CHA2DS2-VASc Score as a Predictor of Adverse Outcomes after Ischemic Stroke in Patients without Atrial Fibrillation.

BACKGROUND: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events. OBJECTIVES: To investigate whether CHA2DS2-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke. METHODS: We analyzed data of 2628 patients, aged 40-65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA2DS2-VASc scores categorized by subgroups (score 2-3, 4-5, or 6-7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months. RESULTS: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40-60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2-3, 4-5, and 6-7, respectively. In a multivariate cox regression model, compared to patients with score 2-3 (reference group), those with score 4-5 and 6-7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41-2.14) and 2.87 (95%CI 2.10-3.93), respectively. The discriminative capacity of CHA2DS2-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60-0.66), although better for myocardial infarction 0.69 (95% CI 0.61-0.77). CONCLUSIONS: CHA2DS2-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

Effect of angiotensin receptor neprilysin inhibitor on physical activity in patients with heart failure with reduced ejection fraction, monitored by implantable electronic device home monitoring.

AIMS: Angiotensin receptor neprilysin inhibitor (ARNI) therapy is a cornerstone in the treatment of heart failure with reduced ejection fraction (HFrEF), with significant improvement in mortality as well as morbidity and quality of life. However, maximal ARNI doses often result in hypotension. Recent studies with 'real world' experience suggest that lower doses of ARNI are as effective as higher doses.In order to evaluate the symptomatic effect of low-dose ARNI in HFrEF patients, we analyzed physical activity data obtained via home monitoring of patients with cardiac implantable electronic devices (CIEDs). METHODS: We retrospectively analyzed physical activity data obtained from HFrEF patients with CIED-active home monitoring during the years 2021-2022. Patients with ARNI therapy were further divided into subgroups according to the administered dose. Low-dose ARNI included doses of up to 24/26 mg sacubitril/valsartan daily. Intermediate dose and high dose included doses of 72/78-120/130 mg/day, and 144/156-194/206 mg/day, respectively. RESULTS: A total of 122 patients had home monitoring-compatible CIEDs and HFrEF during the study period. Sixty-four of these patients were treated with ARNI. Administration of low-dose ARNI resulted in a 20% increase in daily activity when compared with patients without ARNI treatment ( P  = 0.038). Change in physical activity of patients in the intermediate-dose and high-dose groups was not significant. Younger patients, patients with cardiac resynchronization therapy, and patients without diabetes mellitus were more physically active. CONCLUSION: Low-dose ARNI had a beneficial effect on physical activity in HFrEF patients. MH via CIED provided real-life objective data for patients' follow-up.

A common presentation - turning out as an uncommon diagnosis: From hip pain to Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is an uncommon clonal proliferation of myeloid progenitor cells, it is especially rare in adults. We present a case of multi-system LCH in a 53-year-old woman, the sole symptom of which was prolonged, non-resolving hip pain for 18 months prior to the diagnosis. Initial evaluation included imaging studies aimed at identifying a presumed local etiology. X-ray demonstrated non-specific arthritic changes on the left femur. Computed tomography (CT) and magnetic resonance imaging (MRI) scans identified a lytic lesion at the same location, warranting a systemic workup. After non-invasive investigations failed to reveal the underlying etiology, a biopsy was performed, revealing cores of Langerhans cells that stained positive for both CD1a and langerin. These findings verified the surprising, uncommon diagnosis of LCH. A comprehensive workup was conducted in order to determine the extent of the disease and its molecular nature - revealing a BRAFV600E-positive, high-risk, multi-system LCH with skeletal, lung and liver involvement.

A safety and clinical efficacy analysis of PCSK9 monoclonal antibodies in patients with markedly elevated creatine phosphokinase levels.

INTRODUCTION: PCSK9 inhibitors (PCSK9i) are often used in statin-intolerant patients, aiming to reduce low-density lipoprotein cholesterol (LDL-C). Along with the growing experience with their use, there is a lack of evidence regarding the safety, tolerability, and clinical utility of PCSK9i in patients with markedly elevated creatine phosphokinase (CPK) levels. METHODS: We screened a comprehensive HMO database for patients treated with PCSK9i (Jan 2016-Dec 2019), in whom elevated CPK levels (>1,000 U/L) were documented prior to the initiation of therapy. Treatment plans, adherence, and the levels of CPK and LDL-C were analyzed. RESULTS: Of the 1,600 patients initiating treatment with PCSK9i, 26 had prior CPK values >1,000 U/L [median (IQR): 3,687 (1,876-8,344) U/L]. All 26 patients were previously treated with statins, which presumably resulted in adverse effects (myalgia in 24, and rhabdomyolysis in 5 patients) therefore mandating their discontinuation. Concomitant secondary factors for CPK elevation were present in 11 patients, and included renal failure, rheumatoid disorders, hypothyroidism, intensive exercise, proteinuria and genetic muscular disease. Of the 26 patients treated with PCSK9i, alirocumab was administered to 12 patients, and evolocumab to 14. Following the initiation of treatment with either drug, 24 patients (92%) demonstrated a reduction in CPK of >50%, and in 12 (46%) CPK levels have returned to normal values. With regard to treatment goals, 17 patients (65%) have achieved an LDL-C level of <70 mg/dL, and 12 (46%) have reached a level of <55 mg/dL. No serious adverse reactions were documented, and only 2 patients discontinued the treatment (not due to muscle symptoms or CPK elevation). CONCLUSIONS: PCSK9i constitute a safe, tolerable, and effective treatment for hyperlipidemia in patients with markedly elevated CPK. While statin intolerance is a major cause for CPK elevation, concomitant etiologies for increased CPK values were rather common.

COVID-19-Associated Suspected Myocarditis as the Etiology for Recurrent and Protracted Fever in an Otherwise Healthy Adult.

Current reports concerning cardiac involvement in the novel corona virus disease (COVID-19) mostly document acute myocardial injury at presentation. Here, we present a healthy young male, with presumed acute myocarditis, presenting 20 days after initial diagnosis of COVID-19 - and after a clinical, and apparent laboratory, resolution of the original episode. His sole substantial clinical finding upon admission was fever, which was followed by a witnessed elevation in troponin-I.

Effect of Cerebrovascular and/or Peripheral Artery Disease With or Without Attainment of Lipid Goals on Long-Term Outcomes in Patients With Coronary Artery Disease.

Involvement of atherosclerosis in extracardiac vascular territories may identify coronary artery disease (CAD) patients at higher risk for adverse events. We investigated the long-term prognostic implications of polyvascular disease in patients with CAD, and further analyzed lipid goal attainment and its relation to patient outcomes. The study was a retrospective analysis of 10,297 patients who underwent coronary revascularization, categorized as having CAD alone (83.1%) or with multisite artery disease (MSAD) (16.9%) including cerebrovascular disease (CBVD) and/or peripheral artery disease (PAD). Incidence rates and hazard ratios (HR) for major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or all-cause death) according to vascular territories involved, and in relation to most-recent lipid levels attained, were analyzed. Patients with MSAD were older with higher burden of co-morbidities. The rate of MACE (myocardial infarction, ischemic stroke, or all-cause death) and its individual components increased with the number of affected vascular beds. Adjusted HR (95% confidence interval) for MACE was 1.41 (1.24 to 1.59) in patients with CAD and CBVD, 1.46 (1.33 to 1.62) in CAD and PAD, and 1.69 (1.49 to 1.92) in those with CAD and CBVD and PAD, compared with CAD alone. Most-recent low-density lipoprotein cholesterol (LDL-C) levels <55 mg/dl and <70 mg/dl were attained by 21.8% and 44.6% of patients with CAD alone, in comparison to 22.7% and 43.3% in MSAD. Compared with patients with most-recent LDL-C > 100 mg/dl, attaining LDL-C < 70 mg/dl had an adjusted HR for MACE of 0.52 (0.47 to 0.57) in CAD only patients and 0.66 (0.57 to 0.78) in MSAD patients. In conclusion, the presence of CBVD and/or PAD in patients with CAD is associated with higher burden of co-morbidities and progressive increase in long-term MACE. More than half of CAD patients with or without MSAD do not achieve lipid goals, which are associated with a significantly lower risk for adverse events.

A randomized study comparing the use of a pelvic lead shield during trans-radial interventions: Threefold decrease in radiation to the operator but double exposure to the patient.

OBJECTIVES: To determine the efficacy of a 0.5-mm lead apron across the patient's abdomen in addition to standard operator protection for the reduction of scatter radiation on operator and patient radiation exposure BACKGROUND: Cardiac angiography using the radial access compared to the femoral approach is associated with reduced complication rate and improved patient comfort but has significantly increased radiation dose. Improvements in radiation protection are needed METHODS: We randomly assigned 332 patients undergoing coronary angiography to a group with pelvic lead shielding and a group with standard protection. In each procedure, eight digital dosimeters were used to measure operator radiation dose [under the lead apron, outside the thyroid shield, and at the left side of the head], patient dose at the level of the umbilicus [above and beneath the lead apron], and two on the acrylic shielding and one on the image receptor to measure scattered radiation RESULTS: Both groups were similar in BMI, procedures performed, and number of sequences. Usage of lead shielding statistically significantly reduced the radiation dose of the operator at all three sites measured: under lead apron [all in µSv]: 0.53 ± 1.4 vs. 0.17 ± 0.6, on thyroid collar 5.9 ± 7.7 vs. 2.9 ± 3.4, and left side of head 3.3 ± 3.4 vs. 2.1 ± 2.2, P<0.001. However the radiation to the patient was doubled from 15.4 ± 24.1 to 28.9 ± 81.1, P=0.04 CONCLUSIONS: The use of a pelvic lead shield during radial angiography reduced the operator radiation exposure at multiple measurement sites. However there was an increased exposure to the patient. This balance should be further investigated before the widespread adoption of this method. .

Interaction of different antidepressants with acute and chronic methadone in mice, and possible clinical implications.

We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p < 0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn.

The antinociceptive properties of reboxetine in acute pain.

The antinociceptive effects of the selective noradrenaline reuptake inhibitor antidepressant reboxetine and its interaction with various opioid and noradrenaline receptor subtypes were evaluated. Reboxetine (i.p.) induced a weak dose-dependent antinociceptive effect in acute pain, using the hotplate model. The reboxetine-induced antinociception was significantly inhibited by the opioid receptor antagonists naloxone, nor-BNI, naltrindole and b-FNA, implying a non-selective role for the opioid receptors in the reboxetine's antinociceptive effect. The adrenergic antagonists yohimbine and phentolamine attenuated to some extent the reboxetine-induced antinociception, implying a minor adrenergic mechanism of antinociception. The addition of opioid or alpha2 agonists, did not potentiate the antinociception effect of reboxetine. Thus, it seems that reboxetine possesses a weak antinociceptive effect, mediated by non-selective opioid receptors and influenced somewhat by noradrenaline alpha2 receptors. These results suggest that reboxetine as monotherapy does not have sufficient efficacy in the management of acute pain. However, further research is needed in order to establish its possible use alone or in combination with other antidepressants or analgesics in the amelioration of chronic pain disorders.