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Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): ZOLL France supported with an unrestricted grant. Background The wearable cardioverter defibrillator (WCD) has been proven to have efficacy in treating sudden cardiac death (SCD) in patients soon after acute myocardial infarction (AMI) and left ventricular ejection fraction (LVEF) ≤35%. However, data regarding hospitalization rate and length of stay among these patients have not yet been evaluated. Purpose WCD can shorten hospital stays (total length, time in intensive care unit (ICU) and in cardiac intensive care unit (CICU)) of patients post-AMI, with severe reduced LVEF. Methods We performed a single center, retrospective observational study of patients prescribed WCD upon hospital discharge, from June 2016 to June 2022. We selected patients referred for management of SCD, post-AMI, with age over 18 years and LVEF ≤35%. Patients who already had ICD or CRT-D (or who had previously received it) were excluded from the analysis. Patients with the same characteristics, and who were discharged from the hospital without WCD or ICD served as a control group. Clinical characteristics were obtained from hospital electronic and WCD specific database. The clinical characteristics and length of index hospitalization of two groups were compared. An initial propensity score analysis was performed, then a weighted regression models for total hospitalization, days in ICU, and days in CICU were conducted. Results 101 patients in the WCD group and 29 in the control group were enrolled in the analysis (Figure 1). The two groups showed similar clinical characteristics (Table 1), even if patients in the WCD group had lower LVEF (p 30 days), WCD patients showed significantly shorter total hospitalization (p=0.005) and days spent in CICU (p Conclusions At the propensity score analysis, WCD reduce CICU length of stay for patients post-AMI with LVEF ≤35%. The association between WCD use and hospitalization is more relevant for days spent in CICU, but there is also a positive trend for the days spent in ICU. The study has the limitation of a retrospective analysis and can only serve as hypothesis-generating research, which will be verified with further randomized clinical trial.

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a significant proportion of acute myocardial infarction (AMI) population. MINOCA is a working diagnosis and an accurate investigation of the underlying causes should always be performed. In this setting, cardiac magnetic resonance (CMR) imaging plays a pivotal diagnostic role. However, a prognostic stratification based on the CMR findings in ischemic MINOCA is still unavailable. Purpose To evaluate the potential prognostic impact of specific CMR findings - especially ischemic late gadolinium enhancement (LGE) patterns - in order to look for measurable parameters that may guide the management of this still troubled clinical entity. Methods We assessed 461 MINOCA from January 2016 to June 2021. We excluded acute myocarditis, Tako-tsubo syndromes, cardiomyopathies, or non-pathological CMR. According to CMR findings, MINOCA were classified in two phenotypes: LGE-positive (an ischemic subendocardial or transmural LGE pattern) or LGE-negative (cases without LGE but exhibiting regional myocardial injury defined by myocardial edema in a coronary territory with a typically ischemic “wave-front” and/or regional wall motion abnormality consistent with coronary distribution). All-cause mortality, re-infarction, stroke, heart failure (HF) and the composite endpoint (MACE) were evaluated. Extended LGE was considered as the presence of >2 segments with transmural LGE. The mean follow-up was 36.1±15.2 months and CMR was performed at a mean of 6±2.9 days from the acute presentation. Results The final cohort included 175 MINOCA with a likely-ischemic etiology: 121 (69.1%) constituted the LGE-positive group. The mean age of the study population was 62.3±12.9 years and more than 61% were females. During follow-up, HF (15.7% vs 1.9%, p=0.008) and MACE (20.7% vs 7.4%, p=0.029) occurred more frequently in MINOCA “LGE-positive” compared to the “LGE-negative” ones. Extended LGE was significantly more prevalent in patients with versus without subsequent HF. On multivariable Cox regression, extended LGE was an independent predictor of HF occurrence (HR 18.49, 95% CI 4.65–73.61, p Conclusions Our data suggest that in MINOCA patients the detection of LGE is correlated with the incidence of major cardiovascular events and heart failure during long-term follow-up. In fact, LGE extension was identified as the strongest predictor of cardiac adverse events. The early execution of CMR is useful in the prognostic stratification of MINOCA and this could guide the subsequent clinical and therapeutic management. Funding Acknowledgement Type of funding sources: None.

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous clinical entity and in its complex diagnostic approach cardiovascular magnetic resonance (CMR) plays a pivotal role. Purpose To characterize the differences of MINOCA patients with and without late gadolinium enhancement (LGE) at CMR and to identify the predictors for ischemic LGE development and extension. Methods We assessed 461 MINOCA cases from January 2016 to June 2021. MINOCA were defined according to the current European guidelines criteria. We excluded acute myocarditis, Tako-tsubo syndromes, cardiomyopathies, or non-pathological CMR. According to CMR imaging findings, our cohort was divided into two CMR phenotypes based on regional myocardial necrosis detected throughout LGE (“LGE-positive MINOCA”) or regional ischemic injury without LGE (“LGE-negative MINOCA”). Extended LGE was considered as the presence of >2 segments with transmural LGE. Multivariate logistic regression analysis was used to determine the predictors of LGE and extended LGE. Results The final cohort included 175 MINOCA: 121 (69.1%) constituted the LGE-positive group. The mean time delay between acute clinical presentation and CMR was 6±2.9 days. At admission MINOCA LGE-patients more frequently presented angina and ST segment elevation (24% vs 7.4%, p=0.01), compared to LGE negative ones. Furthermore, the LGE positive group had a significantly greater infarct size, measured by peak hs-Troponin I values and left ventricular function (LVEF). The only predictor of LGE was the peak troponin value (OR 1.64, 95% CI 1.18–2.28, p=0.003), while predictors of extended LGE were ST-segment elevation at admission (OR 7.44, 95% CI 1.57–35.22, p=0.01), peak troponin values (OR 1.07, 95% CI 1.02–1.13, p=0.01) and the presence of non-obstructive coronary artery disease at coronary angiography (OR 5.49, 95% CI 1.20–25.09, p=0.028). Conclusion The presence and extension of LGE at early CMR evaluation is an important feature in the setting of MINOCA. In addition, simple baseline characteristics (such as ST elevation, peak troponin value and LVEF) may aid the identification of a greater ischemic necrosis burden at CMR and therefore these high-risk MINOCA subjects could be benefit from a stricter management effort. Funding Acknowledgement Type of funding sources: None.

Background The Fourth Universal Definition of Myocardial Infarction (UDMI) defines acute myocardial infarction (AMI) as an acute myocardial injury associated with clinical evidence of acute myocardial ischemia. However, the prognostic role of each single diagnostic criteria has never been explored. Purpose To evaluate the prognostic role of the different diagnostic criteria of AMI according to the Fourth UDMI in patients with non-ST-segment elevation myocardial infarction. Methods We enrolled all consecutive patients with NSTEMI undergoing coronary angiography at our Centre. The admission diagnosis was performed according to the current guidelines criteria, namely the detection of an increase and/or decrease of high-sensitivity cardiac troponin I, with at least one value above the 99th percentile of the upper reference limit and at least one of the following: symptoms of ischemia, ECG changes (new ST depression or negative T-waves), echocardiographic evidence of new regional wall motion abnormality. Patients with very high-risk NSTEMI were excluded. Patients were then divided into different subgroups according to the combination of diagnostic criteria presented at admission. A composite endpoint of all-cause mortality, re-hospitalization for myocardial reinfarction or heart failure was collected. The predictive value of AMI diagnostic criteria alone and their combination were evaluated using Kaplan-Meier survival curves and subsequent Cox-regression analysis to find independent predictors of major adverse events. Results Our study population consisted of 2791 patients. The mean age was 68.3±13.4 and 31.5% were female. The mean follow-up time was 23.3±14.5 months. Depending on the AMI diagnostic criteria and their combination, patients were divided into three subgroups: 196 patients fulfilling only clinical criteria (group A), 187 with clinical and ECG-graphic criteria (group B) and 829 patients with clinical, ECG-graphic and echo-graphic criteria (group C). Baseline characteristics of the three groups were similar. At two-year follow-up, patients with clinical criteria alone exhibited the best outcome, whereas those with all three criteria fulfilled showed the worse prognosis (14.8% for group A vs 23.6% for group B vs 28.0% for group C; p-value Conclusions In non-very high-risk NSTEMI, not all diagnostic criteria have the same prognostic value. In fact, prognosis is significantly more favorable in patients exhibiting only the clinical criteria at admission. We hypothesize that the absence of ECG-graphic and echocardiographic alterations may indirectly indicate smaller infarct sizes that contribute to patients' outcomes. These findings could enhance the current risk stratification in patients admitted with NSTEMI. Funding Acknowledgement Type of funding sources: None.

Background Myocardial Infarction (MI) with Non–Obstructive Coronary Arteries (MINOCA) accounts above 6 % of patients presenting with acute MI (AMI) and it’s known to be more prevalent in females. Differences in terms of clinical features and prognosis in MINOCA patients according to gender have been poorly understood. Purpose: To evaluate clinical and prognostic differences between male and female patients with MINOCA. Methods We included all consecutive patients with AMI undergoing coronary angiography between 2016 and 2020 in our multicentric Registry. We considered as MINOCA all patients fulfilling the European Society of Cardiology diagnostic criteria. We analyzed the baseline clinical characteristics of MINOCA patients by dividing the population according to gender. We performed a multivariate logistic regression analysis including all AMI patients to determine independent predictors of MINOCA at admission. We considered the composite endpoint (MACE) of death, re AMI, stroke and heart failure at follow–up (FU, mean of 36 ± 14.8 months). Outcomes were evaluated also using Kaplan–Meier survival curves. Results Among 289 patients affected by MINOCA, 191 were female (66%). Males were more frequently smokers (56.1% vs 33.9 %, p=0.001) while females were older (68.9± 13.1 vs 58.4±14.5 years, p=0.0001), more affected by hypertension (69.3% vs 55.1%, p=0.017) and dyslipidemia (65.6% vs 49%, p=0.005), more frequently on beta–blockers (39% vs 20%, p=0.002) and statins (33% vs 19%, p=0.015) and had a lower degree of coronary stenosis (9.1% vs 15.5%, p=0.019) than males. During follow–up, females had more MACE (33% vs 19.3%, p=0.015), also shown at Kaplan Meier curves (χ2 = 5.997, p=0.014). Finally, multivariate analysis revealed that age is an independent predictor of MINOCA (HR 1.04, CI 1.01–2.07, p=0.006), rather than sex, diabetes, and hypertension. Conclusions In our MINOCA population, females had a higher incidence of MACE than males: this could reflect the different pathogenesis of myocardial damage in our subgroups. Statins and estrogens have a well–known protective role towards the progression of atherosclerosis, but they have less impact on other causes of MINOCA more frequent in females.

Funding Acknowledgements Type of funding sources: None. Background Aortic valve replacement (AVR) is a common procedure. While conduction disturbances are well-recognized complications, ventricular tachycardias (VTs) have not been widely reported neither described mainly because prosthetic valves represent a potential practical problem in the access to the ventricles, and this may limit the use of radiofrequency ablation (RF). Purpose and Methods We report three cases of periaortic scar-related VT in patients with AVR. Results The first case was a 85 years old (yo) man, with both aortic and mitral biological valve replacement. The left ventricular ejection fraction (LVEF) was normal and the clinical VT (left bundle branch block (BBB) and inferior axis, cycle length (CL) = 305 ms) was induced. Left ventricle (LV) was mapped with a retrograde transaortic approach: to cross safely the prosthesis, a 6-French (F) pigtail catheter was first placed in the ventricle; a 8.5-F Braided Guiding Introducer (SL1) was placed across the valve over a guidewire. The 8.5-F ablation catheter allowed to locate the VT origin underneath the septal portion of prosthetic aortic valve (PAV). The second case was a 85 yo man, with bioprosthetic AVR and replacement of the ascending aorta. LVEF was 40% with mild PAV degeneration. The clinical VT had left BBB morphology and inferior axis (CL = 352 ms). Transaortic approach was hampered by an unfavorable entry angle and by valve degeneration. Then we opted for the technique commonly used during transcatheter AVR: the access to the LV was obtained using a 6-F coronary catheter (AL1) and a stright tip 0.034" angiographic guidewire; subsequently a 8.5-F, 81 cm long, introducer sheath (SL0) was positioned across the PAV. The reentry circuit was mapped in the high anterior region, just below the PAV insertion. The third case was a 65 yo man, with mechanical PAV. LVEF was normal and the clinical VT had right BBB and left inferior axis (CL = 290 ms). After transseptal puncture, a steerable introducer was placed in left atrium. The mapping catheter allowed to identify early and fractional potentials in the anterior portion of PAV. In all cases, RF applications was delivered at the earliest ventricular activation site with termination of the VTs. Thereafter, no VTs could be induced. At 12 months follow-up, the patients are free of any VT relapses. Conclusions The most common origin of sustained monomorphic VT occurring after PAV is the surgical scar and catheter ablation is a feasible option. In case of mechanical PAV, the only practicable access is the transeptal one; on the contrary, with biological PAV the transaortic approach can also be used. In difficult cases, the access to the LV can be obtained with the technique routinely performed during transcatheter AVR.

Funding Acknowledgements Type of funding sources: None. Background The occurrence of a sustained monomorphic ventricular tachycardias (SMVT) in patients with underlying structural heart disease (SHD) is considered correlated to a poor prognosis, based on historical data in patients with heterogeneous heart disease and clinical presentation; therefore the recommendation for implantation of automatic implantable cardioverter defibrillator (AICD) is strong. Information about prognosis of patients with SMVT is still limited, but recent studies have established that these patients represent a low-risk subgroup for sudden death that could benefit from radiofrequency (RF) ablation of the arrhythmic substrate and the AICD implantation could be deferred during the follow up. Purpose Patients with well-tolerated SMVT, SHD and left ventricular ejection fraction (LVEF) over 30% can benefit from a primary VT ablation strategy without the immediate need for AICD implantation. Methods We reviewed consecutive SHD patients with LVEF over 30% admitted for the occurrence of SMVT and who were treated by RF ablation as a first-choice therapy in a single Italian center, between 2009 and 2020 and who were discharged without AICD implantation. The primary outcome of the study was a composite of all-cause death and recurrence of VT. The secondary outcome was death from all causes. Patients with similar characteristics but who underwent AICD implantation during the same period served as control group. Results Clinical and electrophysiological features of 62 patients were analyzed (Table 1). In the study group, 88% were male; the median age was 72 years (IQR 55-81) and the median LVEF was 50.0% (IQR 40.0-55.0). The estimated success rate of ablative procedures (defined as VT no longer inducible) was around 82%. After a median follow-up of 38.8 months (IQR 15.6-76.1), the primary outcome occurred in 24 patients and the secondary outcome in 11 patients. All-cause mortality was 17%, corresponding to an annual mortality rate of 4.3%. Ten patients died for non-cardiovascular causes and one for advanced heart failure. No patient in the study died from sudden death. During the follow-up, 10 patients (16.1%) underwent AICD implantation due to VT relapse. At 36 months, between study and control groups, there was no difference in either the primary composite outcome (HR 1.03, 95% CI 0.45-2.21, p = 0.98) or in the secondary outcome (HR 1.4, 95% CI 0.48-4.54, p = 0.49). Conclusions Patients with well-tolerated SMVT, SHD and LVEF over 30% represent a subgroup of patients at lower risk that can benefit of RF ablation as a first-choice therapy. Delay in AICD implantation, after a possible VT relapse or clinical worsening, appears to represent a safe therapeutic strategy. Therefore, it is ethical and desirable to start a prospective randomized clinical trial to evaluate the benefit and cost-effectiveness of this strategy, as an alternative to AICD implantation.

Background Libman–Sacks endocarditis (LSE) is the most common cardiac manifestation of the antiphospholipid antibody syndrome (APS), a systemic autoimmune disease characterized by the presence of arterial and venous thrombosis associated with the persistent presence of antiphospholipid antibodies (Sydney criteria). Cardioembolic events, mainly stroke, are important prognostic determinants of APS. Echocardiography, mostly transesophageal, is the main diagnostic tool to early identification and timely management of LSE. Case Summary we report a case of 33–year–old man, with no cardiovascular risk factors. In the last few months, he had a myocardial infarction without obstructive coronary artery disease, a femoral venous thrombosis and a cryptogenic stroke. After clinical and laboratory workout he received diagnosis of primary APS and started an anticoagulation therapy with warfarin. 2D and 3D transesophageal echocardiogram performed after stroke showed two vegetations of the mitral valve. The first one appeared as granular mass, attached to ventricular and atrial surface of the posterior leaflet, measuring 16 x 5 mm. The second one was a smaller, mobile, pedunculated and more hyperechogenic mass apposed on the anterior leaflet. Mitral valve had mild to moderate regurgitation. The patient underwent surgical vegetation excision due to the high embolic risk. Resected specimens revealed sterile fibrinous and verrucous vegetations referable to LSE and a papillary fibroelastoma. Discussion In this case we demonstrated a very rare coexistence of abacterial endocarditis and papillary fibroelastoma. We can assume a predisposing role of fibroelastoma by altering the morphology and structure of the mitral leaflets in LSE development.

A 66–year–old woman with a history of anxious–depressive syndrome and osteoporosis, without significant cardiological history, reported onset of cardiopalmus and dyspnoea for a few days due to moderate efforts, in conjunction with a period of strong emotional stress. Due to the persistence of these symptoms and the onset of epigastric pain, she underwent a cardiological examination which found low blood pressure values associated with the presence of a systolic murmur. The ECG showed diffuse changes in repolarization compatible with ischemia. Access to the emergency room (ER) was recommended. In ER, the first high–sensitivity troponin value was significantly high (1542 ng/L). Therefore, in the suspect of ACS, the patient was transferred to the cardiological intensive care unit. Echocardiogram showed akinesia of the mid–apical segments, hypercontractility of the bases (EF 35%) and a SAM (systolic anterior motion) with a dynamic outflow tract pressure gradient of 80 mmHg which resulted in severe mitral regurgitation. During the first days of hospitalization, persistent hypotension was observed requiring intravenous infusion of fluids to maintain systolic blood pressure values between 90–100 mmHg. Coronary angiography showed only severe ostial stenosis of a branch of the first diagonal branch. At the same time, ventriculography was performed which showed basal hypercontractility with muscle salience at the base and systolic obliteration of the outflow tract with a small apical aneurysm. 5 days after admission, another echocardiogram showed the almost complete normalization of the global systolic function (EF 68%) with apical hypokinesia and hypercontractility of the basal segments. However, the SAM persisted with a dynamic outflow tract pressure gradient of 140 mmHg with the presence of multiple and dislocated papillaries, accessory tendon cords and insertion of muscle tendon at the level of the septum. To complete the diagnosis, cardiac MRI was performed which documented a diffuse increase in T2 relaxation times more evident in the apical area, absence of LGE areas and normalization of contractility of the left ventricle with disappearance of the SAM. These findings, together with the absence of significant hypertrophy and the complete regression of the ECGgraphic changes, allowed us to exclude the presence of an unrecognized hypertrophic cardiomyopathy and to diagnose Takotsubo syndrome.

Cardiac MRI can facilitate the differential diagnosis of myocardial damage in patients without coronary artery disease. Our case report is about a 50–year–old man who was admitted to the Emergency Department of the Maggiore Hospital in Bologna in October 2021 for oppressive chest pain at rest; previously he had experienced a similar episode but of minor intensity. He had not previous medical records. When the patient arrived at the emergency department chest pain had regressed, blood pressure was elevated (170/110 mmHg). The ECG showed sinus tachycardia at 100 bpm without electrocardiographic abnormalities suggestive of acute ischemia. Cardiac biomarkers were elevated (hsTnI 312 ng / L –> 975 ng / L – n.v.

Background The current rise in life expectancy in the general population leads to changes in baseline characteristics of Cardiac Intensive Care Unit (CICU) patients, increasing the risk of non–cardiac complications during the hospitalization. Objectives Evaluate epidemiology and prognostic impact of major non–cardiac complications (respiratory failure, renal insufficiency, haemorrhage and sepsis) during CICU stay. Methods: Retrospective analysis of CICU patients at Ospedale Maggiore of Bologna between March and November 2021. Results Baseline characteristics, cardiovascular risk factors and comorbidities of the patients are reported in Table 1. During the CICU stay, 19.7% of patients suffered from acute respiratory failure, needing for ventilation; 15.0% had renal insufficiency (considered as need for haemodialysis, glomerular filtration rate according to Cockcroft–Gault < 60 ml/min, serum creatinine rise > 25% from baseline); 1.8% reported major haemorrhages (defined as serum haemoglobin < 8 g/dl or need for blood transfusion); 1.7% developed sepsis (positive blood cultures). Mean CICU stay for complicated patients was 6 days, intra–CICU mortality was 1.7% (8 deaths) and 30–days mortality was 7.0% (32 deaths). At univariate logistic regression analysis, acute respiratory failure was the only complication associated with a statistically relevant increase in 30–days mortality (OR 2.37, CI 95%, 1.05–5.34; p = 0.038), although, also the other complications had a negative prognostic effect: haemorrhage (OR 1.58, CI 95%, 1.77–14.16; p = 0.681), renal insufficiency (OR 1.47, CI 95%, 0.56–3.87; p = 0.432) and sepsis (OR 1.25, CI 95%, 0.33–5.87, p = 0.850). Conclusions Epidemiology and baseline characteristics of CICU patients are changing. Older age and frailty make non–cardiac complications more likely to happen. Acute respiratory failure has the worst prognostic effect on mortality. This fact suggests that CICU Cardiologists should improve their management of these major non–cardiac complications.

Background Although an early invasive strategy (coronary angiography performed Purpose This study tested the hypothesis that, compared to early ( Methods From 2016 to 2020, all consecutive MINOCA patients diagnosed according to the current ESC diagnostic criteria (angiographic conventional cut–off of Results 198 NSTE–MINOCA patients were enrolled, of which 79 underwent coronary angiography Conclusions We demonstrated for the first time that in the MINOCA population the prognosis is not influenced by an early versus deferred coronary angiography, as opposed to AMI patients with obstructive coronary arteries. These results add another piece to the puzzle and pave the way for the initial use of a non–invasive imaging strategy (eg. Coronary–CT), mostly in patients with NSTEMI and high clinical suspicion of non–obstructive coronary arteries.

Background The attention about sex disparities in Cardiology has grown in the last few years. Women are still often under–represented in cardiovascular randomised clinical trials (RCTs) and several studies have shown later diagnosis, less aggressive treatments and poor prognosis among women, even though hospitalized in the coronary care unit (CCU). Objective To analyze gender–related differences and their relationships with prognosis among patients admitted to a contemporary CCU Hub. Methods Between 1st March 2021 and 30th November 2021, we prospectively collected the data of patients admitted to the II level CCU of Maggiore Hospital in Bologna. Results The clinical characteristics of 458 enrolled patients are shown in Table 1. Women represent 32% of the population, are older (p Conclusions The study demonstrates that one third of the population of a CCU Hub is represented by women, older and more often hospitalized for ACS. These women receive the same treatments as men, including coronary revascularization. There were no differences about gender prognosis, despite a higher trend towards mortality in females after discharge from the CCU. Therefore, studies where women are more represented are needed, in order to obtain precise indications on how to modulate clinical management according to gender.

Background Sacubitril/Valsartan (SV) has been validated for heart failure (HF) with reduced ejection fraction (EF) treatment. SV is effective on hard end–points as well as symptoms and heart remodeling. Present guidelines reccomend at least 3 month of optimized medical therapy (OMT). However, the best timing of EF assessment after SV initiation in order to proceed with defibrillator (ICD) implantation, is still unknown. Purpose Evaluate timing of improvement of EF after SV initiation in patients (pts) with systolic HF, candidates to primary prevention ICD implantation. Methods From 1 of february 2018, we evaluated retrospectively clinical and echocardiographic data of all consecutive pts with EF Results The study involved 95 pts (mean age 67±10 years, 70% male, ischaemic etiology 48%). Mean EF at enrollment was 30 ± 5% (ED vol 90 ±23 ml/m2; ES vol 62 ± 19 ml/m2, severe MR 23%) and NYHA III–IV 50%. In 58% pts reached the target dose of SV (97/103 mg bid). After a mean Fup of 6 months, mean EF of the study population increased to 37±7% (ED vol 80±19 ml/m2, ES vol 51±17 ml/m2, severe MR 5%, p Conclusions After SV initiation in systolic HF, favourable heart remodeling is clearly evident at 6 months FUP, but could be already observed after 3 months . These findings need to be validated from larger trials but suggest that the best timing of EF reassessment to decide for primary prevention ICD is likely between 3 and 6 months after SV initiation. However decision must be taken following close and individualized FUP for every patient, based on clinical characteristics and response to OMT.

Background There is an increasing awareness of the association between mitral valve prolapse (MVP) and sudden cardiac death (SCD), but risk stratification is still challenging. Mitral annular disjunction (MAD) is a recognized risk factor for arrhythmic complications. A multimodality imaging strategy, including advanced echocardiography, magnetic resonance (CMR) and electromechanical mapping, could improve risk stratification and management by combining anatomical and functional information. Case Review We report a case of a 50–year–old woman without cardiovascular risk factors, complaining for worsening palpitations in the last months. Echocardiogram documented bileaflet MVP with moderate regurgitation, MAD (12 mm in inferolateral wall) and normal ventricular systolic function. 24–hour Holter monitoring revealed a high (13%) premature ventricular complexes burden with ventricular bigeminy and non–sustained ventricular tachycardia. Stress test showed a reduction of the arrhythmias during exercise. CMR confirmed MAD but no late gadolinium enhancement areas were detected. The patient underwent electrophysiological study with electroanatomic mapping (CARTO). The latter revealed multifocal fragmented and delayed low voltage potentials close to the posterior papillary muscle and the posterior anular mitral area, respectively. Both locations were the targets of endoventricular radiofrequency ablation. However, due to her high arrhythmic risk profile the patient implanted a cardioverter defibrillator. Discussion In arrhythmic risk stratification of MVP with MAD, CMR could have technical limitations due to diffuse fibrosis patterns or irregular cardiac rhythm that could undermine a detailed and complete evaluation. Thus, electroanatomical mapping during electrophysiological testing could offer additional and complementary information that could improve risk stratification and further management.

Background The survival of IHCA and OHCA depends on the timeliness and the quality of cardiopulmonary resuscitation (CPR). During transport, in the Cath Lab or when resuscitation is extended, the availability of chest compression systems increases the quality of CPR and it is recommended in these specific situations by the AHA 2020 Guidelines. Methods Retrospective analysis of patients who encountered cardiocirculatory arrest (CCA) in the Cath Lab or in ICU of the Maggiore Hospital managed with CPR and application of a chest compression device (LUCAS® 3) from 2020 to 2021. Results The study population consisted of 21 patients, all undergoing invasive procedure (coronary angiography, angioplasty or aortic valvuloplasty) in peri–arrest: 17 patients (81%) with CCA during STEMI, 3 (14%) during NSTEMI and one patient during acute pulmonary edema caused by severe aortic stenosis. In 6 cases (29%) the onset rhythm of CCA was shockable, the others were pulseless electrical activities. Considering patients admitted with STEMI, 4 (24%) have OHCA and LUCAS® had been applied by 118 operators before entering the Cath Lab. In the other cases LUCAS® was placed in the Cath Lab, before or during the procedure; in all but two cases, the procedure was concluded. The resuscitation maneuvers involved, in addition to LUCAS®, the use of an external defibrillator, orotracheal intubation, administration of inotropes and, in 2 cases (10%) the intra–aortic balloon pump (IABP). The average time between CCA and application of LUCAS® was 14 minutes – the device was always positioned after at least 2 manual ECM cycles without restoring the circulation – and the average CPR duration was 73 minutes. Any complications related to the implantation of the device were observed. The survival at the end of the procedure in the Cath Lab was 24% and on discharge 14%. Conclusion The use of chest compression devices during CCA allows a better management by medical personnel during long–term CPR and a completion of invasive procedure. Unfortunately, it doesn’t substantially changes the survival of patients as reported by the literature.

Background Many abdominal deseases can mimic cardiac symthoms at their presentation and they can lead to electrocardiographic (ECG) changes, acting as a confounding factor for the physichan during the diagnostic process. Case presentation A 77–year–old man, former smoker, with high blood pressure not being treated, came to the emergency room with mesogastric pain and vomiting, since three hours before. The ECG showed a sinus rhythm, at 55 beats per minute and a slight elevation of the ST segment in the leads DII, DIII and aVF, evolving as T waves negativization in the same leads and flattening in V5– V6. Laboratory tests showed increasing Troponin I values from 23 to 277 ng / L. Because of this pathological context, the patient was taken to our Unit to perform a coronary angiography study in the hypothesis of acute myocardial infarction. The examination showed diffuse atheromatous lesions in the coronaries without haemodynamically significant stenosis. The patient developed fever during the hospitalization, abdominal CT study with contrast was performed, with a definitive diagnosis of acute cholecystitis and the patient was finally moved to the Internal Medicine ward. Conclusions ECG alterations in acute cholecystitis are not specific, but some of them are recurrent: among these there are ischemic modifications affecting the ST segment or the T waves, widely described in the scientific literature. All these ECG modifications solve with the treatment of cholecystitis, whether conservative or surgical, without acting on the cardiological side in any way; on the other hand, they can lead to unnecessary diagnostic–therapeutic investigations, to a diagnosis’delay and to complications’ onset. It is important for the clinician being able to consider abdominal pathology in case of diagnostic investigations’ inconsistency. However, ST segment’s changes during cholecystitis may deserve a cardiological study, as they are specific for acute myocardial infarction, especially in patients with high cardiovascular risk. This reminds to us, once again, the importance of anamnesis, physical examination and appropriate tests, to reach the correct diagnosis.

Second messenger nucleotides are produced by bacteria in response to environmental stimuli and play a major role in the regulation of processes associated with bacterial fitness, including but not limited to osmoregulation, envelope homeostasis, central metabolism, and biofilm formation. In this study, we uncovered the biological significance of c-di-AMP in the opportunistic pathogen Enterococcus faecalis by isolating and characterizing strains lacking genes responsible for c-di-AMP synthesis (cdaA) and degradation (dhhP and gdpP). Using complementary approaches, we demonstrated that either complete loss of c-di-AMP (ΔcdaA strain) or c-di-AMP accumulation (ΔdhhP, ΔgdpP and ΔdhhPΔgdpP strains) drastically impaired general cell fitness and virulence of E. faecalis. In particular, the ΔcdaA strain was highly sensitive to envelope-targeting antibiotics, was unable to multiply and quickly lost viability in human serum or urine ex vivo, and was avirulent in an invertebrate (Galleria mellonella) and in two catheter-associated mouse infection models that recapitulate key aspects of enterococcal infections in humans. In addition to evidence linking these phenotypes to altered activity of metabolite and peptide transporters and inability to maintain osmobalance, we found that the attenuated virulence of ΔcdaA could be also attributed to a defect in Ebp pilus production and activity that severely impaired biofilm formation under both in vitro and in vivo conditions. Collectively, these results reveal that c-di-AMP signaling is essential for E. faecalis pathogenesis and a desirable target for drug development.IMPORTANCEEnterococcus faecalis is an opportunistic pathogen and leading cause of multidrug resistant hospital-acquired infections. During the course of an infection, bacteria encounter multiple adverse (stress) conditions and understanding the adaptive mechanisms used by pathogens to survive these stresses can facilitate the development of new antimicrobial therapies. Here, we used in vitro, ex vivo and in vivo approaches to determine the importance of the second messenger nucleotide c-di-AMP, a global regulator essential for bacterial adaptation to osmotic stress, to E. faecalis pathophysiology. We demonstrated that either accumulation of c-di-AMP or complete loss of c-di-AMP impaired cell fitness and virulence of E. faecalis. Remarkably, the strain that was unable to produce c-di-AMP was avirulent in three animal infection models indicating that c-di-AMP signaling is essential for E. faecalis pathogenesis and a suitable antimicrobial target.

Background The term acute myocardial infarction (AMI) reflects cell death of cardiac myocytes caused by ischaemia. The Fourth Universal Definition of Myocardial Infarction (UDMI) defined AMI by a typical rise and fall in the level of biochemical markers of myocardial necrosis together with criteria of myocardial ischaemia. However, the prognostic role of each single diagnostic criteria has never been explored. Purpose To evaluate the prognostic role of the different diagnostic criteria of AMI according to the Fourth UDMI. Methods We enrolled all consecutive patients with AMI admitted from 2016 to 2019. We used a combination of criteria, according to the current ESC guidelines, to meet the diagnosis, namely the detection of an increase and/or decrease of high-sensitivity cardiac troponin I, with at least one value above the 99th percentile of the upper reference limit and at least one of the following: symptoms of ischaemia; ECG changes (new ST-T changes or new LBBB); development of pathological Q waves in the ECG; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, in our study evaluated by transthoracic echocardiogram. All-cause mortality and a composite endpoint of all-cause mortality, re-hospitalization for heart failure and myocardial re-infarction were collected. The predictive value of diagnostic criteria alone and its association were evaluated using Kaplan-Meier survival curves and subsequent Cox-regression analysis to find independent predictors of adverse events. Results 2386 patients were evaluated. The median follow-up time was 23.3±14.5 months. The total number of events was 703 (29.3%). Kaplan-Meier curves showed that major adverse cardiac events (MACE) were statistically different depending on the diagnostic criteria of AMI at admission. Particularly, clinical criteria alone showed a better predictive value (p Conclusions Our data suggest that the prognosis is considerably better among patients with a diagnosis of AMI if clinical criteria alone are present at admission. We also demonstrated that clinical criteria are a strong prognostic predictor of good outcomes in patients with AMI. We hypothesize that the absence of electrocardiographic and echocardiographic alterations could indirectly indicate a smaller infarct sizes that contribute to patients' outcome. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): None

Background Coronavirus disease 2019 (COVID-19), had two pandemic waves in 2020, respectively in April and November. In the general population, the first wave has been characterized by a higher prevalence in Northern Italy and a higher mortality rate compared to the second one. The aim of this study was to compare the characteristics of IBD patients and negative outcomes of COVID-19 (pneumonia, hospitalization, ventilatory support, death) between the two pandemic waves in Italy. Methods Prospective observational cohort study. Patients with diagnosis of IBD and confirmed SARS-CoV-2 infection were enrolled. Differences between first and second wave were tested for significance using the Student’s t test and Fisher’s test, as appropriate. A two-tailed p value Results We enrolled 937 IBD patients from 47 participating IBD centres across Italy (219 in the first wave, 718 in the second wave). There were no significant differences between the first and the second wave in terms of age (46.3 ± 16.0 vs. 44.1 ± 15.5 years, p=0.06) and gender (female 45.7% vs. 48.2%, p= 0.54). In the first wave, a lower percentage of patients was affected by Crohn’s disease (CD): 92 (42.0%) vs. 399 (55.6%) (p Conclusion IBD patients had higher number of COVID-19 negative outcomes in the first wave than in second wave. In the first wave, a significantly higher percentage of patients were from Northern Italy, but no significant differences in negative outcomes were observed in comparison with those from Central- Southern Italy. Overall, findings in IBD population are coherent with those observed in the general population.

Symptomatic uncomplicated diverticular disease of the colon (SUDD) is generally managed by gastroenterologists rather than General Practitioners (GPs). The aim of this study was to assess the efficacy of the treatment of SUDD with rifaximin, a non-absorbable antibiotic, in a primary care setting by GPs.This retrospective, observational study investigated the use of rifaximin at a dose of 400 mg b.i.d. for 5, 7 or 10 days monthly, up to 3 months. The symptoms were reported by the patients using a visual analogic scale (VAS) of 0-10.286 SUDD patients were enrolled (44.4% of men, average age 70.92±10.98). Respectively, 15 (5.2%) patients received the treatment for 5 days, 205 (71.7%) for 7 days and 66 (23.1%) for 10 days. After three months, a significant reduction of VAS score was observed in almost all symptoms assessed: 135 (47.2%) patients reported no abdominal pain (p0.001) and 23 (8.1%) reported no symptom. Adverse events related to the treatment were recorded in 3 (1.04%) patients, all of them mild and not requiring interruption of the treatment. Acute diverticulitis occurred in 9 (3.1%) patients, but only 2 of them [0.7% (n=2)] underwent surgery due to complicated diverticulitis. Analysis within the different treatment groups (5, 7 and 10 days) shows that rifaximin treatment is effective in reducing the severity of symptoms in almost all groups except for the constipation in the 5-day group.Rifaximin can be effectively used by GPs in real-life for the management of SUDD.

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.

Acinetobacter baumannii is known for its intrinsic resistance to conventional antibiotic treatment and hypervirulence during infection. This coupled with its extraordinary capacity to survive in myriad harsh environments has led to increasing rates of infection in clinical settings. Numerous studies have characterized the virulence factors and resistance genes in A. baumannii responsible for the detrimental outcomes seen in patients; however, the role of regulatory factors in controlling the expression of these genes remains less well explored. Herein we discuss the latest and most influential findings on the regulatory network of A. baumannii, focusing on the transcription factors, two-component systems, and sRNAs. We place particular focus on those identified as being crucial for sensing and responding to continually changing environments, and influencing survival and virulence when engaging with the human host.

This paper reviews the recent literature data on minimally invasive surgical approach to early cervical cancer compared to abdominal approach, with the aim of evaluate the oncological outcomes and the appropriateness of current indications. A recent multicenter randomized controlled trial and a concurrent large epidemiological study, contrary to the previous retrospective data, showed that minimally invasive surgery is associated with significantly poorer survival than the open approach. Open surgery is to be considered the standard of care for early cervical cancer as implemented in the current guidelines, and the patients must be carefully counseled if minimally invasive surgery is offered. Minimally invasive surgery can be considered safe only for sentinel lymph node mapping in a fertility-sparing setting and could be considered after preoperative conization and for small tumors, adopting preventive surgical maneuvers and in reference centers. However, prospective evidences about the suggested indications are not yet available.

Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL- and GGDEF-domain proteins and methyl-accepting chemotaxis proteins) despite their small sizes (2.1-3.1 Mbp). An array of sulfur-oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2-6, acquired via horizontal gene transfer. In addition to high-affinity cbb3 cytochrome c oxidase, some also encode cytochrome bd-type quinol oxidase or ba3 -type cytochrome c oxidase, which could facilitate growth under different oxygen tensions, or maintain redox balance. Carboxysome operons are present in most, with genes downstream encoding transporters from four evolutionarily distinct families, which may act with the carboxysomes to form CO2 concentrating mechanisms. These adaptations to habitat variability likely contribute to the cosmopolitan distribution of these organisms.

A morphological and electroanalytical characterization of a glassy carbon electrode modified with multi-walled carbon nanotubes dispersed into cellulose acetate polymer matrix (GC/MWCNT/CA), was reported. The morphology of the modified electrode reveals a favorable distribution of the carbonaceous fibers interconnected within the cellulose acetate matrix, showing an improved active surface area. The electrode was tested as an sensing probe for the detection of some important catecholamines such as dopamine and epinephrine using cyclic volatmmetry and differential pulse voltammetry (DPV) in 50 mM H3PO4. Under DPV conditions, the detection limits of the investigated catecholamines are comprised between 1 μM and 10 μM. A reverse phase chromatographic technique (pH 3.5), coupled with the GC/MWCNT/CA amperometric sensor was optimized for the separation and quantification of the tested catecholamines. Under the optimized conditions, the investigated analytes, including an important urinary catecholamine metabolite such as the vanillylmandelic acid, were eluted and separated in about 10 min with good chromatographic efficiency and resolution. The effects of various common interferents on the analytical signal, were also evaluated. A solid phase extraction pre-concentration procedure accomplished with chromatography and electrochemical detection allows the possibility to lower the detection limits of the investigated molecules at level of 1–5 nM. Real samples of pharmaceutical vials and urine samples were successful analyzed using the proposed amperometric sensor in two different analytical contexts: DPV and amperometry after solid phase extraction procedure coupled with liquid chromatography.

A composite electrode material based on graphene oxide (GO) and polyvinyl alcohol (PVA) containing electrodeposited Ni-Co species was electrochemically characterized in alkaline medium (0.1 M NaOH). The well distinct Ia/Ic redox couple shifts to the cathodic potentials in presence of Co oxide species contained in the active deposit. The effect of the potential scan rates (ν) on the Ia/Ic redox couple was studied in the range comprised between 10 mV s−1 and 250 mV s−1. The plots of the log(peak current) vs log(ν) gave straight lines with slopes between 0.65 and 0.75, showing a diffusive character of the redox currents. Continuous potentiostatic charge/discharge process between 0.4 V and 0.1 V vs SCE were carried out in alkaline medium in order to ascertain the supercapacitor performance of the investigated GC/GO/PVA/Ni-Co electrode. The composite electrode shows significantly higher capacitance (3.1 × 10−4 F). Admitting the only Ni-Co oxide as active electrode material, a specific capacitance of about 2100 ± 200 F g−1, was evaluated. During the charge/discharge process in alkaline medium, the electrode system shows, after an initial physical stabilization, a good electrochemical stability ( sorbitol > glycerol > methanol. Flow injection analysis (FIA), performed under flowing 0.1 M NaOH solution and an applied constant potential of 0.5 V, show well-defined symmetrical and reproducible peaks in a wide range of concentration of investigated analytes.

Objective To test the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) and determine the frequency of specific/prognostic molecular alterations within a cohort of endometrial cancer (EC) women conservatively treated by combined hysteroscopic resection and progestin therapy. Study design We used blocks of formalin-fixed paraffin-embedded tissue from the primary tumors of patients enrolled into the ECCo trial (EudraCT 2010-018581-23) between 2007 and 2016. In order to assign EC resectoscopic specimens to one of four ProMisE subgroups, testing involved sequential assessment of i) immunohistochemistry (IHC) for mismatch repair (MMR) proteins MLH1, MSH2, MSH6 and PMS2; ii) sequencing for POLE/POLD1 exonuclease domain mutations (EDMs); iii) p53 IHC. Results Molecular analysis methods were used in 25 patients (stage IA, G1-2 endometrioid EC), of whom 15 (60%) represented fully evaluable cases. Seven cases (46.7%) had abnormal MMR IHC, POLE/POLD1 EDMs were found in 3 cases (20%), and abnormal p53 IHC in 1 case (6.6%). Three patients (20%) had more than one molecular feature. Among 10 (40%) ‘unclassifiable’ patients, six failures in achieving complete molecular categorization were due to the low tumor volume. Molecular classification of the 15 fully evaluable cases yielded the following ProMisE subtypes: 7 (46.7%) MMR IHC abnormal, 1 (6.6%) POLE EDM, 0 (0%) p53 IHC abnormal, 7 (46.7%) p53 IHC wild-type. Conclusions Although larger series are needed to further assess the feasibility of a molecular categorization in a fertility-sparing setting, data presented are promising. In women with early stage low-volume disease, operative hysteroscopy could be advantageous to provide samples allowing complete genetic risk assessment.

The palladium species were deposited on the multi-walled carbon nanotubes dispersed in nafion membrane by pulsed electrodeposition technique. The resulting modified electrode was defined CNT-Pd. The Pd electrodeposition was carried out in 50 mM H 2 SO 4 solution containing 4.0 mM Pd(NO 3 ) 2 using a double pulse sequence of potentials: E 1 = −0.4 V vs SCE (t 1 = 0.03 s) and E 2 = 0.4 V vs SCE (t 2 = 3 s). SEM analysis showed a well-efficient distribution of Pd nanoparticles dispersed along the nanotubes randomly oriented in the nafion matrix. A surface loading of electrodeposited Pd species comprised between 2.0 nmol and 2.5 nmol was generally observed. The prepared electrode is useful to catalyze the electrooxidation of hydrazine and propranolol. The electroanalytical properties of the electrode were evaluated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Under optimized DPV conditions, the CNT-Pd electrode exhibits interesting analytical performance in terms of linear range of concentrations, low detection limits (i.e., 8 μM and 2 μM for hydrazine and propranolol, respectively) and good temporal stability of the responses (i.e., 4%–5%).

A study regarding the electrodeposition of nickel oxide particles on the activated multi-walled carbon nanotubes from 2 M NaOH solution containing Ni(NO3)2 and EDTA was carried out. The electrodeposition process was carried out using an optimized double-pulse sequence of potentials: E 1 = −0.2 V vs. SCE (t 1 = 0.3 s) and E 2 = 0.7 V vs. SCE (t 2 = 0.03 s). Spectroscopic XPS investigations and SEM analysis were used in order to characterize the surface and morphology of the studied modified electrode. Cyclic voltammetry and chronoamperometry were used in order to evaluate the electrochemical/amperometric performance of the GC/MWCNT-Ni electrode toward the oxidation of some aliphatic alcohols in strong alkaline medium.

A highly thin and perfluorinated porous membrane has been fabricated according to "Breath Figure" approach [1] for treating salt solutions via thermally driven membrane distillation [2]. Nano-assembly of water droplets has been used to form pores [3] through a HYFLON AD nanolfilm standing, in turn, on a high-definition honeycomb PES membrane [4-6]. High permeability and resistance to wetting together with a good mechanical strenght have been combined in a unique membrane, thus leading to an unusual compromise between productivity and thermal efficiency when NaCl solutions 5 mM have been processed. Ultrafast flux together with high thermal efficiency have been regarded as the result of very low resistance to transport and very low thermal conductivity of the materials used. Regular polymeric architecture together with defined chemistry have allowed overcoming the current productivity-efficiency trade-off, resulting promising for the construction of advanced thermally-driven membrane distillation.

An IrOx modified electrode was characterized and proposed as an amperometric sensor for the detection of semicarbazide using cyclic voltammetry, chronoamperometry and amperometry techniques. The modified electrode was characterized as sensing probe in both acid and alkaline medium toward the electrocatalytic oxidation and detection of semicarbazide. A liquid chromatography approach based on the strong cation exchange mode (LC-SCX column) was used in acid conditions for the separation and analysis of semicarbazide in a synthetic mixture. Operating under a constant applied potential of 1.1 V vs. Ag/AgCl and using HClO4 as carrier electrolyte, the limit of detection (LOD) is attested at level of 0.1 μM (i.e., 7.5 μg L−1), while an excellent precision and temporal stability of the amperometric signal, was observed. The linear ranges spanning over three order of magnitude of the detection limit with a correlation coefficients higher than 0.995.

Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL- and GGDEF-domain proteins and methyl-accepting chemotaxis proteins) despite their small sizes (2.1-3.1 Mbp). An array of sulfur-oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2-6, acquired via horizontal gene transfer. In addition to high-affinity cbb

The emergence of Acinetobacter baumannii strains, with broad multidrug-resistance phenotypes and novel virulence factors unique to hypervirulent strains, presents a major threat to human health worldwide. Although a number of studies have described virulence-affecting entities for this organism, very few have identified regulatory elements controlling their expression. Previously, our group has documented the global identification and curation of regulatory RNAs in A. baumannii. As such, in the present study, we detail an extension of this work, the performance of an extensive bioinformatic analysis to identify regulatory proteins in the recently annotated genome of the highly virulent AB5075 strain. In so doing, 243 transcription factors, 14 two-component systems (TCSs), 2 orphan response regulators, 1 hybrid TCS and 5 σ factors were found. A comparison of these elements between AB5075 and other clinical isolates, as well as a laboratory strain, led to the identification of several conserved regulatory elements, whilst at the same time uncovering regulators unique to hypervirulent strains. Lastly, by comparing regulatory elements compiled in this study to genes shown to be essential for AB5075 infection, we were able to highlight elements with a specific importance for pathogenic behaviour. Collectively, our work offers a unique insight into the regulatory network of A. baumannii strains, and provides insight into the evolution of hypervirulent lineages.

The loss of fitness in colistin-resistant (CR) Acinetobacter baumannii was investigated using longitudinal isolates from the same patient. Early CR isolates were outcompeted by late CR isolates for growth in broth and survival in the lungs of mice. Fitness loss was associated with an increased susceptibility to oxidative stress since early CR strains had reduced in vitro survival in the presence of hydrogen peroxide and decreased catalase activity compared to that of late CR and colistin-susceptible (CS) strains.

A composite material based on Polyvinyl alcohol (PVA) and graphene oxide (GO) was used as electrode substrate for the Ni-Co electrodeposition in neutral chloride bath containing 1.5 mM Ni(NO 3 ) 2 and 4.5 mM Co(NO 3 ) 2 . Ni-Co particles were cathodically deposited by voltage cycling between − 0.5 V and 0.2 V vs. SCE (35 cycles). Voltammetric data show clearly an inhibition phenomenon of nickel oxide deposition upon increasing [Co 2+ ] in the electroplating baths. Nevertheless, the presence of electrodeposited Co oxide species induces beneficial effects on the redox electrochemical behavior of the GC/PVA/GO/Ni-Co electrode in alkaline medium (0.1 M NaOH). The resulting electrode shows, a unique and reversible symmetrical cathanodic wave centered at about 0.3 V vs SCE. The SEM analysis shows the graphene oxide disposed as platelets in a agglomerate distribution randomly oriented within the PVA matrix. The electrodeposition process of Ni-Co species proceeds preferentially on the GO platelets surfaces. After the charge/discharge process in alkaline medium, the Ni-Co deposit shows a globular inhomogeneous distribution with an average diameter comprised between 50 nm and 300 nm. The XPS characterization of the electrodeposited Ni-Co catalyst reveals a surface chemical composition of about Ni 16 Co 84 , confirming an “anomalous” co-deposition process of the metals on the PVA/GO electrode substrate.

To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction.A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period.A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction.This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

A simple electrochemical microprobe (EMP) is proposed for the detection of analytes in gaseous atmospheres. The EMP consists of two platinum fibres of 25 and 300 μm in diameter encased into a theta glass pipette to form an electrochemical cell in a two-electrode configuration. Ion conductivity between the two electrodes is ensured by a thin film of the room temperature ionic liquid (RTIL), 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, which is applied onto the EMP tip surface by a simple dip-coating procedure. The ionic liquid-coated microprobe (RTIL-EMP) was preliminarily investigated by using ferrocene as an electroactive species to ascertain the mass transport properties of the analytes that influence the voltammetric responses as well as the stability and reproducibility of the RTIL-EMP in the gas phase. The performance of the RTIL-EMP to gas analysis was afterward evaluated by using oxygen as electroactive species. The RTIL-EMP was exposed to different synthetic O 2 /N 2 (v/v) mixtures and current responses were recorded as a function of O 2 concentration, using either cyclic voltammetry (CV) or chronoamperometry (CA). Regression analysis of the experimental current against % O 2 was linear over the range 0–100% with correlation coefficient and sensitivity of, respectively, 0.996 and 0.29 nA/(v/v) % O 2 in CV and 0.998 and 0.27 nA/(v/v) % O 2 in CA measurements. Long term stability, reproducibility of the RTIL-EMP recovery of the RTIL film layers to the initial conditions and effects of humidity on the current responses were investigated in detail.

A gas sensors based on a room temperature ionic liquid (RTIL) supported on paper is proposed as amperometric sniffer for monitoring volatile amines (VAs) released from fish samples, in order to gain indication of their state of turning spoiled. It was used as a paper electrochemical detector (PED) for a flow injection system in which controlled headspace volumes in equilibrium with ice-stored fish samples were directly injected. The performance of this RTIL-PED sensor was preliminarily tested on synthetic samples of trimethylamine (TMA), dimethylamine (DMA), methylamine (MA) and ammonia (i.e. the main species responsible for the typical flavor of spoiled fish), thus verifying that only TMA, DMA and MA can be detected because NH3 oxidation occurred beyond the solvent discharge. This notwithstanding, detection of the sole TMA, DMA and MA as a whole turned out to be well suited for the rapid assessment of fish spoilage, since during storage the release enhancement for these amines is largely predominant over that of NH3. Repeatable (8 % RSD) sharp peaks were detected for all amines above over a wide range (5–1000 nmol) and a detection limit of a little more than 3 nmol was inferred for a signal-to-noise ratio of 3. This approach was applied to the detection of VAs released from real fish samples (sardines), in parallel to the determination of their total volatile basic nitrogen (TVBN), which is a conventional indicator frequently adopted for the chemical quality assessment of fish. A substantially satisfactory agreement was found by comparing the data achieved by these two approaches.

The rhodium particles can be electrodeposited on a glassy carbon electrode, previously modified with multi-walled carbon nanotubes (MWCNTs), by voltage cycling between 0.4 V and–0.3 V vs. SCE (30 cycles) in 50 mM H2SO4 containing 4.0 mM RhCl3. This proposed modified electrode is useful to facilitate the electrocatalytic reduction of nitrate and nitrite ions in acid medium. The mechanism of the electrocatalytic reduction of nitrate and nitrite ions in the hydrogen region of potentials was critically considered using voltammetric and DC/pulsed amperometric detection techniques. The GC/MWCNT-Rh electrode shows interesting sensitivity and temporal reproducibility towards nitrite and nitrate reduction under constant and pulsed applied potentials, respectively.

Acinetobacter baumannii is a nosocomial opportunistic pathogen that can cause severe infections, including hospital-acquired pneumonia, wound infections, and sepsis. Multidrug-resistant (MDR) strains are prevalent, further complicating patient treatment. Due to the increase in MDR strains, the cationic antimicrobial peptide colistin has been used to treat A. baumannii infections. Colistin-resistant strains of A. baumannii with alterations to the lipid A component of lipopolysaccharide (LPS) have been reported; specifically, the lipid A structure was shown to be hepta-acylated with a phosphoethanolamine (pEtN) modification present on one of the terminal phosphate residues. Using a tandem mass spectrometry platform, we provide definitive evidence that the lipid A isolated from colistin-resistant A. baumannii MAC204 LPS contains a novel structure corresponding to a diphosphoryl hepta-acylated lipid A structure with both pEtN and galactosamine (GalN) modifications. To correlate our structural studies with clinically relevant samples, we characterized colistin-susceptible and -resistant isolates obtained from patients. These results demonstrated that the clinical colistin-resistant isolate had the same pEtN and GalN modifications as those seen in the laboratory-adapted A. baumannii strain MAC204. In summary, this work has shown complete structure characterization including the accurate assignment of acylation, phosphorylation, and glycosylation of lipid A from A. baumannii , which are important for resistance to colistin.