Amit Dhamoon

A Novel Form of Short QT Syndrome (SQT3) Is Caused by a Mutation in the KCNJ2 Gene

Short QT syndrome (SQTS) leads to an abbreviated QTc interval and predisposes patients to life-threatening arrhythmias. To date, two forms of the disease have been identified: SQT1, caused by a gain of function substitution in the HERG (IKr) channel, and SQT2, caused by a gain of function substitution in the KvLQT1 (IKs) channel. Here we identify a new variant, “SQT3”, which has a unique ECG phenotype characterized by asymmetrical T waves, and a defect in the gene coding for the inwardly rectifying Kir2.1 (IK1) channel. The affected members of a single family had a G514A substitution in the KCNJ2 gene that resulted in a change from aspartic acid to asparagine at position 172 (D172N). Whole-cell patch-clamp studies of the heterologously expressed human D172N channel demonstrated a larger outward IK1 than the wild-type (P<0.05) at potentials between −75 mV and −45 mV, with the peak current being shifted in the former with respect to the latter (WT, −75 mV; D172N, −65 mV). Coexpression of WT and mutant channels to mimic the heterozygous condition of the proband yielded an outward current that was intermediate between WT and D172N. In computer simulations using a human ventricular myocyte model the increased outward IK1 greatly accelerated the final phase of repolarization, and shortened the action potential duration. Hence, unlike the known mutations in the two other SQTS forms (N588K in HERG and V307L in KvLQT1), simulations using the D172N and WT/D172N mutations fully accounted for the ECG phenotype of tall and asymmetrically shaped T waves. Although we were unable to test for inducibility of arrhythmia susceptibility due to lack of patients’ consent, our computer simulations predict a steeper steady-state restitution curve for the D172N and WT/D172N mutation, compared with WT or to HERG or KvLQT1 mutations, which may predispose SQT3 patients to a greater risk of reentrant arrhythmias.

Cholinergic atrial fibrillation: IK,ACh gradients determine unequal left/right atrial frequencies and rotor dynamics

OBJECTIVE We tested the hypothesis that left atrial (LA) myocytes are more sensitive to acetylcholine (ACh) than right atrial (RA) myocytes, which results in a greater dose-dependent increase in LA than RA rotor frequency, increased LA-to-RA frequency gradient and increased incidence of wavelet formation during atrial fibrillation (AF). METHODS AND RESULTS AF was induced in seven Langendorff-perfused sheep hearts in the presence of ACh (0.1-4.0 microM) and studied using optical mapping and bipolar recordings. Dominant frequencies (DFs) were determined in optical and electrical signals and phase movies were used to identify rotors and quantify their dynamics. DFs in both atria increased monotonically with ACh concentration until saturation, but the LA frequency predominated at all concentrations. Rotors were also seen more often in the LA, and although their life span decreased, their frequency and number of rotations increased. Patch-clamp studies demonstrated that ACh-activated potassium current (I(K,ACh)) density was greater in LA than RA sheep myocytes. Additionally, ribonuclease protection assay demonstrated that Kir3.4 and Kir3.1 mRNAs were more abundant in LA than in RA. CONCLUSIONS A greater abundance of Kir3.x channels and higher I(K,ACh) density in LA than RA myocytes result in greater ACh-induced speeding-up of rotors in the LA than in the RA, which explains the ACh dose-dependent changes in overall AF frequency and wavelet formation.

Unique Kir2.x Properties Determine Regional and Species Differences in the Cardiac Inward Rectifier K+ Current

The inwardly rectifying potassium (Kir) 2.x channels mediate the cardiac inward rectifier potassium current (IK1). In addition to differences in current density, atrial and ventricular IK1 have differences in outward current profiles and in extracellular potassium ([K+]o) dependence. The whole-cell patch-clamp technique was used to study these properties in heterologously expressed Kir2.x channels and atrial and ventricular IK1 in guinea pig and sheep hearts. Kir2.x channels showed distinct rectification profiles: Kir2.1 and Kir2.2 rectified completely at potentials more depolarized than −30 mV (I≈0 pA). In contrast, rectification was incomplete for Kir2.3 channels. In guinea pig atria, which expressed mainly Kir2.1, IK1 rectified completely. In sheep atria, which predominantly expressed Kir2.3 channels, IK1 did not rectify completely. Single-channel analysis of sheep Kir2.3 channels showed a mean unitary conductance of 13.1±0.1 pS in 15 cells, which corresponded with IK1 in sheep atria (9.9±0.1 pS in 32 cells). Outward Kir2.1 currents were increased in 10 mmol/L [K+]o, whereas Kir2.3 currents did not increase. Correspondingly, guinea pig (but not sheep) atrial IK1 showed an increase in outward currents in 10 mmol/L [K+]o. Although the ventricles of both species expressed Kir2.1 and Kir2.3, outward IK1 currents rectified completely and increased in high [K+]o-displaying Kir2.1-like properties. Likewise, outward current properties of heterologously expressed Kir2.1-Kir2.3 complexes in normal and 10 mmol/L [K+]o were similar to Kir2.1 but not Kir2.3. Thus, unique properties of individual Kir2.x isoforms, as well as heteromeric Kir2.x complexes, determine regional and species differences of IK1 in the heart.

The MD Blues: Under-Recognized Depression and Anxiety in Medical Trainees

Background Mental health disease is under recognized in medical professionals. Objective To screen medical students (MS), residents and fellows for major depressive disorder (MDD) and generalized anxiety disorder (GAD) under the new era of work hour reform with age-matched controls from a large representative cross-sectional survey. Methods We conducted an anonymous online survey at a medical university in 2013–2014. We incorporated the Patient Health Questionnaire 2 (PHQ-2) to screen for MDD and the generalized anxiety disorder scale (GAD-7) to screen for GAD, along with additional questions on life stressors and academic performance. We compared these results to age-matched controls from the National Health and Nutrition Examination Survey (NHANES) database. Results 126 residents/fellows and 336 medical students participated voluntarily. 15.1% and 15.9% of postgraduates as well as 16.4% and 20.3% of MS screened positive for MDD and GAD, respectively. When compared to national estimates, the prevalence of a positive screen for MDD was over five-fold higher in medical trainees compared to age-matched controls (16% vs. 2.8%, p<0.0001). Similarly, the prevalence of a positive screen for GAD was over eight-fold higher in medical trainees (19% vs. 2.3%, p<0.0001).The prevalence was consistently higher within age strata. 33.3% of postgraduates and 32% of MS believe there is a significant impact of depression or anxiety on their academic performance. For stress relief, one fifth of residents/fellows as well as MS reported alcohol use. Conclusions The stresses of medical education and practice may predispose trainees to psychopathological consequences that can affect their academic performance and patient care. The current study showed a significantly higher rate of MDD and GAD positive screens in medical trainees than the prevalence in an age-matched U.S. population, despite significant work hour reform for medical trainees. Increased awareness and support services are required at all levels of medical training. We propose that the ACGME and the Institute of Medicine may consider these findings when implementing future changes to work hour regulations.

Intermediate‐Term Risk of Stroke Following Cardiac Procedures in a Nationally Representative Data Set

Background Studies on stroke risk following cardiac procedures addressed only perioperative and long‐term risk following limited higher‐risk procedures, were poorly generalizable, and often failed to stratify by stroke type. We calculated stroke risk in the intermediate risk period following cardiac procedures compared with common noncardiac surgeries and medical admissions. Methods and Results The Nationwide Readmissions Database contains readmission data for 49% of US admissions in 2013. We compared age‐adjusted stroke readmission rates up to 90 days postdischarge. We used Cox regression to calculate hazard ratios, up to 1 year, of stroke risk comparing transcatheter aortic valve replacement versus surgical aortic valve replacement and coronary artery bypass graft versus percutaneous coronary intervention. Procedures and diagnoses were identified by International Classification of Disease, Ninth Revision, Clinical Modification codes. After cardiac procedures, 90‐day ischemic stroke readmission rate was highest after transcatheter aortic valve replacement (2.05%); 90‐day hemorrhagic stroke rate was highest after left ventricular assist device placement (0.09%). The hazard ratio for ischemic stroke after transcatheter aortic valve replacement, compared with surgical aortic valve replacement, in fully adjusted Cox models was 1.86 (95% confidence interval, 1.12–3.08; P=0.016) and 6.17 (95% confidence interval, 1.97–19.33; P=0.0018) for hemorrhagic stroke. There was no difference between coronary artery bypass graft and percutaneous coronary intervention. Conclusions We demonstrated elevated readmission rates for ischemic and hemorrhagic stroke in the intermediate 30‐, 60‐, and 90‐day risk periods following common cardiac procedures. Furthermore, we found an elevated risk of stroke after transcatheter aortic valve replacement compared with surgical aortic valve replacement up to 1 year.

A Successful Pharmacist-Based Quality Initiative to Reduce Inappropriate Stress Ulcer Prophylaxis Use in an Academic Medical Intensive Care Unit

Stress ulcer prophylaxis (SUP) is often inappropriately utilized, particularly in critically ill patients. The objective of this study is to find an effective way of reducing inappropriate SUP use in an academic medical intensive care unit (ICU). Medical ICU patients receiving SUP were identified over a 1-month period, and their charts were reviewed to determine whether American Society of Health-System Pharmacists guidelines were followed. Inappropriate usage was calculated as inappropriate patient-days and converted to incidence per 100 patient-days. Two interventions were implemented: (1) Pharmacists reviewed indications for SUP on each patient during daily team rounds and daily medication reconciliation and (2) residents rotating on ICU services were educated on a bimonthly basis. Postintervention data were obtained in a similar fashion. Prior to intervention, the incidence of inappropriate SUP usage was calculated to be 26.75 per 100 patient-days (n = 1099 total patient-days). Total cost attributable to the inappropriate use was

Extensive Cutaneous Scalp Angiosarcoma

2433. Post intervention, we were able to decrease the inappropriate incidence of SUP usage to 7.14 per 100 patient-days (n = 1149 total patient-days). In addition, total cost of inappropriate use was reduced to

Carotid artery dissection: a rare complication of Eagle syndrome.

239.80. Our study highlights an effective multidisciplinary approach to reduce the inappropriate use of SUP in an academic medical ICU. We were able to reduce the incidence of inappropriate use of SUP by 73.31% (P < .001). Furthermore, we were able to decrease the costs by approximately

A novel case of Raoultella planticola osteomyelitis and epidural abscess.

2200/month.

Back pain and oedematous Schmorl node: a diagnostic dilemma

Angiosarcoma is a cancer that is derived from endothelial cells that line blood vessels and lymphatic channels. Cutaneous angiosarcoma can appear anywhere on the skin and the clinical presentation is highly variable. Most cases appear on the scalp and face de novo. Our case describes a 91-year-old female with cutaneous scalp angiosarcoma. Our case serves to remind physicians that an abnormal skin finding in older adults should raise their index of suspicion for angiosarcoma and an early biopsy should be performed.