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Background Sinus node (SN) dysfunction is observed in some Long QT syndrome (LQTS) patients, but has not been studied as a function of LQTS genotype. LQTS6 involves mutations in the hERG β-subunit MiRP1, which also interacts with hyperpolarization-activated, cyclic nucleotide gated (HCN) channels - the molecular correlate of SN pacemaker current (If). An LQTS registry search identified a 55 year male with M54T MiRP1 mutation, history of sinus bradycardia (39–56 bpm), and prolonged QTc. Objective We tested if LQTS6 incorporates sinus bradycardia due to abnormal If. Methods We transiently co-transfected neonatal rat ventricular myocytes (to study currents in a myocyte background) with human HCN4 (hHCN4, primary SN isoform) or human HCN2 (hHCN2) and one of the following: empty vector, wildtype hMiRP1 (WT), M54T hMiRP1 (M54T). Current amplitude, voltage dependence and kinetics were measured by whole cell patch clamp. Results M54T co-expression decreased HCN4 current density by 80% compared to hHCN4 alone or with WT, and also slowed HCN4 activation at physiologically relevant voltages. Neither WT nor M54T altered HCN4 voltage dependence. A computer simulation predicts that these changes in HCN4 current would decrease rate and be additive with published effects of M54T mutation on hERG kinetics on rate. Conclusions We conclude that M54T LQTS6 mutation can cause sinus bradycardia through effects on both hERG and HCN currents. Patients with other LQTS6 mutations should be examined for SN dysfunction, and the effect on HCN current determined.

Objectives: With decreasing mortality in PICUs, a growing number of survivors experience long-lasting physical impairments. Early physical rehabilitation and mobilization during critical illness are safe and feasible, but little is known about the prevalence in PICUs. We aimed to evaluate the prevalence of rehabilitation for critically ill children and associated barriers. Design: National 2-day point prevalence study. Setting: Eighty-two PICUs in 65 hospitals across the United States. Patients: All patients admitted to a participating PICU for greater than or equal to 72 hours on each point prevalence day. Interventions: None. Measurements and Main Results: The primary outcome was prevalence of physical therapy– or occupational therapy–provided mobility on the study days. PICUs also prospectively collected timing of initial rehabilitation team consultation, clinical and patient mobility data, potential mobility–associated safety events, and barriers to mobility. The point prevalence of physical therapy– or occupational therapy–provided mobility during 1,769 patient-days was 35% and associated with older age (adjusted odds ratio for 13–17 vs < 3 yr, 2.1; 95% CI, 1.5–3.1) and male gender (adjusted odds ratio for females, 0.76; 95% CI, 0.61–0.95). Patients with higher baseline function (Pediatric Cerebral Performance Category, ≤ 2 vs > 2) less often had rehabilitation consultation within the first 72 hours (27% vs 38%; p < 0.001). Patients were completely immobile on 19% of patient-days. A potential safety event occurred in only 4% of 4,700 mobility sessions, most commonly a transient change in vital signs. Out-of-bed mobility was negatively associated with the presence of an endotracheal tube (adjusted odds ratio, 0.13; 95% CI, 0.1–0.2) and urinary catheter (adjusted odds ratio, 0.28; 95% CI, 0.1–0.6). Positive associations included family presence in children less than 3 years old (adjusted odds ratio, 4.55; 95% CI, 3.1–6.6). Conclusions: Younger children, females, and patients with higher baseline function less commonly receive rehabilitation in U.S. PICUs, and early rehabilitation consultation is infrequent. These findings highlight the need for systematic design of rehabilitation interventions for all critically ill children at risk of functional impairments.

The continuous application and development of blood conservation techniques across the continuum of care allowed bloodless surgery for JW and non-JW patients alike. Blood conservation is a team sport and to make significant strides requires participation and input by all care providers.