Evidence of SARS-CoV-2 Antibody in Mississippi White-Tailed Deer.

Background: Early detection and monitoring of SARS-CoV-2 infections in animal populations living in close proximity to humans is crucial for preventing reverse zoonosis of new viral strains. Evidence accumulated has revealed widespread SARS-CoV-2 infection among white-tailed deer (WTD), (Odocoileus virginianus) populations in the United States except in the southeast region. Therefore, the objective was to conduct surveillance for evidence of SARS-CoV-2 infection among WTD in Mississippi. Materials and Methods: Blood, kidney tissues, and nasal swab samples were collected in 17 counties from hunter-harvested deer during 2021-2022 and 2022-2023.Samples of kidney tissue were collected to evaluate for detecting antibody as a possible alternative to blood that is not always available from dead WTD. Nasal swab samples were tested for SARS-CoV-2 viral RNA by a RT-PCR assay. Sera and kidney tissue samples were tested for SARS-CoV-2 antibody by an enzyme-linked immunoassay (ELISA) and sera by a plaque reduction neutralization test (PRNT80). Results: The results of testing sera and kidney homogenate samples provided the first evidence of SARS-CoV-2 infection among WTD in Mississippi. The infection rate during 2021-2022 was 67% (10/15) based on the detection of neutralizing antibody by the PRNT80 and 26%(16/62) based on the testing of kidney tissue homogenates by an ELISA, and viral RNA was detected in 25% (3/12) of nasal swab samples. In 2022 to 2023, neutralizing antibody was detected in 62% (28/45) of WTD serum samples. In contrast, antibodies were not detected in 220 kidney homogenates by an ELISA nor was viral RNA detected in 220 nasal swab samples. Evidence of WTD activity was common in urban areas during the survey. Conclusion: Overall, the findings documented the first SARS-CoV-2 infection among WTD in Mississippi and showed that WTD commonly inhabited urban areas as a possible source of acquiring infection from humans infected with this virus.

Eliminating Algorithmic Racial Bias in Clinical Decision Support Algorithms: Use Cases from the Veterans Health Administration.

The Veterans Health Administration uses equity- and evidence-based principles to examine, correct, and eliminate use of potentially biased clinical equations and predictive models. We discuss the processes, successes, challenges, and next steps in four examples. We detail elimination of the race modifier for estimated kidney function and discuss steps to achieve more equitable pulmonary function testing measurement. We detail the use of equity lenses in two predictive clinical modeling tools: Stratification Tool for Opioid Risk Mitigation (STORM) and Care Assessment Need (CAN) predictive models. We conclude with consideration of ways to advance racial health equity in clinical decision support algorithms.

Accuracy of remote chest X-ray interpretation using Google Glass technology.

OBJECTIVES: We sought to explore the accuracy of remote chest X-ray reading using hands-free, wearable technology (Google Glass, Google, Mountain View, California). METHODS: We compared interpretation of twelve chest X-rays with 23 major cardiopulmonary findings by faculty and fellows from cardiology, radiology, and pulmonary-critical care via: (1) viewing the chest X-ray image on the Google Glass screen; (2) viewing a photograph of the chest X-ray taken using Google Glass and interpreted on a mobile device; (3) viewing the original chest X-ray on a desktop computer screen. One point was given for identification of each correct finding and a subjective rating of user experience was recorded. RESULTS: Fifteen physicians (5 faculty and 10 fellows) participated. The average chest X-ray reading score (maximum 23 points) as viewed through the Google Glass, Google Glass photograph on a mobile device, and the original X-ray viewed on a desktop computer was 14.1±2.2, 18.5±1.5 and 21.3±1.7, respectively (p<0.0001 between Google Glass and mobile device, p<0.0001 between Google Glass and desktop computer and p=0.0004 between mobile device and desktop computer). Of 15 physicians, 11 (73.3%) felt confident in detecting findings using the photograph taken by Google Glass as viewed on a mobile device. CONCLUSION: Remote chest X-ray interpretation using hands-free, wearable technology (Google Glass) is less accurate than interpretation using a desktop computer or a mobile device, suggesting that further technical improvements are needed before widespread application of this novel technology.

Cardiac-restricted overexpression or deletion of tissue inhibitor of matrix metalloproteinase-4: differential effects on left ventricular structure and function following pressure overload-induced hypertrophy.

Historically, the tissue inhibitors of matrix metalloproteinases (TIMPs) were considered monochromatic in function. However, differential TIMP profiles more recently observed with left ventricular (LV) dysfunction and matrix remodeling suggest more diverse biological roles for individual TIMPs. This study tested the hypothesis that cardiac-specific overexpression (TIMP-4OE) or deletion (knockout; TIMP-4KO) would differentially affect LV function and structure following pressure overload (LVPO). LVPO (transverse aortic constriction) was induced in mice (3.5 ± 0.1 mo of age, equal sex distribution) with TIMP-4OE (n = 38), TIMP-4KO (n = 24), as well as age/strain-matched wild type (WT, n = 25), whereby indexes of LV remodeling and function such as LV mass and ejection fraction (LVEF) were determined at 28 days following LVPO. Following LVPO, both early (7 days) and late (28 days) survival was ~25% lower in the TIMP-4KO group (P < 0.05). While LVPO increased LV mass in all groups, the relative hypertrophic response was attenuated with TIMP-4OE. With LVPO, LVEF was similar between WT and TIMP-4KO (48 ± 2% and 45 ± 3%, respectively) but was higher with TIMP-4OE (57 ± 2%, P < 0.05). With LVPO, LV myocardial collagen expression (type I, III) increased by threefold in all groups (P < 0.05), but surprisingly this response was most robust in the TIMP-4KO group. These unique findings suggest that increased myocardial TIMP-4 in the context of a LVPO stimulus may actually provide protective effects with respect to survival, LV function, and extracellular matrix (ECM) remodeling. These findings challenge the canonical belief that increased levels of specific myocardial TIMPs, such as TIMP-4 in and of themselves, contribute to adverse ECM accumulation following a pathological stimulus, such as LVPO.

Preventing deep wound infection after coronary artery bypass grafting: a review.

The consequences of deep wound infections before, during, and after coronary artery bypass grafting have prompted research to clarify risk factors and explore preventive measures to keep infection rates at an irreducible minimum. An analysis of 42 studies in which investigators used multivariate logistic regression analysis revealed that diabetes mellitus and obesity are by far the chief preoperative risk factors. A 4-point preoperative scoring system based on a patient's body mass index and the presence or absence of diabetes is one practical way to determine the risk of mediastinitis, and other risk-estimate methods are being refined. Intraoperative risk factors include prolonged perfusion time, the use of one or more internal mammary arteries as grafts, blood transfusion, and mechanical circulatory assistance. The chief postoperative risk factor is reoperation, usually for bleeding. Unresolved issues include the optimal approach to Staphylococcus aureus nasal colonization and the choice of a prophylactic antibiotic regimen. We recommend that cardiac surgery programs supplement their audit processes and ongoing vigilance for infections with periodic, multidisciplinary reviews of best-practice standards for preoperative, intraoperative, and postoperative patient care.

Myocardial remodeling with aortic stenosis and after aortic valve replacement: mechanisms and future prognostic implications.

Aortic valve stenosis is a common cause of left ventricular pressure overload, a pathologic process that elicits myocyte hypertrophy and alterations in extracellular matrix composition, both of which contribute to increases in left ventricular stiffness. However, clinical and animal studies suggest that increased myocardial extracellular matrix fibrillar collagen content occurs later in the time course of left ventricular pressure overload at a time coincident with severe abnormalities in diastolic function followed by the development of symptomatic heart failure. Aortic valve replacement remains the most effective treatment for elimination of chronic pressure overload secondary to aortic stenosis but has traditionally been recommended only after the onset of clinical symptoms. Long-term follow-up of patients with symptomatic aortic stenosis after aortic valve replacement suggests that valve replacement may not result in complete reversal of the maladaptive changes that occur within the myocardial extracellular matrix secondary to the pressure overload state. To the contrary, residual left ventricular extracellular matrix abnormalities such as these are likely responsible for persistent abnormalities in diastolic function and increased morbidity and mortality after aortic valve replacement. Defining the mechanisms and pathways responsible for regulating the myocardial extracellular matrix during the natural history of aortic stenosis may provide a means by which to detect crucial structural milestones and thereby permit more precise identification of the development of maladaptive left ventricular remodeling.

Progressive induction of left ventricular pressure overload in a large animal model elicits myocardial remodeling and a unique matrix signature.

OBJECTIVE: Patients with severe left ventricular pressure overload secondary to aortic stenosis can present with signs and symptoms of heart failure despite normal left ventricular ejection fraction. This process occurs, at least in part, as a result of left ventricular pressure overload-induced extracellular matrix remodeling that promulgates increased left ventricular stiffness and impaired diastolic function. However, the determinants that drive extracellular matrix remodeling in this form of left ventricular pressure overload remain to be fully defined. METHODS: Left ventricular pressure overload was induced in mature pigs (n = 15) by progressive ascending aortic cuff inflation (once per week for 4 weeks), whereby left ventricular mass, left ventricular ejection fraction, and regional myocardial stiffness (rK(m)) were compared with referent controls (n = 12). Determinants of extracellular matrix remodeling were assessed by measuring levels of mRNA expression for fibrillar collagens, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinase 1 and 4. RESULTS: With left ventricular pressure overload, left ventricular mass and rK(m) increased by 2- and 3-fold, respectively, compared with control, with no change in left ventricular ejection fraction. Left ventricular myocardial collagen increased approximately 2-fold, which was accompanied by reduced solubility (ie, increased cross-linking) with left ventricular pressure overload, but mRNA expression for fibrillar collagen and matrix metalloproteinases remained relatively unchanged. In contrast, a robust increase in mRNA expression for tissue inhibitors of matrix metalloproteinase-1 and 4 occurred with left ventricular pressure overload. CONCLUSIONS: In a progressive model of left ventricular pressure overload, which recapitulates the phenotype of aortic stenosis, increased extracellular matrix accumulation and subsequently increased myocardial stiffness were not due to increased fibrillar collagen expression but rather to determinants of post-translational control that included increased collagen stability (thereby resistant to matrix metalloproteinase degradation) and increased endogenous matrix metalloproteinase inhibition. Targeting these extracellular matrix post-translational events with left ventricular pressure overload may hold both diagnostic and therapeutic relevance.

Acute thoracic aortic syndromes.

Patients presenting with acute thoracic aortic syndromes require immediate evaluation and stabilization. Although emergent surgical intervention may not be warranted in all cases, managing clinicians should be cognizant of the fact that these diseases are dynamic and that they can rapidly degenerate yielding catastrophic consequences. While traditional surgical intervention has failed to reduce mortality rates in those requiring emergent intervention for descending thoracic aortic syndromes, evolving endovascular techniques hold promise and may prove to extend benefits beyond that which are currently generated with open graft aortic replacement.

Caspase inhibition modulates left ventricular remodeling following myocardial infarction through cellular and extracellular mechanisms.

BACKGROUND: Myocyte death occurs by necrosis and caspase-mediated apoptosis in myocardial infarction (MI). In vitro studies suggest caspase activation causes myocardial contractile protein degradation without inducing apoptosis. Thus, caspase activation may evoke left ventricular (LV) remodeling through independent processes post-MI. The effects of caspase activation on LV geometry post-MI remain unclear. This project applied pharmacologic caspase inhibition (CASPI) to a porcine model of MI. METHODS AND RESULTS: Pigs (34 kg) were instrumented to induce 60 minutes of coronary artery occlusion followed by reperfusion and a 7-day follow-up period. Upon reperfusion, the pigs were randomized to saline (n = 12) or CASPI (n = 10, IDN6734, 6 mg/kg i.v., then 6 mg/kg/h for 24 hours). Plasma troponin-I values were reduced with CASPI compared with saline at 24 hours post-MI (133 +/- 15 vs. 189 +/- 20 ng/mL, respectively, P < 0.05). LV end-diastolic area (echocardiography) and interregional length (sonomicrometry) increased from baseline in both groups but were attenuated with CASPI by 40% and 90%, respectively (P < 0.05). Myocyte length was reduced with CASPI compared with saline (128 +/- 3 vs. 141 +/- 4 microm, respectively, P < 0.05). Plasma-free pro-matrix metalloproteinase-2 values increased from baseline with CASPI (27% +/- 6%, P < 0.05) indicative of reduced conversion to active MMP-2. Separate in vitro studies demonstrated that activated caspase species cleaved pro-MMP-2 yielding active MMP-2 forms and that MMP activity was increased in the presence of activated caspase-3. CONCLUSIONS: CASPI attenuated regional and global LV remodeling post-MI and altered viable myocyte geometry. Caspases increased MMP activity in vitro, whereas CASPI modified conversion of MMP-2 to the active form in vivo. Taken together, the results of the present study suggest that the elaboration of caspases post-MI likely contribute to LV remodeling through both cellular and extracellular mechanisms.

Alternative technique for salvage of donor lungs with insufficient atrial cuffs.

Inadequate left atrial cuff surrounding donor pulmonary veins may present a technical challenge for successful lung transplantation. A simple technique for construction of venous anastomoses during lung transplantation when donor atrial cuff is lacking involves circumferential incorporation of surrounding donor pericardium into the anastomosis without directly suturing or augmenting donor venous structures.

Abdominal aortic aneurysm and significant coronary artery disease: strategies and options.

OBJECTIVES: The optimal treatment for patients requiring intervention for coronary artery disease (CAD) and concomitant large or symptomatic abdominal aortic aneurysm (AAA) remains problematic. METHODS: Retrospective analysis was performed of 32 patients with symptomatic or large (> cm) AAA along with significant CAD treated over the past fifteen years at a university hospital. RESULTS: Mean AAA diameter was 6.6 cm. CAD involved 3 or more vessels in all patients. Fifteen patients underwent staged coronary artery bypass grafting (CABG) followed by open AAA repair, with two (13%) dying as a result of aneurysm rupture in the early postoperative period. No major complications were encountered among five patients receiving staged coronary angioplasty before open AAA repair and two patients undergoing staged CABG followed by endovascular aneurysm repair. Ten patients underwent concomitant CABG and AAA repair, with a single intraoperative death (10%). No differences in morbidity were observed among patients undergoing concomitant procedures as compared with those subjected to staged procedures. CONCLUSIONS: Minimally invasive interventions for coronary revascularization and aortic aneurysm repair appear to be safe and effective options in properly selected high-risk patients. While optimal management must be individualized, these data suggest that either staged or concomitant CABG and AAA repair may be viable options when minimally invasive interventions are not feasible.

Alterations in cultured myocardial fibroblast function following the development of left ventricular failure.

A structural event in the progression of left ventricular (LV) failure is myocardial extracellular matrix (ECM) remodeling. The myocardial fibroblast is a major cell type influencing the ECM, but whether and to what degree specific phenotypic differences in myocardial fibroblasts can be demonstrated to occur in culture with the development of LV failure remains unclear. Adult pigs (25 kg) were used for control myocardial fibroblast preparations (N=5) or following pacing-induced LV failure (N=5; 240 bpm, 3 weeks). LV remodeling occurred with pacing as evidenced by increased LV end diastolic volume (132+/-11 vs. 60+/-4 mL for control; P<0.05). Functional parameters including migration, adhesion, collagen and matrix metalloproteinase release were assessed in fibroblast cultures from passages 1-4. The following findings were consistent with each passage and the results were analyzed with control values set to 100%. Migration of LV failure fibroblasts increased by over 170% (P<0.05). Adhesion to collagen I, laminin and fibronectin was increased by over 160% in LV failure fibroblasts (P<0.05). beta(1) integrin density decreased by 50% in LV failure fibroblasts (P<0.05). Fibrillar collagen release increased by over 130% and matrix metalloproteinase-2 increased by 140% in LV failure fibroblasts (P<0.05). The unique findings of this study are two-fold. First, after a pathological stimulus in-vivo, adult myocardial fibroblasts maintain a consistent phenotype through early passages in-vivo. Second, a differential release of, and response to ECM components occurred in LV failure fibroblasts. Thus, a phenotypic transformation of the myocardial fibroblast occurs with the development of LV failure, which in turn may contribute to matrix remodeling and presents as a potential cellular therapeutic target.

Selective targeting of matrix metalloproteinase inhibition in post-infarction myocardial remodeling.

BACKGROUND: A cause-effect relationship has been established between MMP activation and left ventricular (LV) remodeling following myocardial infarction. The goal of the present study was to examine a selective MMP inhibitor (sMMPi) strategy that effectively spared MMP-1, -3, and -7 with effect to regional and global left ventricular remodeling in a pig model of myocardial infarction. METHODS AND RESULTS: Pigs instrumented with coronary snares and radiopaque markers within the area at risk were randomized to myocardial infarction-only (n = 10) or sMMPi (PGE-530742, 1 mg/kg TID) begun 3 days prior to myocardial infarction. Ten weight-matched noninstrumented pigs served as reference controls. Left ventricular end-diastolic volume in the myocardial infarction-only group was increased from baseline (81 +/- 3 mL versus 55 +/- 4 mL, respectively, P < 0.05) but was attenuated with sMMPi (67 +/- 3 mL, P < 0.05). Fractional area of shortening of marker area was decreased in the myocardial infarction-only group (change from baseline -63 +/- 10%, P < 0.05) but this effect was attenuated with sMMPi (-28 +/- 14%, P < 0.05), indicative of less dyskinesis of the infarct region with sMMPi. Wall stress was reduced within both the septal and posterior wall regions with sMMPi. Myocardial MMP-2 activity was decreased in both remote and border areas of sMMPi-treated samples compared with myocardial infarction-only values, consistent with pharmacologic MMP inhibition. CONCLUSIONS: Selective MMP inhibition favorably affected regional myocardial geometry and decreased left ventricular dilation post-myocardial infarction. This study suggests that a strategy of selective MMP inhibition of a limited array of MMPs may be an achievable goal in preventing pathologic left ventricular remodeling post-myocardial infarction.

Restenosis of a sirolimus drug-eluting stent: aorto-ostial involvement of the proximal right coronary artery.

We present a case of restenosis of a sirolimus drug-eluting stent in the ostium of the right coronary artery due to severe crimping and underexpansion of the stent in an area of heavy calcification, detected by intracoronary ultrasound but not by angiography. We discuss issues relevant to management of the restenotic drug-eluting stent in the aorto-ostial location.

Cardiac support device modifies left ventricular geometry and myocardial structure after myocardial infarction.

BACKGROUND: Whether mechanical restraint of the left ventricle (LV) can influence remodeling after myocardial infarction (MI) remains poorly understood. This study surgically placed a cardiac support device (CSD) over the entire LV and examined LV and myocyte geometry and function after MI. METHODS AND RESULTS: Post-MI sheep (35 to 45 kg; MI size, 23+/-2%) were randomized to placement of the CorCap CSD (Acorn Cardiovascular, Inc) (MI+CSD; n=6) or remained untreated (MI only; n=5). Uninstrumented sheep (n=10) served as controls. At 3 months after MI, LV end-diastolic volume (by MRI) was increased in the MI only group compared with controls (98+/-8 versus 43+/-4 mL; P<0.05). In the MI+CSD group, LV end-diastolic volume was lower than MI only values (56+/-7 mL; P<0.05) but remained higher than controls (P<0.05). Isolated LV myocyte shortening velocity was reduced by 35% from control values (P<0.05) in both MI groups. LV myocyte beta-adrenergic response was reduced with MI but normalized in the MI+CSD group. LV myocyte length increased in the MI group and was reduced in the MI+CSD group. Relative collagen content was increased and matrix metalloproteinase-9 was decreased within the MI border region of the CSD group. CONCLUSIONS: A CSD beneficially modified LV and myocyte remodeling after MI through both cellular and extracellular mechanisms. These findings provide evidence that nonpharmacological strategies can interrupt adverse LV remodeling after MI.

Informed consent: ethical and legal aspects.

The legal doctrine of informed consent looms large over the medical profession with many interest groups trying to expand and narrow the doctrine, including patient rights advocates, managed care organizations, government agencies, and accreditation organizations. The legal profession itself has taken no small part in defining the doctrine. No physician today is practicing without the daily influence of law on his or her practice of medicine. The doctrine of informed consent, with all of its ambiguities and difficulties, has established a medical duty on the physician to make a reasonable attempt to unite the goals of the patient and the physician. Ultimately, physicians gain from the knowledge that their wisdom and skill has fostered a decision that is amenable to the patient. The patient gains from a facilitated decision that truly reflects that individual's self-determined will. As a result, both parties enjoy a newly formed partnership and the return of something that has long been taken for granted--trust in the physician-patient relationship.