Twelve-Month Follow-up from a Randomized Controlled Trial of Simplified Meal Announcement Versus Precise Carbohydrate Counting in Adolescents with Type 1 Diabetes Using the MiniMed™ 780G Advanced Hybrid Closed-Loop System.

Background and Aims: Carbohydrate counting is a well-established tool for self-management of type 1 diabetes (T1D) and can improve glycemic control and potentially reduce long-term complication risk. However, it can also be burdensome, error-prone, and complicated for the patient. A randomized controlled trial was conducted to investigate glycemic control with carbohydrate counting ("flex") versus simplified meal announcement ("fix") in adolescents with T1D using the MiniMed™ 780G system. The present study reports follow-up data to 12 months. Methods: Adolescents with T1D were randomly assigned 1:1 to use the MiniMed™ 780G system alongside the flex versus fix approaches. Participants were followed for 12 months with outcomes recorded at 3, 6, 9, and 12 months. The primary endpoint was the difference in time-in-range (TIR), and secondary endpoints included glycated hemoglobin (HbA1c) and other glucose and insulin metrics. Results: At 12 months, TIR (proportion of time with sensor glucose 70-180 mg/dL) was significantly lower in the fix versus flex group (72.9% vs. 80.1%, respectively; P = 0.001). There was no significant difference in HbA1c between the fix (6.8% ± 0.5%) and flex groups (6.5% ± 0.5%) at 12 months (P = 0.092), and mean HbA1c was below 7% at all time points in both arms. Conclusions: Glycemic control with simplified meal announcement was maintained over 12 months. On average, the international consensus targets were met in both arms for all time points. The simplified approach represents a viable alternative to carbohydrate counting, particularly in people who find the latter burdensome; however, carbohydrate counting resulted in superior TIR. This study is registered with ClinicalTrials.gov, number NCT05069727.

FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.

FANCD2 protein, a key coordinator and effector of the interstrand crosslink repair pathway, is also required to prevent excessive nascent strand degradation at hydroxyurea-induced stalled forks. The RAD51 recombinase has also been implicated in regulation of resection at stalled replication forks. The mechanistic contributions of these proteins to fork protection are not well understood. Here, we used purified FANCD2 and RAD51 to study how each protein regulates DNA resection at stalled forks. We characterized three mechanisms of FANCD2-mediated fork protection: (1) The N-terminal domain of FANCD2 inhibits the essential DNA2 nuclease activity by directly binding to DNA2 accounting for over-resection in FANCD2 defective cells. (2) Independent of dimerization with FANCI, FANCD2 itself stabilizes RAD51 filaments to inhibit multiple nucleases, including DNA2, MRE11 and EXO1. (3) Unexpectedly, we uncovered a new FANCD2 function: by stabilizing RAD51 filaments, FANCD2 acts to stimulate the strand exchange activity of RAD51. Our work biochemically explains non-canonical mechanisms by which FANCD2 and RAD51 protect stalled forks. We propose a model in which the strand exchange activity of FANCD2 provides a simple molecular explanation for genetic interactions between FANCD2 and BRCA2 in the FA/BRCA fork protection pathway.

Simplified Meal Announcement Versus Precise Carbohydrate Counting in Adolescents With Type 1 Diabetes Using the MiniMed 780G Advanced Hybrid Closed Loop System: A Randomized Controlled Trial Comparing Glucose Control.

OBJECTIVE: We aimed to compare glucose control in adolescents with type 1 diabetes (T1D) using the MiniMed 780G system who used simplified meal announcement with those who used precise carbohydrate counting. RESEARCH DESIGN AND METHODS: This randomized controlled trial included 34 participants (age 12-18 years) with T1D who were on multiple daily injections or insulin pump and were scheduled to start using the MiniMed 780G system at Sidra Medicine in Qatar. After a 7-day run-in period, participants were randomly assigned to the fix group (simplified meal announcement by preset of three personalized fixed carbohydrate amounts) or the flex group (precise carbohydrate counting) and followed for 12 weeks. Between-group difference in time in range (TIR) was the primary end point. Secondary end points included HbA1c and other glycometrics. RESULTS: During the 12-week study phase, TIR was 73.5 ± 6.7% in the fix and 80.3 ± 7.4% in the flex group, with a between-group difference of 6.8% in favor of flex (P = 0.043). Time >250 mg/dL was better in the flex group (P = 0.012), whereas HbA1c (P = 0.168), time below range (P = 0.283), and time between 180 and 250 mg/dL (P = 0.114) did not differ. CONCLUSIONS: Adolescents using the MiniMed 780G system with a preset of three personalized fixed carbohydrate amounts can reach international targets of glycemic control. Therefore, it may be a valuable alternative to precise carbohydrate counting in users who are challenged by precise carbohydrate counting. Because carbohydrate counting further improves outcomes, these skills remain important for MiniMed 780G users.

A Novel Oncodental Collaborative Team: Integrating Expertise for Central Line-Associated Bloodstream Infection Prevention in Pediatric Oncology Patients.

PURPOSE: Pediatric oncology and bone marrow transplant patients are at high risk of infection, and limitations to dental expertise among medical providers render patients vulnerable to central line-associated bloodstream infections from oral pathogens. Traditionally, oral health maintenance relied on patients and bedside nurses; however, routine methods are often suboptimal to prevent central line-associated bloodstream infection in high-risk patients. Limited overlap of medical and dental expertise, and limited dental resources in typical oncology units, prevent optimal oral care for children with cancer, requiring novel solutions to better integrate specialties. METHODS: Here, we outline the creation of a novel Pediatric oncodental team to address oral-systemic infection prevention strategies for high-risk patients. RESULTS: Our oncology and dental teams created a systematic approach for increasing oral surveillance and treatment in select high-risk patients. Supervised pediatric dental residents participated in scheduled oncology rounds, and a permanent oral health educator with a background in dental hygiene was also hired as a dedicated dental professional within our oncology department. CONCLUSION: Our pediatric oncodental team aims to sustain optimal oral complication prevention strategies to reduce the risk of infection, provide education on the significance of the oral-systemic link in cancer care, and improve access and continuity of care.

Glycemic outcomes of Advanced Hybrid Closed Loop system in children and adolescents with Type 1 Diabetes, previously treated with Multiple Daily Injections (MiniMed 780G system in T1D individuals, previously treated with MDI).

BACKGROUND: The objective of this study was to evaluate the glycemic outcomes in children and adolescents with Type 1 Diabetes (T1D) previously treated with Multiple Daily Injections (MDI) using a structured initiation protocol for the Advanced Hybrid Closed Loop (AHCL) Minimed 780G insulin pump system. METHODS: In this prospective open label single-arm, single-center, clinical investigation, we recruited children and adolescents (aged 7-17 years) with T1D on MDI therapy and HbA1c below 12.5%. All participants followed a 10-day structured initiation protocol which included 4 steps: step 1: AHCL system assessment; step 2: AHCL system training; step 3: Sensor augmented pump therapy (SAP) for 3 days; step 4: AHCL system use for 12 weeks, successfully completing the training from MDI to AHCL in 10 days. The primary outcome of the study was the change in the time spent in the target in range (TIR) of 70-180 mg/dl and HbA1c from baseline (MDI + CGM, 1 week) to study phase (AHCL, 12 weeks). The paired student t-test was used for statistical analysis and a value < 0.05 was considered statistically significant. RESULTS: Thirty-four participants were recruited and all completed the 12 weeks study. TIR increased from 42.1 ± 18.7% at baseline to 78.8 ± 6.1% in the study phase (p < 0.001). HbA1c decreased from 8.6 ± 1.7% (70 ± 18.6 mmol/mol) at baseline, to 6.5 ± 0.7% (48 ± 7.7 mmol/mol) at the end of the study (p = 0.001). No episodes of severe hypoglycemia or DKA were reported. CONCLUSION: Children and adolescents with T1D on MDI therapy who initiated the AHCL system following a 10-days structured protocol achieved the internationally recommended goals of glycemic control with TIR > 70% and a HbA1c of < 7%.

Levofloxacin prophylaxis for pediatric leukemia patients: Longitudinal follow-up for impact on health care-associated infections.

BACKGROUND: Bloodstream infections (BSIs) cause morbidity and mortality in pediatric patients with leukemia. Antibiotic prophylaxis during periods of chemotherapy-induced neutropenia may reduce the incidence of BSIs. PROCEDURE: A levofloxacin prophylaxis guideline was implemented for pediatric patients with acute myeloid leukemia and relapsed acute lymphoblastic leukemia. We conducted a retrospective cohort study over 4 years (2 years pre and 2 years post implementation) of the practice guideline to assess the impact on central line-associated bloodstream infections (CLABSI) and BSI events. Secondary outcomes included incidence of Clostridioides difficile-associated diarrhea, bacteremia due to multidrug-resistant organisms (MDRO), and bacteremia due to levofloxacin nonsusceptible organisms. STATA was used for data analysis. RESULTS: Sixty-three and 72 patients met inclusion criteria for the pre- and postimplementation cohorts, respectively. Demographics were similar between the groups. We observed 60 BSI events in the pre-group versus 49 events in the post-group (p = .1). Bacteremia due to Gram-negative rods (risk ratio [RR] 0.37 [0.21, 0.66], p < .001) and National Healthcare Safety Network (NHSN) CLABSIs (RR 0.62 [0.44, 0.89], p = .01) were significantly reduced in the postimplementation group. The incidences of C. difficile-associated diarrhea and MDRO bacteremia were similar between groups. However, we observed an increase in the incidence of BSI due to Gram-negative rods that were nonsusceptible to levofloxacin (RR 3.38 [0.72, 6.65], p < .001). CONCLUSION: Following implementation of a levofloxacin prophylaxis guideline, we observed a significant decrease in BSIs due to Gram-negative rods and NHSN CLABSIs. Vigilant monitoring of outcomes post guideline implementation is critical to track emergence of resistant organisms.

Error-prone, stress-induced 3' flap-based Okazaki fragment maturation supports cell survival.

How cells with DNA replication defects acquire mutations that allow them to escape apoptosis under environmental stress is a long-standing question. Here, we report that an error-prone Okazaki fragment maturation (OFM) pathway is activated at restrictive temperatures in rad27Δ yeast cells. Restrictive temperature stress activated Dun1, facilitating transformation of unprocessed 5' flaps into 3' flaps, which were removed by 3' nucleases, including DNA polymerase δ (Polδ). However, at certain regions, 3' flaps formed secondary structures that facilitated 3' end extension rather than degradation, producing alternative duplications with short spacer sequences, such as pol3 internal tandem duplications. Consequently, little 5' flap was formed, suppressing rad27Δ-induced lethality at restrictive temperatures. We define a stress-induced, error-prone OFM pathway that generates mutations that counteract replication defects and drive cellular evolution and survival.

The effect of advanced hybrid closed loop system on glycated hemoglobin (HbA1c) in a young male with type 1 diabetes mellitus and growth hormone treatment: A case report.

The advanced hybrid closed loop system MiniMed 780G can be an effective tool to improve glycemic control and decrease the health burden in a young male with type 1 diabetes and short stature.

Virtual training on advanced hybrid closed-loop system MiniMed 780G in a teenager with type 1 diabetes previously treated with multiple daily injections: A case report.

Virtual pump training program for novel devices in people with type 1 diabetes on multiple daily injections can be an effective tool to initiate an advanced HCL system (MiniMed 780G) and to improve glycemic control in a safe manner without severe hypoglycemia and hyperglycemia.

Healthcare-associated Pediatric Cutaneous Mucormycosis at Texas Children's Hospital, 2012-2019.

Cutaneous mucormycosis in children is an opportunistic fungal infection associated with significant morbidity and mortality. We describe characteristics of 12 patients with healthcare-associated cutaneous mucormycosis at Texas Children's Hospital and results of an outbreak investigation. A definitive source was not identified. Skin lesions near medical device securement sites should raise concern for mucormycosis in patients with underlying medical conditions.

Successful Initiation of Hybrid Closed-Loop System Using Virtual Pump Training Program in a Teenager With Type 1 Diabetes Previously Treated with Multiple Daily Injections.

Due to the coronavirus disease 2019 restrictions in providing diabetes services, we have developed an innovative pump training program, which consisted of technical session, pump training, one in-person practical session, and four consecutive online sessions (Skype Meet Now).A 13-year-old female patient with a 4-year history of type 1 diabetes (T1D) on multiple daily injections (MDI) with glycated hemoglobin 8.9%; 74 mmol/mol) initiated Minimed 670G system using the program. Time in range (70-180 mg/dL) of 39% and sensor glucose (SG) of 214±91 mg/dL (MDI with continuous glucose monitoring) increased to 69% in the first 2 weeks and reached 86% and SG of 140±40 mg/dL in the first month of auto mode initiation, without severe hypoglycemia or hyperglycemia. Virtual pump training program can be an effective tool to initiate a hybrid closed-loop system and to improve glycemic control in people with T1D on MDI.

One-year experience of hybrid closed-loop system in children and adolescents with type 1 diabetes previously treated with multiple daily injections: drivers to successful outcomes.

OBJECTIVE: To evaluate the effect of a 1-year hybrid closed-loop (HCL) system on glycemic control in children and adolescents with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI). METHODS: This was a 1-year observational study, as a continuation of the previous 3 months prospective study of pediatric patients with T1D conducted at Sidra Medicine in Qatar. The study enrolled individuals aged 7-18 years with T1D > 1 year, on MDI with self-monitoring of blood glucose or continuous glucose monitoring, with no prior pump experience, and with an HbA1c level < 12.5% (< 113 mmol/mol). After the first 3 months of HCL use, patients were followed at 6, 9 and 12 months, where HbA1c was obtained and pump data were collected. RESULTS: All 30 participants (age 10.24 ± 2.6 years) who initiated HCL completed 12 months of HCL system use in Auto Mode. The participants used the sensor 88.4 ± 6.5% of the time with Auto Mode usage 85.6 ± 7.4% during 12 months of HCL system use. HbA1c decreased from 8.2 ± 1.4% (66 ± 15.3 mmol/mol) at baseline, to 6.7 ± 0.5% (50 ± 5.5 mmol/mol) at 3 months (p = 0.02) and remained stable to 7.1 ± 0.6 (54 ± 6.6 mmol/mol) at 12 months (p = 0.02). TIR (70-180 mg/dL) increased from 46.9% at baseline to 71.9% at 1 month and remained above 70% during the 12 months of HCL use. CONCLUSION: HCL system (MiniMed 670G) in children and adolescents previously treated with MDI significantly improves glycemic outcomes (HbA1c and Time in Ranges) immediately during the first month. This improved glycemic control was maintained over the 1 year following Auto Mode initiation.

A Surge in Pediatric Coronavirus Disease 2019 Cases: The Experience of Texas Children's Hospital From March to June 2020.

BACKGROUND: An understanding of the clinical characteristics of children with coronavirus disease 2019 in diverse communities is needed to optimize the response of healthcare providers during this pandemic. METHODS: We performed a retrospective review of all children presenting to the Texas Children's Hospital system with testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 10, 2020, through June 28, 2020. Demographics were recorded for all patients undergoing testing and clinical characteristics and outcomes were recorded for children with positive tests. RESULTS: Of 16 554 unique patients ≤ 21 years of age who were tested for SARS-CoV-2, 1215 (7.3%) patients tested positive. Infants under 1 year of age and patients aged 18-21 years had the highest percent of positive tests at 9.9% (230/2329) and 10.7% (79/739), respectively. Hispanic children accounted for 66% (802/1215) of positive tests, though they only represented 42.1% (6972/16 554) of all children tested for SARS-CoV-2. Of the 1215 children with a positive test, 55.7% had fever, 40.9% had cough, 39.8% had congestion or rhinorrhea, 21.9% had gastrointestinal complaints, and 15.9% were asymptomatic. Only 97 (8%) patients were hospitalized (of which 68% were Hispanic). Most of the hospitalized patients had underlying medical conditions (62/97, 63.9%), including obesity. Thirty-one hospitalized patients (31/97, 32%) required respiratory support and 9 patients (9/97, 9.3%) received SARS-CoV-2 antiviral therapy. Two patients died. CONCLUSIONS: A relatively high percentage of Hispanic children tested positive for SARS-CoV-2 and were hospitalized. Most of the children with detection of SARS-CoV-2 had uncomplicated illness courses; some children were critically ill; and 2 patients died.

Developing a communication curriculum for primary and consulting services.

Communication skills are fundamental to effective patient care, and inter-subspecialty communication is frequently identified as a key component of medical education curriculums globally. The team primarily responsible for a patient, the 'primary service', may often request a consult from a specialist, the 'consulting service', for questions of diagnosis, management, or assistance in arranging or performing a procedure or test. Few resources exist to support the development and growth of communication curriculums across primary and consulting services. We provide tips to improve communication across services in patient care and enhance learning for multiple levels of providers. This article provides a guide for the planning and implementation of a communication curriculum and highlights key components for success, based on our experience as teaching faculty on primary and consulting services, at a large academic institution. With the proper collaborations, teaching touch points, specialist consult communication tool, peer coaches, and timely feedback, this course can meet numerous educational and institutional priorities.

Coronavirus Disease 2019 in Children Cared for at Texas Children's Hospital: Initial Clinical Characteristics and Outcomes.

We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. Systemwide patient evaluation processes allowed for prompt identification and management of patients with COVID-19.

10-Day structured initiation protocol from multiple daily injection to hybrid closed-loop system in children and adolescents with type 1 diabetes.

AIM: The aim of this study was to evaluate the 10-day initiation protocol for MiniMed 670G hybrid closed-loop (HCL) system in individuals with type 1 diabetes on multiple daily injection (MDI) in achieving desirable glycemic control. METHODS: An open-label single-arm, single-center, clinical investigation in children aged 7-18 years on MDI following a structured protocol: 2 days, HCL system assessment; 5 days, HCL system training (2-h sessions on 5 consecutive days with groups of 3-5 participants and families); 3 days, Manual Mode use of HCL system; 84 days, Auto Mode use of the HCL system, cumulating in 10 days from MDI to Auto Mode activation. RESULTS: A total of 30 children (age 10.24 ± 2.6 years) were enrolled in the study, and all completed the planned 84 days on Auto Mode. The participants used the sensor for a median of 92% of the time and spent a median of 89% in Auto Mode. The mean HbA1c decreased from 8.2 ± 1.4% (66 ± 15.3 mmol/mol) at baseline to 6.7 ± 0.5% (50 ± 5.5 mmol/mol) at the end of the study (p = 0.017). Time in range (70-180 mg/dL) increased from 46.9 ± 18.5% at baseline to 75.6 ± 6.9% in Auto Mode (p < 0.001). This was achieved while spending 2.8% of the time below 70 mg/dL and without any severe hypoglycemia or DKA. CONCLUSION: Children and adolescents with type 1 diabetes on MDI therapy can successfully initiate the HCL system, using a concise structured 10-day protocol.