Longitudinal Assessment of Left Ventricular Function in Patients with Myopericarditis After mRNA COVID-19 Vaccination.

BACKGROUND: Multiple reports have described myopericarditis following mRNA COVID-19 vaccination. However, data on the persistence of subclinical myocardial injury assessed by left ventricular (LV) longitudinal strain (LVLS) is limited. OBJECTIVES: Our aim was to assess LV function longitudinally in our cohort of COVID-19 vaccine-related myopericarditis using ejection fraction (EF), fractional shortening (FS), LVLS, and diastolic parameters. METHODS: Retrospective, single-center review of demographic, laboratory, and management data was performed on 20 patients meeting diagnostic criteria for myopericarditis after mRNA COVID-19 vaccination. Echocardiographic images were obtained on initial presentation (time 0), at a median of 12 days (7.5, 18.5; time 1), and at a median of 44 days (29.5, 83.5; time 2). FS was calculated by M-mode, EF by 5/6 area-length methods, LVLS by utilization of TOMTEC software, and diastolic function by tissue Doppler. All parameters were compared across pairs of these time points using Wilcoxon signed-rank test. RESULTS: Our cohort consisted predominantly of adolescent males (85%) with mild presentation of myopericarditis. The median EF was 61.6% (54.6, 68.0), 63.8% (60.7, 68.3), 61.4% (60.1, 64.6) at times 0, 1, and 2, respectively. Upon initial presentation, 47% of our cohort had LVLS < -18%. The median LVLS was -18.6% (-16.9, -21.0) at time 0, -21.2% at time 1 (-19.4, -23.5) (p = 0.004) and -20.8% (-18.7, -21.7) at time 2 (p = 0.004, as compared to time 0). CONCLUSIONS: Though many of our patients had abnormal strain during acute illness, LVLS improved longitudinally, indicating myocardial recovery. LVLS can be used as marker of subclinical myocardial injury and risk stratification in this population.

Unsuccessful treatment of methicillin-resistant Staphylococcus aureus endocarditis with dalbavancin.

WHAT IS KNOWN AND OBJECTIVE: Limited evidence describes dalbavancin use in infective endocarditis (IE). CASE DESCRIPTION: A 27-year-old pregnant female received 4 weeks of dalbavancin for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and tricuspid valve IE after conventional therapy was no longer an option due to non-compliance. Despite having a smaller cardiac vegetation following dalbavancin, she was bacteraemic <2 weeks later with vancomycin-intermediate (VISA) and telavancin-non-susceptible S. aureus. WHAT IS NEW AND CONCLUSION: This is the first report of unsuccessful IE treatment with dalbavancin. Blood cultures grew VISA and lipoglycopeptide-non-susceptible S. aureus <2 weeks following dalbavancin. Both outcomes raise concerns about using dalbavancin for IE.

Constitutive and chemokine-dependent internalization and recycling of CXCR7 in breast cancer cells to degrade chemokine ligands.

CXCR7 is a receptor for chemokines including CXCL12 (stromal-derived factor-1), a molecule that promotes tumor growth and metastasis in breast cancer and other malignancies. Building on the recent observation that CXCR7 sequesters CXCL12, we investigated mechanisms for CXCR7-dependent uptake of chemokines. Breast cancer cells expressing CXCR7 accumulated chemokines CXCL12 and CXC11 present at concentrations <1 ng/ml, unlike cells expressing CXCR4. CXCR7-dependent accumulation of chemokines was reduced by inhibitors of clathrin-mediated endocytosis. After CXCR7-mediated internalization, CXCL12 trafficked to lysosomes and was degraded, although levels of CXCR7 remained stable. CXCR7 reduced CXCL12 in the extracellular space, limiting the amounts of chemokine available to acutely stimulate signaling through CXCR4. CXCR7 constitutively internalized and recycled to the cell membrane even in the absence of ligand, and addition of chemokines did not significantly enhance receptor internalization. Chemokines at concentrations less than the Kd values for ligand-receptor binding did not alter levels of CXCR7 at the cell surface. Higher concentrations of chemokine ligands reduced the total cell surface expression of CXCR7 without affecting receptor internalization, indicating that receptor recycling was inhibited. CXCR7-dependent uptake of chemokines and receptor trafficking were regulated by beta-arrestin 2. These studies establish mechanisms through which CXCR7 regulates the availability of chemokine ligands in the extracellular space.

Disease progression in recently diagnosed patients with inherited marrow failure syndromes: a Canadian Inherited Marrow Failure Registry (CIMFR) report.

BACKGROUND: Inherited bone marrow failure syndromes (IMFSs) are genetic disorders characterized by defective single-lineage or multi-lineage hematopoiesis. IMFS patients are at risk for severe cytopenias, development of marrow cytogenetic abnormalities (MCA), myelodysplasia (MDS), and malignancy. The rate of disease progression and proportion of patients at risk for these complications is currently unclear. We examined recently diagnosed IMFS patients to determine distribution of diagnoses, disease progression and development of significant outcomes. METHODS: The CIMFR is a prospective multi-center study established in 2001 to register all IMFS patients in Canada. Analysis was restricted to patients diagnosed after November 30, 1997. Summary statistics were used to depict the study population while survival was described using the Kaplan-Meier method. RESULTS: 74 CIMFR patients were considered recently diagnosed. Median age at diagnosis was 2.7 years (range, birth to 40.6). Annual follow-up data were available for 53 (72%) patients. The five most prevalent diagnoses were Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), dyskeratosis congenita (DKC), and Kostmann's neutropenia (KS). Eighteen (24%) patients were unclassifiable. Twenty-eight (53%) follow-up patients had disease progression as indicated by new or worsening cytopenias, new marrow changes, or initiation of transfusion support and/or medical therapy. Fourteen (19%) fulfilled minimal diagnostic criteria for myelodysplasia. Eleven patients had hematopoietic stem cell transplantation (HSCT) by first follow-up. Five patients have died. Survival at 36 months is 89.8 +/- 5.7%. CONCLUSIONS: IMFS patients are often diagnosed at a young age. The relative distribution of diagnoses is similar to previous reviews of published cases; however, 25% of patients are currently unclassifiable. Disease progression has occurred in approximately 50% of follow-up patients. Early mortality is noted. Continued prospective observation of these patients is warranted.

Magnetic plasmon propagation along a chain of connected subwavelength resonators at infrared frequencies.

A one-dimensional magnetic plasmon propagating in a linear chain of single split ring resonators is proposed. The subwavelength size resonators interact mainly through exchange of conduction current, resulting in stronger coupling as compared to the corresponding magneto-inductive interaction. Finite-difference time-domain simulations in conjunction with a developed analytical theory show that efficient energy transfer with signal attenuation of less then 0.57 dB/microm and group velocity higher than 1/4c can be achieved. The proposed novel mechanism of energy transport in the nanoscale has potential applications in subwavelength transmission lines for a wide range of integrated optical devices.

Plasmons in the metallic nanoparticle-film system as a tunable impurity problem.

We show that the plasmon resonances of a metallic nanoparticle interacting with the surface plasmons of a metallic film is an electromagnetic analogue of the spinless Anderson-Fano model. This is the same model used to describe the interaction of a localized electronic state with a continuous band of electronic states. The three characteristic regimes of this model are realized here, where the energy of the nanoparticle plasmon resonance lies above, within, or below the energy band of surface plasmon states. These three interaction regimes are controlled by film thickness. The latter regime is experimentally observed and identified.

Three statistical technologies with high potential in biological imaging and modeling.

The three technologies that are surveyed here are (1) wavelet approximations, (2) hidden Markov models, and (3) the Markov chain Renaissance. The intention of the article is to provide an introduction to the benefits these technologies offer and to explain as far as possible the sources of their effectiveness. We also hope to suggest some useful relationships between these technologies and issues of importance on the agenda of biological and medical research.

An evaluation of the effectiveness of cardiac teaching during hospitalization.

This evaluation demonstrated that inpatient teaching programs can be effective for short-term outcomes. In this evaluation, patients readily learned information that prepared them to deal with postoperative experiences, that is, ambulation, exercise, resumption of sexual activity, and symptoms to report indicating lack of tolerance to such activities. Areas that showed limited knowledge gain were those that required long-term behavioral change, such as stress modification and dietary changes. These findings are particularly relevant when considered in the light of contemporary events in the payment environment. As lengths of stay decrease and acuity levels increase for hospitalized patients, inpatient teaching must be limited to what is possible and reasonable; that is, what is possible for the staff to teach during the short length of stay and what is reasonable for patients to learn given their acuity. This evaluation was conducted for decision-making purposes about a specific cardiac teaching program. Although the evaluation met the purposes of the evaluators, some of the findings suggested possible research hypotheses. A tightly controlled research study should be conducted using the knowledge acquisition test in clinical settings and accounting for such variables as educational level, years of coronary artery disease, severity of illness, and age. Further study could also be undertaken to validate the finding that hospitalized patients learned priority information necessary for adequate functioning immediately after discharge. With regard to patient confidence level and actual behavior change, a study could be conducted to determine if there is a relationship between patients' reported confidence at discharge and their subsequent behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of survey information to develop a hospital-based medication teaching program.

As the volume of prescribed medications and complexity of regimen continue to rise, medication instruction is imperative, particularly for patients with chronic illness who must care for themselves without direct supervision of health care professionals. However, as hospital acuity levels increase and lengths of stay decrease, limited opportunity exists to adequately prepare hospitalized patients who are to be discharged with new prescriptions. Hospital-based medication teaching programs must be designed so that they encourage patient-professional interaction, yet also conserve nursing staff time. In this project, members of a hospital-based, interdisciplinary committee used survey information to develop a basic medication instruction program that emphasized 'need to know' content. The program was designed to involve patients and also to encourage them to seek additional information from other providers. Potential for successful implementation was enhanced by participation of nurse managers who developed the pilot implementation procedure.

Modification of hemoglobin with analogs of aspirin.

A variety of acyl esters of salicyclic acid and 3,5-dibromosalicylic acid have been prepared and examined for their ability to place the acyl group on hemoglobin. In general, short chain acyl groups (C2 and C3) are more reactive than longer chains (C4 to C10), but longer chains may be more effective with intact red cells because of their enhanced ability to permeate the erythrocyte membrane. The brominated salicyl esters also exhibit enhanced permeation of the membrane, as well as increased activity due to activation at the acyl site. Bis(salicyl) esters, nonbrominated and brominated, are more reactive than corresponding monoesters, and those from C4 dicarboxylic acids connect beta subunits by covalent bridges. These double-headed aspirins have the attractive features of being bound selectively by hemoglobin and of forming a covalent cross-link that may influence the conformation of the tetramer.

Role of intrarenal vascular sclerosis in progression of poststreptococcal glomerulonephritis.

A comparison has been made of the percentage of sclerotic glomeruli found in normal subjects and in 31 patients 6 months to 15 years after an episode of acute poststreptococcal glomerulonephritis (PSGN). The findings establish that a greater than expected incidence of glomerular sclerosis occurs in the course of PSGN. The pattern of glomerular sclerosis frequently was that of contracted collapsed tufts, one known to result from ischemia. In the majority of specimens with significant glomerular sclerosis, there was co-existent vascular sclerosis (arterioles and/or prearterioles), and the incidence of both glomerular and vascular sclerosis increased with time from onset of PSGN. Intrarenal vascular sclerosis may thus be of major importance in the genesis and progression of glomerular sclerosis in PSGN.

Rebound hypertension after sodium nitroprusside-induced hypotension.

Patients undergoing surgical procedures using sodium nitroprusside-induced hypotension were studied to determine the role of the renin-angiotensin system in the pathogenesis of rebound hypertension (RH) after discontinuing sodium nitroprusside (SNP) infusion. Retrospective observations documented RH in 9 of 12 patients (group I) with a systolic blood pressure (SBP) increase from 112 +/- 3.92 before SNP to 144 +/- 5.60 torr 10 min after SNP (p less than 0.001). In 12 patients (group II), plasma renin activity (PRA) rose from 950 +/- 432 to 3,611 +/- 1.874 pg/ml/hr (p less than 0.0005) during SNP and remained elevated (2,504 +/- 792 pg/ml/hr) 30 min after cessation of SNP. SBP rose from a control (pre-SNP) value of 112 +/- 5.24 to 129 +/- 8.52 torr after discontinuation of SNP (p less than 0.05). Significant PRA and SBP changes did not occur in a matched group of patients (group III) who did not receive SNP. That RH after cessation of SNP infusion was associated with persistent elevation of PRA leads us to suggest that RH may be attributable to the unopposed effects of the renin-angiotensin system after the rapid plasma disappearance of SNP.

Effect of a heptapeptide angiotensin analog on aldosterone secretion in the rabbit.

We examined the effects of an angiotensin III (AIII) analog, isoleucine-7 AIII (Ile7-AIII), on the steroidogenic and pressor responses to angiotensin II (AII) and AIII. AII or AIII (25 ng/kg/min) were infused alone or superimposed on an infusion of Ile7-AIII (100 ng/kg/min) in conscious male New Zealand rabbits. AII and AIII induced comparable increases in plasma aldosterone concentration, but AII exhibited significantly greater pressor effect. Ile7-AIII infusion resulted in significant inhibition of AII- but not AIII-induced steroidogenesis. Despite inhibition of aldosterone production, Ile7-AIII failed to block the pressor or renin-suppressing effect of AII. Inhibition of the steroidogenic effect of AII, but not of AII, by Ile7-AIII may be taken as evidence that adrenal stimulation by AII is direct and is not mediated by in vivo conversion to the heptapeptide. The ability of the heptapeptide analog to block aldosterone stimulation by the octapeptide AII suggests that adrenal receptors may, however, have a greater affinity for the heptapeptide.

Unimpaired beta adrenergic responses during prazosin administration.

We have examined insulin-induced hypoglycemia to determine whether prazosin inhibits the response to sympathetic stimulation, either centrally or at beta adrenergic receptors. Nine patients with essential hypertension were studied during administration of prazosin, hydralazine or placebo. Plasma renin activity increased significantly with hydralazine and was unchanged during prazosin administration. In response to insulin, blood glucose decreased equally with both drugs and placebo, and small increases in dopamine beta-hydroxylase occurred. Plasma renin activity and heart rate increased during hypoglycemia; the increases were greater in patients taking prazosin or hydralazine. The unimpaired responses of plasma dopamine beta-hydroxylase, renin activity and heart rate to insulin-induced hypoglycemia provide evidence that prazosin does not block either the sympathetic discharge elicited by central stimulation (hypoglycemia) or the responses mediated through beta adrenergic receptors.

Diaspirins that cross-link beta chains of hemoglobin: bis(3,5-dibromosalicyl) succinate and bis(3,5-dibromosalicyl) fumarate.

Two double-headed aspirins, bis(3,5-dibromosalicyl) succinate and bis(3,5-dibromosalicyl) fumarate, have been found to be potent acylating agents of intracellular hemoglobin (A or S) in vitro. Furthermore, each of these reagents cross-links beta chains of hemoglobin, probably at the beta cleft. The modified hemoglobins show increased oxygen affinities and reduced gelation or sickling tendencies.

Plasma renin and serum dopamine-beta-hydroxylase during orthostatic hypotension in quadriplegic man.

To determine whether orthostatic hypotension in patients with cervical spinal cord lesions is the result of impaired sympathetic nerve response and/or impaired renin release, serum dopamine-beta-hydroxylase (DbetaH) activity and plasma renin activity (PRA) were examined during passive tilting in 6 quadriplegic patients and in 6 able-bodied control subjects. Serum DbetaH was measured by an isotopic enzymatic method and PRA by radioimmunoassay. Following head-up tilting, quadriplegic subjects demonstrated a prompt, significant decrease in mean arterial pressure (MAP) and increase in heart rate (HR). DbetaH and PRA both increased significantly 15 minutes after tilt. In normal subjects, although HR increased, MAP was unchanged; DbetaH and PRA did not increase significantly during head-up tilt. The finding of increased DbetaH during tilt hypotension in quadriplegic patients provides evidence that reflex sympathetic nerve stimulation persists despite cervical cord transection. Increased PRA may be attributed to decreased renal perfusion pressure and increased sympathetic stimulation during tilt hypotension. These data suggest that orthostatic hypotension in quadriplegia patients cannot be attributed solely to failure of the sympathetic nervous system or the renin-angiotensin system to respond to the stimulus of orthostasis.

Aldosterone production during dietary sodium restriction and beta-adrenergic blockade.

The role of the renin-angiotensin system in mediating the aldosterone response to sodium depletion was examined by administration of propranolol during dietary sodium restriction. The beta-adrenergic antagonist prevented the expected increase of plasma renin activity in response to sodium restriction in six of twelve studies. Plasma angiotensin II concentration failed to increase in four of five subjects in whom the renin response was abolished. Despite unchanged or decreased plasma renin activity and plasma angiotensin II concentration, plasma aldosterone concentration increased significantly in response to dietary sodium restriction. The increase in aldosterone production could not be attributed to changes in plasma sodium or potassium concentration or increased ACTH secretion. It is suggested that the aldosterone response to sodium restriction is mediated not only by increased plasma renin activity and angiotensin II concentration, but also another mechanism, possibly related to increased adrenal sensitivity to angiotensin during sodium depletion.