time of huge reduction of body weight, monitoring of γGT and US is crucial for prompt diagnosis and treatment. Conservative medical treatment and LEN dosage titration, together with dietary and rehabilitative supports, can limit or avoid the need for drug withdrawal and cholecystectomy., Competing Interests: M.D.S., C.C., S.D.L., M.P., M.V., and L.P. have no conflicts of interest to declare. L.F. has a consultant relationship with Eisai., (Copyright © 2020 by European Thyroid Association Published by S. Karger AG, Basel.)

The aim of this work is to establish inclusive guidelines on electroencephalography (EEG) applicable to all neonatal intensive care units (NICUs). Guidelines on ideal EEG monitoring for neonates are available, but there are significant barriers to their implementation in many centres around the world. These include barriers due to limited resources regarding the availability of equipment and technical and interpretive round-the-clock personnel. On the other hand, despite its limitations, amplitude-integrated EEG (aEEG) (previously called Cerebral Function Monitor [CFM]) is a common alternative used in NICUs. The Italian Neonatal Seizure Collaborative Network (INNESCO), working with all national scientific societies interested in the field of neonatal clinical neurophysiology, performed a systematic literature review and promoted interdisciplinary discussions among experts (neonatologists, paediatric neurologists, neurophysiologists, technicians) between 2017 and 2020 with the aim of elaborating shared recommendations. A consensus statement on videoEEG (vEEG) and aEEG for the principal neonatal indications was established. The authors propose a flexible frame of recommendations based on the complementary use of vEEG and aEEG applicable to the various neonatal units with different levels of complexity according to local resources and specific patient features. Suggestions for promoting cooperation between neonatologists, paediatric neurologists, and neurophysiologists, organisational restructuring, and teleneurophysiology implementation are provided., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: The most widely used diagnostic technique for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is real-time reverse transcriptase-polymerase chain reaction (RT-PCR). It can be done on different samples: nasopharyngeal swabs (NPS) or oropharyngeal swabs (OPS), and self-collected saliva. However, negative findings do not rule out infection., Methods: A review was conceived to discuss advantages and limitations of the available diagnostic modalities for nonserologic diagnosis of SARS-CoV-2 based on RT-PCR; the article also proposes some practical suggestions to improve diagnostic reliability., Results: A total of 16 papers (corresponding to 452 patients) of the 56 initially identified were included. Most of the papers describe findings from different samples obtained in limited case series; comparative studies are missing., Conclusions: Diagnostic accuracy of NPS and OPS is suboptimal and the risk of contaminated aerosol dispersal is not negligible. The SARS-CoV-2 RNA can be found in self-collected saliva specimens of many infected patients within 7 to 10 days after symptom onset. There is an urgent need for comparative trials to define the diagnostic modality of choice. Adequate education and training of health care personnel is mandatory.

Very preterm infants may manifest neurodevelopmental impairments, even in the absence of brain lesions. Pathogenesis is complex and multifactorial. Evidence suggests a role of early adversities on neurodevelopmental outcomes, via epigenetic regulation and changes in brain architecture. In this context, we focused on cumulative pain exposure which preterm neonates experience in neonatal intensive care unit (NICU). We systematically searched for: i) evidence linking pain with brain development and exploring the potential pathogenetic role of epigenetics; ii) preclinical research supporting clinical observational studies. Nine clinical neuroimaging studies, during neonatal or school age, mostly from the same research group, revealed volume reduction of white and gray matter structures in association with postnatal pain exposure. Three controlled animal studies mimicking NICU settings found increased cell death or apoptosis; nevertheless, eligible groups were limited in size. Epigenetic modulation (SLC6A4 promoter methylation) was identified in only two clinical trials. We call for additional research and, although knowledge gaps, we also point out the urgent need of minimizing painful procedures in NICUs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Acquired perinatal brain injuries are a set of conditions that remains a key challenge for neonatologists and that have significant social, emotional and financial implications for our communities. In our perspective article, we will introduce perinatal brain injury focusing specifically on the events leading to brain damage in preterm born infants and outcomes for these infants. Then we will summarize and discuss the preclinical and clinical studies testing the efficacy of stem cells as neuroprotectants in the last ten years in perinatal brain injury. There are no therapies to treat brain damage in preterm born infants and a primary finding from this review is that there is a scarcity of stem cell trials focused on overcoming brain injuries in these infants. Overall, across all forms of perinatal brain injury there is a remarkable heterogeneity in previous and on-going preclinical and clinical studies in terms of the stem cell type, animal models/patient selection, route and time of administration. Despite the quality of many of the studies this variation makes it difficult to reach a valid consensus for future developments. However, it is clear that stem cells (and stem cell derived exosomes) can reduce perinatal brain injury and our field needs to work collectively to refine an effective protocol for each type of injury. The use of standardized stem cell products and testing these products across multiple models of injury will provide a stronger framework for clinical trials development., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We assessed the accuracy of homogenous (semi-infinite, spherical) photon diffusion models in estimating absolute hemodynamic parameters of the neonatal brain in realistic scenarios (ischemia, hyperoxygenation, and hypoventilation) from 1.5 cm interfiber distance TD NIRS measurements. Time-point-spread-functions in 29- and 44-weeks postmenstrual age head meshes were simulated by the Monte Carlo method, convoluted with a real instrument response function, and then fitted with photon diffusion models. The results show good accuracy in retrieving brain oxygen saturation, and severe underestimation of total cerebral hemoglobin, suggesting the need for more complex models of analysis or of larger interfiber distances to precisely monitor all hemodynamic parameters., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Importance: The management of mother-infant dyads during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic constitutes a major issue for neonatologists. In mothers with SARS-CoV-2 infection, current recommendations suggest either to separate the dyad or encourage protected rooming-in under appropriate precautions. No data are available regarding the risk of mother-to-infant transmission of SARS-CoV-2 during rooming-in., Objective: To evaluate the risk of postnatal transmission of SARS-CoV-2 from infected mothers to their neonates following rooming-in and breastfeeding., Design, Setting, and Participants: A prospective, multicenter study enrolling mother-infant dyads from March 19 to May 2, 2020, followed up for 20 days of life (range, 18-22 days), was performed. The study was conducted at 6 coronavirus disease 2019 maternity centers in Lombardy, Northern Italy. Participants included 62 neonates born to 61 mothers with SARS-CoV-2 infection who were eligible for rooming-in practice based on the clinical condition of the mother and infants whose results of nasopharyngeal swabs were negative at birth., Exposures: Mothers with SARS-CoV-2 infection were encouraged to practice rooming-in and breastfeeding under a standardized protocol to minimize the risk of viral transmission., Main Outcomes and Measures: Clinical characteristics and real-time reverse transcriptase-polymerase chain reaction for SARS-CoV-2 on neonatal nasopharyngeal swabs at 0, 7, and 20 days of life., Results: Of the 62 neonates enrolled (25 boys), born to 61 mothers (median age, 32 years; interquartile range, 28-36 years), only 1 infant (1.6%; 95% CI, 0%-8.7%) was diagnosed as having SARS-CoV-2 infection at postbirth checks. In that case, rooming-in was interrupted on day 5 of life because of severe worsening of the mother's clinical condition. The neonate became positive for the virus on day 7 of life and developed transient mild dyspnea. Ninety-five percent of the neonates enrolled were breastfed., Conclusions and Relevance: The findings of this cohort study provide evidence-based information on the management of mother-infant dyads in case of SARS-CoV-2 maternal infection suggesting that rooming-in and breastfeeding can be practiced in women who are able to care for their infants.

Background: Animal models and few clinical reports suggest the involvement of the complement system in the onset of severe manifestations of coronavirus disease-2019 (COVID-19). However, complement contribution to endotheliopathy and hypercoagulability has not been elucidated yet., Objective: To evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients., Methods: In this single-centre cohort study, 148 patients with COVID-19 of different severity were evaluated upon hospital admission and 30 days later. Markers of complement activation (SC5b-9 and C5a) and endothelial perturbation (von Willebrand factor [vWF], tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor-1 [PAI-1], soluble thrombomodulin [sTM], and soluble endothelial selectin [sE-selectin]) were measured in plasma., Results: The patients had high plasma levels of SC5b-9 and C5a (p = 0.0001 for both) and vWF, t-PA and PAI-1 (p = 0.0001 for all). Their SC5b-9 levels correlated with those of vWF (r = 0.517, p = 0.0001) and paralleled disease severity (severe vs mild p = 0.0001, severe vs moderate p = 0.026 and moderate vs mild p = 0.001). The levels of sE-selectin were significantly increased only in the patients with severe disease. After 30 days, plasma SC5b-9, C5a and vWF levels had significantly decreased (p = 0.0001 for all), and 43% of the evaluated patients had normal levels., Conclusions: Complement activation is boosted during the progression of COVID-19 and dampened during remission, thus indicating its role in the pathophysiology of the disease. The association between complement activation and the biomarkers of endothelial damage suggests that complement may contribute to tissue injury and could be the target of specific therapy., (Copyright © 2020. Published by Elsevier Ltd.)

Based on mortality data from 93% of Italian municipalities, there was an over 50% excess total mortality in March and a 38% excess in April, corresponding to over 46,000 excess deaths in those two months - as compared to 28,000 deaths attributed to COVID-19 in March and April. No subsequent excess mortality was observed, and in June reported total deaths were 6.2% less than expected. In the first 6 months of 2020, an 11.1% excess mortality was observed in Italy, and an almost 50% excess in Lombardy, the most affected region. Timely monitoring of total mortality has relevant implications for monitoring the COVID-19 pandemic and controlling occupational and social exposures.

The aim of the study was to investigate General Movements'(GMs) neonatal trajectories and their association with neurodevelopment at three months corrected age (CA) in preterm infants. We conducted an observational, longitudinal study in 216 very low birth weight infants. GMs were recorded at 31 ± 1, 35 ± 1, 40 ± 1 weeks of postmenstrual age and at three months of corrected age (CA). More than 90% of infants showing neonatal trajectories with persistent Normal (N-N) or initial Poor Repertoire to Normal (PR-N) movements presented fidgety pattern at three months CA. On the contrary, fidgety movements were not detected in any infant with a trajectory of persistent Cramped-Synchronized (CS-CS) or an initial Poor-Repertoire to Cramped-Synchronized (PR-CS) movements. Trajectories with initial Normal to Poor-Repertoire (N-PR) or persistent Poor-Repertoire (PR-PR) movements showed an increased risk of having a non-normal Fidgety pattern compared with the N-N group (OR = 8.43, 95% CI: 2.26-31.45 and OR = 15.02, 95% CI: 6.40-35.26, respectively). These results highlight the importance to evaluate neonatal GMs' trajectory to predict infants' neurodevelopment. N-N or PR-N trajectories suggest normal short-term neurodevelopment, especially a lower risk of Cerebral Palsy; whereas findings of N-PR and PR-PR trajectories indicate the need for closer follow up to avoid delay in programming intervention strategies.

Background: Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia (ie, a significant fall in hemoglobin oxygen saturation [Spo 2 ]) during sea level exercise in endurance-trained athletes. It is unknown whether there are specific properties of pulmonary vascular function in athletes exhibiting oxygen desaturation., Methods: Ten endurance-trained athletes with exercise-induced hypoxemia (EIH), nine endurance-trained athletes with no exercise-induced hypoxemia (NEIH), and 10 untrained control subjects underwent an incremental exercise stress echocardiography coupled with lung diffusion capacity for carbon monoxide (Dlco) and lung diffusion capacity for nitric oxide (Dlno) testing. Functional adaptation of the pulmonary circulation was evaluated with measurements of mean pulmonary arterial pressure (mPAP), pulmonary capillary pressure, pulmonary vascular resistance (PVR), cardiac output (Qc), and pulmonary vascular distensibility (alpha) mathematically determined from the curvilinearity of the multi-point mPAP/Qc relation., Results: EIH athletes exhibited a lower exercise-induced PVR decrease compared with the untrained and NEIH groups (P < .001). EIH athletes showed higher maximal mPAP compared with NEIH athletes (45.4 ± 0.9 mm Hg vs 41.6 ± 0.9 mm Hg, respectively; P = .003); there was no difference between the NEIH and untrained subjects. Alpha was lower in the EIH group compared with the NEIH group (P < .05). Maximal mPAP, Pcap, and alpha were correlated with the fall of Spo 2 during exercise (P < .01, P < .01, and P < .05). Dlno and Dlco increased with exercise in all groups, with no differences between groups. Dlno/Qc was correlated to the exercise-induced Spo 2 changes (P < .05)., Conclusions: EIH athletes exhibit higher maximal pulmonary vascular pressures, lower vascular distensibility, or exercise-induced changes in PVR compared with NEIH subjects, in keeping with pulmonary capillary stress failure or intrapulmonary shunting hypotheses., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Neonatal brain sonography is part of routine clinical practice in neonatal intensive care units, but ultrasound imaging of the posterior fossa has gained increasing attention since the burden of perinatal acquired posterior fossa abnormalities and their impact on motor and cognitive neurodevelopmental outcome have been recognized. Although magnetic resonance imaging (MRI) is often superior, posterior fossa abnormalities can be suspected or detected by optimized cranial ultrasound (CUS) scans, which allow an early and bed-side diagnosis and monitoring through sequential scans over a long period of time. Different ultrasound appearances and injury patterns of posterior fossa abnormalities are described according to gestational age at birth and characteristics of the pathogenetic insult. The aim of this review article is to describe options to improve posterior fossa sequential CUS image quality, including the use of supplemental acoustic windows, to show standard views and normal ultrasound anatomy of the posterior fossa, and to describe the ultrasound characteristics of acquired posterior fossa lesions in preterm and term infants with effect on long-term outcome. The limitations and pitfalls of CUS and the role of MRI are discussed.

In the context of SARS-CoV-2 pandemic, the hospital management of mother-infant pairs poses to obstetricians and neonatologists previously unmet challenges. In Lombardy, Northern Italy, 59 maternity wards networked to organise the medical assistance of mothers and neonates with suspected or confirmed SARS-CoV-2 infection. Six "COVID-19 maternity centres" were identified, the architecture and activity of obstetric and neonatal wards of each centre was reorganised, and common assistance protocols for the management of suspected and proven cases were formulated. Here, we present the key features of this reorganization effort, and our current management of the mother-infant dyad before and after birth, including our approach to rooming-in practice, breastfeeding and neonatal follow-up, based on the currently available scientific evidence. Considered the rapid diffusion of COVID-19 all over the world, we believe that preparedness is fundamental to assist mother-infant dyads, minimising the risk of propagation of the infection through maternity and neonatal wards.

Objectives: A new device that combines, for the first time, two photonic technologies (time-resolved near-infrared spectroscopy and diffuse correlation spectroscopy) was provided and tested within the BabyLux project. Aim was to validate the expected changes in cerebral oxygenation and blood flow., Methods: A pulse oximeter and the BabyLux device were held in place (right hand/wrist and frontoparietal region, respectively) for 10 min after birth in healthy term infants delivered by elective caesarean section. Pulse oximeter saturation (SpO 2 ), cerebral tissue oxygen saturation (StO 2 ) and blood flow index (BFI) were measured over time. Tissue oxygen extraction (TOE) and cerebral metabolic rate of oxygen index (CMRO 2 I) were calculated., Results: Thirty infants were enrolled in two centres. After validity check of data, 23% of infants were excluded from TOE and CMRO 2 I calculation due to missing data. As expected, SpO 2 (estimate 3.05 %/min; 95% CI 2.78 to 3.31 %/min) and StO 2 (estimate 3.95 %/min; 95% CI 3.63 to 4.27 %/min) increased in the first 10 min after birth, whereas BFI (estimate -2.84×10 -9 cm 2 /s/min; 95% CI -2.50×10 -9 to -3.24×10 -9 cm 2 /s/min) and TOE (estimate -0.78 %/min; 95% CI -1.12 to -0.45 %/min) decreased. Surprisingly, CMRO 2 I decreased (estimate -7.94×10 -8 /min; 95% CI -6.26×10 -8 to -9.62×10 -8 /min)., Conclusions: Brain oxygenation and BFI during transition were successfully and simultaneously obtained by the BabyLux device; no adverse effects were recorded, and the BabyLux device did not limit the standard care. The preliminary results from clinical application of the BabyLux device are encouraging in terms of safety and feasibility; they are consistent with previous reports on brain oxygenation during transition, although the interpretation of the decreasing CMRO 2 I remains open., Trial Registration Number: NCT02815618., Competing Interests: Competing interests: UMW is the CEO, has equity ownership in HemoPhotonics S.L. and is an employee in the company. His role in the project has been defined by the project objectives, tasks and work-packages and was reviewed by the European Commission., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders., Methods: This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline's criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates., Results: Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2-3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1-7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1-0.7) and need for surfactant (OR = 0.5, CI: 0.2-0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2-3 only, RC = 6.5 days, CI: 2-11). No other outcome was affected., Conclusions: IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable., Competing Interests: The authors have declared that no competing interests exist.

Background: Regulating thermogenesis is a major task of thyroid hormones (THs), and involves TH-responsive energetic processes at the central and peripheral level. In severe obesity, little is known on the relationship between THs and resting energy expenditure (REE) before and after weight loss., Methods: We enrolled 100 euthyroid subjects with severe obesity who were equally distributed between genders. Each was examined before and after completion of a 4-wk inpatient multidisciplinary dieting program and subjected to measurement of thyroid function, REE, fat-free mass (FFM, kg) and percent fat mass (FM)., Results: Baseline REE was lower than predicted in 70 obese patients, and overall associated with BMI, FFM and FM but not thyroid-related parameters. By the study end, both BMI and REE decreased (5.5% and 4.1%, p<0.001 vs. baseline) and their percent changes were significantly associated (p<0.05), while no association related percent changes of REE and FFM or FM. Individually, REE decreased in 66 and increased in 34 patients irrespective of gender, BMI and body composition. Weight loss significantly impacted TSH (-6.3%), FT3 (-3.3%) and FT4 levels (3.9%; p<0.001 for all). By the study end, a significant correlation became evident between REE and FT4 (r = 0.42, p<0.001) as well as FT3 (r = 0.24, p<0.05). In stepwise multivariable regression analysis, however, neither THs nor body composition entered the regression equation for REE response to weight loss., Conclusions: In severe obesity, short-term weight loss discloses a positive relationship between REE and THs., Competing Interests: The authors have declared that no competing interests exist.