Population Of Symptomatic Patients Research Articles

The prognostic value of contrast stress echocardiography in a real-world population of symptomatic patients without known coronary artery disease

Abstract Background Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. In addition to diagnosis, non-invasive tests may also provide prognostic information useful in the risk stratification and management of CAD patients. Stress echocardiography (SE) is an accurate, non-invasive method for the detection of obstructive CAD. However, in real-world clinical practice the test performance may vary among different centres, depending on availability, local protocols, and operator expertise. Purpose To evaluate the prognostic value of contrast SE in a real-world population of symptomatic patients without known CAD. Methods This was a cohort follow-up study of patients without known CAD and symptoms of atypical chest pain, unexplained dyspnoea or palpitations who were referred to the echocardiography lab of a tertiary hospital for SE between January 2020 and December 2021. Patients with resting regional wall motion abnormalities were excluded. All patients underwent treadmill exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) if unable to exercise. Contrast agents were used in almost all patients (99%). The study population was followed-up for at least 2 years after SE by phone and/or electronic hospital records. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, acute coronary syndrome (ACS), or cardiac-related death. Results The study comprised 266 patients (mean age 58±12 years, 63% male) who underwent either ESE (58%) or DSE (42%). The patients' details are reported in Table 1. The most common indication for the exam was atypical chest pain, with a prevalence of 73%. SE exams were positive for inducible ischaemia in 14 (5%) patients. Symptoms during the exam were present in 3 (21%) patients with positive SE and 4 patients (2%) with negative SE (p=0.004). No serious complications (sustained ventricular tachycardia, myocardial infarction, or death) were recorded. During the follow-up (median 30, IQR 23–38 months), 264 patients (99%) were successfully contacted. Cardiac outcome occurred in 10 patients. Among 14 patients with positive SE, 8 underwent revascularization due to significant coronary artery stenosis. Among 250 patients with negative SE, 1 underwent revascularization due to significant coronary artery stenosis and 1 presented with ACS 13 months after the test (both patients underwent DSE). Negative predictive value was 99% over a median follow-up of 30 months, corresponding to an annualized event rate of 0.32% per year. A positive SE was significantly associated with cardiac outcome (log-rank test p<0.0001, Figure 1). Conclusion Contrast SE carries significant prognostic implications in symptomatic patients without known CAD. A positive test is strongly associated with the need for revascularization, while a normal test result has an excellent negative predictive value regarding cardiovascular morbidity and mortality.Figure 1

Eighteen-Month Real-World Experience Using Mavacamten for Treatment of Obstructive Hypertrophic Cardiomyopathy in a Racially Diverse Population.

Patients with obstructive hypertrophic cardiomyopathy have increased symptomatic burden. Mavacamten was recently approved for treatment of obstructive hypertrophic cardiomyopathy based on 2 randomized controlled trials. However, its use under real-world conditions and in diverse populations is under-studied. This was a prospective observational cohort study of patients seen at the Johns Hopkins HCM center and prescribed mavacamten for obstructive hypertrophic cardiomyopathy between July 7, 2022 and January 6, 2024. Patients were followed longitudinally, with serial echocardiography and clinical evaluation as mandated by the risk evaluation and mitigation strategy program. Sixty-six patients received mavacamten (mean age 59 years, 47% male, 29% non-White [Black, Hispanic/Latino, Asian, Native Hawaiian or Pacific Islander], 47% obese). Before treatment, all patients had New York Heart Association class II (51.5%) or III (48.5%) heart failure symptoms. Initial maximum peak left ventricular outflow tract gradient was 107±46 mm Hg. Median treatment duration was 9 months. For patients on mavacamten after ≥6 months (n=43), symptoms improved by ≥1 New York Heart Association class in 72% of patients, and peak left ventricular outflow tract gradient decreased by 80±46 mm Hg, eliminating hemodynamically significant left ventricular outflow tract obstruction in 79.1% of patients. Mavacamten was temporarily discontinued in 3 patients due to left ventricular ejection fraction decrease <50%. There were no medication-related adverse events. Effectiveness and safety were similar between White and non-White patients, but symptomatic relief was attenuated in patients with body-mass index ≥35 kg/m2. Mavacamten was effective and safe when used under real-world conditions in a racially diverse population of symptomatic patients with obstructive hypertrophic cardiomyopathy. Patients with comorbid obesity were less likely to experience symptomatic improvement while on mavacamten.

Music-Based Interventions for Symptom Management in Critically Ill, Mechanically Ventilated Adults: A Scoping Review of the Literature.

Background: Patients in intensive care units experience high symptom burden during mechanical ventilation (MV). Pharmacologic symptom management is associated with side effects and increased morbidity. Music-based interventions (MBIs) have been associated with reductions in both anxiety in MV adults and pain for critically ill adults, yet their use for the management of other burdensome symptoms has not been evaluated. The purpose of this scoping review is to map the state of evidence for the use of prerecorded music listening MBIs for symptom management in MV adults. Methods: A systematic search of the literature was conducted across four electronic databases (PubMed, EMBASE, CINAHL, and Web of Science) for experimental designed studies that measured the efficacy of MBIs for the management of physical and psychological symptoms including anxiety, sedation/agitation, dyspnea, distress, delirium, sleep, stress, fear, loneliness, or depression in critically ill, MV adults between January 1, 1998, and April 18, 2023. Results: A total of 643 abstracts and 29 clinical trials were included. Overall, the risk of bias, assessed using the Evidence Project tool, was moderate. MBIs were mostly delivered with headphones using music selected either by investigators or from a limited selection. MBIs were associated with reduced pain, agitation, dyspnea, distress and anxiety, and improved tolerance of MV and sedative weaning. Outcomes of delirium were mixed. No studies explored sleep disturbances, fear, or loneliness. Conclusions: Use of MBIs improved symptom experience for critically ill adults during MV. Future studies employing unrestricted patient-preferred music selections and exploring outcomes of sleep quality, psychological distress, and delirium are needed in this highly symptomatic patient population.

Innovative Ultrasound Criteria for the Diagnosis of Adenomyosis and Correlation with Symptoms: A Retrospective Re-Evaluation.

The 2022 Delphi revision of the MUSA (Morphological Uterus Sonographic Assessment) criteria for the ultrasound diagnosis of adenomyosis divides the ultrasound signs for diagnosis into direct and indirect ones, considering the presence of at least one direct sign as a mandatory criterion. This study aimed to reclassify the patients referred to the Pelvic Pain specialist outpatient clinic of the Gynecological Clinic of Udine according to the new criteria, evaluating the number of overdiagnoses and the possible correlation between the direct and indirect signs and the patients' symptoms. 62 patients affected by adenomyosis were retrospectively recruited. The patients were then re-evaluated by ultrasound and clinically. At least one direct sign of adenomyosis was found in 52 patients, while 16% of the population examined did not present any. There was no statistically significant difference between patients presenting direct signs and those presenting none for the symptoms considered. According to the new criteria, 16% of the patients examined were not affected by adenomyosis; applying the new consensus to symptomatic patients could increase false negatives. In a population of symptomatic patients, the diagnosis of adenomyosis is still highly probable even without direct ultrasound signs, given the clinical symptoms and having ruled out other causes of such symptoms.

A212 SYMPTOMS IN PATIENTS WITH NORMAL ESOPHAGEAL MOTILITY MAY DIFFER BASED ON AGE AND SEX

Abstract Background High resolution esophageal manometry (HREM) is used to diagnose esophageal motility disorders. While esophageal symptoms including dysphagia are common and seen in up to 20% of adults, a minority of symptomatic patients have esophageal dysmotility, when defined by the Chicago Classification v4 (CCv4). The generation of esophageal symptoms in a patient with normal esophageal motor function is complex, but may relate to visceral hypersensitivity, inappropriate pain perception or unidentified contraction abnormalities. The Esophageal Symptom Questionnaire (ESQ-30) is a validated tool in the assessment of esophageal symptoms and measures the frequency and severity of dysphagia, reflux and globus through three separate sub-scales (ESQ-D, ESQ-R, ESQ-G respectively). Aims To determine age and sex in esophageal symptoms (as measured by ESQ-30 sub-scales) in a population of symptomatic patients with normal esophageal motility. Methods Retrospective analysis of consecutive reports from HRM studies performed between October 2021 – March 2023 who provided consent for inclusion in the motility databank and completed ESQ-30 questionnaires. All values expressed as median (IQR: 25-75-centile). Spearman’s bivariate correlations were performed between ESQ-D, ESQ-R, ESQ-G and manometric variables (IRP, DCI, % failed, and % weak) as well as demographic variables (age). Group means were compared with the non-parametric Mann-Whitney U test. Results Within the study period, 681 patients underwent HREM and had complete ESQ-30 questionnaires. Of these patients, 151 female and 73 male participants (mean age 51.8 +/- 15.2 years) had normal esophageal motility by CCv4. ESQ-D and ESQ-R scores were significantly higher in women in comparison to men. ESQ-D was 10 in women and 5 in men (p=.021), and ESQ-R was 28 in women and 19 in men (p=.029). There was a weak negative correlation between age and reflux symptoms (R2 -.139, p = 0.038). There was no significant difference in manometric parameters between males and females (p ampersand:003E .05 for all comparisons). Dysphagia and globus weakly negatively correlated with median IRP (R2 -.156, p = .019 and R2 -.139, p = .038 for dysphagia and globus respectively). Conclusions In a population of symptomatic patients with normal esophageal motility, symptom profile differed based on age and sex. Women had higher dysphagia and reflux symptoms compared to men, while older patients had lower reflux symptoms. These findings suggest that esophageal sensitivity may vary with age and sex in patients with normal esophageal motility. The finding of higher dysphagia and globus symptoms in patients with lower median IRP (integrated relaxation pressure) is an unexpected finding and may reflect reflux effect. Further studies to assess for the impact of GERD (using 24h pH-metry/MII) on patients with normal esophageal motor function are warranted. Funding Agencies None

Transcatheter aortic valve implantation in severe aortic stenosis does not necessarily reverse left ventricular myocardial damage: data of long-term follow-up.

Aortic stenosis (AS) is causing myocardial damage and replacement is mainly indicated based on symptoms. Non-invasive estimation of myocardial work (MW) provides a less afterload-dependent too for assessing myocardial function. We sought to look at the impact of transcatheter aortic valve implantation (TAVI) on the myocardium at long-term follow-up and according to current indications. We conducted an observational, cross-sectional, single-centre study. Patients were selected based on the validated indication for a TAVI. Standardized echocardiographies were repeated. A total of 102 patients were included. The mean age was 85 years, 45% were female, 68% had high blood pressure, and 52% had a coronary disease. One-fifth was suffering from low-flow-low-gradient AS. A follow-up was performed at 22 ± 9.5 months after the TAVI. No TAVI dysfunction was observed. Left ventricular (LV) ejection fraction was stable (62 ± 8%), and global longitudinal strain had improved (-14.0 ± 3.7 vs. -16.0 ± 3.6%, P < 0.0001). No improvement of the MW parameters was noticed (LV global work index 2099 ± 692 vs. 2066 ± 706 mmHg%, P = 0.8, LV global constructive 2463 ± 736 vs. 2463 ± 676 mmHg%, P = 0.8). Global wasted work increased [214 (149; 357) vs. 247 (177; 394) mmHg%, P = 0.0008]. In a population of severe symptomatic AS patients who had undergone a TAVI, the non-invasive myocardial indices that assess the LV performance at long-term follow-up did not improve. These results are questioning the timing of the intervention and the need for more attention in the pharmacological management of these AS patients.

Intracranial stenting versus aggressive medical therapy for symptomatic intracranial stenosis: A meta-analysis of multicenter randomized controlled trials and an expert assessment of the current data.

Intracranial atherosclerotic stenosis (ICAS) is associated with high risk of recurrent strokes despite best medical management (MM). We aimed to synthesize the evidence from randomized studies comparing intracranial stenting plus MM versus MM alone. Comprehensive search of MEDLINE database was performed until May 2023. The data were extracted and pooled as risk ratio (RR) with 95% confidence interval (95% CI). We included three multicenter RCTs totaling 919 patients. As compared to MM alone, intracranial stenting was associated with statistically significant higher risks of any stroke or death (RR = 2.93, 95%CI [1.80-4.78], p < 0.0001), stroke in the same territory of qualifying artery (RR = 3.56, 95%CI [1.97-6.44], p < 0.0001), any ischemic stroke (RR = 2.22, 95%CI [1.27-3.87], p = 0.005), hemorrhagic stroke (RR = 13.49, 95%CI [2.59-70.15], p = 0.0002), and death (RR = 5.43, 95%CI [1.21-24.40], p = 0.003) within 30 days of randomization. There was a persistent lack of benefit and signals of harm at the last follow up within 1-3 years: any stroke or death (RR = 1.57, 95%CI [0.92-2.67], p = 0.1), stroke in the same territory of qualifying artery (RR = 1.84, 95%CI [0.97-3.50], p = 0.06), any ischemic stroke (RR = 1.56, 95%CI [1.11-2.20], p = 0.01), death (RR = 1.61, 95%CI [0.77-3.38], p = 0.2). The cumulative rate of stroke in the same territory of qualified artery with MM alone within the 1-3-year follow up was lower than expected, with only 47 out of the 450 (10.4%) MM alone patients suffering such events. The findings from this meta-analysis do not recommend stenting as a routine care option for the broader symptomatic ICAS patient population. The rates of recurrent strokes in ICAS patients managed with aggressive MM do not seem to be as high as anticipated. Additional multicenter RCTs including safer devices, larger sample sizes, and patients at higher risk of recurrent events are warranted.

Prevelance of Common Aeroallergens in Allergic Rhinitis and its Correlation with Bronchial Asthma: A Study on 798 Patients by Skin Prick Test.

Allergic rhinitis affects 30% of the Indian population (Dey et al. in Int Arch Allergy Immunol 178:60-65, 2019). Patients can be sensitive to single or multiple allergens. Polysensitization is more common (Bousquet et al. in Ann Epidemiol 20:797-803, 2010; Arbes et al. in J Allergy Clin Immunol 116:377-383, 2005). Sensitization to multiple allergens may have a role in the severity and the association of Asthma in such patients. A total of 798 patients with allergic rhinitis (SFAR ≥ 7) were included. Disease severity and associated symptoms were evaluated using questionnaire. Each patient underwent a Skin prick test with an allergen panel of 35 allergens each (Annesi-Maesano et al. in Allergy 57:107-114, 2002) and the results were evaluated to study the association of asthma and severity of Allergic rhinitis. Data consisting of 389 (48.7%) males and 409 (51.3%) females were assessed. A total of 82.2% of the study population of symptomatic patients were sensitized to at least one of the allergens. Seventy patients (8.78%) had associated asthma. Forty-four patients were polysensitized and fifteen were mono sensitized. Among polysensitized patients, 36 patients had sensitization to at least 6 different allergens. Dermatophagoides pteronyssinus was the most common allergen among asthma patients. This study provides a thorough knowledge of locally prevalent aeroallergens which is essential for the prompt diagnosis and treatment of allergic patients. Skin prick test can be a non-invasive vital tool in analyzing patterns of allergen exposure, the prevalence of allergen, sensitizing potential of different allergens in that specific geographic area.

150 ECHO-DERIVED LEFT VENTRICULAR MECHANO-ENERGETIC EFFICACY CHARACTERIZES HYPERTENSIVE PATIENTS WITH IMPAIRED PET-DERIVED MYOCARDIAL BLOOD FLOW

Abstract Background Chronic left ventricular (LV) pressure overload determines both morphological and functional alterations in the heart and in the vascular system with occurrence of LV hypertrophy, coronary rarefaction and metabolic impairment, predisposing to heart failure. We aim at investigating early cardiac involvement in hypertensive disease by both Positron emission tomography (PET) and echo assessment and possible associations between alterations of PET-derived myocardial blood flow (MBF) and echocardiographic parameters of LV performance including mechano-energetic efficiency indexed for myocardial mass (MEEi), in a population of symptomatic hypertensive patients without flow-limiting epicardial coronary artery disease (CAD). Methods The study population included 78 symptomatic hypertensive patients without flow-limiting epicardial CAD. All patients underwent standard echocardiographic assessment, including evaluation of LV MEEi, and PET assessment with evaluation of MBF and MBF/mass ratio at rest and after stress and myocardial flow reserve (MFR). Results The study population included 67% males, 55% with dyslipidaemia, 42% with smoking habits and 21% obese. Prevalence of LV hypertrophy was of 43%. Among parameters of LV systolic performance, hyperaemic MBF/mass ratio resulted significantly correlated with LV MEEi (r=0.54, p&amp;lt;0.0001), midwall fractional shortening (r=0.38, p=0.001) but not with LVEF (r=0.10, p=0.47). Similarly, resting MBF/mass ratio resulted to have statistically significant correlations with LV MEEi (r=0.51, p&amp;lt;0.0001), midwall fractional shortening (r=0.29, p=0.01) but not with LVEF (r=0.11, p=0.39). LV MEEi reached the highest correlation coefficient with both resting and stress MBF/mass ratio. On the other hand, the correlation between MEEi and MFR did not reach statistical significance (r=0.11, p=0.33). In a multiple linear regression analysis, after adjusting for sex, systolic blood pressure, prevalence of LV hypertrophy and therapy with diuretics, the association between LV MEEi and hyperaemic MBF/mass ratio remained significant (beta coefficient =0.40, p=0.007). In a subsequent multivariate model, adjusting for the same confounders, by replacing hyperaemic MBF/mass ratio with resting MBF/mass ratio, LV MEEi and resting MBF/mass ratio continued to be significantly associated (beta coefficient =0.32, p=0.015). Conclusions In a population of hypertensive patients without flow-limiting epicardial CAD, an early myocardial impairment possibly related to coronary rarefaction and inadequate angiogenesis contributing to the altered myocardial metabolic demand and efficacy is detectable by both PET and echo-derived LV MEEi. Indeed, an independent association between LV MEEi and both MBF/mass ratio at rest and after stress exists, LV MEEi having the advantage over PET of being easily derived from standard echocardiography and not needing radiation exposure.

Relationship between coronary artery calcification and myocardial ischemia on computed tomography myocardial perfusion in patients with stable chest pain

BackgroundCoronary artery calcium (CAC) score has shown to provide incremental prognostic information when added to the Framingham risk score. Although the relation between CAC and myocardial ischemia has been evaluated, there has been little evaluation of the relationship between CAC score and inducible myocardial ischemia on computed tomography myocardial perfusion (CTP). Methods and ResultsPatients who were referred with stable chest pain from the outpatient clinic and who underwent non-contrast computed tomography scan, coronary computed tomography angiography, and adenosine stress CTP were included in this study. CAC score was subdivided in four groups (1 to 99; 100 to 399, 400 to 999, and ≥ 1000). Inducible myocardial ischemia was considered when reversible perfusion defects were observed in ≥ 1 segment. A total of 131 patients (age 62 ± 9.4 years; 56% male) were included. The median CAC score was 241 (73 to 539). Forty-nine patients (37%) had evidence of inducible myocardial ischemia. The presence of inducible myocardial ischemia increased with increasing CAC score from 22% in the CAC score 1 to 99 subgroup to 35, 47, and 65% in the 100 to 399, 400 to 999, and ≥ 1000 CAC score subgroup, respectively. In multivariable analysis CAC score was the only determinant that significantly predicted the presence of inducible myocardial ischemia on CTP. ConclusionsIn a population of symptomatic patients, the majority of patients with extensive calcification had evidence of inducible myocardial ischemia on CTP. CAC score was the only independent predictor of inducible myocardial ischemia on CTP.

Global longitudinal strain to determine optimal timing for surgery in primary mitral regurgitation: A systematic review.

Primary mitral regurgitation (PMR) results in adverse remodeling changes and left ventricular (LV) dysfunction. Assessing LV function has prognostic value in predicting morbidity and mortality. Indications for surgery include parameters such as LV ejection fraction (LVEF) and systolic dimensions. Current guidelines are limited in identifying patients at optimal time for surgery. Impaired postoperative LVEF indicates poor prognostic outcomes and subsequent heart failure. Global longitudinal strain (GLS) via speckle tracking echocardiography (STE) presents as a promising parameter to detect subclinical dysfunction in asymptomatic patients. Following PRISMA guidelines, a literature search was conducted with Cochrane Library, PudMed, SCOPUS, and Web of Science. Key MeSH terms included "mitral regurgitation," "mitral valve insufficiency," "global longitudinal strain," "deformation," "LV-GLS," and "GLS." Inclusion criteria included (1) patients with severe PMR, (2) mixed population of symptomatic and asymptomatic patients, (3) standardized methods in assessing LV systolic function using 2D-STE, (4) valve repair or replacement surgery, and (5) patient outcomes measured after surgery. Search returned 234 papers, 12 of which met the inclusion criteria and were subsequently reviewed. Baseline GLS is an independent predictor of postoperative outcomes, ranging from -17.9 to -21.7% GLS. A significant negative correlation was observed between preoperative GLS and postoperative LVEF. Impaired baseline GLS was associated with higher mortality rates. Better long-term survival rates were seen in patients who underwent early surgery. GLS shows sensitivity in predicting long-term postoperative outcomes. Further analysis is required to determine preoperative GLS threshold to identify asymptomatic patients at the optimal time for mitral valve surgery.

Idiopathic HFrEF. Is there room left for defibrillators?

Abstract Background and aim Prophylactic implantation of an implantable cardioverter-defibrillator (ICD) is class 1 recommendation for heart failure (HF) patients with reduced ejection fraction (HFrEF) even though its proven advantage is weaker among nonischemic aetiology. In fact, in an era where both optimal medical therapy (OMT) and cardiac resynchronization therapy (CRT) significantly reduce sudden cardiac death (SCD), it is questionable whether ICD still have additional value. The aim of this study was to assess the current benefit of ICDs in preventing sudden cardiac death through resuscitated cardiac arrest (RCA), appropriate therapy for sustained ventricular tachycardia (VT) or fibrillation (VF) in a contemporary population of idiopathic HFrEF patients. Methods Single-centre retrospective study of consecutive symptomatic (NYHA class II to IV) idiopathic HFrEF patients with an ICD (either alone or in association with CRT), and remote monitoring with the corresponding software (MerlinTM, LatitudeTM, CarelinkTM, MicroPortTM or BiotronikTM) to assure appropriate event supervising. Idiopathic aetiology was assumed after excluding other probable causes. Coronary angiogram was required to exclude ischemic aetiology. Only those with prophylactic ICD implantation were included. RCA was defined as collapse with clinical signs of cardiac arrest and VF or VT appropriately terminated by ICD. In order to be sustained, VT episode had to have last at least 30 seconds. Results From 781 remote monitoring controlled patients, a total of 187 consecutive symptomatic idiopathic HFrEF patients with an ICD (125 men, mean age 64±18 years) were enrolled. Patients were on optimal medical therapy (ACEi/ARB: n=168, 90%; BB: n=154, 82%; mineralocorticoid antagonists: n=91, 49%; CRT: n=130, 70%; see Table). After a median follow-up of 99 months (IQR 62.2), RCA occurred in 10.7% (n=20) and 36.9% (n=69) had appropriately terminated VT. Both left ventricular ejection fraction (LVEF) improvement and CRT implantation did not independently reduce the incidence of RCA and VT requiring ICD therapy (OR, 1.02; 95% CI, 0.99–1.05; P=0.146 and OR, 0.85; 95% CI, 0.34–2.13; P=0.728; respectively). All cause mortality was 20 (10.7%). Inappropriate therapy was given as shocks to 41 patients (21.9%) and as antitachycardia pacing (ATP) to 30 (16%), opposing with appropriately given therapy to 43 (23%) and 63 (33.7%) patients, respectively (see Figure), contributing to a net clinical benefit (NCB) of 18.8%, favouring ICD implantation. Conclusion In this contemporaneous real-world population of symptomatic idiopathic HFrEF patients, episodes of impending cardiac death were frequent. Prophylactic ICD implantation seems to have added further benefit reducing SCD on top of optimal medical therapy, LVEF improvement and coexisting CRT. Funding Acknowledgement Type of funding source: None

Cerebrospinal fluid and plasma biomarkers in individuals at risk for genetic prion disease

BackgroundPrion disease is neurodegenerative disease that is typically fatal within months of first symptoms. Clinical trials in this rapidly declining symptomatic patient population have proven challenging. Individuals at high lifetime risk for genetic prion disease can be identified decades before symptom onset and provide an opportunity for early therapeutic intervention. However, randomizing pre-symptomatic carriers to a clinical endpoint is not numerically feasible. We therefore launched a cohort study in pre-symptomatic genetic prion disease mutation carriers and controls with the goal of evaluating biomarker endpoints that may enable informative trials in this population.MethodsWe collected cerebrospinal fluid (CSF) and blood from pre-symptomatic individuals with prion protein gene (PRNP) mutations (N = 27) and matched controls (N = 16), in a cohort study at Massachusetts General Hospital. We quantified total prion protein (PrP) and real-time quaking-induced conversion (RT-QuIC) prion seeding activity in CSF and neuronal damage markers total tau (T-tau) and neurofilament light chain (NfL) in CSF and plasma. We compared these markers cross-sectionally, evaluated short-term test-retest reliability over 2–4 months, and conducted a pilot longitudinal study over 10–20 months.ResultsCSF PrP levels were stable on test-retest with a mean coefficient of variation of 7% for both over 2–4 months in N = 29 participants and over 10–20 months in N = 10 participants. RT-QuIC was negative in 22/23 mutation carriers. The sole individual with positive RT-QuIC seeding activity at two study visits had steady CSF PrP levels and slightly increased tau and NfL concentrations compared with the others, though still within the normal range, and remained asymptomatic 1 year later. T-tau and NfL showed no significant differences between mutation carriers and controls in either CSF or plasma.ConclusionsCSF PrP will be interpretable as a pharmacodynamic readout for PrP-lowering therapeutics in pre-symptomatic individuals and may serve as an informative surrogate biomarker in this population. In contrast, markers of prion seeding activity and neuronal damage do not reliably cross-sectionally distinguish mutation carriers from controls. Thus, as PrP-lowering therapeutics for prion disease advance, “secondary prevention” based on prodromal pathology may prove challenging; instead, “primary prevention” trials appear to offer a tractable paradigm for trials in pre-symptomatic individuals.

Outpatient Urinary-Tract-Infection-Like Symptoms: Causative Microbial Survey Utilizing Multiplex Quantitative Polymerase Chain Reaction Methodology

Urinary tract infections (UTIs) are among the most common maladies afflicting the human population globally. A wide variety of microbial pathogens are responsible for causing UTIs that are often recurrent, especially in the elderly population, resulting in an economic burden of billions of dollars annually. In this study, we present data from a large population of symptomatic UTI patients tested using a multiplexed, real time quantitative polymerase chain reaction (qRT-PCR) strategy. Our data demonstrate that instances of UTI increase with age for all the tested pathogens, with the exception of Mycoplasma spp. and Ureaplasma spp., which were found to be significantly higher in the younger population. Furthermore, the use of the qRT-PCR approach was also found to be effective in detecting polymicrobial UTIs. With the limitations of classical microbial culture techniques traditionally used for UTI diagnosis, we demonstrate that a rapid and comprehensive technique like RT-PCR can be an effective tool for detecting and managing UTIs.

Carotid Endarterectomy and Carotid Artery Stenting in a Predominantly Symptomatic Real-World Patient Population

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are well-established treatments that have been shown to decrease stroke recurrence in patients with underlying carotid artery disease. We assessed clinical outcome, safety, and restenosis rates for patients who underwent standardized CEA or CAS at our tertiary care center using patient selection criteria based on available scientific evidence. Retrospective chart review of patients who underwent CEA or CAS between 2009 and2016. In total, 314 cases (204 with CEA and 110 with CAS) were analyzed. Patients were predominantly white (84.4%), men (61.1%) with hypertension (86.9%) and hyperlipidemia (81.8%). Most patients (84.5%) had symptomatic carotid disease. No significant differences were observed in median postoperative National Institutes of Health Stroke Scale and modified Rankin scale (mRS) scores based on pretreatment symptomatic status or treatment modality (CEA vs. CAS). Most patients (85.9%) had favorable outcomes (mRS score 0-2) at a median follow-up of 11.7 months (interquartile range, 1.8-28.8). The perioperative complication rate was low (3.2%), and permanent neurologic deficit was seen in only 3 patients (1%). Restenosis was found in 7.3%, without significant difference between CEA and CAS at last follow-up. Restenosis was asymptomatic in most patients. Our findings in a real-world predominantly symptomatic cohort demonstrate that favorable patient outcomes and low restenosis and complication rates can be achieved with both CEA and CAS by the utilization of a consistent institutional patient selection and treatment process.

Evidence for histidine-rich protein 2 immune complex formation in symptomatic patients in Southern Zambia

BackgroundRapid diagnostic tests based on histidine-rich protein 2 (HRP2) detection are the primary tools used to detect Plasmodium falciparum malaria infections. Recent conflicting reports call into question whether α-HRP2 antibodies are present in human host circulation and if resulting immune complexes could interfere with HRP2 detection on malaria RDTs. This study sought to determine the prevalence of immune-complexed HRP2 in a low-transmission region of Southern Zambia.MethodsAn ELISA was used to quantify HRP2 in patient sample DBS extracts before and after heat-based immune complex dissociation. A pull-down assay reliant on proteins A, G, and L was developed and applied for IgG and IgM capture and subsequent immunoprecipitation of any HRP2 present in immune complexed form. A total of 104 patient samples were evaluated using both methods.ResultsImmune-complexed HRP2 was detectable in 17% (18/104) of all samples evaluated and 70% (16/23) of HRP2-positive samples. A majority of the patients with samples containing immune-complexed HRP2 had P. falciparum infections (11/18) and were also positive for free HRP2 (16/18). For 72% (13/18) of patients with immune-complexed HRP2, less than 10% of the total HRP2 present was in immune-complexed form. For the remaining samples, a large proportion (≥ 20%) of total HRP2 was complexed with α-HRP2 antibodies.ConclusionsEndogenous α-HRP2 antibodies form immune complexes with HRP2 in the symptomatic patient population of a low-transmission area in rural Southern Zambia. For the majority of patients, the percentage of HRP2 in immune complexes is low and does not affect HRP2-based malaria diagnosis. However, for some patients, a significant portion of the total HRP2 was in immune-complexed form. Future studies investigating the prevalence and proportion of immune-complexed HRP2 in asymptomatic individuals with low HRP2 levels will be required to assess whether α-HRP2 antibodies affect HRP2 detection for this portion of the transmission reservoir.

Medical management of stable peripheral artery disease: the COMPASS trial. Perspectives from a vascular standpoint.

The late-breaking presentation of the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial at the European Society of Cardiology Congress in 2017 with a simultaneous publication in The New England Journal of Medicine described important information on the relative risk/benefit of combining anticoagulation with antiplatelet therapy in both coronary artery disease and/or peripheral artery disease (PAD) patients. In this special article, a review of the literature addressing the effects of antiplatelets and anticoagulants in symptomatic PAD patients focusing on the two most relevant clinical endpoints: major adverse cardiovascular events and major adverse limb events is addressed. In addition, a critical review of the COMPASS trial results, with emphasis on the PAD population is performed from a vascular surgery standpoint. It is concluded that this important study validated the combined anticoagulation/antiplatelet strategies in the management of vascular disorders including stable atherosclerotic patients. However, challenges in implementing this strategy in clinical practice are expected, with bleeding complications still remaining as major concern, particularly for vascular surgeons. Further studies with different combinations of different anticoagulants/antiplatelets, eventually on top of new strategies such as PCSK9 inhibition are warranted to address the significant unmet medical need in this population of symptomatic atherosclerotic patients.

Patterns of Cervical Disc Degeneration: Analysis of Magnetic Resonance Imaging of Over 1000 Symptomatic Subjects.

Study Design:Cross-sectional study.Objectives:The aim of this study was to evaluate cervical disc degeneration on magnetic resonance imaging (MRI) in a large population of symptomatic patients and to provide baseline data on the pattern of degeneration in order to understand how the cervical spine ages.Methods:We performed a cross-sectional study of 1059 patients who underwent upright cervical MRI for neck pain with and without neurological symptoms. A total of 6354 cervical discs from C2/3 to C7/T1 were evaluated. Cervical disc degeneration was evaluated on T2-weighted MRI and graded into 4 categories (Grades 0-III). Positive degeneration was defined as greater than Grade II. The correlation between age and total grade of degeneration of each patient was evaluated, as well as the prevalence and pattern of degeneration.Results:The average number of degenerated disc levels and the total grade of cervical disc degeneration significantly increase with age. In the patient group with 1-level degeneration, C5/6 was the most common degenerated level followed by C4/5 and C6/7. In the group with 2-level degeneration, C5/6 & C6/7 was most common followed by C4/5 & C5/6 and C3/4 & C4/5. Skip level degeneration was significantly rarer than contiguous level degeneration, and C7/T1 and C2/3 were the most unlikely to degenerate in multilevel degeneration.Conclusion:Disc degeneration is most common in the middle cervical spine (C5/6) and progresses to contiguous levels, except for C7/T1 and C2/3. This pattern may play a role in adjacent-level disc degeneration associated with spinal fusion.

Detection of potentially relevant extracolonic and colorectal findings at CT colonography in a low-risk symptomatic patient population.

CT colonography (CTC) is a widely accepted examination tool for detection of colorectal lesions but evidence of the proportions of relevant extracolonic findings (ECF) in a large symptomatic but still relatively low-risk cohort is lacking, as well as their relationship to symptoms, age, and sex. All patients (n=3208) with colorectal symptoms, imaged between January 2007 and September 2016 with first-time CTC, were retrospectively selected. The majority (96.7%) was examined with low-dose unenhanced protocol. The most relevant ECF and colorectal lesions (≥6mm) were prospectively assessed according to C-RADS classifications. Follow-up was elaborated based on the electronic record review. Chi-square test was utilized for evaluating the associations between relevant findings and symptoms, age, and sex. A total of 270 (8.4%) patients were classified as C-RADS E3, 63 (2.0%) patients as C-RADS E4, and 437 (13.6%) patients were assessed with colorectal lesions (C-RADS C2-4). At follow-up, two thirds of ECF turned out to be a malignancy or relevant disease that required further medical attention. The proportion of ECF was not related to specific colorectal symptoms. Patients aged ≥65years and men had significantly higher proportions of ECF than younger patients (C-RADS E3 p=0.005; C-RADS E4 p<0.001) and women (C-RADS E3 p=0.013; C-RADS E4 p=0.009), respectively. Proportions of relevant ECF and colorectal findings are relatively low in symptomatic low-risk patients. By use of CTC as a singular examination, especially in elderly patients, most colonoscopies can be avoided with the benefit of diagnosing relevant ECF without introducing substantial over-diagnosis.

Physician preferences for management of patients with heart failure and arrhythmia

Heart failure (HF) is one of the most important causes of morbidity and mortality in the world. It is a progressive and irreversible disorder. Survey and questionnaires are helpful verify that real-life daily practice is keeping with what is recommended in the guidelines. In this questionnaire which is consisted of 32 questions about current diagnostic and therapeutic strategies of HF and arrhythmia, we aimed to evaluate awareness of physicians who are interested in HF and arrhythmias about current diagnostic and therapeutic strategies of HF.This survey was conducted in university hospitals, state hospitals, training and research hospitals, private hospitals and medical centers in seven geographical region of Turkey between January and February 2017. The study groups were consisted of 177 physicians (163 cardiologists, 7 cardiovascular surgeons, 6 internal medicine physicians and 1 primary care physician). Less than half of the physicians (N:71, 40.1%) have used natriuretic peptides in the diagnosis of HF and 76.3% of physicians were aware of HF with mid-range EF (HFmrEF)patients with HF and a left ventricular ejection fraction (LVEF) that ranges from 40 to 49%. Despite optimal medical therapy with diuretic, ACEIs, ARBs, BB and mineralocorticoid receptor antagonists (MRAs), the ratio of physicians who have >50% symptomatic patient population were 6.8%. In this patient, angiotensin receptor neprilysin inhibitor (ARNI) was the treatment choice among 62.7% of physicians. Interestingly, 10.2% of physicians have never heard before ARNI. While only 13.6% physicians had >30% patients with HFpEF, most of the physicians (30.5%) had between 21% and 30% patients with HFpEF.In this questionnaire we want to see a picture from daily practice of physicians who are interested in heart failure. We aimed to measure awareness about current European Society of Cardiology (ESC) heart failure guideline recommendations, new classification of HF according to LVEF and new diagnostic and therapeutic improvements.