Cardiac Safety of Pegylated Liposomal Doxorubicin After Conventional Doxorubicin Exposure in Patients With Sarcoma and Breast Cancer.

BACKGROUND: Lifetime cumulative doses of conventional doxorubicin (>450 mg/m2) are associated with dose-dependent cardiotoxicity. In sarcoma and breast cancer, conventional doxorubicin is often utilized in the adjuvant setting, whereas pegylated liposomal doxorubicin (PLD) is typically reserved for recurrent and metastatic disease. PLD is believed to be associated with reduced cardiotoxicity compared to conventional doxorubicin. Limited data exists evaluating the cardiotoxicity associated with PLD treatment after conventional doxorubicin, especially when doxorubicin lifetime doses approach the established cumulative total lifetime dose of 450-550 mg/m2. This study aims to further qualify the cardiac safety of PLD use in patients who have had prior exposure to conventional doxorubicin. METHODS: This was a single-center, observational, retrospective cohort study conducted in patients ≥18 years with sarcoma or breast cancer who were exposed to conventional doxorubicin from an earlier line of treatment before PLD between January 2010 to May 2022. Patients were evaluated for the presence of cardiac toxicity at any point in their treatment course. Cardiac toxicity was defined as ≥ 10% decrease in left ventricle ejection fraction (LVEF) or a new diagnosis of heart failure within six months after PLD cessation. The time interval between the last conventional doxorubicin exposure and PLD initiation and the time interval between PLD initiation and LVEF monitoring were also analyzed. RESULTS: 494 patients were screened, and 50 met inclusion criteria: eight with sarcoma and 42 with breast cancer. The median lifetime cumulative conventional doxorubicin dose in patients with sarcoma was 450 mg/m2 with a maximum dose of 825 mg/m2 and 240 mg/m2 with a maximum dose of 300 mg/m2 in breast cancer patients. The median lifetime cumulative PLD dose was 105 mg/m2 (range: 35-150 mg/m2) in the sarcoma group and 105 mg/m2 (range: 35-510 mg/m2) in the breast cancer group. A decrease of ≥ 10% in LVEF was not observed in the sarcoma group. Patients with breast cancer had available LVEF data on PLD, and three of these patients experienced ≥ 10% in LVEF drop, with one of these patients diagnosed with heart failure. The average cumulative dose of PLD administered in patients with > 10% decrease in LVEF was 177 mg/m2 and had an average of 3.5 cycles. Five sarcoma patients initiated PLD treatment within two years after conventional doxorubicin exposure, while most breast patients initiated PLD treatment at least 10 years following conventional doxorubicin exposure. The average time from PLD initiation to first and second available LVEF monitoring was one and five months in the sarcoma group and three and eight months in the breast cancer group, respectively. CONCLUSION: PLD administration in patients with prior exposure to conventional doxorubicin appears to be safe, with limited cardiotoxicity in patients with sarcoma and breast cancer. Future research is needed to determine if and how often routine cardiac monitoring is needed for patients on PLD without existing cardiac risk.

Hybrid Delivery of Mindfulness Meditation and Perceived Stress in Pediatric Resident Physicians: A Randomized Clinical Trial of In-Person and Digital Mindfulness Meditation.

Physicians are experiencing epidemic levels of work-related stress and burnout. Determine efficacy of mindfulness meditation delivered as a hybrid (in-person and digital) format to reduce perceived stress in pediatric residents. Pediatric residents (n = 66) were block randomized to a hybrid Mindful Awareness Practices (MAPs) intervention, comprised of one in-person 60-min session and 6-week access to a digitally delivered MAPs curriculum (n = 27) or wait-list control (n = 39). Perceived Stress Scale (PSS) was administered at baseline and post-intervention as the primary outcome measure. A priori secondary outcomes were measured using the Abbreviated Maslach Burnout Inventory-9, Beck Depression Inventory, Beck Anxiety Inventory, UCLA Loneliness Scale, and Pittsburgh Sleep Quality Index. After the first session, 58% participated at least one digital session (M = 2.0; SD = 1.3). MAPs participants showed significant decrease in PSS compared to controls, with between-group mean difference of 2.20 (95% CI 0.47-3.93) at post-intervention (effect size 0.91; 0.19-1.62). No secondary outcome group differences were detected. Exposure to a hybrid mindfulness intervention was associated with improvement in perceived stress among pediatric residents.Trial Registration: NCT03613441.

Shared Mental Models Among Clinical Competency Committees in the Context of Time-Variable, Competency-Based Advancement to Residency.

PURPOSE: To evaluate response process validity evidence for clinical competency committee (CCC) assessments of first-year residents on a subset of General Pediatrics Entrustable Professional Activities (EPAs) and milestones in the context of a national pilot of competency-based, time-variable (CBTV) advancement from undergraduate to graduate medical education. METHOD: Assessments of 2 EPAs and 8 milestones made by the trainees' actual CCCs and 2 different blinded "virtual" CCCs for 48 first-year pediatrics residents at 4 residency programs between 2016 and 2018 were compared. Residents had 3 different training paths from medical school to residency: time-variable graduation at the same institution as their residency, time-fixed graduation at the same institution, or time-fixed graduation from a different institution. Assessments were compared using ordinal mixed-effects models. RESULTS: Actual CCCs assigned residents higher scores than virtual CCCs on milestones and one EPA's supervision levels. Residents who graduated from a different institution than their residency received lower milestone ratings than either group from the same institution; CBTV residents received higher ratings on one milestone (ICS4) and similar ratings on all others compared with non-CBTV residents who completed medical school at the same institution. CONCLUSIONS: First-year residents who graduated from CBTV medical school programs were assessed as having the same level of competence as residents who graduated from traditional medical school programs, but response process evidence suggests that members of CCCs may also draw on undocumented personal knowledge of the learner to draw conclusions about resident competence.

Copper Deficiency Anemia and Neutropenia Due to Ketogenic Diet.

Copper deficiency is an uncommon cause of hematologic abnormalities in children that is often overlooked or misdiagnosed. Although cases have been reported because of malabsorption syndromes or after gastrointestinal surgeries, we report a case of copper deficiency-associated anemia and neutropenia in a child because of dietary restrictions, specifically, transitioning from a formula-based ketogenic diet to a pureed food-based ketogenic diet. On copper supplementation, the patient's anemia and neutropenia resolved. To our knowledge, this report is the first revealing copper deficiency anemia and neutropenia developing because of a ketogenic diet.

Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in Patients at High Risk for Fungal Infections.

The purpose of our study was to determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed-release tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs) and to examine the effect of demographic traits and treatment characteristics on PCZ serum levels. A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that had received PCZ and obtained PCZ serum levels for either treatment or prophylaxis between 1 August 2014 and 31 August 2015. High-risk patients were defined as those undergoing chemotherapy for a primary hematologic malignancy and those undergoing hematopoietic cell transplantation (HCT) or solid organ transplantation. Serum trough concentrations of ≥700 µg/liter and ≥1,000 µg/liter were considered appropriate for prophylaxis and treatment, respectively. The most frequent underlying medical condition was a hematological malignancy (43/53, 81%). Twenty-six of 53 patients (49%) received PCZ for prophylaxis; the rest received PCZ for treatment. A total of 37/53 (70%) patients had PCZ serum levels of ≥700 µg/liter regardless of indication, including 22/26 (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for treatment, only 12/27 (44%) had PCZ serum levels of ≥1,000 µg/liter. The odds of having therapeutic PCZ serum levels were not statistically different in patients with a weight of ≥90 kg, a diarrhea grade of ≥2, a mucositis grade of ≥2, or poor dietary intake. However, the odds of having therapeutic PCZ serum levels was 5.85 times higher in patients without graft-versus-host disease (GVHD) treatment than in those with GVHD treatment. Four patients on prophylaxis (15%) developed breakthrough IFIs, one of which had a subtherapeutic level. We concluded that the use of PCZ DRT provided adequate concentrations in only 70% of our patients and that recommended dosing may lead to insufficient levels in patients treated for IFIs. Lower concentrations noted among high-risk patients with GVHD suggest a need for prospective studies evaluating therapeutic drug monitoring and/or dose adjustments among these patients.

Continuous alloy-composition spatial grading and superbroad wavelength-tunable nanowire lasers on a single chip.

By controlling local substrate temperature in a chemical vapor deposition system, we have successfully achieved spatial composition grading covering the complete composition range of ternary alloy CdSSe nanowires on a single substrate of 1.2 cm in length. Spatial photoluminescence scan along the substrate length shows peak wavelength changes continuously from approximately 500 to approximately 700 nm. Furthermore, we show that under strong optical pumping, every spot along the substrate length displays lasing behavior. Thus our nanowire chip provides a spatially continuously tunable laser with a superbroad wavelength tuning range, unmatched by any other available semiconductor-based technology.

Photoluminescence of GaN nanowires of different crystallographic orientations.

We utilized time-integrated and time-resolved photoluminescence of a-axis and c-axis gallium nitride nanowires to elucidate the origin of the blue-shifted ultraviolet photoluminescence in a-axis GaN nanowires relative to c-axis GaN nanowires. We attribute this blue-shifted ultraviolet photoluminescence to emission from surface trap states as opposed to previously proposed causes such as strain effects or built-in polarization. These results demonstrate the importance of accounting for surface effects when considering ultraviolet optoelectronic devices based on GaN nanowires.

Mechanisms of 1D crystal growth in reactive vapor transport: indium nitride nanowires.

Indium nitride (InN) nanowire synthesis using indium (In) vapor transport in a dissociated ammonia environment (reactive vapor transport) is studied in detail to understand the nucleation and growth mechanisms involved with the so-called "self-catalysis" schemes. The results show that the nucleation of InN crystal occurs first on the substrate. Later, In droplets are formed on top of the InN crystals because of selective wetting of In onto InN crystals. Further growth via liquid-phase epitaxy through In droplets leads the growth in one dimension (1D), resulting in the formation of InN nanowires. The details about the nucleation and growth aspects within these self-catalysis schemes are rationalized further by demonstrating the growth of heteroepitaxially oriented nanowire arrays on single-crystal substrates and "tree-like" morphologies on a variety of substrates. However, the direct nitridation of In droplets using dissociated ammonia results in the spontaneous nucleation and basal growth of nanowires directly from the In melt surface, which is quite different from the above-mentioned nucleation mechanism with the reactive vapor transport case. The InN nanowires exhibit a band gap of 0.8 eV, whereas the mixed phase of InN and In(2)O(3) nanowires exhibit a peak at approximately 1.9 eV in addition to that at 0.8 eV.