The Two-Bag Method for Management of Adult Diabetic Ketoacidosis-Experience With 634 Patients.

PURPOSE: To compare key resource utilization and safety outcomes of adult emergency department (ED) patients in diabetic ketoacidosis (DKA) managed via the Two-Bag or traditional One-Bag method. MATERIALS AND METHODS: This is a retrospective review at an academic medical center ED. Patients were included if >18 years, met diagnostic criteria for DKA (pH ≤ 7.30, bicarbonate ≤ 18 mmol/L, anion gap ≥ 10), and were managed via a standardized order set (either Two-Bag or One-Bag Method). Comparisons used independent-groups t-tests for continuous variables and χ2 tests for binary variables. RESULTS: We identified 634 patients with DKA managed via the Two-Bag method, and 107 managed via the One-Bag method. Cohorts were similar in demographics and presenting laboratories. The Two-Bag Method was associated with 8.1 h shorter to first bicarbonate >18 mmol/L (11.9 vs 20.0, P < .001), and 24 fewer IV fluid bags (5.3 vs 29.7, P < .001). Incidence of hypokalemia (potassium <3.0 mmol/L) was 53% lower in the Two-Bag cohort (6.6 vs 14.0%, P = .03); incidence of hypoglycemia (glucose <70 mg/dL) was 5.8 versus 10.3%, P = .16. CONCLUSIONS: For adult ED patients in DKA, the Two-Bag Method was associated with faster resolution of acidosis, fewer IV fluid bags charged, lower incidence of hypokalemia, and trend toward lower incidence of hypoglycemia compared to the One-Bag Method.

Performance of peripheral catheters inserted with ultrasound guidance versus landmark technique after a simulation-based mastery learning intervention.

PROBLEM: Ultrasound-guided peripheral intravenous catheter (USGPIV) insertion is an effective method to gain vascular access in patients with difficult intravenous access (DIVA). While USGPIV success rates are reported to be high, some studies have reported a concerning incidence of USGPIV premature failures. AIMS: The purpose of this study was to compare differences in USGPIV and landmark peripheral intravenous catheter (PIV) utilization and failure following a hospital-wide USGPIV training program for nurses. METHODS: The authors performed a retrospective, electronic medical record review of all USGPIVs and PIVs inserted at a tertiary, urban, academic medical center from September 1, 2018, through September 30, 2019. The primary outcome was differences between USGPIV and PIV time to failure. RESULTS: A total of 43,470 short peripheral intravenous catheters (PIVCs) were inserted in 23,713 patients. Of these, 7972 (16.8%) were USGPIV. At 30 days of follow-up, for PIVCs with an indication for removal documented, USGPIVs had higher Kaplan-Meier survival probabilities than PIVs (p < 0.001). CONCLUSIONS: The use of simulation-based mastery associated with USGPIVs, demonstrated lower failure rates than standard PIVs after 2 days and USGPIVs exhibited improved survival rates in patients with DIVA. These findings suggest that rigorous simulation-based insertion training demonstrates improved USGPIV survival when compared to traditional PIVCs. SBML is an extremely useful tool to ensure appropriately trained clinicians acquire the necessary knowledge and skillset to improve USGPIV outcomes.

Euglycemic Diabetic Ketoacidosis: Experience with 44 Patients and Comparison to Hyperglycemic Diabetic Ketoacidosis.

Introduction: Euglycemic diabetic ketoacidosis (DKA) (glucose <250 milligrams per deciliter (mg/dL) has increased in recognition since introduction of sodium-glucose co-transporter 2 (SGLT2) inhibitors but remains challenging to diagnose and manage without the hyperglycemia that is otherwise central to diagnosing DKA, and with increased risk for hypoglycemia with insulin use. Our objective was to compare key resource utilization and safety outcomes between patients with euglycemic and hyperglycemic DKA from the same period. Methods: This is a retrospective review of adult emergency department patients in DKA at an academic medical center. Patients were included if they were >18 years old, met criteria for DKA on initial laboratories (pH ≤7.30, serum bicarbonate ≤18 millimoles per liter [mmol/L], anion gap ≥10), and were managed via a standardized DKA order set. Patients were divided into euglycemic (<250 milligrams per deciliter [mg/dL]) vs hyperglycemic (≥250 mg/dL) cohorts by presenting glucose. We extracted and analyzed patient demographics, resource utilization, and safety outcomes. Etiologies of euglycemia were obtained by manual chart review. For comparisons between groups we used independent-group t-tests for continuous variables and chi-squared tests for binary variables, with alpha 0.05. Results: We identified 629 patients with DKA: 44 euglycemic and 585 hyperglycemic. Euglycemic patients had milder DKA on presentation (higher pH and bicarbonate, lower anion gap; P < 0.05) and lower initial glucose (195 vs 561 mg/dL, P < 0.001) and potassium (4.3 vs 5.3 mmol/L, P < 0.001). Etiologies of euglycemia were insulin use prior to arrival (57%), poor oral intake with baseline insulin use (29%), and SGLT2 inhibitor use (14%). Mean time on insulin infusion was shorter for those with euglycemic DKA: 13.5 vs 19.4 hours, P = 0.003. Mean times to first bicarbonate >18 mmol/L and first long-acting insulin were similar. Incidence of hypoglycemia (<70 mg/dL) while on insulin infusion was significantly higher for those with euglycemic DKA (18.2 vs 4.8%, P = 0.02); incidence of hypokalemia (<3.3 mmol/L) was 27.3 vs 19.1% (P = 0.23). Conclusion: Compared to hyperglycemic DKA patients managed in the same protocolized fashion, euglycemic DKA patients were on insulin infusions 5.9 hours less, yet experienced hypoglycemia over three times more frequently. Future work can investigate treatment strategies for euglycemic DKA to minimize adverse events, especially iatrogenic hypoglycemia.

Partial and complete loss of myosin binding protein H-like cause cardiac conduction defects.

A premature truncation of MYBPHL in humans and a loss of Mybphl in mice is associated with dilated cardiomyopathy, atrial and ventricular arrhythmias, and atrial enlargement. MYBPHL encodes myosin binding protein H-like (MyBP-HL). Prior work in mice indirectly identified Mybphl expression in the atria and in small puncta throughout the ventricle. Because of its genetic association with human and mouse cardiac conduction system disease, we evaluated the anatomical localization of MyBP-HL and the consequences of loss of MyBP-HL on conduction system function. Immunofluorescence microscopy of normal adult mouse ventricles identified MyBP-HL-positive ventricular cardiomyocytes that co-localized with the ventricular conduction system marker contactin-2 near the atrioventricular node and in a subset of Purkinje fibers. Mybphl heterozygous ventricles had a marked reduction of MyBP-HL-positive cells compared to controls. Lightsheet microscopy of normal perinatal day 5 mouse hearts showed enrichment of MyBP-HL-positive cells within and immediately adjacent to the contactin-2-positive ventricular conduction system, but this association was not apparent in Mybphl heterozygous hearts. Surface telemetry of Mybphl-null mice revealed atrioventricular block and atrial bigeminy, while intracardiac pacing revealed a shorter atrial relative refractory period and atrial tachycardia. Calcium transient analysis of isolated Mybphl-null atrial cardiomyocytes demonstrated an increased heterogeneity of calcium release and faster rates of calcium release compared to wild type controls. Super-resolution microscopy of Mybphl heterozygous and homozygous null atrial cardiomyocytes showed ryanodine receptor disorganization compared to wild type controls. Abnormal calcium release, shorter atrial refractory period, and atrial dilation seen in Mybphl null, but not wild type control hearts, agree with the observed atrial arrhythmias, bigeminy, and atrial tachycardia, whereas the proximity of MyBP-HL-positive cells with the ventricular conduction system provides insight into how a predominantly atrial expressed gene contributes to ventricular arrhythmias and ventricular dysfunction.

Simulation-Based Mastery Learning Improves Ultrasound-Guided Peripheral Intravenous Catheter Insertion Skills of Practicing Nurses.

INTRODUCTION: Difficult intravenous (IV) access (DIVA) is frequently encountered in the hospital setting. Ultrasound-guided peripheral IV catheter (USGPIV) insertion has emerged as an effective procedure to establish access in patients with DIVA. Despite the increased use of USGPIV, little is known about the optimal training paradigms for bedside nurses. Therefore, we developed and evaluated a novel, sustainable, USGPIV simulation-based mastery learning (SBML) curriculum for nurses. METHODS: This is a prospective cohort study of an USGPIV SBML training program for bedside nurses over a 12-month period. We evaluated skills and self-confidence before and after training and measured the proportion of the nurses achieving independent, proctor, and instructor status. Procedure logs and surveys were used to explore the nurse experience and utilization of USGPIV on real patients with DIVA 3 months after the intervention. RESULTS: Two hundred thirty-eight nurses enrolled in the study. The USGPIV skill checklist scores increased from median of 6.0 [interquartile range = 4.0-9.0 (pretest) to 29.0, interquartile range = 28-30 (posttest), P < 0.001]. The USGPIV confidence improved from before (mean = 2.32, SD = 1.17) to after (mean = 3.85, SD = 0.73, P < 0.001) training (5-point Likert scale). Sixty-two percent of the nurses enrolled achieved independent status, 47.5% became proctors, and 11.3% course trainers. At 3-month posttraining, the nurses had attempted a mean of 35.6 USGPIV insertions with an 89.5% success rate. CONCLUSIONS: This novel USGPIV SBML curriculum improves nurses' insertion skills, self-confidence, and progresses patient care through USGPIV insertions on hospitalized patients with DIVA.

Ultrasound-Guided Peripheral Intravenous Catheter Insertion Training Reduces Use of Midline Catheters in Hospitalized Patients With Difficult Intravenous Access.

OBJECTIVES: Difficult intravenous (IV) access (DIVA) is a prevalent condition in the hospital setting and increases utilization of midline catheters (MCs) and peripherally inserted central catheters (PICCs). Ultrasound-guided peripheral intravenous (USGPIV) insertion is effective at establishing intravenous access in DIVA but remains understudied in the inpatient setting. We evaluated the effect of an USGPIV simulation-based mastery learning (SBML) curriculum for nurses on MC and PICC utilization for hospitalized patients. METHODS: We performed a quasi-experimental observational study. We trained nurses across all inpatient units at a large tertiary care hospital. We queried the electronic medical record to compare PICC and MC utilization for patients with DIVA during 3 periods: before USGPIV SBML training (control), during pilot testing of the intervention, and during the SBML intervention. To account for variations in insertion practices over time, we performed an interrupted time series (ITS) analysis between 2 periods, the combined control and pilot periods and the intervention period. RESULTS: One hundred forty-eight nurses completed USGPIV SBML training. Midline catheters inserted monthly per 1000 patient-days for DIVA decreased significantly from 1.86 ± 0.51 (control) to 2.31 ± 0.28 (pilot) to 1.33 ± 0.51 (intervention; P = 0.001). The ITS analysis indicated a significant intervention effect (P < 0.001). Peripherally inserted central catheters inserted monthly per 1000 patient-days for DIVA also significantly decreased over the study periods; however, the ITS failed to show an intervention effect as PICC insertions were already decreasing during the control period. CONCLUSIONS: A hospital-wide USGPIV SBML curriculum for inpatient nurses was associated with a significant reduction in MCs inserted for DIVA.

Loss of dysferlin or myoferlin results in differential defects in excitation-contraction coupling in mouse skeletal muscle.

Muscular dystrophies are disorders characterized by progressive muscle loss and weakness that are both genotypically and phenotypically heterogenous. Progression of muscle disease arises from impaired regeneration, plasma membrane instability, defective membrane repair, and calcium mishandling. The ferlin protein family, including dysferlin and myoferlin, are calcium-binding, membrane-associated proteins that regulate membrane fusion, trafficking, and tubule formation. Mice lacking dysferlin (Dysf), myoferlin (Myof), and both dysferlin and myoferlin (Fer) on an isogenic inbred 129 background were previously demonstrated that loss of both dysferlin and myoferlin resulted in more severe muscle disease than loss of either gene alone. Furthermore, Fer mice had disordered triad organization with visibly malformed transverse tubules and sarcoplasmic reticulum, suggesting distinct roles of dysferlin and myoferlin. To assess the physiological role of disorganized triads, we now assessed excitation contraction (EC) coupling in these models. We identified differential abnormalities in EC coupling and ryanodine receptor disruption in flexor digitorum brevis myofibers isolated from ferlin mutant mice. We found that loss of dysferlin alone preserved sensitivity for EC coupling and was associated with larger ryanodine receptor clusters compared to wildtype myofibers. Loss of myoferlin alone or together with a loss of dysferlin reduced sensitivity for EC coupling, and produced disorganized and smaller ryanodine receptor cluster size compared to wildtype myofibers. These data reveal impaired EC coupling in Myof and Fer myofibers and slightly potentiated EC coupling in Dysf myofibers. Despite high homology, dysferlin and myoferlin have differential roles in regulating sarcotubular formation and maintenance resulting in unique impairments in calcium handling properties.

Difficult intravenous access in the emergency department: Performance and impact of ultrasound-guided IV insertion performed by nurses.

BACKGROUND: Difficult intravenous access (DIVA) is a common problem in Emergency Departments (EDs), yet the prevalence and clinical impact of this condition is poorly understood. Ultrasound-guided peripheral intravenous catheter (USGPIV) insertion is a successful modality for obtaining intravenous (IV) access in patients with DIVA. OBJECTIVES: We aimed to describe the prevalence of DIVA, explore how DIVA affects delivery of care, and determine if nurse insertion of USGPIV improves care delays among patients with DIVA. METHODS: We retrospectively queried the electronic medical record for all ED patients who had a peripheral IV (PIV) inserted at a tertiary academic medical center from 2015 to 2017. We categorized patients as having DIVA if they required ≥3 PIV attempts or an USGPIV. We compared metrics for care delivery including time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED length of stay (LOS) between patients with and without DIVA. We also compared these metrics in patients with DIVA with a physician-inserted USGPIV versus those with a nurse-inserted USGPIV. RESULTS: A total of 147,260 patients were evaluated during the study period. Of these, 13,192 (8.9%) met criteria for DIVA. Patients with DIVA encountered statistically significant delays in time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED LOS compared to patients without DIVA (all p < 0.001). Patients with nurse-inserted USGPIVs also had statistically significant improvements in time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED LOS compared to patients with physician-inserted USGPIVs (all p < 0.001). CONCLUSION: DIVA affects many ED patients and leads to delays in PIV access-related care. Nurse insertion of USGPIVs improves care in patients with DIVA.

Recombinant annexin A6 promotes membrane repair and protects against muscle injury.

Membrane repair is essential to cell survival. In skeletal muscle, injury often associates with plasma membrane disruption. Additionally, muscular dystrophy is linked to mutations in genes that produce fragile membranes or reduce membrane repair. Methods to enhance repair and reduce susceptibility to injury could benefit muscle in both acute and chronic injury settings. Annexins are a family of membrane-associated Ca2+-binding proteins implicated in repair, and annexin A6 was previously identified as a genetic modifier of muscle injury and disease. Annexin A6 forms the repair cap over the site of membrane disruption. To elucidate how annexins facilitate repair, we visualized annexin cap formation during injury. We found that annexin cap size positively correlated with increasing Ca2+ concentrations. We also found that annexin overexpression promoted external blebs enriched in Ca2+ and correlated with a reduction of intracellular Ca2+ at the injury site. Annexin A6 overexpression reduced membrane injury, consistent with enhanced repair. Treatment with recombinant annexin A6 protected against acute muscle injury in vitro and in vivo. Moreover, administration of recombinant annexin A6 in a model of muscular dystrophy reduced serum creatinine kinase, a biomarker of disease. These data identify annexins as mediators of membrane-associated Ca2+ release during membrane repair and annexin A6 as a therapeutic target to enhance membrane repair capacity.

TnI Structural Interface with the N-Terminal Lobe of TnC as a Determinant of Cardiac Contractility.

The heterotrimeric cardiac troponin complex is a key regulator of contraction and plays an essential role in conferring Ca2+ sensitivity to the sarcomere. During ischemic injury, rapidly accumulating protons acidify the myoplasm, resulting in markedly reduced Ca2+ sensitivity of the sarcomere. Unlike the adult heart, sarcomeric Ca2+ sensitivity in fetal cardiac tissue is comparatively pH insensitive. Replacement of the adult cardiac troponin I (cTnI) isoform with the fetal troponin I (ssTnI) isoform renders adult cardiac contractile machinery relatively insensitive to acidification. Alignment and functional studies have determined histidine 132 of ssTnI to be the predominant source of this pH insensitivity. Substitution of histidine at the cognate position 164 in cTnI confers the same pH insensitivity to adult cardiac myocytes. An alanine at position 164 of cTnI is conserved in all mammals, with the exception of the platypus, which expresses a proline. Prolines are biophysically unique because of their innate conformational rigidity and helix-disrupting function. To provide deeper structure-function insight into the role of the TnC-TnI interface in determining contractility, we employed a live-cell approach alongside molecular dynamics simulations to ascertain the chemo-mechanical implications of the disrupted helix 4 of cTnI where position 164 exists. This important motif belongs to the critical switch region of cTnI. Substitution of a proline at position 164 of cTnI in adult rat cardiac myocytes causes increased contractility independent of alterations in the Ca2+ transient. Free-energy perturbation calculations of cTnC-Ca2+ binding indicate no difference in cTnC-Ca2+ affinity. Rather, we propose the enhanced contractility is derived from new salt bridge interactions between cTnI helix 4 and cTnC helix A, which are critical in determining pH sensitivity and contractility. Molecular dynamics simulations demonstrate that cTnI A164P structurally phenocopies ssTnI under baseline but not acidotic conditions. These findings highlight the evolutionarily directed role of the TnI-cTnC interface in determining cardiac contractility.