Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.

BACKGROUND: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). METHODS: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. RESULTS: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). CONCLUSION: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.     

Differences in receipt of recommended eye examinations by comorbidity status and healthcare utilization among nonelderly adults with diabetes

BackgroundTo evaluate the effect of diabetes comorbidities by baseline healthcare utilization on receipt of recommended eye examinations.MethodsRetrospective analysis of 310 691 nonelderly adults with type 2 diabetes in the IBM MarketScan Commercial Database from 2016 to 2019. Patients were grouped based on diabetes‐concordant (related) or ‐discordant (unrelated) comorbidities. Logistic regression was used to estimate the prevalence ratio (PR) for eye examinations by comorbidity status, healthcare utilization, and an interaction between comorbidities and utilization, controlling for age, sex, region, and major eye disease.ResultsPrevalence of biennial eye examinations varied by the four comorbidity groups: 43.5% (diabetes only), 52.7% (concordant + discordant comorbidities), 48.0% (concordant comorbidities only), and 45.3% (discordant comorbidities only). In the lowest healthcare utilization tertile, the concordant‐only and concordant + discordant groups had lower prevalence of examinations compared to diabetes only (PR 0.95 [95% CI 0.92–0.98] and PR 0.91 [95% CI 0.88–0.95], respectively). In the medium utilization tertile, the discordant‐only and concordant + discordant groups had lower prevalence of examinations (PR 0.89 [0.83–0.95] and PR 0.94 [0.90–0.98], respectively). In the highest utilization tertile, the concordant‐only and concordant + discordant groups had higher prevalence of examinations.ConclusionsAmong patients with low healthcare utilization, having comorbid conditions is associated with lower prevalence of eye examinations. Among those with medium healthcare utilization, patients with diabetes‐discordant comorbidities are particularly vulnerable. This study highlights populations of diabetes patients who would benefit from increased assistance in receiving vision‐preserving eye examinations.     

Multispecies Outbreak of Nocardia Infections in Heart Transplant Recipients and Association with Climate Conditions,Australia

A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia, during 2018–2019. We performed a retrospective review of 23 HTR and LTR who had Nocardia spp. infections during June 2015–March 2021, compared risk factors for Nocardia infection, and evaluated climate conditions before, during, and after the period of the 2018–2019 outbreak. Compared with LTR, HTR had a shorter median time from transplant to Nocardia diagnosis, higher prevalence of diabetes, greater use of induction immunosuppression with basiliximab, and increased rates of cellular rejection before Nocardia diagnosis. During the outbreak, Sydney experienced the lowest monthly precipitation and driest surface levels compared with time periods directly before and after the outbreak. Increased immunosuppression of HTR compared with LTR, coupled with extreme weather conditions during 2018–2019, may explain this outbreak of Nocardia infections in HTR.     

The safety and tolerability of levodopa eye drops for the treatment of ocular disorders: A randomized first‐in‐human study

Myopia is the leading cause of low vision worldwide and can lead to significant pathological complications. Therefore, to improve patient outcomes, the field continues to develop novel interventions for this visual disorder. Accordingly, this first‐in‐human study reports on the safety profile of a novel dopamine‐based ophthalmic treatment for myopia, levodopa/carbidopa eye drops. This phase I, first‐in‐human, monocenter, placebo‐controlled, double‐blind, paired‐eye, multidose, randomized clinical trial was undertaken in healthy adult males aged 18–30 years (mean age 24.9 ± 2.7) at the University of Canberra Eye Clinic, Australia. Participants were randomly assigned to receive either a low (1.4 levodopa:0.34 carbidopa [μmoles/day], n = 14) or standard dose (2.7 levodopa:0.68 carbidopa [μmoles/day], n = 15) of levodopa/carbidopa eye drops in one eye and placebo in the fellow eye once daily for 4 weeks (28 days). Over this 4‐week trial, and after a 4‐month follow‐up visit, levodopa/carbidopa treatment had no significant effect on ocular tolerability and anterior surface integrity, visual function, ocular health, refraction/ocular biometry, and did not induce any non‐ocular adverse events. These results indicate that topical levodopa/carbidopa is safe and tolerable to the eye, paving the way for future studies on the efficacy of this novel ophthalmic formulation in the treatment of human myopia. The findings of this study have implications not only for the treatment of myopia, but in a number of other visual disorders (i.e., amblyopia, diabetic retinopathy, and age‐related macular degeneration) in which levodopa has been identified as a potential clinical intervention.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Preclinical data indicate that levodopa/carbidopa eye drops can safely inhibit the development of experimental myopia in animal models.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study investigated whether levodopa/carbidopa eye drops are safe and tolerable to the human eye.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

In this phase I, first‐in‐human, monocenter, randomized, double‐blind, placebo‐controlled, multidose trial, levodopa/carbidopa eye drops were found to be safe and well tolerated in healthy adult males over a 4‐week period. Furthermore, no non‐ocular adverse events were reported.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

As topical administration of levodopa/carbidopa eye drops is well tolerated in humans, the efficacy of this novel ophthalmic treatment at inhibiting the development of myopia in patient populations can now be assessed. If found to be effective, this will provide a powerful new method for inhibiting the onset and development of the leading cause of low vision worldwide. This topical formulation may also provide a valuable tool in the treatment of other visual disorders shown to be responsive to levodopa therapy (i.e., amblyopia, diabetic retinopathy, and age‐related macular degeneration).     

Adolescent Knowledge,Attitudes and Practices of Healthy Eating: Findings of Qualitative Interviews among Hong Kong Families

To tackle unhealthy eating among adolescents, it is crucial to understand the dietary knowledge, attitudes, and practices (KAP) on which adolescent eating habits are based. This qualitative study identifies the gaps in KAP by exploring what Chinese adolescents know, perceive, and practice regarding healthy eating to better inform targeted interventions for this important health problem. Parent–adolescent dyads were purposively sampled based on, for example, the dietary intake, age, and gender of the adolescent and household income, and each completed a 30 to 60 min interview. Twelve themes were synthesized: knowledge: (1) dietary recommendations, (2) health outcomes of healthy eating, (3) nutrition content in food, and (4) access to healthy meals; attitudes: (5) outcome expectation for healthy eating, (6) food preferences, and (7) self-efficacy regarding adopting healthy eating; and practices: (8) going grocery shopping for healthy food, (9) eating home-prepared meals. (10) eating out in restaurants or consuming takeaway food, (11) fruit and vegetable consumption, and (12) snacking, perceived unhealthy eating to be low risk, made unhealthy choices regarding snacking and eating out, and had insufficient fruit and vegetable intake. Programs should emphasize the positive short-term health outcomes of healthy eating and empower adolescents to acquire food preparation skills to sustain healthy eating habits.     

Cec and You Shall Find: Cecal Perforation in a Patient with COVID-19

Digestive Diseases and Sciences -