Long-term outcomes of hospitalized patients with SARS-CoV-2/COVID-19 with and without neurological involvement: 3-year follow-up assessment.

BACKGROUND: Acute neurological manifestation is a common complication of acute Coronavirus Disease 2019 (COVID-19) disease. This retrospective cohort study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization. METHODS AND FINDINGS: Patients hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection between 03/01/2020 and 4/16/2020 in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to 01/23/2023 (3 years post-COVID-19). This cohort consisted of 414 patients with COVID-19 with significant neurological manifestations and 1,199 propensity-matched patients (for age and COVID-19 severity score) with COVID-19 without neurological manifestations. Neurological involvement during the acute phase included acute stroke, new or recrudescent seizures, anatomic brain lesions, presence of altered mentation with evidence for impaired cognition or arousal, and neuro-COVID-19 complex (headache, anosmia, ageusia, chemesthesis, vertigo, presyncope, paresthesias, cranial nerve abnormalities, ataxia, dysautonomia, and skeletal muscle injury with normal orientation and arousal signs). There were no significant group differences in female sex composition (44.93% versus 48.21%, p = 0.249), ICU and IMV status, white, not Hispanic (6.52% versus 7.84%, p = 0.380), and Hispanic (33.57% versus 38.20%, p = 0.093), except black non-Hispanic (42.51% versus 36.03%, p = 0.019). Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were neuroimaging findings (hemorrhage, active and prior stroke, mass effect, microhemorrhages, white matter changes, microvascular disease (MVD), and volume loss). More patients in the neurological cohort were discharged to acute rehabilitation (10.39% versus 3.34%, p < 0.001) or skilled nursing facilities (35.75% versus 25.35%, p < 0.001) and fewer to home (50.24% versus 66.64%, p < 0.001) than matched controls. Incidence of readmission for any reason (65.70% versus 60.72%, p = 0.036), stroke (6.28% versus 2.34%, p < 0.001), and MACE (20.53% versus 16.51%, p = 0.032) was higher in the neurological cohort post-discharge. Per Kaplan-Meier univariate survival curve analysis, such patients in the neurological cohort were more likely to die post-discharge compared to controls (hazard ratio: 2.346, (95% confidence interval (CI) [1.586, 3.470]; p < 0.001)). Across both cohorts, the major causes of death post-discharge were heart disease (13.79% neurological, 15.38% control), sepsis (8.63%, 17.58%), influenza and pneumonia (13.79%, 9.89%), COVID-19 (10.34%, 7.69%), and acute respiratory distress syndrome (ARDS) (10.34%, 6.59%). Factors associated with mortality after leaving the hospital involved the neurological cohort (odds ratio (OR): 1.802 (95% CI [1.237, 2.608]; p = 0.002)), discharge disposition (OR: 1.508 (95% CI [1.276, 1.775]; p < 0.001)), congestive heart failure (OR: 2.281 (95% CI [1.429, 3.593]; p < 0.001)), higher COVID-19 severity score (OR: 1.177 (95% CI [1.062, 1.304]; p = 0.002)), and older age (OR: 1.027 (95% CI [1.010, 1.044]; p = 0.002)). There were no group differences in radiological findings, except that the neurological cohort showed significantly more age-adjusted brain volume loss (p = 0.045) than controls. The study's patient cohort was limited to patients infected with COVID-19 during the first wave of the pandemic, when hospitals were overburdened, vaccines were not yet available, and treatments were limited. Patient profiles might differ when interrogating subsequent waves. CONCLUSIONS: Patients with COVID-19 with neurological manifestations had worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for patients with COVID-19 with neurological manifestations, as their disease course involving initial neurological manifestations is associated with enhanced morbidity and mortality.

Impact of iodinated contrast shortage on contrast-associated acute kidney injury: a single center experience.

Background: In March 2022, a COVID-19 outbreak disrupted the global supply of iodine contrast media (ICM). Healthcare systems implemented contrast-saving strategies to maintain their remaining ICM supplies. This study sought to determine the impact of contrast shortage on the incidence of contrast-associated acute kidney injury (CA-AKI). Methods: This was a retrospective study of 265 patients undergoing 278 percutaneous coronary interventions (PCI) during 4-month periods prior to (9/1/2021 to 12/31/2021) and during (5/1/2022 to 8/31/2022) contrast shortage at a single center. The primary endpoint was the incidence of CA-AKI between study periods. Results: A total of 148 and 130 PCIs were performed before and during contrast shortage, respectively. The incidence of CA-AKI significantly decreased from 11.5% to 4.6% during contrast shortage (P = 0.04). During the shortage, average contrast volume per PCI was significantly lower (123 ± 62 mL vs 88 ± 46 mL, P < 0.001), while coronary imaging was significantly higher (34.3% vs 50%, P = 0.009) compared to preshortage. All-cause mortality at discharge was comparable between study periods (2.8% vs 3.3%, respectively; P = 0.90). Conclusion: The scarcity of ICM for PCI procedures in this single-center experience was associated with a significant increase in the utilization of intravascular imaging and a significant reduction in CA-AKI.

Hospitalization, Critical Illness, and Mortality Outcomes of COVID-19 in Patients With Rheumatoid Arthritis.

OBJECTIVE: To investigate the clinical outcomes of patients with rheumatoid arthritis (RA) with COVID-19. METHODS: This retrospective study consisted of 361 patients with RA+ and 45,954 patients with RA- (March 2020 to August 2022) who tested positive for SARS-CoV-2 by polymerase-chain-reaction in the Montefiore Health System, which serves a large low-income, minority-predominant population in the Bronx and was an epicenter of the initial pandemic and subsequent surges. Primary outcomes were hospitalization, critical illness, and all-cause mortality associated with SARS-CoV-2 infection. Comparisons were made with and without adjustment for covariates, as well as with 1083 matched controls of patients with RA- and COVID-19. RESULTS: Patients with RA+ and COVID-19 were older (62.2 ± 23.5 vs. 45.5 ± 26.3; P < 0.001), were more likely females (83.1% vs. 55.8%; P < 0.001), were Black (35.5% vs. 30.3%; P < 0.05), and had higher rates of comorbidities (P < 0.05), hospitalization (52.4% vs. 32.5%; P < 0.005), critical illness (10.5% vs. 6.9%; P < 0.05), and mortality (11.1% vs. 6.2%; P < 0.01) compared with patients with RA- and COVID-19. Patients with RA+ with COVID-19 had higher odds of critical illness (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.09-1.93; P = 0.008) but no differences in hospitalization (aOR = 1.18 [95% CI: 0.93-1.49]; P = 0.16) and mortality (aOR = 1.34 [95% CI: 0.92-1.89]; P = 0.10) after adjusting for covariates. Odds ratio analysis identified age, hospitalization status, female sex, chronic kidney disease, chronic obstructive pulmonary disease, and Black race to be significant risk factors for COVID-19-related mortality. Pre-COVID-19 steroid and biologic therapy to treat RA were not significantly associated with worse outcomes (P > 0.05). Outcomes were not different between patients with RA+ and propensity-matched RA- controls (P > 0.05). CONCLUSION: Our findings suggest that risk factors for adverse COVID-19 outcomes were not attributed to RA per se but rather age and preexisting medical conditions of patients with RA.

Plasma free H2S levels are elevated in patients with cardiovascular disease.

BACKGROUND: Hydrogen sulfide (H2S) has been implicated in regulating cardiovascular pathophysiology in experimental models. However, there is a paucity of information regarding the levels of H2S in health and cardiovascular disease. In this study we examine the levels of H2S in patients with cardiovascular disease as well as bioavailability of nitric oxide and inflammatory indicators. METHODS AND RESULTS: Patients over the age of 40 undergoing coronary or peripheral angiography were enrolled in the study. Ankle brachial index (ABI) measurement, measurement of plasma-free H2S and total nitric oxide (NO), thrombospondin-1 (TSP-1), Interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) levels were performed. Patients with either coronary artery disease alone (n = 66), peripheral arterial disease (PAD) alone (n = 13), or any vascular disease (n = 140) had higher plasma-free H2S levels compared to patients without vascular disease (n = 53). Plasma-free H2S did not distinguish between disease in different vascular beds; however, total NO levels were significantly reduced in PAD patients and the ratio of plasma free H2S to NO was significantly greater in patients with PAD. Lastly, plasma IL-6, ICAM-1, and TSP-1 levels did not correlate with H2S or NO bioavailability in either vascular disease condition. CONCLUSIONS: Findings reported in this study reveal that plasma-free H2S levels are significantly elevated in vascular disease and identify a novel inverse relationship with NO bioavailability in patients with peripheral arterial disease.

Retroperitoneal hematoma: an unexpected complication during intervention on an occluded superficial femoral artery via a retrograde popliteal artery approach.

Peripheral arterial disease involvement of the superficial femoral artery (SFA) is common. Different endovascular techniques are used successfully for revascularization of this artery. A retrograde approach to chronic total occlusion (CTO) of the SFA through the ipsilateral popliteal artery has been used occasionally if an antegrade approach is not feasible or has failed. Some of the known complications encountered during this approach are arteriovenous fistula formation at the access site, occlusion of the popliteal artery if closure devices are used, and bleeding. There are no reports of perforation or bleeding of the SFA or the external iliac artery (EIA) during a popliteal approach, probably due to lack of flow in the occluded segment of the SFA. We report a case in which a retroperitoneal hematoma occurred due to retrograde blood flow through the established true channel in the proximal SFA and subsequently to the dissection plane with a wire tip perforation in the EIA, which was treated by stopping retrograde filling with prolonged balloon inflation in the distal SFA before the CTO.

Fracture of a guiding catheter in a tortuous iliac artery and its retrieval by a larger sheath.

Intravascular fracture of catheters, especially guiding catheters, is uncommon. We present an unusual case in which a guide twisted and broke in a tortuous iliac artery during manipulation of the guiding catheter with a 0.014 inch wire firmly trapped inside and was retrieved by a larger sheath.

Retrograde orbital atherectomy in an occluded superficial femoral artery.

Superficial femoral artery (SFA) is commonly diseased in patients with symptomatic peripheral arterial disease. Endovascular treatments have been more effectively used for SFA occlusions with new techniques and devices. Retrograde popliteal access has been used as an alternative to increase the success rate of percutaneous transluminal angioplasty (PTA) of SFA after a failed antegrade attempt. Although orbital atherectomy (OA) has been used effectively to treat SFA occlusions, there are no reports of use of OA by retrograde popliteal approach.

Twisting of peripheral balloon appearing as a non-dilating peroneal artery lesion.

Peripheral arterial lesions are usually longer than coronary artery lesions and require longer balloons and stents. Theoretically while advancing a long balloon in a long, high grade lesion with aggressive manipulation, the balloon can twist inside the lesion, but this has not been described before in the literature. Herein we are reporting a case where peripheral balloon (PB) twisted and appeared as a non-dilating lesion.

Percutaneous treatment of delayed post-atherectomy superficial femoral artery pseudoaneurysm.

SilverHawk atherectomy is commonly used in lower extremity percutaneous interventions. Minor perforations during SilverHawk atherectomy procedures are reported at a range of 0.8%. There are few reported cases in the literature about very late pseuodoaneursym formation after SilverHawk atherectomy. Herein we report a very unusual, late, concealed, acute rupture of superficial femoral artery with a large, painful pseuodoaneursym formation, 1 week after Silver- Hawk atherectomy and its treatment with Viabahn stent graft (W.L. Gore & Associates).

Reasoning and evidence-based medicine: common pitfalls.

It is impossible to answer every potential clinical question through randomized controlled trials. Hence, assumptions, rational thinking, logic, and reasoning are used in making recommendations; however, these methods may interfere with the judicious application of evidence-based medicine and, as discussed in this article, may result in logical fallacies. We also explain how we may incorporate recommendations based on assumptions and rational thinking in patient care. Extrapolations of study content and confusing association with causation are common pitfalls in the application of the evidence-based medicine process. Personal bias can be another barrier in the adoption of evidence-based medicine. It can be difficult to modify personal bias despite the evidence; keeping up with the medical literature in a busy practice can be daunting.

Prediction of hypertension improvement after stenting of renal artery stenosis: comparative accuracy of translesional pressure gradients, intravascular ultrasound, and angiography.

OBJECTIVES: We investigated the comparative accuracy of renal translesional pressure gradients (TPG), intravascular ultrasound (IVUS), and angiographic parameters in predicting hypertension improvement after stenting of renal artery stenosis (RAS). BACKGROUND: The degree of RAS that justifies stenting is unknown. METHODS: In 62 patients with RAS, TPG (resting and hyperemic systolic gradient [HSG], fractional flow reserve, and mean gradient) were measured by a pressure guidewire; IVUS and angiographic parameters (minimum lumen area and diameter, area stenosis, and diameter stenosis) were measured by quantitative analyses. RESULTS: The HSG had a larger area under the curve than most other parameters and an HSG >or=21 mm Hg had the highest sensitivity, specificity, and accuracy (82%, 84%, and 84%, respectively) in predicting hypertension improvement after stenting of RAS. The average IVUS area stenosis was markedly greater in RAS with an HSG >or=21 mm Hg versus <21 mm Hg (78% vs. 38%, respectively; p < 0.001). After stenting, hypertension improved in 84% of patients with an HSG >or=21 mm Hg (n = 36) versus 36% of patients with an HSG <21 mm Hg (n = 26) at 12 months, p < 0.01; the number of antihypertensive medications was significantly lower in patients with an HSG >or=21 mm Hg versus <21 mm Hg (2.30 +/- 0.90 vs. 3.40 +/- 0.50, respectively; p < 0.01). By multivariable analysis, HSG was the only independent predictor of hypertension improvement (odds ratio: 1.39; 95% confidence interval: 1.05 to 1.65; p = 0.013). CONCLUSIONS: An HSG >or=21 mm Hg provided the highest accuracy in predicting hypertension improvement after stenting of RAS, suggesting that an HSG >or=21 mm Hg is indicative of significant RAS.

Postinfarct cytokine therapy regenerates cardiac tissue and improves left ventricular function.

We systematically investigated the comparative efficacy of three different cytokine regimens, administered after a reperfused myocardial infarction, in regenerating cardiac tissue and improving left ventricular (LV) function. Wild-type (WT) mice underwent a 30-minute coronary occlusion followed by reperfusion and received vehicle, granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL), G-CSF+stem cell factor (SCF), or G-CSF alone starting 4 hours after reperfusion. In separate experiments, chimeric mice generated by reconstitution of radioablated WT mice with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice underwent identical protocols. Mice were euthanized 5 weeks later. Echocardiographically, LV function was improved in G-CSF+FL- and G-CSF+SCF-treated but not in G-CSF-treated mice, whereas LV end-diastolic dimensions were smaller in all three groups. Morphometrically, cytokine-treated hearts had smaller LV diameter and volume. Numerous EGFP-positive cardiomyocytes, capillaries, and arterioles were noted in the infarcted region in cytokine-treated chimeric mice treated with G-CSF+FL or G-CSF+SCF, but the numbers were much smaller in G-CSF-treated mice. G-CSF+FL therapy mobilized bone marrow-derived cells exhibiting increased expression of surface antigens (CD62L and CD11a) that facilitate homing. We conclude that postinfarct cytokine therapy with G-CSF+FL or G-CSF+SCF limits adverse LV remodeling and improves LV performance by promoting cardiac regeneration and probably also by exerting other beneficial actions unrelated to regeneration, and that G-CSF alone is less effective.

Cardiovascular death in patients with atrial fibrillation is better predicted by left atrial thrombus and spontaneous echocardiographic contrast as compared with clinical parameters.

We hypothesized that altered intra-atrial thrombogenicity, as reflected by the presence of left atrial (LA) thrombus or spontaneous echocardiographic contrast (SEC), would predict cardiovascular death in patients with atrial fibrillation (AF). In 175 patients with AF and no more than mild mitral regurgitation as detected by transesophageal echocardiography (TEE), 13 cardiovascular deaths occurred during a mean follow-up of 31 +/- 20 months. Multivariate logistic regression analysis using clinical variables identified the presence of congestive heart failure (relative risk [RR] = 4.22; P = .02) as the only positive predictor of cardiovascular death. However, when the TEE variables were added to the model, LA thrombus (RR = 5.52; P = .024) and LA SEC (RR = 7.96; P = .013) emerged as the only positive predictors of cardiovascular death. Kaplan-Meier analysis demonstrated a lower event-free survival from cardiovascular death in patients with LA thrombus and/or SEC ( P = .0013). These findings support AF as a contributing cause of cardiovascular death independent of clinically associated risk factors, such as hypertension, diabetes mellitus, smoking, congestive heart failure, and prior myocardial infarction.

Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function.

The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.

Tumor necrosis factor-alpha does not modulate ischemia/reperfusion injury in naïve myocardium but is essential for the development of late preconditioning.

The role of tumor necrosis factor (TNF)-alpha in myocardial ischemia/reperfusion injury remains controversial. We used homozygous TNF-alpha null mice (TNF-alpha(-/-)) to determine whether TNF-alpha modulates myocardial ischemia/reperfusion injury. Mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. When wild-type mice were preconditioned with six cycles of 4-min coronary occlusion/4-min reperfusion 24 h before the 30-min occlusion, infarct size was reduced from 58.6 +/- 1.9% of the risk region to 19.3 +/- 3.6%, indicating a late preconditioning (PC) effect. In non-preconditioned TNF-alpha(-/-) mice, infarct size was similar to that observed in wild-type mice (55.5 +/- 3.7%). However, in TNF-alpha(-/-) mice preconditioned with six occlusion/reperfusion cycles 24 h earlier, infarct size was not reduced (55.2 +/- 5.7%), indicating that the late PC protection against infarction was completely abolished. While minimal TNF-alpha immunoreactivity was detected in sham-operated hearts, extensive TNF-alpha expression was noted in the cytoplasm of cardiomyocytes in the ischemic/reperfused region 30 min after the PC ischemia. At 30 min after PC, wild-type mice exhibited increased DNA-binding activity of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) and nuclear translocation of p65, c-Jun and c-Fos; all of these changes were absent in TNF-alpha(-/-) mice. These data demonstrate that TNF-alpha does not modulate infarct size in the naïve (non-preconditioned) state but is essential for the development of the late phase of ischemic PC, possibly via the activation of NF-kappa B and AP-1 transcription factors.

Recurrent aortic dissection in Marfan's syndrome: possible effects of anticoagulation.

Recent reports support the role of a valve-sparing procedure in ascending aortic dissection in patients with Marfans syndrome. A 49-year-old woman with Marfans syndrome and prior aortic aneurysm repaired with a composite graft presented with sudden-onset chest pain. Following an initial negative computed tomographic (CT) scan, a long dissection involving the descending thoracic and abdominal aorta was discovered on a repeat CT scan a few hours later. Symptoms improved gradually with optimal medical management and the patient was discharged home on anticoagulant therapy. Although no direct cause-and-effect relationship can be established, chronic anticoagulant therapy may accelerate the progression of recurrent dissection in these patients. A valve-sparing procedure should be considered in eligible patients with Marfans syndrome who need operative correction to avoid possible future untoward effects of long-term anticoagulant therapy.