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Purpose: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [225Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB. Methods: [68Ga]Ga- and [225Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice. The efficacy of up to three cycles of 60 kBq [225Ac]Ac-FAPI-46 was evaluated as monotherapy and in combination with an anti-PD-1 antibody. Efficacy of [225Ac]Ac-FAPI-46 and/or ICB was further compared in FAP-overexpressing FSA (FSA-F) tumors that were sensitive to ICB or rendered ICB-resistant by tumor-induction in the presence of Abatacept. Results: [225Ac]Ac-FAPI-46 was well tolerated up to 3 × 60 kBq but had minimal effect on FSA tumor growth. The combination of three cycles [225Ac]Ac-FAPI-46 and ICB resulted in growth delay in 55% of mice (6/11) and partial tumor regression in 18% (2/11) of mice. In FSA-F tumors with FAP overexpression, both [225Ac]Ac-FAPI-46 and ICB were effective without additional benefits from the combination. In locally immunosuppressed and ICB resistant FAP-F tumors, however, [225Ac]Ac-FAPI-46 restored responsiveness to ICB, resulting in significant tumor regression and tumor-free survival of 56% of mice in the combination group up to 60 days post treatment. Conclusion: [225Ac]Ac-FAPI-46 efficacy is correlated with tumoral FAP expression levels and can restore responsiveness to PD-1 ICB. These data illustrate that careful patient selection based on target expression and rationally designed combination therapies are critically important to maximize the therapeutic impact of FAP-targeting radioligands. [ABSTRACT FROM AUTHOR]

On the other hand, analogue phenomenology is compared to Husserl's genetic approach and Merleau-Ponty's phenomenology of perception, which is based on the idea of tension or force and, consequently, on intensive or forceful quality. The field of investigation is particularly defined by the phenomenology of perception in relation to the ongoing processes of transformation involving the digital, artificial intelligence, and hybridization. This Special Issue takes inspiration from the debate occurred during the international conference "Phenomenology and Digital Knowledge - Fenomenologia e saperi digitali", which took place in Udine from September 1 to 4, 2021. [Extracted from the article]

This article is based on Gibson's "experimental phenomenology" and ecological perspective. It aims to develop Merleau-Ponty's concept of "incarnate" by relating it to the more general concept of "illusion" in order to apply it to digital environments and immersive virtual realities. First of all, we should clarify, from a phenomenological point of view, the notion of "world." Although the concept of "world" is closely linked to that of "reality," it cannot be superimposed on it. We will analyze this distinction by focusing on specific cases of optical-geometric illusions and their ontological and epistemological implications. We will then extend them from the natural to the digital world. [ABSTRACT FROM AUTHOR]

In this multicenter retrospective study we aimed to evaluate the outcome of cardiac involvement in children affected by multisystem inflammatory syndrome (MIS-C), assessed through cardiac magnetic resonance (CMR). Children referring to three Italian tertiary pediatric centers between February 2020 and November 2021 with a diagnosis of MIS-C, who underwent CMR during a follow-up visit, were enrolled. Demographic, clinical, laboratory, treatment, and outcome data were collected. Twenty MIS-C patients (aged 9–17, median 12 years) were included in the study. Heart involvement at onset was testified by hypotension/shock (55%), laboratory evidence of myocardial involvement (100%), reduced LV ejection fraction (EF) on echocardiography (83%), and/or need for inotrope agents (40%); they all presented good clinical, laboratory, and echocardiographic response to treatment. CMR was performed after a median interval of 3 months from discharge. Pericardial effusion and myocardial edema were found in 5% of patients. Mild residual left ventricular (LV) dysfunction was found in 20% of patients, all showing normal echocardiographic LVEF at discharge. Minimal myocardial scars were found in 25% by late gadolinium enhancement (LGE). One patient was evaluated at two consecutive time points, showing partial resolution of a myocardial scar after 7 months from its first finding. Conclusion: Despite the severity of heart involvement in the acute MIS-C phase, the mid-term cardiac outcome is good. Direct cardiac tissue viral invasion may be involved in MIS-C pathogenesis. What is Known: • Heart involvement is common in MIS-C, but conflicting findings have been shown regarding cardiac outcome when assessed through cardiac MRI. What is New: • Midterm cardiac MRI shows mild abnormalities in patients recovered from MIS-C with any grade of severity of cardiac involvement at presentation. [ABSTRACT FROM AUTHOR]

Drug-associated harm is common but difficult to detect in the hospital setting. In critically ill children, we sought to evaluate drug-associated hepatic injury following enteral acetaminophen error, defined as acetaminophen dosing that exceeds daily maximum recommendations. This retrospective cohort study took place in two pediatric intensive care units within a pediatric hospital center. The included patients are children (< 18 years of age) admitted to the pediatric and cardiac intensive care unit between January 2008 and January 2018, and receiving enteral acetaminophen. We defined acetaminophen dosing error as exceeding daily acetaminophen dosing by > 10% the upper limit of maximum recommended dose for weight and age (> 82.5 mg/kg/day or > 4400 mg/day). We included 14,146 admissions, who received 147,485 doses of acetaminophen. Acetaminophen dosing errors occurred 1 in every 9.5 patient-days on acetaminophen. ALT and AST decreased significantly over the course of ICU admission (p < 0.0001). In patients with acetaminophen errors, ALT and AST measured in the 24 to 96 h post error were not significantly different than when measured outside this window. A sensitivity analysis using > 100 mg/kg/day as the upper daily acetaminophen error cut-off did not reveal any subsequent significant increase in ALT or ALT in the 24 to 96-h post-error window, compared to measurements taken outside the window. Conclusion: Although the administration of acetaminophen in critically ill children frequently exceeds the daily recommended limit and vigilance is needed, we did not find any associated increase in liver transaminases following acetaminophen errors. What is Known: • Acetaminophen dosing errors are common in pediatric outpatients. • Excessive acetaminophen dosing can be associated with harm, including hepatic injury. What is New: • Exceeding daily acetaminophen dosing limit occurs 1 in every 9.5 patient-days in children admitted to the critical care unit. • In patients with daily dose excess of acetaminophen, we did not find a significant increase in the measured liver enzymes in the 24 to 96 h following the overdosing. [ABSTRACT FROM AUTHOR]

Purpose: The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting 64Cu-labelled abatacept. Procedures: Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR. 64Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution. Results: The number of CD80+ and CD86+ immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation, 64Cu-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86+ immune cells at the LPS inoculation site. Conclusions: CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. 64Cu-NODAGA-abatacept PET allowed following APC activation over time. [ABSTRACT FROM AUTHOR]

The objective of the study is to evaluate the efficacy of corticosteroids in Sydenham chorea. This is a retrospective observational study. Clinical information of children with Sydenham chorea were collected. Outcome of Sydenham chorea was evaluated in consideration of presence or absence of corticosteroid therapy. Thirty patients were enrolled. A total of 15 were treated with prednisone, 15 received symptomatic drugs or no treatment. Patients who were treated with prednisone showed faster improvement (4 vs 16 days; p = 0.002) and shorter median time of remission (30 vs 135 days; p < 0.001).Conclusion: Our study showed that corticosteroid therapy is an effective treatment of Sydenham chorea.What is Known:• Steroid treatment in Sydenham chorea is widely used but it is not standardized.• Few manuscript report a beneficial use of steroids in Sydenham chorea if compared with no treatment.What is New:• Steroid treatment seems to be effective in both clinical remission and clinical improvement of symptoms among patients with Sydenham chorea.• Steroid treatment seems to be superior to conventional treatment. [ABSTRACT FROM AUTHOR]

Background: Computerized physician order entry and clinical decision support systems are electronic prescribing strategies that are increasingly used to improve patient safety. Previous reviews show limited effect on patient outcomes. Our objective was to assess the impact of electronic prescribing strategies on medication errors and patient harm in hospitalized patients.Methods: MEDLINE, EMBASE, CENTRAL, and CINAHL were searched from January 2007 to January 2018. We included prospective studies that compared hospital-based electronic prescribing strategies with control, and reported on medication error or patient harm. Data were abstracted by two reviewers and pooled using random effects model. Study quality was assessed using the Effective Practice and Organisation of Care and evidence quality was assessed using Grading of Recommendations Assessment, Development, and Evaluation.Results: Thirty-eight studies were included; comprised of 11 randomized control trials and 27 non-randomized interventional studies. Electronic prescribing strategies reduced medication errors (RR 0.24 (95% CI 0.13, 0.46), I2 98%, n = 11) and dosing errors (RR 0.17 (95% CI 0.08, 0.38), I2 96%, n = 9), with both risk ratios significantly affected by advancing year of publication. There was a significant effect of electronic prescribing strategies on adverse drug events (ADEs) (RR 0.52 (95% CI 0.40, 0.68), I2 0%, n = 2), but not on preventable ADEs (RR 0.55 (95% CI 0.30, 1.01), I2 78%, n = 3), hypoglycemia (RR 1.03 (95% CI 0.62-1.70), I2 28%, n = 7), length of stay (MD - 0.18 (95% - 1.42, 1.05), I2 94%, n = 7), or mortality (RR 0.97 (95% CI 0.79, 1.19), I2 74%, n = 9). The quality of evidence was rated very low.Discussion: Electronic prescribing strategies decrease medication errors and adverse drug events, but had no effect on other patient outcomes. Conservative interpretations of these findings are supported by significant heterogeneity and the preponderance of low-quality studies. [ABSTRACT FROM AUTHOR]

Objectives: Anti-tumor necrosis factor alpha (anti-TNF-α) agents are generally well tolerated, yet they can be associated with serious adverse events (SAEs) in a minority of patients. We examined the incidence of SAEs in a pediatric referral center for chronic rheumatologic and gastroenterological inflammatory disorders.Methods: Retrospective analysis of SAEs occurring during treatment with anti-TNF-α agents in patients with juvenile idiopathic arthritis (JIA) (n = 78)  or pediatric-onset inflammatory bowel disease (IBD) (n = 105) seen at the Institute for Maternal and Child Health IRCCS “Burlo Garofolo” in Trieste, Italy, between June 2001 and February 2016. Only SAEs grade 3-5 according to the Common Terminology Criteria for Adverse Events version 4.03 and/or requiring definitive therapy discontinuation were reported.Results: Total anti-TNF-α exposure was 390.5 patient-years (PYs). The overall incidence rate of SAEs for etanercept was 4.14/100 PYs. Four patients developed uveitis, two had anxiety disorders, one had a serious zoster infection, and one developed TNF-α antagonist-induced lupus-like syndrome (TAILS). The overall incidence rate of SAEs for infliximab was 22.49/100 PYs. The most common SAEs were anaphylactoid reactions (n = 18), followed by infectious events (n = 9) and TAILS (n = 3). The overall incidence rate of SAEs for adalimumab was 4.71/100 PYs (two infectious SAEs). No malignancies or deaths were observed. A greater incidence rate of infectious SAEs was observed in IBD patients receiving infliximab compared to JIA patients receiving etanercept (8.11 vs 0.52 per 100 PYs).Conclusions: Anti-TNF-α therapy was generally well tolerated. SAEs leading to anti-TNF-α discontinuation were rare and non-fatal. Infliximab was associated with the highest incidence of SAEs. Infectious SAEs were more frequently observed in IBD patients treated with infliximab than in JIA patients receiving etanercept. [ABSTRACT FROM AUTHOR]

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteomyelitis (CNO), is a rare inflammatory disorder that primarily affects children. It is characterized by pain, local bone expansion, and radiological findings suggestive of osteomyelitis, usually at multiple sites. CRMO predominantly affects the metaphyses of long bones, but involvement of the clavicle or mandible are suggestive of the diagnosis. CRMO is a diagnosis of exclusion, and its pathogenesis remains unknown. Differential diagnosis includes infection, malignancies, benign bone tumors, metabolic disorders, and other autoinflammatory disorders. Biopsy of the bone lesion is not often required but could be necessary in unclear cases, especially for differentiation from bone neoplasia. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment. Alternative therapies have been used, including corticosteroids, methotrexate, bisphosphonates, and tumor necrosis factor (TNF)-α inhibitors. No guidelines have been established regarding diagnosis and treatment options. This manuscript gives an overview of the most recent findings on the pathogenesis of CRMO and clinical approaches for patients with the condition. [ABSTRACT FROM AUTHOR]

Kawasaki shock syndrome (KSS) is a rare manifestation of Kawasaki disease (KD) characterized by systolic hypotension or clinical signs of poor perfusion. The objectives of the study are to describe the main clinical presentation, echocardiographic, and laboratory findings, as well as the treatment options and clinical outcomes of KSS patients when compared with KD patients. This is a retrospective study. All children referred to two pediatric rheumatology units from January 1, 2012, to December 31, 2014, were enrolled. Patients were divided into patients with or without KSS. We compared the two groups according to the following variables: sex, age, type of KD (classic, with less frequent manifestations, or incomplete), clinical manifestations, cardiac involvement, laboratory findings, therapy administered, response to treatment, and outcome. Eighty-four patients with KD were enrolled. Of these, five (6 %) met the criteria for KSS. Patients with KSS had higher values of C-reactive protein ( p = 0.005), lower hemoglobin levels ( p = 0.003); more frequent hyponatremia ( p = 0.004), hypoalbuminemia ( p = 0.004), and coagulopathy ( p = 0.003); and increase in cardiac troponins ( p = 0.000). Among the KSS patients, three had a coronary artery involvement, but none developed a permanent aneurysm. Intravenous immunoglobulin resistance was more frequent in the KSS group, although not significantly so (3/5, 60 % vs. 23/79, 30 %, P = NS). None of the five cases was fatal, and all recovered without sequelae. KSS patients are more likely to have higher rates of cardiac involvement. However, most cardiovascular abnormalities resolved promptly with therapy. [ABSTRACT FROM AUTHOR]

Unlabelled: The aim of the study is to investigate if the presence of medical clowns during painful procedures in the emergency department (ED) affects children's anxiety and pain. Forty children (4-11 years) admitted to the ED with the need of painful procedures were prospectively enrolled. They were randomly assigned to the clown group, where children interacted with clowns or to the control group in which they were entertained by parents and ED nurses. The children's anxiety was assessed by the Children's Anxiety and Pain Scales; pain was evaluated with the Numerical Rating Scale and Wong-Backer Scale, according to the children's age. Staff and clown's opinions were evaluated by means of dedicated questionnaires. Children's anxiety levels in the clown group were significantly lower than those compared with the control group, while children's pain levels did not change between the two groups.Conclusion: The presence of clowns in the ED before and during painful procedures was effective in reducing children's anxiety.What Is Known: • Anxiety and fear caused by medical procedures exacerbate children's pain and may interfere with the procedure. • To reduce anxiety, fear, and pain and to facilitate patient's evaluation, different non-pharmacological approaches have been proposed and positive effects of laughter and humor have been reported. What is New: • The presence of clowns in the waiting room and in the ED during medical evaluation and painful procedures helps to reduce children's anxiety. [ABSTRACT FROM AUTHOR]

The article provides answers to a question about clinical diagnosis of a 50-day-old girl who was presented to a clinic due to recurrent vomiting, moderate failure to thrive and poor feeding and the importance of salt in growth and development.

Inflammatory bowel disease (IBD) is a cause of chronic intestinal inflammation in children. In a subset of patients affected by IBD, arthropathy may be the leading presenting sign. In the past years, remarkable advances in gastrointestinal endoscopy techniques have been achieved; recently, the development of capsule endoscopy (CE) provided a non-invasive method for the complete endoscopic evaluation, including small bowel assessment. We report three children suffering from IBD but presenting with articular complaints in whom CE was a useful tool for detecting gut inflammation. Patients were investigated with the wireless CE: PillCam SB2 (Given Imaging, Yoqneam, Israel) capsule, the second-generation capsule, was used in our paediatric patients. Three patients were initially evaluated for arthropathy. Enteropathic arthritis was suspected for gastrointestinal symptoms and/or persistence of inflammatory markers elevation. In one of these children, conventional endoscopy was refused by parents, while in the other two children, CE was proposed as first-line diagnostic tool. In all patients, CE revealed to be safe and provided information that led to diagnosis. Paediatric rheumatologists should consider CE as a valid, non-invasive tool, eventually first level diagnostic approach in order to evaluate the presence of IBD in children presenting with chronic articular complaints. [ABSTRACT FROM AUTHOR]

Objective:To determine the effect of morphine on duration of mechanical ventilation, apnoea and hypotension among full-term neonates who underwent thoracic or abdominal surgery in a level III neonatal intensive care unit.Method:Medical records of 82 infants were reviewed retrospectively and data including patient demographics, clinical diagnosis, type of surgery, postoperative opioid administration, duration of mechanical ventilation, hypotension, apnoea and pain scores (premature infant pain profile (PIPP) score) were collected.Result:Sixty-two neonates (76%) received morphine following surgery as a continuous intravenous infusion during the postoperative period. Linear regression analysis showed that morphine dosage and duration were significantly associated with the duration of mechanical ventilation. An increase in morphine infusion rate by 10 μg kg−1 h−1 was associated with an increase in the duration of mechanical ventilation by 24 h (P<0.0001) and an increase in morphine duration of 1 hour was associated with a longer duration of mechanical ventilation by 38 min (P<0.0001). Logistic regression analysis showed no association between morphine infusion rate or duration and hypotension. Apnoea was not associated with morphine dosage or duration of infusion in neonates receiving morphine following extubation. Score on the PIPP correlated significantly with morphine infusion rate across time (r=0.47, P<0.01).Conclusion:Postoperative morphine dose and duration may prolong the duration of mechanical ventilation but there are no significant dose-dependent effects on other parameters including apnoea or hypotension following extubation in term neonates. More research is needed to determine the safety profile of morphine for management of pain in non-ventilated neonates.Journal of Perinatology (2007) 27, 444–447; doi:10.1038/sj.jp.7211764 [ABSTRACT FROM AUTHOR]

BACKGROUND: Early diagnosis and treatment with gluten-free diet reduces mortality and the prevalence of associated disorders in celiac disease (CD). A simple “in the office” test of anti-transglutaminase antibodies might be of great help in first-line screening for CD. AIMS: We evaluated the sensitivity and specificity of two commercial kits based, respectively, on rapid detection of IgA-IgG anti-human-transglutaminase antibodies (anti-h-tTG) in serum and IgA anti-h-tTG antibody in one drop of whole blood. These assays were compared to a well-established enzyme-linked immunosorbent assay technique. METHODS: Serum samples were analyzed from 114 biopsy-confirmed celiacs, 120 healthy controls, 20 first-degree relatives of celiacs, and 75 diseased controls. The whole blood samples were analyzed from 51 biopsy-confirmed celiacs and 100 controls. RESULTS: The serum-based test was positive in all 114 celiacs (sensitivity 100%). Among the controls there were seven healthy blood donors, one first-degree relative, and three diseased controls who tested positive (specificity 94.9%). The blood drop-based assay testing IgA antibodies was positive in 46 of 51 (sensitivity 90.2%), and since three of the five patients testing negative had total IgA deficiency, the sensitivity value can be increased to 95.8%. All 100 controls tested negative (specificity 100%). CONCLUSIONS: The commercial kits described here produce high values of sensitivity and specificity, offering the general practitioner who suspects a possible case of CD the real possibility to look for anti-h-tTG antibodies in his own medical office during a standard visit at a satisfyingly low cost. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization predicts that by 2012, depression will be the number one disease in the world. Thus, many women who become pregnant will require treatment with antidepressants. We are aware that women and their health care providers remain hesitant to prescribe and take these drugs during pregnancy, despite evidence of the relative safety. Objectives: 1) To determine perception of risk of antidepressant drugs by pregnant women with depression, 2) to determine the efficacy of evidence-based counseling, and 3) to identify determinants that influence women in their decision making regarding the continuation/discontinuation of antidepressants during pregnancy. Methods: Women who called The Motherisk Program requesting information about the safety of an antidepressant during pregnancy were compared with two other groups: 1) Women who called about antibiotic use (i.e., non-teratogenic drugs used short-term) and 2) women who called about gastric medications (i.e., non-teratogenic drugs used long-term). Their perception of risk was measured before and after evidenced-based information was given and determinants of decision making was also evaluated. Results: We recruited 100 women taking antidepressants during pregnancy and 100 in each comparison group. Despite receiving evidence-based reassuring information, 15% of antidepressant users, compared to 4% using gastric drugs and 1% using antibiotics, chose to discontinue their medication. The main determinants of decision making were based on: information received prior to calling Motherisk, family and friends advice, the internet, sequence of advice given and if a women was undecided at the time of call. Conclusions: Women continue to fear taking antidepressants during pregnancy, more so than non psychiatric drugs, however, evidence based counseling can lower this fear, although not totally. Deciding whether to continue to take a medication or not during pregnancy, is a complex decision for women and their healthcare providers to make. [ABSTRACT FROM AUTHOR]

Iatrogenic pain is commonplace in newborn infants yet we know very little about its long-term effects. This article reviews the evidence for and against the suggestion that painful procedures experienced in the perinatal period influence subsequent pain responses in infancy or in childhood. The evidence suggests that early experiences with pain are associated with altered pain responses later in infancy. The direction of the altered response depends, in part, on the infant's developmental stage (full-term vs preterm), and his or her cumulative experience with pain. Preterm infants that are hospitalized as neonates and subjected to painful procedures appear to have a dampened response to painful procedures later in infancy. Full-term neonates exposed to extreme stress during delivery, or to a surgical procedure, react to later noxious procedures with heightened behavioral responsiveness. Studies in which analgesic agents (local anesthetics or opioids) have been administered prior to noxious procedures demonstrate less procedural pain and a reduction in the magnitude of long-term changes in pain behaviors. The precise determinants of these changes, their extent, and their permanence are not known but they appear to involve noxious stimulus-induced peripheral and central sensitization, as well as classical conditioning. [ABSTRACT FROM AUTHOR]

A topical formulation of the ester-type local anesthetic amethocaine (tetracaine) [Ametop™] is currently available for reducing pain from cutaneous procedures such as venipuncture. The Ametop™ preparation contains 40mg of amethocaine base (4% w/w) and produces anesthesia within 30–45 minutes of application; duration of action ranges from 4 to 6 hours. Clinical studies have demonstrated the superiority of the 4% amethocaine preparation over placebo in pediatric populations for indications such as intravenous cannulation, vaccination, and venipuncture. Amethocaine has been shown to produce anesthesia comparable to that of 5% lidocaine-prilocaine for procedures such as venipuncture and accessing centrally placed devices; in general, anesthesia was achieved more rapidly with amethocaine than lidocaine-prilocaine. In the neonatal population amethocaine was found to be ineffective at reducing the pain of heel prick and peripherally inserted central catheters. Depending on the type of procedure, amethocaine application times between 30 and 60 minutes have produced clinically acceptable anesthesia; application times <30 minutes have not been associated with reliable anesthesia. The 4% amethocaine preparation is well tolerated; the most commonly reported local skin reaction is transient local erythema while local edema and itching have been reported more rarely. There have been no accounts of systemic toxicity with topical use of the preparation. Several cases of sensitization have been described in adults upon repeated exposure to topical amethocaine. In summary, the novel preparation of 4% amethocaine gel has been shown to be clinically effective for managing pain associated with minor cutaneous procedures while maintaining a good tolerability profile. Amethocaine has also demonstrated similar efficacy to lidocaine-prilocaine when appropriate application times are used; the more rapid onset of action and extended duration of action of amethocaine may make it more useful than lidocaine-prilocaine in busy clinical settings. [ABSTRACT FROM AUTHOR]

Depression during pregnancy is common, affecting an estimated 20% of women. However, conflicting data exist concerning the outcomes of this disorder. Thus, we reviewed studies that presented evidence for the use of antidepressants and those that examined untreated depression during the gestational period, in terms of clinical and epidemiological aspects. Observational studies have provided reassuring evidence of the safety of antidepressant use during pregnancy. However, due to the reluctance of healthcare providers to prescribe and patients to take medication during the obstetric period, approximately three-quarters of those diagnosed with depression remain untreated. Furthermore, healthcare providers apparently do not recognise the disorder in up to 50% of pregnant women who experience depression. Increased antidepressant dosing during pregnancy may be required to maintain euthymia; however, guidelines for effective dosing levels are absent. Consequently, many patients remain inadequately treated. Substantial maternal and fetal morbidity including substance abuse, functional impairment, increased risk of postnatal depression, and poor pregnancy outcomes have resulted from untreated depression. The consequences of those outcomes are likely to be associated with substantial clinical, social and economic burdens. An incidence-based assessment of the consequences of prenatal depression would be useful in order to: (i) establish the impact on the quality of life of these patients and their families; (ii) assess the associated economic burden on individual families and the healthcare system; and (iii) to provide epidemiological data to enable the provision of suitable management strategies for these patients. [ABSTRACT FROM AUTHOR]

Children with cancer often cite procedural pain as the most distressing part of their disease. Pharmacologic interventions that decrease the pain and anxiety of invasive procedures have been shown to be beneficial, particularly when these interventions are a routine part of every procedure. However, despite the known benefits of analgesia and sedation, guidelines for the management of pediatric pain and stress during oncology procedures have not been established. Thus, children may not be receiving optimal pain relief. Various drugs have been investigated in pediatric populations to provide local anesthesia, systemic analgesia, conscious sedation, deep sedation, and general anesthesia. These agents include lidocaine-prilocaine, amethocaine, lidocaine, methohexital, propofol, midazolam, meperidine, nitrous oxide, fentanyl, ketamine, and diazepam. Local anesthesia with lidocaine-prilocaine and amethocaine decreases pain from accessing centrally placed venous devices (ports) and venipuncture; however, neither, is sufficient as a sole intervention for bone marrow aspirations (BMA), bone marrow biopsies (BMB) or lumbar punctures (LP). Transient local skin reactions are common with the use of lidocaine-prilocaine and amethocaine. Deep sedation or general anesthesia can be achieved with a variety of agents and are ideal interventions if pain and movement are to be prevented during more invasive procedures such as LP, BMA, and BMB. Titration of doses and monitoring to detect early adverse effects increase the safety of these interventions. Systemic analgesia with fentanyl or nitrous oxide in combination with local anesthesia may be appropriate for older children more comfortable and familiar with these procedures; conscious sedation may also be an option for these children, but deep sedation and general anesthesia should always be made available if it is the child's preferred method of pain relief. [ABSTRACT FROM AUTHOR]

Circumcision is the most common surgical procedure performed in the neonatal period in North America. If untreated, the pain of circumcision causes both short and long term changes in infant behaviours. The most widely studied pharmacological intervention for pain management during circumcision is dorsal penile nerve block (DPNB) by injected lidocaine (lignocaine). Randomised controlled trials have demonstrated its efficacy; infants premedicated with lidocaine have significantly smaller changes in physiological and pain-related behaviours compared with infants who are not given analgesics. A meta-analysis of injection-related adverse effects (bruising/haematoma) yielded a risk of 6.7% (95% confidence interval, 0.5 to 12.9%). Systemic toxicity from injected local anaesthesia has not been reported. Less effective modalities include topical anaesthesia with lidocaine-prilocaine cream [Eutectic Mixture of Local Anaesthetics (EMLA)], lidocaine cream and oral administration of sucrose. The good tolerability of lidocaine-prilocaine cream has been demonstrated by a lack of clinically significant methaemoglobinaemia when used appropriately. Nonpharmacological interventions (pacifier, specially designed restraint chair) reduce distress during the procedure, and paracetamol (acetaminophen) may provide postoperative analgesia. No single agent has been demonstrated to ameliorate pain for all infants undergoing circumcision. A multimodal approach of pharmacotherapy is currently recommended. Studies evaluating the efficacy of combined analgesia have demonstrated significant benefits for combinations of 2 or more forms of treatment (such as DPNB and sucrose-dipped pacifier) compared with single interventions. The instrument used to perform the circumcision is also important. The Mogen clamp has been shown to be associated with a shorter procedure time and less pain compared with the Gomco clamp. If circumcision is to be performed on infants, it is, therefore, recommended that combined analgesia and the Mogen clamp technique are used, and nonpharmacological stress reducing interventions such as pacifiers and comfortable restraining chairs should also be employed. [ABSTRACT FROM AUTHOR]

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The article asks the clinical diagnosis of a 50-day-old girl who was presented to a clinic due to recurrent vomiting, moderate failure to thrive and poor feeding and the importance of salt in growth and development.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare acquired disorder associated with several different conditions but mostly with systemic lupus erythematosus (SLE). LAHPS probably results from the presence of anti-Factor II antibodies, which usually counterbalance the prothrombotic effect of the lupus anticoagulant (LAC). In fact, Factor II deficiency in SLE is invariably associated with the presence of LAC. No consensus exists for the treatment of LAHPS. Corticosteroids, with or without the addition of vitamin K or blood products, have been a successful first-line treatment. Immunoglobulin (IVIG) treatment has been shown to be effective in the setting of acute bleeding. However, in some patients, conservative treatment is not enough to control bleeding, and the addition of immunosuppressive therapy, usually azathioprine, is needed. In our patients, Factor II deficiency reappeared after tapering steroids. Both children achieved normal Factor II levels with cyclophosphamide. This effect was long-lasting, a phenomenon that has not been documented in children prior to this report. [ABSTRACT FROM AUTHOR]

A commentary about nutritional and immunosuppressive therapy. The authors describes a case of a 1-month-old male suffering from severe eczema. They explains the immunodusregulation, polyendocrinopathy, enteropathy, X-linked disorder. They mentions the therapeutic use of hematopoietic stem cell transplantation (HSCT). They believe an early and substantial control of inflammation with good nutrition is fundamental as a bridge to transplant.

A letter to the editor is presented in response to the article "Sedation for Intra-Articular Corticosteroid Injections in Juvenile Idiopathic Arthritis: The Views of Patients and Their Parents" by authors including R. Casado, J. Lumbreras and R. Merino, in a 2013 issue of the journal.

The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.Methods: The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.Results: The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.Conclusion: The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.Graphical abstract: The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management. [ABSTRACT FROM AUTHOR]

Setting: Task sharing can fill health workforce gaps, improve access to care, and enhance health equity by redistributing health services to providers with less training. We report learnings from a demonstration project designed to assess whether lay student vaccinators can support community immunizations., Intervention: Between July 2022 and February 2023, 27 undergraduate and graduate students were recruited from the University of Toronto Emergency First Responders organization and operated 11 immunization clinics under professional supervision. Medical directives, supported with online and in-person training, enabled lay providers to administer and document vaccinations when supervised by nurses, physicians, or pharmacists. Participants were invited to complete a voluntary online survey to comment on their experience., Outcomes: Lay providers administered 293 influenza and COVID-19 vaccines without adverse events. A total of 141 participants (122 patients, 17 lay vaccinators, 1 nurse, and 1 physician) responded to our survey. More than 80% of patients strongly agreed to feeling safe and comfortable with lay providers administering vaccines under supervision, had no concerns with lay vaccinators, and would attend another lay vaccinator clinic. Content and thematic analysis of open-text responses revealed predominantly positive experiences, with themes about excellent vaccinators, organized and efficient clinics, and the importance of training, communication, and access to regulated professionals. The responding providers expressed comfort working in collaborative immunization teams., Implications: Lay student providers can deliver vaccines safely under a medical directive while potentially improving patient experiences. Rather than redeploying scarce professionals, task sharing strategies could position trained lay vaccinators to support immunizations, improve access, and foster community engagement., (© 2024. The Author(s).)