Physiologic Pacing Targeting the His Bundle and Left Bundle Branch: a Review of the Literature.

PURPOSE OF REVIEW: Conduction system pacing (CSP) has emerged as a means to preserve or restore physiological ventricular activation via pacing at the His bundle or at more distal targets in the conduction system, including the left bundle branch area. This review examines strengths, weaknesses, and clinical applications of CSP performed via these approaches. RECENT FINDINGS: His bundle pacing (HBP) has been successfully utilized for standard bradyarrhythmia indications and for QRS correction among patients receiving devices for cardiac resynchronization therapy (CRT). Limitations of HBP pacing have included implant complexity and rising pacing thresholds over time. Left bundle branch area pacing (LBBAP) appears to deliver similar physiological benefits with shorter implant times and more stable thresholds. More recently, hybrid systems utilizing HBP or LBBAP in combination with left ventricular leads have been used to treat heart failure (HF) patients, and may be useful in multilevel or mixed conduction blocks. There is growing interest in CSP for bradycardia and HF indications, although high quality data with randomized controlled trials are needed to help guide future treatment paradigms.

Improving Direct Admissions to Internal Medicine Services.

BACKGROUND: Direct admissions from clinic or home to the hospital may improve efficiency and reduce emergency room utilization, but nonoptimized processes may increase the risk of harm during the transition of care. Our multidisciplinary team aimed to understand and improve the process of directly admitting patients to inpatient medicine services at a large academic medical center. METHODS: In this single-institution quality improvement initiative, we identified key communication gaps within the direct admission process and implemented a handoff tool in the form of a templated note and order set to bridge those communication gaps. The primary outcome measure was the monthly utilization rate of the handoff note as a surrogate for handoffs and uptake of the intervention. RESULTS: We launched our intervention in April 2022. We achieved sustained use of the SmartText and a peak of 24% of direct admissions utilizing the SmartText in January 2023. Based on feedback during Plan-Do-Study-Act cycles, we added direct admission instructions for outpatient teams to follow in the order set and reduced text in the handoff note. CONCLUSIONS: This study demonstrates the design and implementation of a quality improvement initiative to identify and address communication gaps for direct admissions of adult medicine patients.

A human Tau expressing zebrafish model of progressive supranuclear palsy identifies Brd4 as a regulator of microglial synaptic elimination.

Progressive supranuclear palsy (PSP) is an incurable neurodegenerative disease characterized by 4-repeat (0N/4R)-Tau protein accumulation in CNS neurons. We generated transgenic zebrafish expressing human 0N/4R-Tau to investigate PSP pathophysiology. Tau zebrafish replicated multiple features of PSP, including: decreased survival; hypokinesia; impaired optokinetic responses; neurodegeneration; neuroinflammation; synapse loss; and Tau hyperphosphorylation, misfolding, mislocalization, insolubility, truncation, and oligomerization. Using automated assays, we screened 147 small molecules for activity in rescuing neurological deficits in Tau zebrafish. (+)JQ1, a bromodomain inhibitor, improved hypokinesia, survival, microgliosis, and brain synapse elimination. A heterozygous brd4+/- mutant reducing expression of the bromodomain protein Brd4 similarly rescued these phenotypes. Microglial phagocytosis of synaptic material was decreased by (+)JQ1 in both Tau zebrafish and rat primary cortical cultures. Microglia in human PSP brains expressed Brd4. Our findings implicate Brd4 as a regulator of microglial synaptic elimination in tauopathy and provide an unbiased approach for identifying mechanisms and therapeutic targets in PSP.

Preservation of Circumferential and Radial Left Ventricular Function as a Mitigating Mechanism for Impaired Longitudinal Strain in Early Cardiac Amyloidosis.

BACKGROUND: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden. METHODS: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CAHFpEF, CAHFrEF) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CAHFpEF and CAHFrEF and between ECV quartiles. RESULTS: While echocardiography-derived GLS was impaired in both CAHFpEF (-13.4% ± 3.1%, P < .003) and CAHFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CAHFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CAHFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CAHFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles. CONCLUSIONS: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective.

Non-invasive diagnosis of transthyretin cardiac amyloidosis utilizing typical late gadolinium enhancement pattern on cardiac magnetic resonance and light chains.

AIMS: While cardiac magnetic resonance (CMR) is often obtained early in the evaluation of suspected cardiac amyloidosis (CA), it currently cannot be utilized to differentiate immunoglobulin (AL) and transthyretin (ATTR) CA. We aimed to determine whether a novel CMR and light-chain biomarker-based algorithm could accurately diagnose ATTR-CA. METHODS AND RESULTS: Patients with confirmed AL or ATTR-CA with typical late gadolinium enhancement (LGE) and Look-Locker pattern for CA on CMR were retrospectively identified at three academic medical centres. Comprehensive light-chain analysis including free light chains, serum, and urine electrophoresis/immunofixation was performed. The diagnostic accuracy of the typical CMR pattern for CA in combination with negative light chains for the diagnosis of ATTR-CA was determined both in the entire cohort and in the subset of patients with invasive tissue biopsy as the gold standard. A total of 147 patients (age 70 ± 11, 76% male, 51% black) were identified: 89 ATTR-CA and 58 AL-CA. Light-chain biomarkers were abnormal in 81 (55%) patients. Within the entire cohort, the sensitivity and specificity of a typical LGE and Look-Locker CMR pattern and negative light chains for ATTR-CA was 73 and 98%, respectively. Within the subset with biopsy-confirmed subtype, the CMR and light-chain algorithm were 69% sensitive and 98% specific. CONCLUSION: The combination of a typical LGE and Look-Locker pattern on CMR with negative light chains is highly specific for ATTR-CA. The successful non-invasive diagnosis of ATTR-CA using CMR has the potential to reduce diagnostic and therapeutic delays and healthcare costs for many patients.

Pulmonary Presentation of Kaposi-Sarcoma in a Renal Transplant Recipient.

Renal transplant patients on immunosuppression are at risk for malignancy. One form of malignancy that commonly affects this population is Kaposi-sarcoma. Kaposi-sarcoma is a human herpesvirus-8 (HHV-8)-driven process classically associated with skin lesions in immunocompromised patients. The pulmonary system may be involved in disseminated disease. In this case, a renal transplant patient was re-admitted with acute hypoxic respiratory failure and hemoptysis of an unclear etiology. Following a broad workup, HHV-8 PCR and a lymph node biopsy confirmed pulmonary Kaposi-sarcoma. Workup for multicentric Castleman disease was negative. The patient was treated with liposomal doxorubicin, ganciclovir, and prednisone. Her immunosuppression was changed to sirolimus and she is scheduled to complete six cycles of liposomal doxorubicin.

Teaching neurological disorders with ultrasound: A novel workshop for medical students.

INTRODUCTION: The goal of this study was to assess if a neurological disorder ultrasound workshop for the first-year medical students significantly enhanced the students' ability to retain and apply concepts related to neuroanatomy and neurophysiology. MATERIALS AND METHODS: We performed a prospective study to evaluate student performance before and after an optional ultrasound workshop. Data were collected through a within-population pretest-posttest design. Purposive sampling was used to recruit first-year medical students for this study. The six stations were transcranial doppler ultrasound, ocular ultrasound, ultrasound-guided external ventricular drain placement, high-intensity focused ultrasound for brain lesions, carotid artery scan with ultrasound, and ultrasound-guided central line placement. We used a pre-post workshop survey to identify opinions and perceptions about ultrasound and a pre-post workshop test to assess knowledge about neuroanatomy, neurophysiology, and related ultrasound topics. RESULTS: Twenty-two 22 first-year medical students consented to participate in this study. The Wilcoxon signed-rank test showed a statistically significant difference in pre- and posttest scores, suggesting that participants demonstrated higher levels of medical knowledge related to neurological physiology, anatomy, and ultrasound after participating in the workshop. The analysis of the pre-post survey showed participants attributed greater value to ultrasound as a useful tool for their future medical practice after participation in the event (Z = -2.45, P = 0.014). CONCLUSIONS: There is value in integrating experiences with ultrasound into the neurological disorder block of medical school. Future studies, with a larger sample size, are needed to further explore the efficacy of this workshop in enhancing knowledge retention.

Chronic mesenteric ischaemia masked by candida esophagitis in a renal transplant patient.

Chronic mesenteric ischaemia is a severe disease that is often missed due to its non-specific presentation. Immunosuppressed patients are at risk for infectious gastrointestinal disease, which may further obscure the diagnosis of chronic mesenteric ischaemia. In this case, a patient's symptoms and diagnostic workup were consistent with candida esophagitis. Worsening leukocytosis despite treatment, however, prompted re-evaluation ultimately revealing a superior mesenteric artery thrombus causing mesenteric ischaemia. The patient required urgent surgical intervention for the management of his disease.

Retrospective Analysis of Perioperative Variables Associated With Postoperative Delirium and Other Adverse Outcomes in Older Patients After Spine Surgery.

BACKGROUND: The aim of this retrospective study was to identify perioperative variables predictive of the development of delirium in older surgical patients after spine surgery. MATERIALS AND METHODS: We collected preoperative, intraoperative, and postoperative data on patients 65 years of age and above having spine surgery between July 1, 2015 and March 15, 2017. The primary outcome was the development of postoperative delirium. Data were analyzed using univariate and multivariable analysis. RESULTS: Among the 716 patients included in this study 127 (18%) developed postoperative delirium. On multivariable analysis, independent predictors of postoperative delirium included older age (odds ratio [OR]=1.04; 95% confidence interval [CI], 1.00-1.09; P=0.048), American Society of Anesthesiologists physical status >2 (OR=1.89 [95% CI, 1.04-3.59]; P=0.042), metabolic equivalents of task <4 (OR=1.84 [95% CI, 1.10-3.07]; P=0.019), depression (OR=2.01 [95% CI, 1.21-3.32]; P=0.006), nonelective surgery (OR=4.81 [95% CI, 1.75-12.79]; P=0.002), invasive surgical procedures (OR=1.97 [95% CI, 1.10-3.69]; P=0.028) and higher mean pain scores on postoperative day 1 (OR=1.28 [95% CI, 1.11-1.48]; P<0.001). CONCLUSIONS: Postoperative delirium is a common complication in older patients after spine surgery, and there are several perioperative risk factors associated with its development.

Modulation of the zebrafish optokinetic reflex by pharmacologic agents targeting GABAA receptors.

Optokinetic reflex (OKR) responses provide a convenient means to evaluate visual, integrative and oculomotor function in larval zebrafish. We measured multiple aspects of the OKR response in zebrafish exposed systemically to compounds altering signaling at GABAA receptors in order to derive quantitative concentration-response relationships. The GABAA antagonist picrotoxin caused concentration-dependent decreases in reflex gain, saccade velocity, saccade amplitude, interocular concordance and interocular gain. Conversely, the GABAA agonist gaboxadol provoked increases in reflex gain, saccade velocity, saccade amplitude and ocular range at low concentrations, and decreases in some of these parameters at higher concentrations. These data show that GABAA signaling influences multiple aspects of the OKR (including gain, generation of saccades, and coordination between the two eyes) and provide proof of concept that quantitative OKR analysis can be used as a tool for chemical biology and neuropharmacology applications.

An open-source method to analyze optokinetic reflex responses in larval zebrafish.

BACKGROUND: Optokinetic reflex (OKR) responses provide a convenient means to evaluate oculomotor, integrative and afferent visual function in larval zebrafish models, which are commonly used to elucidate molecular mechanisms underlying development, disease and repair of the vertebrate nervous system. NEW METHOD: We developed an open-source MATLAB-based solution for automated quantitative analysis of OKR responses in larval zebrafish. The package includes applications to: (i) generate sinusoidally-transformed animated grating patterns suitable for projection onto a cylindrical screen to elicit the OKR; (ii) determine and record the angular orientations of the eyes in each frame of a video recording showing the OKR response; and (iii) analyze angular orientation data from the tracking program to yield a set of parameters that quantify essential elements of the OKR. The method can be employed without modification using the operating manual provided. In addition, annotated source code is included, allowing users to modify or adapt the software for other applications. RESULTS: We validated the algorithms and measured OKR responses in normal larval zebrafish, showing good agreement with published quantitative data, where available. COMPARISON WITH EXISTING METHOD(S): We provide the first open-source method to elicit and analyze the OKR in larval zebrafish. The wide range of parameters that are automatically quantified by our algorithms significantly expands the scope of quantitative analysis previously reported. CONCLUSIONS: Our method for quantifying OKR responses will be useful for numerous applications in neuroscience using the genetically- and chemically-tractable zebrafish model.