Impaired Glucose Tolerance and Visceral Adipose Tissue Thickness among Lean and Non-Lean People with and without Spinal Cord Injury.

After spinal cord injury (SCI), multiple adaptations occur that influence metabolic health and life quality. Prolonged sitting and inactivity predispose people with SCI to body composition changes, such as increased visceral adipose tissue (VAT) thickness, which is often associated with impaired glucose tolerance. Our goal is to understand whether VAT is an index of leanness, and, secondarily, whether mobility methods influence glucose tolerance for people living with SCI.

Model for Integration of Monogenic Diabetes Diagnosis Into Routine Care: The Personalized Diabetes Medicine Program.

Objective: To implement, disseminate, and evaluate a sustainable method for identifying, diagnosing, and promoting individualized therapy for monogenic diabetes.

Research Design And Methods: Patients were recruited into the implementation study through a screening questionnaire completed in the waiting room or through the patient portal, physician recognition, or self-referral. Patients suspected of having monogenic diabetes based on the processing of their questionnaire and other data through an algorithm underwent next-generation sequencing for 40 genes implicated in monogenic diabetes and related conditions.

Neonatal Myocardial Infarction: A Proposed Algorithm for Coronary Arterial Thrombus Management.

Background: Neonatal myocardial infarction is rare and is associated with a high mortality of 40% to 50%. We report our experience with neonatal myocardial infarction, including presentation, management, outcomes, and our current patient management algorithm.

Methods: We reviewed all infants admitted with a diagnosis of coronary artery thrombosis, coronary ischemia, or myocardial infarction between January 2015 and May 2021.

Further Characterization of Loss of Function Epilepsy Distinct From Cornelia de Lange Syndrome.

Cornelia de Lange syndrome is a rare developmental malformation syndrome characterized by small stature, limb anomalies, distinctive facial features, developmental delays, and behavioral issues. The diagnosis of Cornelia de Lange syndrome is made clinically or on the basis of an identified variant in one of the genes associated with Cornelia de Lange syndrome. variants are the cause of 5% of the cases of Cornelia de Lange syndrome.

Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas.

The PI3K/Akt/mTOR (PAM) axis is constitutively activated in multiple lymphoma subtypes and is a promising therapeutic target. The mTOR inhibitor temsirolimus (TEM) and the immunomodulatory agent lenalidomide (LEN) have overlapping effects within the PAM axis with synergistic potential. This multicenter phase I/II study evaluated combination therapy with TEM/LEN in patients with relapsed and refractory lymphomas.

Phase 1b/2 study of ibrutinib and lenalidomide with dose-adjusted EPOCH-R in patients with relapsed/refractory diffuse large B-cell lymphoma.

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is difficult to cure; non-germinal center B-cell-like (non-GCB) and activated B-cell-like (ABC) DLBCL have worse outcomes than GCB DLBCL. Ibrutinib and lenalidomide are synergistic in vitro in ABC DLBCL and may augment salvage chemotherapy. In part 1 of this phase 1b/2 study (NCT02142049), patients with relapsed/refractory DLBCL received ibrutinib 560 mg and escalating doses of lenalidomide on Days 1-7 with DA-EPOCH-R (Days 1-5) in 21-day cycles.

A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China.

The second-generation proteasome inhibitor carfilzomib produces superior outcomes in relapsed or refractory multiple myeloma (MM). We conducted a single-arm trial of twice-weekly carfilzomib (27 mg/m)-dexamethasone (Kd27) for relapsed and refractory MM in China. Kd27 was administered in 28-day cycles to 123 patients previously treated with ≥ 2 other regimens, including treatment with bortezomib and an immunomodulatory drug, and refractory to their most recent therapy.

A phase 1b study of once-weekly carfilzomib combined with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma.

Twice-weekly carfilzomib with lenalidomide-dexamethasone (Rd) is an effective regimen for newly diagnosed multiple myeloma (NDMM). Here we evaluated once-weekly carfilzomib with Rd (once-weekly KRd) in NDMM patients. The NDMM patients were enrolled regardless of transplant eligibility.

Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development.

De novo germline mutations in the RNA helicase DDX3X account for 1%-3% of unexplained intellectual disability (ID) cases in females and are associated with autism, brain malformations, and epilepsy. Yet, the developmental and molecular mechanisms by which DDX3X mutations impair brain function are unknown. Here, we use human and mouse genetics and cell biological and biochemical approaches to elucidate mechanisms by which pathogenic DDX3X variants disrupt brain development.

Lack of Equipoise in the PDA-TOLERATE Trial: A Comparison of Eligible Infants Enrolled in the Trial and Those Treated Outside the Trial.

The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <28 weeks of gestation; however 137 potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to "lack-of-physician-equipoise" (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6.

Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups.

Introduction: The phase III RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial showed significantly improved progression-free survival and overall survival (OS) with carfilzomib (56 mg/m) and dexamethasone (Kd56) versus bortezomib and Kd56 (Vd) in patients with relapsed or refractory multiple myeloma (RRMM). We report updated OS and safety data after 6 months of additional follow-up.

Patients And Methods: Patients with RRMM (1-3 previous lines of therapy) were randomized 1:1 to Kd56 or Vd.

Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study.

Twice-weekly carfilzomib (27 mg/m ) with lenalidomide-dexamethasone (KRd) is a standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received carfilzomib (30-minute infusion; 56 or 70mg/m ) on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28-day cycles.

Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320).

Objective: To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks.

Methods: We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.

Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR.

In ENDEAVOR, carfilzomib (56 mg/m) and dexamethasone (Kd56) demonstrated longer progression-free survival (PFS) over bortezomib and dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma (RRMM). Here we evaluated Kd56 vs Vd by baseline renal function in a post hoc exploratory subgroup analysis. The intent-to-treat population included 929 patients (creatinine clearance [CrCL] ≥15 to <50 mL/min, n = 85 and n = 99; CrCL 50 to <80 mL/min, n = 186 and n = 177; and CrCL ≥80 mL/min, n = 193 and n = 189 for Kd56 and Vd arms, respectively).

Whole body heat exposure modulates acute glucose metabolism.

Aim: Exercise modulates glucose tolerance and homeostasis in both healthy and diabetic individuals. Heat stress is a fundamental element of exercise. The acute glycemic response and alterations in glucose clearance following whole body passive heat stress in the absence of muscle activity has yet to be examined in humans.

A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma.

Background: The proteasome inhibitor bortezomib has demonstrated marked preclinical activity when combined with the histone deacetylase inhibitor vorinostat in leukemia, multiple myeloma, and mantle cell lymphoma (MCL) cells. The present study evaluated the efficacy and safety of the combination in patients with relapsed or refractory MCL and diffuse large B-cell lymphoma (DLBCL).

Patients And Methods: The present multicenter, nonrandomized phase II trial used a Simon 2-stage design with 3 cohorts: cohort A, MCL with no previous bortezomib (including untreated MCL); cohort B, MCL with previous bortezomib; and cohort C, relapsed or refractory DLBCL with no previous bortezomib.

Heliox Adjunct Therapy for Neonates With Congenital Diaphragmatic Hernia.

Background: Congenital diaphragmatic hernia remains a complex disease with significant morbidity and mortality. Hypercarbia is a common derangement in this population, which often requires escalating ventilator support. By decreasing airway turbulence and enhancing CO removal, inhaled helium-oxygen mixture (heliox) has the potential to improve ventilation and thereby decrease ventilator support and its associated lung injury.

Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.

Background: The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups.

Noonan syndrome in diverse populations.

Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology.

A Multicenter, Open-Label, Phase 1b Study of Carfilzomib, Cyclophosphamide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients (CHAMPION-2).

Introduction: This phase 1b study evaluated the safety and efficacy of 3 dose levels of carfilzomib when provided with fixed dose oral cyclophosphamide and dexamethasone (KCyd) in patients with newly diagnosed multiple myeloma (MM).

Patients And Methods: CHAMPION-2 was a multicenter single-arm study. Patients with newly diagnosed secretory MM were enrolled and received KCyd treatment for up to 8 cycles.

A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma.

A phase 1 study was conducted to determine the dose-limiting toxicities and maximum-tolerated dose (MTD) for bortezomib followed by romidepsin on days 1, 8, and 15 in patients with relapsed/refractory CLL/SLL or B- or T-cell lymphoma. Eighteen treated patients were evaluable for response. The MTD was 1.

Low-Force Muscle Activity Regulates Energy Expenditure after Spinal Cord Injury.

Unlabelled: Reduced physical activity is a primary risk factor for increased morbidity and mortality. People with spinal cord injury (SCI) have reduced activity for a lifetime, as they cannot volitionally activate affected skeletal muscles. We explored whether low-force and low-frequency stimulation is a viable strategy to enhance systemic energy expenditure in people with SCI.