A strange case of Transthyretin Cardiac Amyloidosis in the Elderly: a diagnostic challenge.

Abstract: Transthyretin (TTR)-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive, hypertrophic heart disease and may go undiagnosed. We here report the case of a 83-year-old woman, which has rapresented an unique case of transthyretin-related cardiac amyloidosis, as a patient with an initial diagnosis of hypertensive heart disease later develops an infiltrative cardiomyopathy due to amyloid deposits.

Spanish-language cognitive screening tests: a critical review.

INTRODUCTION: Dementia is a chronic, degenerative disease with a strong impact on families and health systems. The instruments currently in use for measuring cognitive impairment have different psychometric characteristics in terms of application time, cut-off point, reliability, and validity. The objective of this review is to describe the characteristics of the validated, Spanish-language versions of the Mini-Cog, Clock-Drawing Test, and Mini-Mental State Examination scales for cognitive impairment screening. DEVELOPMENT: We performed a three-stage literature search of articles published on Medline since 1953. We selected articles on validated, Spanish-language versions of the scales that included data on reliability, validity, sensitivity, and specificity. CONCLUSIONS: The 3 screening tools assessed in this article provide support for primary care professionals. Timely identification of mild cognitive impairment and dementia is crucial for the prognosis of these patients.

State of the art approach to managing angina and ischemia: tailoring treatment to the evidence.

Stable angina represents a chronic and often debilitating condition that affects daily activities and quality of life in patients with chronic coronary syndromes (CCS). Current European Society of Cardiology guidelines recommend a four-step approach for the medical treatment of patients taking into consideration hemodynamic variables (heart rate and blood pressure) and the presence or absence of left ventricular dysfunction. However, CCS patients often have several comorbidities and risk factors. Thus, a tailored approach that takes into consideration patient risk factors and comorbidities may have additional benefits beyond angina relief. This is a state of the art review of stable angina treatment based on the currently available evidence.

Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: A Phase II Trial.

AIMS: We assessed the efficacy and safety of total neoadjuvant therapy, including targeted agent plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified chemoradiotherapy (CRT) and surgical resection, in patients with locally advanced rectal cancer. MATERIALS AND METHODS: This was a single-arm, single-centre phase II trial. Eligible patients had non-metastatic locally advanced rectal adenocarcinoma. Based on Ras-BRAF status, patients were treated with bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) plus FOLFOXIRI regimen followed by oxaliplatin-5-fluorouracil-based CRT and surgery. The primary end point was pathological complete response rate. Secondary end points were toxicity, compliance, tumour downstaging, complete resection, surgical complications, local and distant failures and overall survival. The sample size was planned to expect an absolute 20% improvement in pathological complete response rate over historical literature data with an α error of 0.05 and a power of 80%. RESULTS: Between October 2015 and September 2019, 28 patients (median age 66 years) were enrolled. All patients had regional lymph node involvement at diagnosis. FOLFOXIRI plus bevacizumab was administered in 11 mutated Ras-BRAF patients, whereas the 17 wild-type Ras-BRAF patients received FOLFOXIRI plus panitumumab/cetuximab. Overall, total neoadjuvant therapy was well tolerated and 26 patients (92.9%) completed the programmed strategy. A complete response was achieved in nine cases (32.1%) and a nearly pathological complete response (ypT1 ypN0) in two patients (7.2%). There was no evidence of febrile neutropenia and no grade 4 adverse events were recorded. Radical resection was achieved in all cases. CONCLUSION: FOLFOXIRI plus targeted agent-based induction chemotherapy and intensified CRT before surgery showed promising clinical activity and was well tolerated in locally advanced rectal cancer patients. This phase II trial provides a strong rationale for phase III studies.

Blood pressure control in type 2 diabetes mellitus with arterial hypertension. The important ancillary role of SGLT2-inhibitors and GLP1-receptor agonists.

Type 2 diabetes mellitus and arterial hypertension are major cardiovascular risks factors which shares metabolic and haemodynamic abnormalities as well as pathophysiological mechanisms. The simultaneous presence of diabetes and arterial hypertension increases the risk of left ventricular hypertrophy, congestive heart failure, and stroke, as compared to either condition alone. A number of guidelines recommend lifestyle measures such as salt restriction, weight reduction and ideal body weight mainteinance, regular physical activity and smoking cessation, together with moderation of alcohol consumption and high intake of vegetables and fruits, as the basis for reduction of blood pressure and prevention of CV diseases. Despite the availability of multiple drugs effective for hypertension, BP targets are reached in only 50 % of patients, with even fewer individuals with T2DM-achieving goals. It is established that new emerging classes of type 2 diabetes mellitus treatment, SGLT2 inhibitors and GLP1-receptor agonists, are efficacious on glucose control, and safe in reducing HbA1c significantly, without increasing hypoglycemic episodes. Furthermore, in recent years, many CVOT trials have demonstrated, using GLP1-RA or SGLT2-inihibitors compared to placebo (in combination with the usual diabetes medications) important benefits on reducing MACE (cardio-cerebral vascular events) in the diabetic population. In this hypothesis-driven review, we have examined the anti-hypertensive effects of these novel molecules of the two different classes, in the diabetic population, and suggest that they could have an interesting ancillary role in controlling blood pressure in type 2 diabetic patients.

Impact of covalent functionalization by diazonium chemistry on the electronic properties of graphene on SiC.

Plenty of strategies focused on covalent interaction have been developed to functionalize graphene's surface in order to employ it in a wide range of applications. Among them, the use of radical species including nitrene, carbene and aryl diazonium salts is regarded as a promising strategy to establish the covalent functionalization of graphene. In this work, we highlight the effect of diazonium chemistry on the electronic properties of graphene on SiC. On the basis of X-ray and synchrotron-based photoemission experiments, we were able to prove that 3,4,5-trimethoxybenzenediazonium (TMeOD) units, reduced and chemisorbed onto graphene using electrochemistry, preserve the electronic structure of the Dirac cone, through inducing a slightly additional n-type doping of graphene, as revealed by a downshift of the Dirac cone probed by angle-resolved photoemission experiments.

Transcatheter aortic valve replacement acutely improves left ventricular mechanical efficiency in severe aortic stenosis: effects of different phenotypes.

AIM: Aortic stenosis is a frequent valvular disease, with transcatheter aortic valve implantation (TAVI) being performed when surgical replacement is at increased risk. However, TAVI-induced effects on myocardial efficiency are unknown. We aimed to investigate changes in LV mechano-energetic pre-/post-TAVI and their prognostic impact. METHODS: A total of 46 patients (25 males) received transesophageal and simultaneous radial pressure plus transaortic gradient monitoring before/immediately after prosthesis deployment. Efficiency was computed as external work/potential energy, as derived from LV pressure-volume plots; myocardial oxygen consumption (MVO2) was estimated as PWImod, i.e. a noninvasively validated alternative for MVO2 estimation. RESULTS: TAVI was successful in all patients, peak transaortic gradient decreasing - 40 ± 20 mmHg (p < 0.001). Efficiency improved post-TAVI (+ 0.6 ± 0.12; p = 0.004), with a concomitant PWImod reduction (- 16 ± 31%; p < 0.001). When contextualized to fixed PWImod value (5 ml/min/100 g), efficiency significantly affected survival (p = 0.029). Over 1026 ± 450-day follow-up, a change in efficiency pre-/post-TAVI ≤ 0.021 (median of the difference) predicted more deaths from any cause (30%) as compared with a change > 0.021 (17%), particularly in those patients with a pre-TAVI mean high-gradient (HG ≥ 40 mmHg) phenotype (p < 0.05). In particular, HG patients exhibited the lowest efficiency/PWImod ratio pre-/post-TAVI (p = 0.048), relative to the other aortic stenosis patients, suggestive of an unfavourable matching between cardiac function and metabolic demand, which foreshortens some intrinsic damaged muscle condition in these patients. CONCLUSION: LV mechanical efficiency improves immediately post-TAVI, notwithstanding an inhomogeneous mechano-energetic matching among the aortic stenosis patients, which can impact negatively on their long-term prognosis, particularly in those with the HG phenotype.

The ESC 2019 CCS guidelines: Have we left our patients and scientific evidence behind?

The ESC CCS 2019 guidelines recognize that successful management of anginal symptoms relies on effective therapy tailored to individual patient characteristics but do not provide any specific advice or clarity on how to utilize pharmacotherapy in order to achieve these goals. In this review, we are going to summarize and discuss the main points of disagreement.

Spanish-language screening scales: A critical review. / Escalas de tamizaje cognitivo en habla hispana: una revisión crítica.

INTRODUCTION: Dementia is a chronic, degenerative disease with a strong impact on families and health systems. The instruments currently in use for measuring cognitive impairment have different psychometric characteristics in terms of application time, cut-off point, reliability, and validity. The objective of this review is to describe the characteristics of the validated, Spanish-language versions of the Mini-Cog, Clock-Drawing Test, and Mini-Mental State Examination scales for cognitive impairment screening. DEVELOPMENT: We performed a three-stage literature search of articles published on Medline since 1953. We selected articles on validated, Spanish-language versions of the scales that included data on reliability, validity, sensitivity, and specificity. CONCLUSIONS: The 3 screening tools assessed in this article provide support for primary care professionals. Timely identification of mild cognitive impairment and dementia is crucial for the prognosis of these patients.

Elevated serum uric acid concentration at discharge confers additive prognostic value in elderly patients with acute heart failure.

BACKGROUND AND AIMS: Elevated serum uric acid (sUA) concentrations have been associated with worse prognosis in heart failure (HF) but little is known about elderly patients. We aimed to assess long-term additive prognostic value of sUA in elderly patients hospitalized for HF. METHODS AND RESULTS: Clinical and echocardiographic characteristics of 310 consecutive elderly patients hospitalized for HF were collected. During index period, 206 had sUA concentrations available, which were obtained within 24 h prior to discharge; 10 patients were lost to follow-up, leaving 196 patients available. Patients had a median age of 77 (IQR 69-83) years, and were mostly male (64.5%). sUA ranges for tertiles I-III were: 1.5-6.1, 6.2-8.3, and 8.4-18.9 mg/dl, respectively. During a median follow-up of 27 months (IQR 10.5-39.5), 122 combined events occurred (87 deaths and 73 HF rehospitalizations). Four-year event-free survival for the combined endpoint was 46 ± 7% for tertile I, 34 ± 7% for tertile II, and 21 ± 5% for tertile III (P = 0.001). By multivariable Cox backward analysis, sUA was retained as a significant predictor. Compared with the lowest sUA tertile, tertile III showed a strong association with outcome, also after adjustment for other predictors (HR 1.84, 95% CI 1.16-2.93; P = 0.01). Importantly, addition of sUA to the other significant predictors of outcome resulted in improved risk classification (net reclassification improvement 0.19, P = 0.017). CONCLUSIONS: High sUA at discharge is a strong predictor of adverse outcome in elderly hospitalized for HF, and it significantly improves risk classification. Measuring sUA can be a simple and useful tool to identify high-risk elderly hospitalized for HF.

Sensitivity analysis of ventricular activation and electrocardiogram in tailored models of heart-failure patients.

Cardiac resynchronization therapy is not effective in a variable proportion of heart failure patients. An accurate knowledge of each patient's electroanatomical features could be helpful to determine the most appropriate treatment. The goal of this study was to analyze and quantify the sensitivity of left ventricular (LV) activation and the electrocardiogram (ECG) to changes in 39 parameters used to tune realistic anatomical-electrophysiological models of the heart. Electrical activity in the ventricles was simulated using a reaction-diffusion equation. To simulate cellular electrophysiology, the Ten Tusscher-Panfilov 2006 model was used. Intracardiac electrograms and 12-lead ECGs were computed by solving the bidomain equation. Parameters showing the highest sensitivity values were similar in the six patients studied. QRS complex and LV activation times were modulated by the sodium current, the cell surface-to-volume ratio in the LV, and tissue conductivities. The T-wave was modulated by the calcium and rectifier-potassium currents, and the cell surface-to-volume ratio in both ventricles. We conclude that homogeneous changes in ionic currents entail similar effects in all ECG leads, whereas the effects of changes in tissue properties show larger inter-lead variability. The effects of parameter variations are highly consistent between patients and most of the model tuning could be performed with only ~10 parameters.

A modified sentinel lymph node technique combined with endoluminal loco-regional resection for the treatment of rectal tumours: a 14-year experience.

AIM: After endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgey (TEM) the N parameter may remain undefined. Nucleotide-guided mesorectal excision (NGME) improves the lymph node harvest. The aim of the present study is to evaluate the long-term oncological results after ELRR with NGME. METHOD: A total of 57 patients were enrolled over the period January 2001 to June 2015. All patients underwent ELRR by TEM. Prior to surgery, 99 m-technetium-marked nanocolloid was injected into the peritumoural submucosa. After removal of the specimen, the residual defect was probed to detect any residual radioactivity and 'hot' mesorectal fat was excised. All patients were included in a 5-year follow-up programme. RESULTS: Significant radioactivity in the residual cavity was found in 28 out of 57 patients (49%). The mean number of lymph nodes harvest in irradiated and nonirradiated patients was 1.66 and 2.76, respectively. After 68.2 months' follow-up overall survival was 91.2%, disease-related mortality 3.5% and disease-free survival 89.5%. Two patients developed pulmonary metastases: one ypT3N0 patient underwent lung lobectomy after chemotherapy and one pT2N0 patient was managed with lung radiotherapy. Both patients are currently alive and disease-free at 48 months' follow-up. Two patients developed local recurrence 1 year after ELRR, both treated with neoadjuvant chemo-radiotherapy and total mesorectal excision. Comparing the present series with previous patients who did not undergo NGME, an increased number of harvested lymph nodes were observed, with a statistically significant difference (P = 0.0085). CONCLUSION: NGME during ELRR improves the lymph node harvest and staging accuracy. The long-term results showed satisfactory local (3.5%) and distant (7%) recurrence rates.

Anal function after endoluminal locoregional resection by transanal endoscopic microsurgery and radiotherapy for rectal cancer.

AIM: In patients with rectal cancer, surgery and chemoradiotherapy may affect anal sphincter function. Few studies have evaluated anorectal function after neoadjuvant chemoradiotherapy (n-CRT) and/or transanal endoscopic microsurgery (TEM). The aim of this study was to evaluate the effects of n-CRT and TEM on anorectal function. METHOD: Thirty-seven patients with rectal cancer underwent anorectal manometry and Wexner scoring for faecal incontinence at baseline, after n-CRT (cT2-T3N0 cancer) and at 4 and 12 months after surgery. Water-perfused manometry measured anal tone at rest and during squeezing, rectal sensitivity and compliance. Twenty-seven and 10 patients, respectively, underwent TEM without (Group A) or with n-CRT (Group B). RESULTS: In Group A, anal resting pressure decreased from 68 ± 23 to 54 ± 26 mmHg at 4 months (P = 0.04) and improved 12 months after surgery (60 ± 30 mmHg). The Wexner score showed a significant increase in gas incontinence (59%), soiling (44%) and urgency (37%) rates at 4 months, followed by clinical improvement at 1 year (41%, 26% and 18%, respectively). In group B, anal resting pressure decreased from 65 ± 23 to 50 ± 18 mmHg at 4 months but remained stable at 12 months (44 ± 11 mmHg, P = 0.02 vs preoperative values - no significant difference compared with evaluation at 4 months). Gas incontinence, soiling and urgency were observed in 50%, 50%, 25% and in 38%, 12% and 12% of cases, respectively, 4 and 12 months after treatment. CONCLUSION: TEM does not significantly affect anal function. Instead, n-CRT does affect anal function but without causing major anal incontinence.

Value and Anisotropy of the Electron and Hole Mass in Pure Wurtzite InP Nanowires.

The effective mass of electrons and holes in semiconductors is pivotal in determining the dynamics of carriers and their confinement energy in nanostructured materials. Surprisingly, this quantity is still unknown in wurtzite (WZ) nanowires (NWs) made of III-V compounds (e.g., GaAs, InAs, GaP, InP), where the WZ phase has no bulk counterpart. Here, we investigate the magneto-optical properties of InP WZ NWs grown by selective-area epitaxy that provides perfectly ordered NWs featuring high-crystalline quality. The combined analysis of the energy of free exciton states and impurity levels under magnetic field (B up to 29 T) allows us to disentangle the dynamics of oppositely charged carriers from the Coulomb interaction and thus to determine the values of the electron and hole effective mass. By application of B⃗ along different crystallographic directions, we also assess the dependence of the transport properties with respect to the NW growth axis (namely, the WZ c axis). The effective mass of electrons along c is me∥ = (0.078 ± 0.002) m0 (m0 is the electron mass in vacuum) and perpendicular to c is me⊥ = (0.093 ± 0.001) m0, resulting in a 20% mass anisotropy. Holes exhibit a much larger (∼320%) and opposite mass anisotropy with their effective mass along and perpendicular to c equal to mh∥ = (0.81 ± 0.18) m0 and mh⊥ = (0.250 ± 0.016) m0, respectively. While no full consensus is found with current theoretical results on WZ InP, our findings show trends remarkably similar to the experimental data available in WZ bulk materials, such as InN, GaN, and ZnO.

Patent foramen ovale and cryptogenic stroke: from studies to clinical practice: Position paper of the Italian Chapter, International Society Cardiovascular Ultrasound.

BACKGROUND: Over the last two decades the interest on patent foramen ovale (PFO) as a cause of cardioembolism in cryptogenic stroke has tremendously increased, thanks to the availability of better techniques to diagnose cardiac right-to-left shunt by ultrasounds and of percutaneous means of PFO treatment with interventional techniques. Many studies have been published that have attempted to define diagnostic methodology, prognosis, and optimal treatment (pharmacological or percutaneous closure) of PFO patients with cryptogenic stroke. Unfortunately, even today, definitive evidence is still lacking, and clinical management is not consistent among cardiologists. AIMS: This review aims to evaluate the role of PFO in cryptogenic stroke, the diagnostic accuracy of transcranial Doppler, contrast transthoracic and transesophageal echocardiography in the diagnosis of left-fright shunt and PFO; and discuss the indications to medical treatment and percutaneous closure of PFO. METHODS: All studies published in the literature on PFO and cryptogenic stroke are considered and discussed. RESULTS: We define an appropriate diagnostic and clinical management of PFO patients with cryptogenic stroke. CONCLUSION: After many years of interest on PFO and many concluded studies, there are still no definitive data. However, we are on good track for an appropriate management of PFO patients and cryptogenic stroke.

Left bundle branch block, chest pain and catheterization laboratory activation: an unavoidable cascade reaction?

Identification of acute myocardial infarction (AMI) in the presence of left bundle branch block (LBBB) remains challenging. European guidelines recommend prompt reperfusion therapy in patients with suspected ongoing myocardial ischemia and new or presumably new LBBB, whereas AHA/ACC guidelines state that LBBB should not be considered diagnostic of AMI in isolation. Sgarbossa criteria and their recent modified version with the introduction of ST/S ratio can be helpful in this setting. A clinical-instrumental algorithm to manage suspected AMI in the presence of LBBB has been recently proposed. We present five paradigmatic clinical cases.

The value of multifocal electroretinography to predict progressive visual acuity loss in early AMD.

BACKGROUND: To investigate, in a prospective study, the role of multifocal electroretinography (mfERG) for predicting visual acuity decline in early age-related macular degeneration (AMD) with time. METHODS: Twenty-six early AMD patients (12 males and 14 females, mean age 66.9 ± 9.8; range 46-82 years) were included in the study. A complete ophthalmic examination and mfERG (Retiscan, Roland Germany, ISCEV standard protocol) were performed at the study entry (baseline), after 20 and 24 months. The first-order kernel mfERG responses were analyzed by ring analysis. The amplitude density (AD) of the first positive peak (P1, nV/deg(2)), the P1 amplitude (µV) and P1 implicit time (ms) for Rings 1 (central) to 6 (most peripheral) were evaluated. Data were statistically analyzed by analysis of variance and receiver operating characteristic (ROC) curves. RESULTS: The loss in the mfERG Ring 1 AD from normal control values, recorded at baseline, was correlated with the decrease in ETDRS visual acuity with time (P = 0.004). ROC analysis showed that, after 24 months, the average decline in visual acuity was greater (3 letters vs 0.4 letters, P = 0.0021) in patients whose Ring 1 P1 AD at baseline was equal to or less than 65.9 nV/deg(2), compared to those with higher AD values. Both P1 amplitude and AD of Ring 1 had an area under the curve of 0.702 (95% confidence interval 0.50-0.92) with a sensitivity of 64.3% (35.14-87.24%) and a specificity of 91.7% (61.52-99.79%). CONCLUSIONS: The present results indicate that mfERG P1 amplitude and AD of Ring 1 may be highly specific to predict visual acuity decline in early AMD.

A meta-analysis of published studies of endothelial dysfunction does not support its routine clinical use.

BACKGROUND: Endothelial dysfunction is a marker of future cardiovascular disease (CVD) risk, yet epidemiological studies have yielded inconsistent results. We therefore studied the association between endothelial dysfunction and CVD under diverse circumstances. METHODS AND RESULTS: Literature-based meta-analysis of prospective observational studies with ≥ 12 months of follow-up published in Medline and having information on endothelial function and CVD outcomes. Tabular data on participant characteristics, endothelial function assessments and incident CVD outcomes were abstracted from individual studies. Random-effects meta-analysis was used to quantify pooled associations, and I(2) statistic to evaluate between-study heterogeneity. Potential sources of heterogeneity were explored by subgroup analyses and meta-regression. Thirty five studies involving 17,206 participants met the inclusion criteria. During more than 80,000 person-years of observation, up to 2755 CVD events were accrued, yielding a pooled relative risk (RR) of 1.25 (95% confidence interval 1.15-1.35) for CVD comparing top (i.e. more severe) vs. bottom (less severe) third of endothelial dysfunction. There was significant between-study heterogeneity and evidence of publication bias. RRs varied importantly according to the method used to ascertain endothelial function, and were higher among older individuals and among participants with risk factors for CVD or established CVD at baseline. CONCLUSIONS: Although endothelial dysfunction is an important determinant of cardiovascular outcomes in people with pre-existing CVD, current evidence base does not support its use as a potentially useful measurement for risk stratification in people at lower risk of CVD.

Fostering diffusion of scientific contents of National Society Cardiovascular Journals:the new ESC search engine.

European Society of Cardiology (ESC) National Society Cardiovascular Journals (NSCJs) are high-quality biomedical journals focused on cardiovascular diseases. The Editors' Network of the ESC devises editorial initiatives aimed at improving the scientific quality and diffusion of NSCJ. In this article we will discuss on the importance of the Internet, electronic editions and open access strategies on scientific publishing. Finally, we will propose a new editorial initiative based on a novel electronic tool on the ESC web-page that may further help to increase the dissemination of contents and visibility of NSCJs.

Aberrant expression of the neuronal-specific protein DCDC2 promotes malignant phenotypes and is associated with prostate cancer progression.

By integrating gene profiling and immunohistochemical data with functional experiments in cell lines in this study we show for the first time that doublecortin (DCX) domain containing 2 (DCDC2), a protein belonging to the DCX family and involved in neuronal cell migration, is aberrantly expressed in prostate tumors whereas absent in normal prostate. Furthermore, in patients treated with radical prostatectomy, high levels of DCDC2 RNA were significantly associated with increased biochemical relapse (LogRank Mantel-Cox=0.012). Mechanistically, we found that the ETS transcription factor ESE3/EHF, which is expressed in normal prostate and frequently lost in prostate tumors, maintained DCDC2 repressed by binding to a novel identified ETS binding site in the gene promoter. Consistently, in prostate tumors and in cellular models of gain and loss of ESE3/EHF, the expression of DCDC2 and ESE3/EHF were inversely correlated. In prostate cancer cells, DCDC2 colocalized with microtubules and promoted cell migration and resistance to the microtubule-targeting drug taxol. Collectively, this study establishes DCDC2 as a novel ESE3/EHF oncogenic target in prostate cancer. These findings may be relevant for the clinical management of prostate cancer as DCDC2 may signal tumors more prone to relapse and resistant to taxol treatment.