Influence of left ventricular ejection fraction in patients undergoing contemporary pLVAD-supported high-risk PCI.

BACKGROUND: Left ventricular (LV) systolic dysfunction worsens outcomes in patients undergoing percutaneous coronary intervention (PCI). The objective of this study, therefore, was to evaluate outcomes of pLVAD-supported high-risk PCI (HRPCI) patients according to LV ejection fraction (LVEF). METHODS: Patients from the PROTECT III study undergoing pLVAD-supported HRPCI were stratified according to baseline LVEF: severe LV dysfunction (LVEF <30%), mild and moderate LV dysfunction (LVEF ≥30% to <50%), or preserved LV function (LVEF ≥50%). Major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization), and PCI-related complications were assessed at 90 days and mortality was assessed at 1-year. RESULTS: From March 2017 to March 2020, 940 patients had evaluable baseline LVEF recorded in the study database. Patients with preserved LV function were older, more frequently presented with myocardial infarction, and underwent more left main PCI and atherectomy. Immediate PCI-related coronary complications were infrequent (2.7%, overall), similar between groups (P = 0.98), and not associated with LVEF. Unadjusted 90-day MACCE rates were similar among LVEF groups; however, as a continuous variable, LVEF was associated with both 90-day MACCE (adj.HR per 5% 0.89, 95% CI [0.80, 0.98], P = 0.018) and 1-year mortality (adj.HR per 5% 0.84 [0.78, 0.90], P <0.0001). CONCLUSIONS: Patients who underwent pLVAD-supported HRPCI exhibited low incidence of PCI-related complications, regardless of baseline LVEF. However, LVEF was associated with 90-day MACCE and 1-year mortality.

The Association between Marital Status and Outcomes of Patients Hospitalized with Heart Failure.

BACKGROUND: Little is known about the association between marital status and long-term outcomes of patients hospitalized with heart failure (HF). We aimed to examine the association between marital status and early as well as long-term outcomes of patients hospitalized with HF. METHOD: We analyzed data of 4089 patients hospitalized with HF and were enrolled in the multicenter national survey in Israel between March and April 2003 and were followed until December 2014. Patients were classified into married (N = 2462, 60%) and unmarried (N = 1627, 40%). RESULTS: Married patients were more likely to be males, younger, and more likely to have past myocardial infarction and previous revascularization. Also, they tended to have higher rates of diabetes mellitus (DM) and dyslipidemia, as well as smokers. Survival analysis showed that unmarried patients had higher mortality rates at 1 and 10 years (33% vs. 25%, at 1 year, 89% vs. 80% at 10 years, all p < 0.001). Consistently, multivariable analysis showed that unmarried patients had independently 44% and 35% higher risk of mortality at 1- and 10-year follow-up respectively (1-year HR = 1.44; 95%CI 1.14-1.81; p = 0.002, 10-year HR = 1.35; 95%CI 1.19-1.53; p ≤ 0.001). Other consistent predictors of mortality at both 1- and 10-year follow-up include age, renal failure, and advanced HF. CONCLUSIONS: Being unmarried is independently associated with worse short- and long-term outcomes, particularly among women. Thus, attempts to intensify secondary preventive measures should focus mainly on unmarried patients and mainly women.

Female gender is associated with a worse prognosis amongst patients hospitalised for de-novo acute heart failure.

BACKGROUND: Recent evidence showed that new-onset (de-novo) acute heart failure (AHF) is a distinct type of AHF. However, the prognostic implication of gender on these patients remains unclear. AIMS: We aimed to investigate the impact of gender on both short and long-term mortality outcomes after hospitalisation for de-novo AHF. METHODS: We analysed the data of 721 patients with de-novo AHF, who were enrolled in the HF survey in Israel between March and April 2003 and were followed until December 2014. RESULTS: Fifty-four percent (N = 387) of the patients were men. In comparison to women, men patients were more likely to be younger, smokers, and with ischemic HF aetiology. At 30 days, mortality rates were higher in women (12% vs 7%, P = .013). Survival analysis showed that at 1 and 10 years the all-cause mortality rates were significantly higher in women (28% vs 17%, and 78% vs 67%, 1 and 10 years, P < .001, respectively). Consistently, multivariable analysis showed that women had an independently 82% and 24% higher mortality risk at 1 and 10 years, respectively, (1-year hazard ratio = 1.82; 95% confidence interval = 1.07 to 3.11, P = .03; 10-year hazard ratio = 1.24; 95% confidence interval = 1.03 to 1.48, P = .02). CONCLUSIONS: Amongst patients with de-novo AHF, women had higher mortality rates compared with men. The observed gender-related differences in de-novo AHF patients highlight the need for further and deeper research in this field.

High fitness might be associated with the development of new-onset atrial fibrillation in obese non-athletic adults.

BACKGROUND: Data on the association between AF and fitness are conflicting. OBJECTIVES: The aim of this analysis was to investigate the association between fitness, obesity and incidence of atrial fibrillation (AF) among apparently healthy non-athlete adults. METHODS: We investigated 20 410 self-referred subjects who were annually screened in a tertiary medical centre. All subjects were free of AF and completed maximal exercise stress test according to the Bruce protocol at baseline. Fitness was categorised into age- and sex-specific quintiles (Q) according to the treadmill time. Subjects were categorised to low (Q1-Q2) and high fitness (Q3-5) groups. The primary end point was new-onset AF during follow-up. RESULTS: Mean age was 48 ± 10 years and 72% were men. A total of 463 (2.3%) events occurred during an average follow-up of 8 ± 5 years corresponding to an AF event rate of 0.3% per person year. Univariate and multivariate models showed that AF risk was similar in both fitness groups. However, AF event rate was 0.55% per person year among high fitness obese subjects, compared with 0.31% for low fitness obese subjects (P < .01). Subgroup interaction analysis showed that AF risk is obesity-dependent, such that in the obese group (≥30 kg/m2 ) high fitness was independently associated with a significant 79% increased AF risk (95% CI 1.15-2.78; P = .01), whereas among non-obese subjects the rate of events was similar between both fitness groups (P for interaction = (.02)). CONCLUSIONS: Our findings suggest that high fitness might be associated with increased AF risk among obese subjects.

Vitamin D and rheumatoid arthritis: an ongoing mystery.

PURPOSE OF REVIEW: In recent years, there has been a growing interest in the value of vitamin D and its effects on autoimmunity. The aim of this review is to summarize the current knowledge on the association between vitamin D and rheumatoid arthritis (RA) in terms of prevalence, disease activity, clinical expression, serology and gene polymorphisms of vitamin D receptors. RECENT FINDINGS: Studies have shown contrasting findings concerning the association between vitamin D levels and RA. Vitamin D seems to have immunomodulatory properties. Therefore, low vitamin D levels could contribute to increased immune activation. However, the potential role of vitamin D supplementation in preventing RA manifestation and its beneficial role as a component of RA treatment remain controversial. The relationship between RA susceptibility and vitamin D polymorphisms is also unclear. SUMMARY: Despite advancements synthesized by some recent meta-analyses, the relationship between vitamin D and RA requires further evaluation. Further research is needed to confirm the relationship between RA susceptibility and vitamin D polymorphisms and to determine whether vitamin D plays a role in preventing the manifestation of RA. Finally, additional studies are required to determine the impact and optimal amount of vitamin D supplementation in the treatment of RA patients.

The "Burden" of Malignancy in a Tertiary Hospital Intensive Cardiovascular Care Unit.

OBJECTIVES: During the past decade, the most common causes of mortality and morbidity were cardiovascular diseases and malignancies. The aim of the current study was to describe the incidence, course of admission, and short-term (30-day) prognosis of patients with and without malignancy, admitted to a tertiary center intensive cardiovascular care unit (ICCU). METHODS: A prospective observational study of 2,259 patients admitted to the ICCU was conducted between January 2014 and December 2015. Patients with malignancies (n = 256) were divided into 2 groups: those with solid and those with homogenous tumors. RESULTS: The time of diagnosis was categorized into 3 patient groups: recent (<6 months), 59 patients (23%); late (6-24 months), 49 patients (19%), and very late (>24 months), 148 patients (58%). Those with a history of malignancy were older (73 ± 12 vs. 64 ± 15, p < 0.001) and were more likely to be female (p = 0.002). After using a multivariate logistic regression model analysis, no differences were found in therapeutic interventions and clinical outcomes, including major bleeding and acute renal failure, between patients with and without malignancies. CONCLUSIONS: Patients with a malignancy comprised about 10% of the entire ICCU population. While mortality was independently associated with advanced age, renal failure, and a diagnosis of ST-elevation myocardial infarction, malignancy alone was not found to be independently associated with a higher mortality rate at 30 days of follow-up.

Association between seasonal factors and multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system. MS is causing progressive and relapsing neurological disability, due to demyelination and axonal damage. The etiopathogenesis of MS is poorly understood. A number of environmental factors have been previously suggested, including: month of birth, vitamin D levels, smoking and viral infections. Previous studies assessing seasonal variation of relapses in multiple sclerosis have had conflicting results. The aim of this review is to assess the association between seasonal factors and MS, in terms of disease onset, relapses and activity.

Prevalence of Cardiac Sarcoidosis in Middle-Aged Adults Diagnosed with High-Grade Atrioventricular Block.

INTRODUCTION: Atrioventricular block may be idiopathic or a secondary manifestation of an underlying systemic disease. Cardiac sarcoidosis is a significant underlying cause of high-grade atrioventricular block, posing diagnostic challenges and significant clinical implications. This study aimed to assess the prevalence and clinical characteristics of cardiac sarcoidosis among younger patients presenting with unexplained high-grade atrioventricular block. METHODS: We evaluated patients aged between 18 and 65 years presenting with unexplained high-grade atrioventricular block, who were systematically referred for cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, prior to pacemaker implantation. Subjects with suspected cardiac sarcoidosis based on imaging findings were further referred for tissue biopsy. Cardiac sarcoidosis diagnosis was confirmed based on biopsy results. RESULTS: Overall, 30 patients with high-grade atrioventricular block were included in the analysis. The median age was 56.5 years (interquartile range 53-61.75, years). In 37%, cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, were suggestive of cardiac sarcoidosis, and in 33% cardiac sarcoidosis was confirmed by tissue biopsy. Compared with idiopathic high-grade atrioventricular block patients, all cardiac sarcoidosis patients were males (100% vs 60%, P = .029), were more likely to present with heart failure symptoms (50% vs 10%, P = .047), had thicker inter-ventricular septum on echocardiography (12.2 ± 2.7 mm vs 9.45 ± 1.6 mm, P = .002), and were more likely to present with right ventricular dysfunction (33% vs 10%, P = .047). CONCLUSIONS: Cardiac sarcoidosis was confirmed in one-third of patients ≤ 65 years, who presented with unexplained high-grade atrioventricular block. Cardiac sarcoidosis should be highly suspected in such patients, particularly in males who present with heart failure symptoms or exhibit thicker inter-ventricular septum and right ventricular dysfunction on echocardiography.

Angiographic Characteristics and Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention: Insights From the cVAD PROTECT III Study.

BACKGROUND: Prior studies have found that patients with chronic kidney disease (CKD) have worse outcomes following percutaneous coronary intervention (PCI). There are no data about patients with advanced CKD undergoing Impella-supported high-risk PCI. We, therefore, aimed to evaluate angiographic characteristics and clinical outcomes in patients with CKD who received Impella-supported high-risk PCI as part of the catheter-based ventricular assist device PROTECT III study (A Prospective, Multi-Center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump [IABP] in Patients Undergoing Non Emergent High Risk PCI). METHODS: Patients enrolled in the PROTECT III study were analyzed according to their baseline estimated glomerular filtration rate (eGFR). The primary outcome was 90-day major adverse cardiovascular and cerebrovascular events (the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization). RESULTS: Of 1237 enrolled patients, 1052 patients with complete eGFR baseline assessment were evaluated: 586 with eGFR ≥60 mL/min per 1.73 m2, 190 with eGFR ≥45 to <60, 105 with eGFR ≥30 to <45, and 171 with eGFR <30 or on dialysis. Patients with lower eGFR (all groups with eGFR <60) were more frequently females and had a higher prevalence of hypertension, diabetes, anemia, and peripheral artery disease. The baseline Synergy Between PCI With Taxus and Cardiac Surgery score was similar between groups (28.2±12.6 for all groups). Patients with lower eGFR were more likely to have severe coronary calcifications and higher usage of atherectomy. There were no differences in individual PCI-related coronary complications between groups, but the rates of overall PCI complications were less frequent among patients with lower eGFR. Major adverse cardiovascular and cerebrovascular events at 90 days and 1-year mortality were significantly higher among patients with eGFR <30 mL/min per 1.73 m2 or on dialysis. CONCLUSIONS: Patients with advanced CKD undergoing Impella-assisted high-risk PCI tend to have higher baseline comorbidities, severe coronary calcification, and higher atherectomy usage, yet CKD was not associated with a higher rate of immediate PCI-related complications. However, 90-day major adverse cardiovascular and cerebrovascular events and 1-year mortality were significantly higher among patients with eGFR<30 mL/min per 1.73 m2 or on dialysis. Future studies of strategies to improve intermediate and long-term outcomes of these high-risk patients are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136392.

Clinical characteristics and outcomes of patients requiring prolonged mechanical circulatory support after high-risk percutaneous coronary intervention.

BACKGROUND: There are limited data on the clinical characteristics and outcomes of patients who require prolonged mechanical circulatory support (MCS) after Impella-supported high-risk percutaneous coronary intervention (HR-PCI). AIMS: The aim of this study is to describe the contemporary clinical characteristics, outcomes, and predictors associated with prolonged MCS support after assisted HR-PCI. METHODS: Patients enrolled in the prospective, multicentre, clinical endpoint-adjudicated PROTECT III study who had undergone HR-PCI using Impella were evaluated. Patient and procedural characteristics and outcomes for those who received prolonged MCS beyond the duration of their index procedure were compared to those in whom MCS was successfully weaned and explanted at the conclusion of the index PCI. RESULTS: Among 1,155 patients who underwent HR-PCI with Impella between 2017 and 2020 and had sufficient data to confirm the duration of Impella support, 16.5% received prolonged MCS (mean duration 25.2±31.1 hours compared with 1.8±5.8 hours for those who only received intraprocedural MCS). Patients receiving prolonged support presented with more urgent indications (e.g., acute coronary syndromes [ACS], lower ejection fraction [EF], elevated baseline heart rate and lower systolic blood pressure). Use of the Impella CP, intraprocedural complications, periprocedural complications and in-hospital mortality were all more common amongst the prolonged MCS group. Prolonged MCS was associated with increased rates of major adverse cardiovascular and cerebrovascular events, cardiovascular death, and all-cause mortality at 90-day follow-up. CONCLUSIONS: Patients receiving prolonged MCS after Impella-supported HR-PCI presented with more ACS, reduced EF and less favourable haemodynamics. Additionally, they were more likely to experience intraprocedural and periprocedural complications as well as increased in-hospital and post-discharge mortality.

Pacemaker in patients undergoing mammography: A limitation for breast cancer diagnosis?

INTRODUCTION: A pacemaker may affect the utility of a mammogram in several ways. The aim of this study is to summarize our institution's experience with mammograms among patients with a cardiac pacemaker, focusing on the diagnostic workup among patients with a newly diagnosed ipsilateral breast cancer. METHODS: A retrospective search of all mammography reports between January 2011 and April 2021 was conducted for identifying cases of patients with a pacemaker. Demographic and clinical characteristics as well as mammography-derived quality parameters and findings were categorized and statistically compared. RESULTS: The incidence of pacemaker concurrence in mammographic examination, although apparently slightly under-documented, accounted for 0.33% of cases. Population mean age was 71.7 years, and most patients (79%) had a left-sided pacemaker. The pacemaker was much more likely to be projected on the medio-lateral-oblique (96%) than on the cranio-caudal view (10%), on the axilla rather than the breast, and on the retro-pectoral rather than the pre-pectoral region (P < 0.001 for all). Compression force decreased by up to 23.0% (P < 0.001) and breast thickness increased by up to 9.5% (P < 0.001) for the ipsilateral vs. the contralateral side. Among 11 patients with newly diagnosed ipsilateral breast cancer, the pacemaker partially projected on the tumour region in two cases, and significantly obscured the tumour in another two. CONCLUSION: Although rare, the coexistence of a pacemaker in patients undergoing mammography is associated with reduced image quality due to suboptimal breast visualization and reduced compression, and as a result, this may eventually lead to decreased diagnostic efficacy.

Optical Coherence Tomography-Guided Percutaneous Coronary Intervention: Practical Application.

Optical coherence tomography (OCT) provides high-resolution imaging of coronary arteries and can be used to optimize percutaneous coronary intervention (PCI). Intracoronary OCT, however, has had limited adoption in clinical practice. Novelty and relative complexity of OCT interpretation compared with the more established intravascular ultrasound, lack of a standardized algorithm for PCI guidance, paucity of data from randomized trials, and lack of rebate for intravascular imaging have contributed to the modest practical adoption of OCT. We provide a practical step-by-step guide on how to use OCT in PCI, including device set-up, simplified image interpretation, and an algorithmic approach for PCI. optimization.

Sex Differences in pLVAD-Assisted High-Risk Percutaneous Coronary Intervention: Insights From the PROTECT III Study.

BACKGROUND: Prior studies have found that female patients have worse outcomes following high-risk percutaneous coronary intervention (HRPCI). OBJECTIVES: The authors sought to evaluate sex-based differences in patient and procedural characteristics, clinical outcomes, and safety of Impella-supported HRPCI in the PROTECT III study. METHODS: We evaluated sex-based differences in the PROTECT III study; a prospective, multicenter, observational study of patients undergoing Impella-supported HRPCI. The primary outcome was 90-day major adverse cardiac and cerebrovascular events (MACCE)-the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization. RESULTS: From March 2017 to March 2020, 1,237 patients (27% female) were enrolled. Female patients were older, more often Black, more often anemic, and had more prior strokes and worse renal function, but higher ejection fractions compared to male patients. Preprocedural SYNTAX score was similar between sexes (28.0 ± 12.3). Female patients were more likely to present with acute myocardial infarction (40.7% vs 33.2%; P = 0.02) and more often had femoral access used for PCI and nonfemoral access used for Impella device implantation. Female patients had higher rates of immediate PCI-related coronary complications (4.2% vs 2.1%; P = 0.004) and a greater drop in SYNTAX score post-procedure (-22.6 vs -21.0; P = 0.04). There were no sex differences in 90-day MACCE, vascular complications requiring surgery, major bleeding, or acute limb ischemia. After adjustment using propensity matching and multivariable regression, immediate PCI-related complications was the only safety or clinical outcome that was significantly different by sex. CONCLUSIONS: In this study, rates of 90-day MACCE compared favorably to prior cohorts of HRPCI patients and there was no significant sex differences. (The PROTECT III Study is a substudy of The Global cVAD Study [cVAD]; NCT04136392).

Significance of Anteroseptal Late Gadolinium Enhancement Among Patients With Acute Myocarditis.

Anteroseptal location of late gadolinium enhancement (LGE) in patients with acute myocarditis (AM) detected by cardiovascular magnetic resonance may indicate an independent marker of unfavorable outcomes according to recent data. We aimed to evaluate the clinical characteristics, management, and inhospital outcomes in patients with AM with positive LGE based on its presence in the anteroseptal location. We analyzed data from 262 consecutive patients hospitalized with a diagnosis of AM with positive LGE within 5 days of hospitalization (n = 425). Patients were divided into 2 groups: those with anteroseptal LGE (n = 25, 9.5%) and those with non-anteroseptal LGE (n = 237, 90.5%). Except for age that was higher in patients with anteroseptal LGE, the demographic and clinical characteristics did not differ significantly between both groups including past medical history, clinical presentation, electrocardiogram parameters, and lab values. Moreover, patients with anteroseptal LGE were more likely to present with reduced left ventricular ejection fraction and to receive congestive heart failure treatments. Although univariate analysis showed that patients with anteroseptal LGE were more likely to have inhospital major adverse cardiac events (28% vs 9%, p = 0.003), there was no difference inhospital outcomes on multivariable analysis between both groups (hazard ratio, 1.17 [95% confidence interval, 0.32 to 4.22], p = 0.81). A higher left ventricular ejection fraction in either echocardiography or cardiovascular magnetic resonance corresponded to better inhospital outcomes regardless of the presence or absence of anteroseptal LGE. In conclusion, the presence of anteroseptal LGE did not confer additional prognostic value for inhospital outcomes.

Preparation and characterization of flexible furosemide-loaded biodegradable microneedles for intradermal drug delivery.

Transdermal drug delivery systems are a useful and minimally invasive alternative to other drug administration routes. Biodegradable polymeric microneedles (MNs) are widely used in controlled-release drug delivery due to their tunable properties and ease of patient self-administration. Polylactic-co-glycolic acid (PLGA) is often used for sustained drug release owing to special intrinsic properties including biocompatibility and biodegradability, which offer excellent applicability in preparing MNs. Congestive heart failure (CHF) is characterized by fluid overload during acute exacerbation, necessitating frequent patient hospitalization for continuous intravenous (i.v.) diuretic therapy. In the present study, we incorporated furosemide (FUR) as a model drug into flexible PLGA MN skin patches for potential intradermal delivery to overcome the limitations associated with i.v. diuresis. The MNs were fabricated by a casting-mold technique and consisted of two main parts, PLGA needle tips loaded with varying concentrations of FUR and a flexible backing layer comprising sodium alginate and glycerol. MN formulations were characterized by SEM and exhibited a uniform pyramidal shape. The measured surface pH of all samples suggested that no skin irritation is expected upon application. High encapsulation efficiency was obtained for FUR-MN formulations in which a decrease was noted as the FUR/PLGA ratio decreased. Drug loading content ranged from 19.1 ± 1% to 28.9 ± 1.4%. Successful insertion of MNs into a Parafilm® skin simulant model suggested that MNs will easily penetrate the skin's outermost layer, the stratum corneum, and will permit intradermal delivery of FUR. The MNs were further characterized by analytical methods. Finally, the MNs exhibited an initial burst release followed by a sustained release of FUR. Self-administered FUR-MNs can open new avenues to overcome i.v. drip limitations and increase patient compliance.

Prevalence and clinical implication of thrombocytopenia and heparin-induced thrombocytopenia in patients who are critically ill with COVID-19.

As the COVID-19 pandemic continues to evolve, different clinical manifestations are better understood and studied. These include various haematologic disorders that have been shown to be associated with increased morbidity and mortality. We studied the prevalence of one unusual manifestation, heparin-induced thrombocytopenia (HIT) and its clinical implications in patients who are severely ill with COVID-19 in a single tertiary centre in Israel. The presence of thrombocytopenia, disseminated intravascular coagulation (DIC) and HIT, and their association with clinical course and outcomes were studied. One-hundred and seven patients with COVID-19 were included. Fifty-seven (53.2%) patients developed thrombocytopenia, which was associated with the worst outcomes (ventilation, DIC and increased mortality). Sixteen (28.0%) patients with thrombocytopenia were positive for HIT, all of which were supported by extracorporeal devices. HIT was independently associated with ventilation days, blood product transfusions, longer hospitalisation and mortality.Platelet abnormalities and HIT are common in patients who are critically ill with COVID-19 and are associated with the worst clinical outcomes. The mechanisms underlying HIT in COVID-19 are yet to be studied; HIT may contribute to the dysregulated immunologic response associated with COVID-19 critical illness and may play a significant part in the coagulopathy seen in these patients. As many patients with COVID-19 require aggressive thromboprophylaxis, further understanding of HIT and the implementation of appropriate protocols are important.

The Utility of 18FDG-PET/CT in Diagnosing Fever of Unknown Origin: The Experience of a Large Tertiary Medical Center.

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18-93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.

Ethnic Disparity in Mortality Among Ischemic Heart Disease Patients. A-20 Years Outcome Study From Israel.

Background: Long-term morbidity and mortality data among ischemic heart disease (IHD) patients of different ethnicities are conflicting. We sought to determine the independent association of ethnicity and all-cause mortality over two decades of follow-up of Israeli patients. Methods: Our study comprised 15,524 patients including 958 (6%) Arab patients who had been previously enrolled in the Bezafibrate Infarction Prevention (BIP) registry between February 1, 1990, and October 31, 1992, and subsequently followed-up for long-term mortality. We compared clinical characteristics and outcomes of Israeli Arabs and Jews. Propensity score matching (PSM) (1:2 ratios) was used for validation. Results: Arab patients were significantly younger (56 ± 7 years vs. 60 ± 7 years; p < 0.001; respectively), and had more cardiovascular disease (CVD) risk factors. Kaplan-Meier survival analysis showed that all-cause mortality was significantly higher among Arab patients (67 vs. 61%; log-rank p < 0.001). Multivariate adjusted analysis showed that mortality risk was 49% greater (HR 1.49; 95% CI: 1.37-1.62; p < 0.001) among Arabs. Conclusions: Arab ethnicity is independently associated with an increased 20-year all-cause mortality among patients with established IHD.

CHADS2 and CHA2DS2-VASc scores as predictors of platelet reactivity in acute coronary syndrome.

BACKGROUND: Platelet function testing (PFT) in patients treated with P2Y12 inhibitors has been widely evaluated for the prediction of stent thrombosis, myocardial infarction, and bleeding events following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). Thus, PFT-guided treatment could positively affect patient outcomes. Data regarding clinical parameters for predicting platelet reactivity in ACS patients are limited. Therefore, our study aims to evaluate CHADS2 and CHA2DS2-VASc scores as predictors for platelet reactivity in ACS patients. METHODS: Two hundred and ninety-one consecutive patients who underwent PCI and were treated with aspirin and clopidogrel due to ACS were tested for their CHADS2, CHA2DS2-VASc scores and platelet reactivity using adenosine diphosphate (ADP)-induced aggregation (conventional aggregometry). Patients were classified into groups according to their CHADS2 and CHA2DS2-VASc scores. Low-risk group (0-1 score) for CHADS2 and CHA2DS2-VASc scores and high-risk group (2-6, 2-9) for CHADS2 and CHA2DS2-VASc scores, respectively. Furthermore, platelet reactivity in each group were compared (low CHADS2 group vs high CHADS2 group, and low CHA2DS2-VASc vs high CHA2DS2-VASc). Platelet reactivity was defined as low platelet reactivity (<19 U), optimal platelet reactivity [(OPR); 19-46 U], and high on-treatment platelet reactivity [(HPR); >46 U]. Thereafter receiver operating characteristic curve analysis was conducted to verify whether CHADS2 and CHA2DS2-VASc scores could predict platelet reactivity. RESULTS: Low CHADS2 and CHA2DS2-VASc scores were significantly correlated with lower mean platelet ADP-induced aggregation as compared with high CHADS2 and CHA2DS2-VASc scores [45.5 U (± 16) vs. 54.8 U (±15) and 44.2 U (±16) vs. 51.0 U (±17), respectively, p = 0.01 for both]. CONCLUSION: In ACS patients treated with clopidogrel following PCI, high CHADS2 and CHA2DS2-VASc scores correlated with HPR and lower scores correlated with OPR. Further studies are needed to evaluate our findings' clinical implications.

Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination.

BACKGROUND: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. METHODS: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. FINDINGS: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. INTERPRETATION: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. FUNDING: none.