Sonographic Assessment of Renal Growth in Patients with Beckwith-Wiedemann Syndrome: The Beckwith-Wiedemann Syndrome Renal Nomogram

BACKGROUND: Beckwith-Wiedemann syndrome is a disorder of somatic overgrowth. Evidence of kidney overgrowth is a diagnostic criterion that may be used to help identify those patients who are at the greatest risk of developing Wilms tumors. In such subjects, kidney size is typically larger than that of age-matched normal controls. OBJECTIVE: The purpose of our study was to generate a nomogram that could be used to measure renal dimensions in children with Beckwith-Wiedemann syndrome in a clinical setting. MATERIALS & METHODS: All of the Beckwith-Wiedemann syndrome patients followed at our institution from 1996 to 2004 were eligible for inclusion in our study. Renal length was measured with a curvilinear transducer and with the patient supine. Renal lengths were measured for both kidneys using real-time ultrasound for all patients. Their data were compared with those of age-matched controls reported in the 1984 study by Rosenbaum et al. RESULTS: Ninety-six children with Beckwith-Wiedemann syndrome were followed from 1996 to 2004. Forty-three of these patients met our criteria for inclusion in the study: 28 girls (65%) and 15 boys (35%). We identified a linear relationship between kidney length and patient age. No statistically significant differences in renal length were found between boys and girls (p=0.2153) or between the kidneys on either side of the body (p=0.9613). CONCLUSION: Our study provides a practical, simple renal growth chart that offers a reasonable, sensitive method for evaluating kidney size in children with Beckwith-Wiedemann syndrome

Prospective evaluation of the impact of sonography on the management and surgical intervention of neonates with necrotizing enterocolitis

Background/aimEstablished indications for surgery in necrotizing enterocolitis (NEC) are pneumoperitoneum and failure to improve or clinical deterioration with medical treatment alone. It has been proposed that infants with intestinal necrosis may benefit from surgery in the absence of one of these indications yet the diagnosis of definitive intestinal necrosis is challenging. Recent data suggest that abdominal ultrasound (US) examination focused on the gastrointestinal tract and the peritoneal cavity may be of utility in this regard. The aim of this study was to evaluate the ability of abdominal US to detect intestinal necrosis in infants with radiographically confirmed NEC.MethodsTwenty-six consecutive infants with Bell stage II or III NEC were prospectively included in the study between September 2013 and July 2014. Infants with a pre-existing indication for surgery were excluded. At least one abdominal US examination was performed in each patient using a standardized previously described method. Surgery was performed at the discretion of the attending surgeon based on clinical and imaging findings. Clinical, radiographic, US, and intra-operative data were recorded to allow comparison between US findings, surgical findings and outcome.ResultsUS demonstrated signs of intestinal necrosis in 5 of the 26 patients. All of these five had laparotomy. Intestinal necrosis requiring resection was confirmed in four and the other was found to have NEC but no necrosis was identified. In 21 patients US did not suggest intestinal necrosis. Of these, only one had surgery in whom NEC but no necrosis was identified. The remaining 20 responded to medical treatment for NEC and were assumed not to have had intestinal necrosis based on improvement without surgical intervention. The sensitivity, specificity, positive predictive value and negative predictive values of US for the detection of bowel necrosis were calculated as 100, 95.4, 80.0, and 100 %, respectively.ConclusionOur prospective findings suggest that abdominal US can identify those infants with NEC who may need surgery by detecting bowel necrosis (prior to the development of perforation or medical deterioration) with high sensitivity and specificity. Early surgical intervention in the clinical pathway of NEC may lead to improved outcomes

Mild Idiopathic Infantile Hypercalcemia—Part 1: Biochemical and Genetic Findings

Context: Idiopathic infantile hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25 dihydroxyvitamin D (1,25(OH)2D) and low parathyroid hormone (PTH) levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms. Objective: This work aims to characterize the genetic associations and biochemical profile of mild IIH. Methods: This is a cross-sectional study including children between age 6 months and 17 years with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. Twenty children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analyzed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands. Results: The median age was 16 months. Median serum levels of calcium (2.69 mmol/L), urinary calcium:creatinine ratio (0.72 mmol/mmol), and 1,25(OH)2D (209 pmol/L) were elevated, whereas intact PTH was low normal (22.5 ng/L). Mean 1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven individuals (55%) had renal calcification. Genetic variants were common (65%), with the majority being heterozygous variants in SLC34A1 and SLC34A3, while a minority showed variants of CYP24A1 and other genes related to hypercalciuria. Conclusion: The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants. Keywords: CYP24A1; genetic; hypercalcemia; nephrocalcinosis; nephrolithiasis; vitamin

Author Correction: Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial (Nature Medicine, (2021), 27, 11, (2012-2024), 10.1038/s41591-021-01488-2)

In the version of this Article initially published, there was an omission in the member list for the CONCOR-1 Study Group. Valérie Arsenault (Héma-Québec, Montreal, Quebec, Canada) has now been included in the CONCOR-1 Study Group in the online version of the article

Prospective evaluation of the impact of sonography on the management and surgical intervention of neonates with necrotizing enterocolitis

Background/aimEstablished indications for surgery in necrotizing enterocolitis (NEC) are pneumoperitoneum and failure to improve or clinical deterioration with medical treatment alone. It has been proposed that infants with intestinal necrosis may benefit from surgery in the absence of one of these indications yet the diagnosis of definitive intestinal necrosis is challenging. Recent data suggest that abdominal ultrasound (US) examination focused on the gastrointestinal tract and the peritoneal cavity may be of utility in this regard. The aim of this study was to evaluate the ability of abdominal US to detect intestinal necrosis in infants with radiographically confirmed NEC.MethodsTwenty-six consecutive infants with Bell stage II or III NEC were prospectively included in the study between September 2013 and July 2014. Infants with a pre-existing indication for surgery were excluded. At least one abdominal US examination was performed in each patient using a standardized previously described method. Surgery was performed at the discretion of the attending surgeon based on clinical and imaging findings. Clinical, radiographic, US, and intra-operative data were recorded to allow comparison between US findings, surgical findings and outcome.ResultsUS demonstrated signs of intestinal necrosis in 5 of the 26 patients. All of these five had laparotomy. Intestinal necrosis requiring resection was confirmed in four and the other was found to have NEC but no necrosis was identified. In 21 patients US did not suggest intestinal necrosis. Of these, only one had surgery in whom NEC but no necrosis was identified. The remaining 20 responded to medical treatment for NEC and were assumed not to have had intestinal necrosis based on improvement without surgical intervention. The sensitivity, specificity, positive predictive value and negative predictive values of US for the detection of bowel necrosis were calculated as 100, 95.4, 80.0, and 100 %, respectively.ConclusionOur prospective findings suggest that abdominal US can identify those infants with NEC who may need surgery by detecting bowel necrosis (prior to the development of perforation or medical deterioration) with high sensitivity and specificity. Early surgical intervention in the clinical pathway of NEC may lead to improved outcomes

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

From short-term store to multicomponent working memory: The role of the modal model

The term “modal model” reflects the importance of Atkinson and Shiffrin’s paper in capturing the major developments in the cognitive psychology of memory that were achieved over the previous decade, providing an integrated framework that has formed the basis for many future developments. The fact that it is still the most cited model from that period some 50 years later has, we suggest, implications for the model itself and for theorising in psychology more generally. We review the essential foundations of the model before going on to discuss briefly the way in which one of its components, the short-term store, had influenced our own concept of a multicomponent working memory. This is followed by a discussion of recent claims that the concept of a short-term store be replaced by an interpretation in terms of activated long-term memory. We present several reasons to question these proposals. We conclude with a brief discussion of the implications of the longevity of the modal model for styles of theorising in cognitive psychology

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Neurosonography: In Pursuit Of An Optimized Examination

This article emphasizes technical factors that are helpful for optimizing sonographic examinations of the brain in preterm and term neonates. It also reviews existing data regarding the accuracy of neurosonographic examinations relative to MR. Many neurosonographic signs are subtle and can be easily overlooked, which could lead to delayed diagnosis or misdiagnosis. Therefore meticulous attention to sonographic technique is required to maximize the diagnostic utility of this modality. Although MR images of the brain often depict abnormalities more clearly than sonography, neurosonography continues to be an exceptionally valuable tool for evaluation of the neonatal brain, even in full-term neonates. Furthermore, its accuracy is greater, even in the latter age group, than many older publications suggest. Prospective studies using state-of-the-art equipment comparing findings on sonography and MR are needed to better understand how the accuracy of these modalities changes with refinements in equipment and to help us better understand the role of neurosonography relative to MR