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Type 2 diabetes mellitus (T2DM) is a serious metabolic disorder impacting millions globally. A full understanding of the mechanisms implicated in diabetes genesis remain elusive, but exposure to environmental endocrine disruptors has emerged as a potential association of diabetes. Cadmium (Cd) has been investigated for its diabetogenic potential, yet the reported evidence is inconsistent. This overview of systematic reviews reports the association between Cd exposure and T2DM risk globally. Systematic reviews were identified by searching Medline, Embase, Web of Science, GEOBASE, BIOSIS Previews, and Cochrane Database of Systematic Reviews. Two reviewers independently completed screening, data abstraction, risk of bias evaluation, and confidence in level of evidence assessments using GRADE. The primary outcome involved estimating the association between Cd exposure, defined through measurement of Cd in urine (U-Cd) or blood (B-Cd), and T2DM. The quantitative data synthesis was conducted at the primary study level. While there was a trend for U-Cd (OR = 1.30, 95% CI 1.00–1.68) association with diabetes risk, B-Cd (OR = 1.37, 95% CI 1.02–1.83) levels were associated with diabetes risk. The risk of bias was high in 4 out of 5 included systematic reviews, and GRADE rating was very low. In conclusion, while current evidence suggests a link between cadmium levels and T2DM in the general population, these results should be interpreted with caution due to the methodological limitations of current studies, and additional studies should be undertaken to clarify this question. Systematic Review Registration: PROSPERO CRD42019125956.

Primary adrenal insufficiency is a potentially life-threatening condition that provides a diagnostic challenge because many patients have months to years of insidious symptomatology. Adrenal crisis is the extreme acute manifestation of primary adrenal insufficiency, presenting with any, or all, of severe weakness, altered mental status, hypotension, and rarely cardiorespiratory arrest. Primary adrenal insufficiency should be considered in patients with clinical features of glucocorticoid and/or mineralocorticoid deficiency. These features however, such as hyperpigmentation, may be subtle, and so a degree of suspicion is needed to make the diagnosis. In extremis, children may present with fluid and catecholamine refractory shock. The management of an adrenal crisis includes prompt delivery of stress-dose corticosteroids together with aggressive organ support and correction of metabolic and electrolyte disturbances. We report the case of a previously healthy 10-year-old child that presented to a community emergency department in pulseless arrest, in whom adrenal crisis was suspected as well as treated early, and was subsequently successfully resuscitated.

ABSTRACT:Introduction:Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. Methods:A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. Results:Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. Conclusion:Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

IMPORTANCE: Hypertension and albuminuria are markers of diabetes-related nephropathy and important factors associated with kidney outcomes in pediatric type 2 diabetes. However, their prevalence in these patients is unknown. OBJECTIVE: To measure the prevalence of hypertension and albuminuria in pediatric patients with type 2 diabetes and to evaluate the association of sex and race/ethnicity with these conditions. DATA SOURCES: MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, the gray literature, and references of the screened articles were searched for human studies from date of database inception to February 20, 2020. STUDY SELECTION: Observational studies with at least 10 participants reporting the prevalence of hypertension and/or albuminuria in pediatric patients with type 2 diabetes were included. Three teams of 2 independent reviewers screened 7614 papers, of which 60 fulfilled the eligibility criteria. DATA EXTRACTION AND SYNTHESIS: Three teams of 2 independent reviewers performed data extraction, risk of bias analysis, and level of evidence analyses. The meta-analysis was conducted using a random-effects model and followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. MAIN OUTCOMES AND MEASURES: The primary outcomes included the pooled prevalence rates (percentages with 95% CI) for hypertension and albuminuria. The secondary outcomes assessed pooled prevalence rates by sex and racial/ethnic group. RESULTS: Sixty studies were included in the systematic review. Diabetes duration varied from inclusion at diagnosis to 15.0 years after diagnosis, and the reported mean age at diagnosis ranged from 6.5 to 21.0 years. Hypertension prevalence among 3463 participants was 25.33% (95% CI, 19.57%-31.53%). Male participants had higher hypertension risk than female participants (odds ratio [OR], 1.42 [95% CI, 1.10-1.83]), with Pacific Islander and Indigenous youth having the highest prevalence of all racial/ethnic groups (Pacific Islander youth: 26.71% [95% CI, 14.54%-40.72%]; Indigenous youth: 26.48% [95% CI, 17.34%-36.74%]; White youth: 20.95% [95% CI, 12.65%-30.57%]; African American youth: 19.04% [95% CI, 12.01%-27.23%]; Hispanic/Latino youth: 15.11% [95% CI, 6.56%-26.30%]; Asian youth: 18.37% [95% CI, 9.49%-29.23%]). Albuminuria prevalence among 2250 participants was 22.17% (95% CI, 17.34%-27.38%). Pacific Islander youth, Indigenous youth, and Asian youth had higher prevalence rates than White youth (Pacific Islander youth: 31.84% [95% CI, 11.90%-55.47%]; Indigenous youth: 24.27% [95% CI, 14.39%-35.73%]; Asian youth: 23.00% [95% CI, 18.85%-27.41%]; White youth: 12.59% [95% CI, 7.75%-18.33%]), with no sex differences (OR for male vs female participants, 0.68 [95% CI, 0.46-1.01]). Heterogeneity was high among studies, with a low to moderate risk of bias. CONCLUSIONS AND RELEVANCE: In this study, markers of diabetes-related nephropathy were commonly detected in pediatric patients with type 2 diabetes, with a disproportionate burden noted among Pacific Islander and Indigenous youth. Personalized management strategies to target kidney outcomes are urgently needed in pediatric patients with type 2 diabetes to alleviate the burden of this condition on the kidneys.