Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey.

Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian neonatal units. A prospective cross-sectional study was conducted in Italian and Spanish neonatal units using a web-based survey with 43 questions. A modified Delphi method involved experts refining the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices. CONCLUSIONS: The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in neonatal units. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe. WHAT IS KNOWN: • Neonates in intensive care face a high risk of nephrotoxicity and ototoxicity from drugs like aminoglycosides, vancomycin, loop diuretics, and ibuprofen. • Therapeutic drug monitoring is key for managing these risks, optimizing dosing for efficacy and minimizing side effects. WHAT IS NEW: • NICUs in Spain and Italy show high drug toxicity awareness but differ in ototoxic/nephrotoxic drug management. • Urgent need for standard guidelines and practices to address nephrotoxic risks from aminoglycosides, vancomycin, loop diuretics, and ibuprofen.

Global cross-sectional survey on neonatal pharmacologic sedation and analgesia practices and pain assessment tools: impact of the sociodemographic index (SDI).

BACKGROUND: There is variability in the use of sedatives and analgesics in neonatal intensive care units (NICUs). We aimed to investigate the use of analgesics and sedatives and the management of neonatal pain and distress. METHODS: This was a global, prospective, cross-sectional study. A survey was distributed May-November 2022. The primary outcome of this research was to compare results between countries depending on their socio-sanitary level using the sociodemographic index (SDI). We organized results based on geographical location. RESULTS: The survey collected 1304 responses, but we analyzed 924 responses after database cleaning. Responses from 98 different countries were analyzed. More than 60% of NICUs reported having an analgosedation guideline, and one-third of respondents used neonatal pain scales in more than 80% of neonates. We found differences in the management of sedation and analgesia between NICUs on different continents, but especially between countries with different SDIs. Countries with a higher SDI had greater availability of and adherence to analgosedation guidelines, as well as higher rates of analgosedation for painful or distressing procedures. Countries with different SDIs reported differences in analgosedation for neonatal intubation, invasive ventilation, and therapeutic hypothermia, among others. CONCLUSIONS: Socio-economic status of countries impacts on neonatal analgosedation management. IMPACT: There is significant variability in the pain management practices in neonates. There is a lack of knowledge related to how neonatal pain management practices differ between regions. Sociodemographic index is a key factor associated with differences in neonatal pain management practices across global regions.

Information manipulation and historical revisionism: Russian disinformation and foreign interference through manipulated history-based narratives.

Background: Disinformation and historical revisionism have been acknowledged as tools for foreign interference that belong to the landscape of hybrid threats. Historical revisionism plays an essential role in Russian foreign policy towards the post-Soviet space and is in strong relation with the concepts of Near Abroad and Russkii Mir ('Russian World') and with certain ideas contained in the neo-Eurasianist Movement. This article examines Russian revisionist narratives disseminated in information and influencing campaigns in Europe and against the West.       Methods: This study uses a mixed methodology combining desk research, including literature review, and analysis of the EUvsDisinfo database of cases identified before the February 2022 invasion of Ukraine. R esults: The manipulation of historical events has been largely employed by the Kremlin as a tool for foreign interference to achieve strategic objectives. First World War treaties, mainly the Trianon Peace Treaty, as well as the Second World War and the communist and fascist historical experiences in countries within the post-Soviet space, are the pivotal topics from which hostile influencing narratives are built. From the analysis of the EUvsDisinfo database, the article identifies seven topic themes.       Conclusions:  Our findings suggest that pre-emptively elaborated counter-narratives based on historical evidence and sound historiography can be an effective tool against hostile revisionist narratives that exploit vulnerabilities and specific target groups within European societies.

Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner.

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3-6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.

Current pain management practices for preterm infants with necrotizing enterocolitis: a European survey.

BACKGROUND: Necrotizing enterocolitis (NEC) is a highly painful intestinal complication in preterm infants that requires adequate pain management to prevent short- and long-term effects of neonatal pain. There is a lack of international guidelines for pain management in NEC patients. Therefore, this study aims to describe current pain management for NEC patients in European neonatal intensive care units (NICUs). METHODS: An online survey was designed and conducted to assess current practices in pain management for NEC patients in European NICUs. The survey was distributed via neonatal societies, digital platforms, and professional contacts. RESULTS: Out of the 259 responding unique European NICUs from 36 countries, 61% had a standard protocol for analgesic therapy, 73% assessed pain during NEC, and 92% treated NEC patients with intravenous analgosedatives. There was strong heterogeneity in the used pain scales and initial analgesic therapy, which mainly included acetaminophen (70%), fentanyl (56%), and/or morphine (49%). A third of NICU representatives considered their pain assessment adequate, and half considered their analgesic therapy adequate for NEC patients. CONCLUSIONS: Various pain scales and analgesics are used to treat NEC patients in European NICUs. Our results provide the first step towards an international guideline to improve pain management for NEC patients. IMPACT: This study provides an overview of current pain management practices for infants with necrotizing enterocolitis (NEC) in European neonatal intensive care units. Choice of pain assessment tools, analgosedatives, and dosages vary considerably among NICUs and countries. A third of NICU representatives were satisfied with their current pain assessment practices and half of NICU representatives with their analgesic therapy practices in NEC patients in their NICU. The results of this survey may provide a first step towards developing a European pain management consensus guideline for patients with NEC.

Description of the Exposure of the Most-Followed Spanish Instamoms' Children to Social Media.

There is evidence of the risk of overexposure of children on social networks by parents working as influencers. A cross-sectional study of the profiles of the sixteen most-followed Instamoms in Spain was carried out. An analysis of these profiles was performed over a full month (April 2022), three times a week, to describe the representation of influencers' children in the posts shared by them, as well as their role in the Instamoms' marketing. A total of 192 evaluations of the profiles were performed in the study period. The average number of children exposed by an Instamom was three, generally preschoolers and schoolchildren. The children appear in a context of the family home and accompanied by their mother. The type of advertising that accompanies the appearance of underage children is usually women or children's clothing, but also food products, leisure, etc. Appearance of children in the posts had a statistically significant influence on followers measured by the number of likes. Results provided the identification of two Instamom clusters with differentiated behaviors in relation to appearance of children in posts. It is important to involve Social Pediatrics in the protection of the privacy and interests of children given the increase in sharenting. The authors believe that there are concerns about their explicit consent to public exposure from early childhood and about the medium and long-term effect that this may have on their future well-being.

Age-dependent nasal immune responses in non-hospitalized bronchiolitis children.

Bronchiolitis in children is associated with significant rates of morbidity and mortality. Many studies have been performed using samples from hospitalized bronchiolitis patients, but little is known about the immunological responses from infants suffering from mild/moderate bronchiolitis that do not require hospitalization. We have studied a collection of nasal lavage fluid (NLF) samples from outpatient bronchiolitis children as a novel strategy to unravel local humoral and cellular responses, which are not fully characterized. The children were age-stratified in three groups, two of them (GI under 2-months, GII between 2-4 months) presenting a first episode of bronchiolitis, and GIII (between 4 months and 2 years) with recurrent respiratory infections. Here we show that elevated levels of pro-inflammatory cytokines (IL1ß, IL6, TNFα, IL18, IL23), regulatory cytokines (IL10, IL17A) and IFNγ were found in the three bronchiolitis cohorts. However, little or no change was observed for IL33 and MCP1, at difference to previous results from bronchiolitis hospitalized patients. Furthermore, our results show a tendency to IL1ß, IL6, IL18 and TNFα increased levels in children with mild pattern of symptom severity and in those in which non RSV respiratory virus were detected compared to RSV+ samples. By contrast, no such differences were found based on gender distribution. Bronchiolitis NLFs contained more IgM, IgG1, IgG3 IgG4 and IgA than NLF from their age-matched healthy controls. NLF from bronchiolitis children predominantly contained neutrophils, and also low frequency of monocytes and few CD4+ and CD8+ T cells. NLF from infants older than 4-months contained more intermediate monocytes and B cell subsets, including naïve and memory cells. BCR repertoire analysis of NLF samples showed a biased VH1 usage in IgM repertoires, with low levels of somatic hypermutation. Strikingly, algorithmic studies of the mutation profiles, denoted antigenic selection on IgA-NLF repertoires. Our results support the use of NLF samples to analyze immune responses and may have therapeutic implications.

Responses to digital disinformation as part of hybrid threats: a systematic review on the effects of disinformation and the effectiveness of fact-checking/debunking.

The dissemination of purposely deceitful or misleading content to target audiences for political aims or economic purposes constitutes a threat to democratic societies and institutions, and is being increasingly recognized as a major security threat, particularly after evidence and allegations of hostile foreign interference in several countries surfaced in the last five years. Disinformation can also be part of hybrid threat activities. This research paper examines findings on the effects of disinformation and addresses the question of how effective counterstrategies against digital disinformation are, with the aim of assessing the impact of responses such as the exposure and disproval of disinformation content and conspiracy theories. The paper's objective is to synthetize the main scientific findings on disinformation effects and on the effectiveness of debunking, inoculation, and forewarning strategies against digital disinformation. A mixed methodology is used, combining qualitative interpretive analysis and structured technique for evaluating scientific literature such as a systematic literature review (SLR), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework.

Variations in Antibiotic Use and Sepsis Management in Neonatal Intensive Care Units: A European Survey.

Management of neonatal sepsis and the use of antimicrobials have an important impact on morbidity and mortality. However, there is no recent background on which antibiotic regimens are used in different European neonatal intensive care units (NICUs). Our study aimed to describe the use of antibiotics and other aspects of early- and late-onset sepsis (EOS and LOS, respectively) management by European NICUs. We conducted an online survey among NICUs throughout Europe to collect information about antibiotic stewardship, antibiotic regimens, and general aspects of managing neonatal infections. NICUs from up to 38 European countries responded, with 271 valid responses. Most units had written clinical guidelines for EOS (92.2%) and LOS (81.1%) management. For EOS, ampicillin, penicillin, gentamicin, and amikacin were the most commonly used antibiotics. Analysis of the combinations of EOS regimens showed that the most frequently used was ampicillin plus gentamicin (54.6%). For LOS, the most frequently used antibiotics were vancomycin (52.4%), gentamicin (33.9%), cefotaxime (28%), and meropenem (15.5%). Other aspects of the general management of sepsis have also been analyzed. The management of neonatal sepsis in European NICUs is diverse. There was high self-reported adherence to the local clinical guidelines. There was homogeneity in the combination of antibiotics in EOS but less in LOS.

[Significance of free perigastric fluid detected by echoendoscopy in patients with gastric cancer]. / Significado del líquido libre perigástrico identificado por ecoendoscopia en pacientes con cáncer gástrico.

OBJECTIVES: To determine the diagnostic value of free perigastric fluid identified by echoendoscopy in patients with gastric cancer and to establish the factors related to the presence of peritoneal carcinomatosis in these patients. MATERIAL AND METHODS: We retrospectively included 100 patients with a histological diagnosis of gastric adenocarcinoma referred for echoendoscopy. A positive result was defined as the echoendoscopic identification of free perigastric fluid. This result was compared with the final study based on exploratory laparoscopy-laparotomy. The histological and endoscopic characteristics were compared with the final result. RESULTS: Free perigastric fluid was found in 21 patients (21%). Among these, 15 (71%) showed peritoneal carcinomatosis, confirmed by laparoscopy (12 patients) or echoendoscopy-guided fine-needle-aspiration biopsy (three patients). In seven of the 79 patients (8%) not showing the presence of ascites, peritoneal implants were identified by exploratory laparoscopy-laparotomy. The sensitivity, specificity, positive predictive value and diagnostic accuracy of free fluid in the diagnosis of carcinomatosis was 68%, 92%, 71%, 91% and 87%, respectively. No histologic or endoscopic factors related to the malignancy of echoendoscopically-detected fluid were identified. CONCLUSION: In patients with gastric cancer, free perigastric fluid identified by echoendoscopy is an important predictive factor of peritoneal carcinomatosis and may have significant implications in the management of these patients.