[Ascending aortic disease: is general perception updated to current guidelines?] / Patologie dell'aorta ascendente: quanto si correla la percezione in ambito di medicina generale e specialistico con le attuali linee guida?

BACKGROUND: Thoracic aorta diseases represent a frequent cause of hospitalization and up to 15% of workload of a modern cardiac surgery centre. A dedicated thoracic aorta disease clinic was launched at our Division in January 2020. The clinic was open for new referrals as well as for preoperative and postoperative follow-up of patients. Here we report a summary of the activity of such dedicated clinic correlated to current international guidelines. METHODS: Overall, 288 patients were seen at the clinic: 84 (29%) new referrals; 28 (10%) for preoperative follow-up and 176 (61%) for postoperative follow-up. New referrals included urgent referral (n = 57, 68%) and scheduled referral (n = 27, 32%). The majority of urgent new referrals were from general practitioners (n = 34, 60%). Postoperative follow-up also included a minority (n = 27, 15%) of urgent referrals. RESULTS: Within new referrals, according to current guidelines, only 7% (n = 6) had surgical indication at time of referral (40% of urgent referral); 34% (n = 28) were in the so-called grey zone and required close follow-up (26% of urgent referrals); 59% (n = 50) had no significant aortic disease to require neither urgent specialist consultation nor close follow-up (85% of urgent referrals). Within postoperative follow-up, 7% (n = 12) required surgical reintervention (none with urgent referral). Furthermore, the majority of new referrals (especially within urgent referrals) showed only moderate aortic dilation. CONCLUSIONS: Current perception of clinical severity of thoracic aorta diseases is still suboptimal. Most patients are indeed referred as urgent despite non-significant aortic dilation. In contrast, potentially dangerous situations are frequently underestimated. An accurate territorial policy of sensitization and updating focused on thoracic aorta diseases is therefore essential in order to reduce the risks of acute aortic syndromes in our country.

Learning models for classifying Raman spectra of genomic DNA from tumor subtypes.

An early and accurate detection of different subtypes of tumors is crucial for an effective guidance to personalized therapy and in predicting the ability of tumor to metastasize. Here we exploit the Surface Enhanced Raman Scattering (SERS) platform, based on disordered silver coated silicon nanowires (Ag/SiNWs), to efficiently discriminate genomic DNA of different subtypes of melanoma and colon tumors. The diagnostic information is obtained by performing label free Raman maps of the dried drops of DNA solutions onto the Ag/NWs mat and leveraging the classification ability of learning models to reveal the specific and distinct physico-chemical interaction of tumor DNA molecules with the Ag/NW, here supposed to be partly caused by a different DNA methylation degree.

Revealing Low Amplitude Signals of Neuroendocrine Cells through Disordered Silicon Nanowires-Based Microelectrode Array.

Today, the key methodology to study in vitro or in vivo electrical activity in a population of electrogenic cells, under physiological or pathological conditions, is by using microelectrode array (MEA). While significant efforts have been devoted to develop nanostructured MEAs for improving the electrophysiological investigation in neurons and cardiomyocytes, data on the recording of the electrical activity from neuroendocrine cells with MEA technology are scarce owing to their weaker electrical signals. Disordered silicon nanowires (SiNWs) for developing a MEA that, combined with a customized acquisition board, successfully capture the electrical signals generated by the corticotrope AtT-20 cells as a function of the extracellular calcium (Ca2+ ) concentration are reported. The recorded signals show a shape that clearly resembles the action potential waveform by suggesting a natural membrane penetration of the SiNWs. Additionally, the generation of synchronous signals observed under high Ca2+ content indicates the occurrence of a collective behavior in the AtT-20 cell population. This study extends the usefulness of MEA technology to the investigation of the electrical communication in cells of the pituitary gland, crucial in controlling several essential human functions, and provides new perspectives in recording with MEA the electrical activity of excitable cells.

Statistical Classification for Raman Spectra of Tumoral Genomic DNA.

We exploit Surface-Enhanced Raman Scattering (SERS) to investigate aqueous droplets of genomic DNA deposited onto silver-coated silicon nanowires, and we show that it is possible to efficiently discriminate between spectra of tumoral and healthy cells. To assess the robustness of the proposed technique, we develop two different statistical approaches, one based on the Principal Components Analysis of spectral data and one based on the computation of the ℓ2 distance between spectra. Both methods prove to be highly efficient, and we test their accuracy via the Cohen's κ statistics. We show that the synergistic combination of the SERS spectroscopy and the statistical analysis methods leads to efficient and fast cancer diagnostic applications allowing rapid and unexpansive discrimination between healthy and tumoral genomic DNA alternative to the more complex and expensive DNA sequencing.

Biological Response to Bioinspired Microporous 3D-Printed Scaffolds for Bone Tissue Engineering.

The scaffold is a key element in the field of tissue engineering, especially when large defects or substitutions of pathological tissues or organs need to be clinically addressed. The expected outcome is strongly dependent on the cell-scaffold interaction and the integration with the surrounding biological tissue. Indeed, mimicking the natural extracellular matrix (ECM) of the tissue to be healed represents a further optimization that can limit a possible morphological mismatch between the scaffold and the tissue itself. For this aim, and referring to bone tissue engineering, polylactic acid (PLA) scaffolds were 3D printed with a microstructure inspired by the trabecular architecture and biologically evaluated by means of human osteosarcoma SAOS-2 cells. The cells were seeded on two types of scaffolds differing for the designed pore size (i.e., 400 and 600 µm), showing the same growth exponential trend found in the control and no significant alterations in the actin distribution. The microporous structure of the two tested samples enhanced the protein adsorption capability and mRNA expression of markers related to protein synthesis, proliferation, and osteoblast differentiation. Our findings demonstrate that 3D-printed scaffolds support the adhesion, growth, and differentiation of osteoblast-like cells and the microporous architecture, mimicking the natural bone hierarchical structure, and favoring greater bioactivity. These bioinspired scaffolds represent an interesting new tool for bone tissue engineering and regenerative medicine applications.

Mechanical Hemolysis Complicating Transcatheter Interventions for Valvular Heart Disease: JACC State-of-the-Art Review.

Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.

Pulmonary endarterectomy in the octogenarian population: safety and outcomes.

AIMS: Aim of the study was to verify the feasibility, safety and efficacy of pulmonary endarterectomy (PEA) in octogenarian patients with chronic thromboembolic pulmonary hypertension. METHODS: We retrospectively analyzed 635 chronic thromboembolic pulmonary hypertension patients who underwent PEA at our center and were followed-up for at least 1 year. The end-points of the study were in-hospital mortality, hemodynamic results at 1 year and long-term survival. RESULTS: In-hospital mortality was 4, 10 and 17%, respectively, for 259 patients under the age of 60 years, 352 aged between 60 and 79 years and 24 octogenarians (P = 0.006 octogenarians vs. <60 years). At multivariable analysis, age and pulmonary vascular resistances were independent risk factors for mortality (P = 0.021 and P < 0.001, respectively). At 1 year, the improvement in cardiac index was lower and the distance walked in 6 min was poorer for octogenarians than for the other two groups (both P = 0.001). Survival after hospital discharge was similar over a median follow-up period of 59 months (P = 0.113). Although in-hospital mortality and long-term survival are similar in octogenarians as compared with patients aged between 60 and 79, the improvement in cardiac index and in functional capacity at 1 year are lower in this very elderly population. CONCLUSION: Age over 80 years should not be a contraindication to PEA surgery in selected patients operated on in referral centers.

Persistent exercise limitation after successful pulmonary endoarterectomy: frequency and determinants.

BACKGROUND: After successful pulmonary endoarterectomy (PEA), patients may still suffer from exercise limitation, despite normal pulmonary vascular resistance. We sought to assess the proportion of these patients after the extension of PEA to frail patients, and the determinants of exercise limitation. METHODS: Out of 553 patients treated with PEA from 2008 to 2016 at our institution, a cohort of 261 patients was followed up at 12 months. They underwent clinical, haemodynamic, echocardiographic, respiratory function tests and treadmill exercise testing. A reduced exercise capacity was defined as Bruce test distance < 400 m. RESULTS: Eighty patients did not had exercise testing because of inability to walk on treadmill and/or ECG abnormalities Exercise limitation 12 months after PEA was present in 74/181 patients (41, 95%CI 34 to 48%). The presence of COPD was more than double in patients with exercise limitation than in the others. Patients with persistent exercise limitation had significantly higher mPAP, PVR, HR and significantly lower RVEF, PCa, CI, VC, TLC, FEV1, FEV1/VC, DLCO, HbSaO2 than patients without. The multivariable model shows that PCa at rest and TAPSE are important predictors of exercise capacity. Age, COPD, respiratory function parameters and unilateral surgery were also retained. CONCLUSIONS: After successful PEA, most of the patients recovered good exercise tolerance. However, about 40% continues to suffer from limitation to a moderate intensity exercise. Besides parameters of right ventricular function, useful information are provided by respiratory function parameters and COPD diagnosis. This could be useful to better address the appropriate therapeutic approach.

High preoperative plasma endothelin-1 levels are associated with increased acute kidney injury risk after pulmonary endarterectomy.

OBJECTIVES: The only curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). PEA requires cardiopulmonary bypass (CPB) which is associated with a high acute kidney injury (AKI) risk. Circulating endothelin-1 (ET-1) levels are elevated in CTEPH, and ET-1 plays a pivotal role in AKI. Because AKI is burdened by high morbidity and mortality, we aimed to evaluate the association between preoperative ET-1 and the risk to develop AKI in CTEPH individuals who undergo PEA. We also evaluated the association of AKI and ET-1 with kidney function and mortality at 1 year after PEA. METHODS: In 385 consecutive patients diagnosed with CTEPH who underwent PEA at the Foundation IRCC Policlinico San Matteo (Pavia, Italy) from January 2009 to April 2015, we assessed preoperative circulating ET-1 by ELISA and identified presence of AKI based on 2012 KDIGO criteria. RESULTS: AKI occurred in 26.5% of the 347 patients included in the analysis, and was independently associated with preoperative ET-1 (p = 0.008), body mass index (BMI) (p = 0.022), male gender (p = 0.005) and duration of CPB (p = 0.002). At 1-year post PEA, estimated glomerular filtration rate (eGFR) significantly improved in patients who did not develop AKI [ΔeGFR 5.6 ml/min/1.73 m2 (95% CI 3.6-7.6), p < 0.001] but not in those with perioperative AKI. AKI (p < 0.001), age (p < 0.001), preoperative eGFR (p < 0.001) and systemic hypertension diagnosis (p = 0.015) were independently associated with 1-year ΔeGFR. Neither perioperative AKI nor preoperative ET-1 was associated with 1-year survival. CONCLUSION: Perioperative AKI is associated with higher preoperative circulating ET-1 and it negatively influences long-term kidney function in patients with CTEPH who undergo PEA.

Routine MRCP in the management of patients with gallbladder stones awaiting cholecystectomy: a single-centre experience.

OBJECTIVES: To assess the frequency of choledocolithiasis and the role of preoperative laboratory findings, ultrasound (US) and magnetic resonance cholangio-pancreatography (MRCP) in the detection of choledocolithiasis in patients with gallbladder stones awaiting cholecystectomy. METHODS: A consecutive sample of 104 patients underwent MRCP prior to cholecystectomy. The patients were classified into different groups on the basis of the risk of choledocolithiasis. A specialised doctor with more 10 years of experience performed the US interpretation and a radiologist performed the MRCP interpretation blinded to US or aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (ALP) results. A chi-square (χ2) test was performed to assess the statistical significance of differences in the frequency of choledocolithiasis based on laboratory findings, choledocal diameter on US and group risk. RESULTS: MRCP showed calculi in 7 out of 104 patients (6.7%), with no statistically significant differences between the high/moderate risk and low/no risk groups and between the patients with normal and altered laboratory findings or choledocal diameter on preoperative US. The sensitivity and specificity of AST/ALT [positive predictive value (PPV): 12%; negative predictive value (NPV): 94%], ALP (PPV: 7%; NPV: 94%), total serum bilirubin (PPV: 6%; NPV: 93%) and choledocal diameter (PPV: 20%; NPV: 94%) were, respectively, 28.6 and 94.8%, 85.7 and 17.5%, 14.3 and 93.8%, and 14.3 and 95.9%. CONCLUSIONS: MRCP is a reliable evaluation for the detection of common bile duct (CBD) stones, reducing the misdiagnosis of retained choledocholithiasis with normal biochemical predictors and US examination. MAIN MESSAGES: • MRCP is a non-invasive method for the detection of CBD stones. • Preoperative MRCP reduces the misdiagnosis of retained choledocholithiasis. • Detection of choledocholithiasis is mandatory prior to cholecystectomy to avoid surgical morbidity.

Neuropsychological outcomes after pulmonary endarterectomy using moderate hypothermia and periodic circulatory arrest.

BACKGROUND: In this prospective, single-center, observational study, we investigated the association between repeated short periods of circulatory arrest with moderate hypothermia during pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and different neuropsychological dimensions. METHODS: We examined 70 patients with CTEPH, >18 to 80 years of age, who had been treated with PEA. Neuropsychological testing was performed. RESULTS: Learning ability and delayed memory remained well within the normal range for patients' age. We found a statistically significant post-surgical improvement in motor speed, which was accompanied by a better quality of life and reduced symptoms of depression and anxiety. CONCLUSION: PEA with repeated short periods of circulatory arrest in CTEPH did not result in any neuropsychological complications and may even lead to post-surgical psychological improvements.

Pavia Experience in Reoperative Pulmonary Endarterectomy.

In our experience, we reperformed pulmonary endarterectomy (PEA) in 10 patients who previously underwent a first PEA. We analyzed this cohort of patients to investigate the main causes of recurrence of symptomatic pathology and the clinical and hemodynamic results of redo surgery. Between 1994 and April 2016, 10 of 716 patients were reoperated at our institution. Available postoperative data were analyzed, and a comparison between first and second PEA hemodynamic and clinical results was carried out. In-hospital mortality rate was also evaluated. After reoperation, mean pulmonary arterial pressure decreased from 45?±?9 to 34?±?10?mm Hg, and pulmonary vascular resistance reduced from 932?±?346?dyne*s*cm?5 to 428?±?207?dyne*s*cm?5. Hemodynamic data revealed worthy results of redo PEA, although they are less important than after first PEA. The World Health Organization (WHO) functional class improvement demonstrated satisfactory clinical results. In-hospital mortality of repeat PEA is 40%. Reoperative PEA operative candidacy should be assessed in case of young patients, no other risk factor, and recent medical history of pulmonary hypertension. In the other cases, in-hospital mortality rate is very high and pulmonary hypertension-specific drug therapy or interventional approach should be previously considered.

Changes in surface electrocardiogram in patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary endarterectomy. Correlations with hemodynamic and echocardiographic improvements after surgery.

BACKGROUND: The aim of the present study was to evaluate the changes of electrocardiographic (ECG) markers of right ventricular (RV) hypertrophy/overload in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA). METHODS AND RESULTS: We evaluated 99 CTEPH patients who underwent PEA. P wave amplitude in DII, R wave amplitude in V1 and the number of patients with negative T wave in V1-V3 decreased significantly at 1month after surgery with no further change at 1year, in parallel with the rapid improvement in right heart hemodynamics. S wave amplitude in V1, R:S wave ratio in lead V6 and prevalence of SIQIII pattern improved significantly at 1year, in parallel with the progressive reverse remodeling of the right ventricle at echocardiography. CONCLUSIONS: The study shows that some of the ECG markers of RV hypertrophy/overload better reflect RV hemodynamic overload while others better reflect the pathologic remodeling of the right ventricle.