Optimizing care of patients undergoing cardiac surgery using a digital platform and a multidisciplinary team approach.

OBJECTIVE: Restrictions to care access during the pandemic along with the increasing complexity of patients awaiting cardiac surgery provides unique challenges for care delivery. The University of Ottawa Heart Institute has developed a novel multidisciplinary digital platform, the Prehab Automated Follow-Up (AFU) Program, which delivers patient/caregiver teaching regarding risk factor mitigation, tracks patient symptoms, and screens for optimization using best practice guidelines. This study was conducted to quantify patient outcomes following initiation of the AFU Program. METHODS: Patients awaiting elective cardiac surgery are enrolled and screened via automated telephone conversation, according to best practice guidelines, and a Short Form-12 preoperative assessment. Following this screen, patients are referred for an in-person assessment by an appropriate multidisciplinary team member; namely, a diabetes specialist, physiotherapist, dietitian, smoking cessation counselor, social worker, vocational counselor, and/or psychologist. RESULTS: Since initiation in February 2021, the AFU Program has enrolled more than 1237 patients with 508 multidisciplinary team referrals prompted by the AFU screening platform. Before program initiation, there were no multidisciplinary team referrals for preoperative optimization. Compared with patients treated between February 2020 and February 2021, there was a 2.5% decrease in hospital readmission rate within 30 days of surgery, a 0.6-day shorter hospital stay, and a 2.5% decrease in surgical site infection. CONCLUSIONS: Our cardiac surgery AFU Program reduced adverse health outcomes for patients by identifying and optimizing risk factors that increased quality of patient care. The AFU Program provides patient/caregiver engagement through educational support and multidisciplinary team counseling.

De novo deletion of TBL1XR1 in a child with non-specific developmental delay supports its implication in intellectual disability.

We report on a 6-year-old child with a de novo 1.6 Mb deletion in the 3q26.31q26.32 region identified by SNP array, involving only one relevant gene: TBL1XR1. The girl shows non-specific, mild to moderate intellectual deficiency but no autistic behavior. Point mutations in TBL1XR1 have recently been implicated in three patients with intellectual disability (ID) and autistic features. Our report supports that haploinsufficiency for TBL1XR1 could be implicated in non-ASD autosomal dominant ID.

Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.

Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) - detected exclusively in patients with ADHD - for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.

Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.

Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls). Concerning GPR50, we detected a significant association between ASD and two variations, Delta502-505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients.