Specific Therapy in Transthyretin Amyloid Cardiomyopathy: Future Perspectives Beyond Tafamidis.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a relatively prevalent cause of morbidity and mortality. Over the recent years, development of disease-modifying treatments has enabled stabilization of the circulating transthyretin tetramer and suppression of its hepatic production, resulting in a remarkable improvement in survival of patients with ATTR-CM. Second-generation drugs for silencing are currently under investigation in randomized clinical trials. In vivo gene editing of transthyretin has been achieving unanticipated suppression of hepatic production in ATTR-CM. Trials of antibodies inducing the active removal of transthyretin amyloid deposits in the heart are ongoing, and evidence has gathered for exceptional spontaneous regression of ATTR-CM.

Cardiopulmonary exercise testing complements both spirometry and nuclear imaging for assessing sarcoidosis stage and for monitoring disease activity.

BACKGROUND: Pulmonary sarcoidosis is a systemic disease that can confound established follow-up tools. Pulmonary function tests (PFTs) are recommended in initial and follow-up patient evaluations yet are imperfect predictors of disease progression. The cardiopulmonary exercise test (CPET) is another potentially useful monitoring tool, although previous studies report conflicting findings regarding which variables are altered by the disease. Nuclear imaging tests are also employed to assess inflammatory activity and may be predictive of functional deterioration. AIM: We asked whether PFTs or CPET are more diagnostic of disease stage, which subsets of functional variables are impacted by the disease, and how these relate to nuclear imaging signs of active inflammation. STUDY DESIGN AND METHODS: We collected retrospective data (spirometry, CPET, Gallium-67 scintigraphy, 18F-FDG PET/CT) from 48 patients and 10 controls. Disease severity was assessed following Scadding classification. First, we correlated individual PFTs and CPET parameters to Scadding stage and nuclear imaging data. Next, we performed Principal Component Analysis (PCA) on PFTs and CPET parameters, separated into respiratory, cardiovascular and metabolic subsets. Finally, we constructed multiple regression models to determine which variable subsets were the best predictors of Scadding stage and disease activity. RESULTS: The majority of PFTs and CPET single parameters were significantly correlated with patient stage, while only few correlated with disease activity. Nevertheless, multiple regression models were able to significantly relate PFTs and CPET to both disease stage and activity. Additionally, these analyses highlighted CPET cardiovascular parameters as the best overall predictors of disease stage and activity. CONCLUSIONS: Our results display how CPET and spirometry data complement each other for sarcoidosis disease staging, and how these tests are able to detect disease activity. Our findings suggest that CPET, a repeatable and non-invasive functional test, should be more routinely performed and taken into account in sarcoidosis patient follow-up.

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: The extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome. METHODS: Consecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body planar and cardiac single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre and 4 Italian centers were included. Cardiac uptake was defined according to the Perugini classification: 0=absent cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=high uptake greater than bone. Extent of right ventricular (RV) uptake was defined as focal (basal segment of the RV free wall only) or diffuse (extending beyond basal segment) on the basis of SPECT imaging. The primary outcome was all-cause mortality. RESULTS: Among 1422 patients with ATTR-CM, RV uptake accompanying left ventricular uptake was identified by SPECT imaging in 100% of cases at diagnosis. Median follow-up in the whole cohort was 34 months (interquartile range, 21 to 50 months), and 494 patients died. By Kaplan-Meier analysis, diffuse RV uptake on SPECT imaging (n=936) was associated with higher all-cause mortality compared with focal (n=486) RV uptake (77.9% versus 22.1%; P<0.001), whereas Perugini grade was not associated with survival (P=0.27 in grade 2 versus grade 3). On multivariable analysis, after adjustment for age at diagnosis (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), presence of the p.(V142I) TTR variant (HR, 1.42 [95% CI, 1.20-1.81]; P=0.004), National Amyloidosis Centre stage (each category, P<0.001), stroke volume index (HR, 0.99 [95% CI, 0.97-0.99]; P=0.043), E/e' (HR, 1.02 [95% CI, 1.007-1.03]; P=0.004), right atrial area index (HR, 1.05 [95% CI, 1.02-1.08]; P=0.001), and left ventricular global longitudinal strain (HR, 1.06 [95% CI, 1.03-1.09]; P<0.001), diffuse RV uptake on SPECT imaging (HR, 1.60 [95% CI, 1.26-2.04]; P<0.001) remained an independent predictor of all-cause mortality. The prognostic value of diffuse RV uptake was maintained across each National Amyloidosis Centre stage and in both wild-type and hereditary ATTR-CM (P<0.001 and P=0.02, respectively). CONCLUSIONS: Diffuse RV uptake of bone tracer on SPECT imaging is associated with poor outcomes in patients with ATTR-CM and is an independent prognostic marker at diagnosis.

When surgical option is not provided: a successful multidisciplinary approach to a refractory case of sternal osteomyelitis following coronary surgery.

PURPOSE: Sternal osteomyelitis is a major complication of cardiac operations performed through median sternotomy. The surgical treatment, which involves the debridement and removal of whole infected and necrotic tissue is the standard of care, although it is sometimes unachievable. This may occur, for instance, when the infectious-inflammatory process invades the anterior mediastinum and tenaciously incorporates one or more of vital anatomical structures. METHODS AND RESULTS: An inoperable case of postoperative sternal osteomyelitis that involved the right ventricle and the right coronary artery, and that was successfully treated using a nonsurgical multidisciplinary approach, is reported here. CONCLUSION: For highly selected patients with sternal osteomyelitis for whom surgery is a too risky option, an approach including the contribution of various specialists might be a viable way out.

Using illusions to understand hallucinations: differences in perceptual performances on illusory figures may underscore specific visuoperceptual impairments in Parkinson's disease.

Visual hallucinations are prevalent, potentially disabling symptoms of Parkinson's Disease. Multiple impairments in bottom-up sensory processing and top-down perceptual modulation are implicated in the pathophysiology of these phenomena. In healthy individuals, visual illusions are elicited by illusory figures through parametric manipulations of geometrical configurations, contrast, color, or spatial relationships between stimuli. These illusory percepts provide insight on the physiologic processes subserving conscious and unconscious perception. In this exploratory, cross-sectional, controlled study, perceptual performance on illusory figures was assessed on 11 PD patients with hallucinations, 10 non-hallucinating PD patients, and 10 age-matched healthy individuals. In order to characterize potential neural substrates of perceptual performances, patients' brain metabolic patterns on FDG PET were also analyzed. Illusions relying on attentional modulation and global perception were attenuated in PD patients without hallucinations. This pattern was no longer recognizable in hallucinating patients. Conversely, illusory effects normally counteracted by figure to background segregation and overlapping figures recognition were enhanced in PD patients with hallucinations. FDG PET findings further suggest that perceptual differences between PD patients might be linked to abnormal top-down perceptual modulation.

A case report of isolated cardiac light chain amyloidosis without clinically overt heart failure: an under-recognized presentation.

Background: Cardiac involvement in amyloid light-chain (AL) amyloidosis usually represents a brick in the wall of a multi-system disease. The presence of cardiac deposition of free light chains (FLCs) is the main determinant of survival. Isolated cardiac AL is an uncommon scenario characterized by a challenging diagnostic and therapeutic workup. Case summary: A 57-year-old asymptomatic man was presented for an incidental finding of myocardial necrosis at the electrocardiogram (ECG) performed for newly diagnosed arterial hypertension. Alongside signs of previous myocardial infarction, transthoracic echocardiography showed a severely increased left ventricular (LV) wall thickness not consistent with ECG voltages, segmental akinaesia with normal LV systolic function with 'apical sparing' pattern. Laboratory assessment showed an unexpectedly high level of natriuretic peptide and persistently abnormal troponin in the absence of symptoms or signs of heart failure or ongoing ischaemia. Coronary angiogram confirmed the coronary artery disease. Before revascularization, a complete diagnostic workup was carried. Serum electrophoresis detected a monoclonal gammopathy that was further investigated by serum immunofixation, revealing high lambda FLCs concentration. Fat pad, bone marrow, and salivary glands biopsies resulted negative for amyloid deposition. Finally, endomyocardial biopsy was consistent with AL amyloidosis. Urgent percutaneous revascularization was performed, and the patients was timely started on chemotherapy. Discussion: The diagnosis of isolated cardiac AL amyloidosis is challenging and carries important therapeutic implications. As the short-term prognosis might be severely compromised, an accurate diagnostic flowchart has to be systematically pursued to obtain a precise diagnosis and address the optimal, tailored management.

Ischemic wound revascularization by the stromal vascular fraction relies on host-donor hybrid vessels.

Nonhealing wounds place a significant burden on both quality of life of affected patients and health systems. Skin substitutes are applied to promote the closure of nonhealing wounds, although their efficacy is limited by inadequate vascularization. The stromal vascular fraction (SVF) from the adipose tissue is a promising therapy to overcome this limitation. Despite a few successful clinical trials, its incorporation in the clinical routine has been hampered by their inconsistent results. All these studies concluded by warranting pre-clinical work aimed at both characterizing the cell types composing the SVF and shedding light on their mechanism of action. Here, we established a model of nonhealing wound, in which we applied the SVF in combination with a clinical-grade skin substitute. We purified the SVF cells from transgenic animals to trace their fate after transplantation and observed that it gave rise to a mature vascular network composed of arteries, capillaries, veins, as well as lymphatics, structurally and functionally connected with the host circulation. Then we moved to a human-in-mouse model and confirmed that SVF-derived endothelial cells formed hybrid human-mouse vessels, that were stabilized by perivascular cells. Mechanistically, SVF-derived endothelial cells engrafted and expanded, directly contributing to the formation of new vessels, while a population of fibro-adipogenic progenitors stimulated the expansion of the host vasculature in a paracrine manner. These data have important clinical implications, as they provide a steppingstone toward the reproducible and effective adoption of the SVF as a standard care for nonhealing wounds.

Evolving trends in epidemiology and natural history of cardiac amyloidosis: 30-year experience from a tertiary referral center for cardiomyopathies.

Objective: Natural history of cardiac amyloidosis (CA) is poorly understood. We aimed to examine the changing mortality of different types of CA over a 30-year period. Patients and methods: Consecutive patients included in the "Trieste CA Registry" from January 1, 1990 through December 31, 2021 were divided into a historical cohort (diagnosed before 2016) and a contemporary cohort (diagnosed after 2016). Light chain (AL), transthyretin (ATTR) and other forms of CA were defined according to international recommendations. The primary and secondary outcome measures were all-cause mortality and cardiac death, respectively. Results: We enrolled 182 patients: 47.3% AL-CA, 44.5% ATTR-CA, 8.2% other etiologies. The number of patients diagnosed with AL and ATTR-CA progressively increased over time, mostly ATTR-CA patients (from 21% before 2016 to 67% after 2016) diagnosed non-invasively. The more consistent increase in event-rate was observed in the long-term (after 50 months) in ATTR-CA compared to the early increase in mortality in AL-CA. In the contemporary cohort, during a median follow up of 16 [4-30] months, ATTR-CA was associated with improved overall and cardiac survival compared to AL-CA. At multivariable analysis, ATTR-CA (HR 0.42, p = 0.03), eGFR (HR 0.98, p = 0.033) and ACE-inhibitor therapy (HR 0.24, p < 0.001) predicted overall survival in the contemporary cohort. Conclusion: Incidence and prevalence rates of ATTR-CA and, to a less extent, of AL-CA have been increasing over time, with significant improvements in 2-year survival of ATTR-CA patients from the contemporary cohort. Reaching an early diagnosis and starting disease-modifying treatments will improve long-term survival in CA.

Re-Definition of the Epidemiology of Cardiac Amyloidosis.

The epidemiology of cardiac amyloidosis (CA), traditionally considered a rare and incurable disease, has changed drastically over the last ten years, particularly due to the advances in diagnostic methods and therapeutic options in the field of transthyretin CA (ATTR-CA). On the one hand, the possibility of employing cardiac scintigraphy with bone tracers to diagnose ATTR-CA without a biopsy has unveiled the real prevalence of the disease; on the other, the emergence of effective treatments, such as tafamidis, has rendered an early and accurate diagnosis critical. Interestingly, the following subgroups of patients have been found to have a higher prevalence of CA: elderly subjects > 75 years, patients with cardiac hypertrophy hospitalized for heart failure with preserved ejection fraction, subjects operated on for bilateral carpal tunnel syndrome, patients with cardiac hypertrophy not explained by concomitant factors and individuals with aortic valve stenosis. Many studies investigating the prevalence of CA in these particular populations have contributed to rewriting the epidemiology of the disease, increasing the awareness of the medical community for a previously underappreciated condition. In this review, we summarized the latest evidence on the epidemiology of CA according to the different clinical settings typically associated with the disease.

Light-chain cardiac amyloidosis: a case report of extraordinary sustained pathological response to cyclophosphamide, bortezomib, and dexamethasone combined therapy.

Background: Heart involvement represents the most ominous prognostic factor in light-chain amyloidosis (AL), often foreclosing curative therapies such as high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). Heart transplantation (HTx) may be considered before ASCT in rigorously selected cases of advanced AL cardiac amyloidosis (CA). In ASCT-ineligible patients, chemotherapy with cyclophosphamide, bortezomib, and dexamethasone combined (CyBorD) regimen, even at low-dose, is feasible and effective in obtaining hematological and organ response. Case Summary: A previously healthy 50-year-old woman presented with severely symptomatic new-onset heart with preserved ejection fraction, significant cardiac hypertrophy, and an 'apical sparing' pattern. Bone marrow and abdominal fat biopsy revealed AL amyloidosis due to a smouldering micromolecular λ-type myeloma with severe cardiac involvement, and the patient was judged a good candidate to HTx followed by ASCT. Despite fragile conditions, she tolerated a full course of low-dose combination therapy with bortezomib and was withdrawn from HTx list because of unexpected persistent complete hematologic response and major cardiac improvement. Disease remission was achieved in the long term (>3 years). Discussion: We report a case of exceptional persistent hematologic and cardiac response after CyBorD therapy in a patient with advanced AL-CA who left the transplantation lists (both HTx and ASCT). In ASCT-ineligible patients, chemotherapy with CyBorD regimen, even at low-dose, can lead to durable remission of the disease with excellent cardiac response.

Isolated aphasic status epilepticus: CT perfusion, SPECT and EEG reveal neurovascular coupling and support the differential diagnosis.

Objective Among the clinical manifestations of stroke mimics, isolated aphasia is one of the most challenging due to its aetiopathogenic diagnosis. This short communication describes a specific perfusion and brain oscillatory pattern in a challenging case of prolonged isolated aphasia caused by status epilepticus, jointly investigated by computed tomography (CT) perfusion, single-photon emission computerized tomography (SPECT)/CT and EEG qualitative and quantitative analysis. Methods We discuss the different patterns of perfusion neuroimaging and EEG between SE and ischaemic stroke or postictal (Todd's)-related isolated aphasia, and propose these differences as a basis to support the differential diagnosis. Results The pattern associated with SE was characterized by focal hyperperfusion on CT perfusion maps (the left mean transit time was shorter with >10% asymmetry, and left cerebral blood volume and cerebral blood flow increased or slightly altered, relative to the contralateral side) and SPECT (focal left temporal hyperperfusion), without any early ischaemic signs on non-enhanced CT, while the EEG showed a predominant left hemispheric slow delta power. The aforementioned perfusion pattern contrasts with postictal epileptic Todd's phenomenon, which is characterized by hypoperfusion on CT perfusion (the mean transit time is prolonged and cerebral blood volume and cerebral blood flow are reduced, compared to the contralateral hemisphere) and SPECT (focal hypoperfusion), not restricted to the specific vascular territories. Significance CT perfusion patterns may add valuable information to support the differential diagnosis of status epilepticus, rather than acute ischaemic stroke or postictal Todd's phenomenon, in cases with challenging symptoms of prolonged isolated aphasia.

[Ten questions for the cardiologist about cardiac scintigraphy with bone tracers, amyloidosis and the heart]. / I dieci punti che il cardiologo deve conoscere su scintigrafia miocardica con traccianti ossei, amiloidosi e cuore.

Although traditionally considered a rare and incurable condition, the perspective on cardiac amyloidosis (CA) has changed deeply over the last 10 years following major advances in diagnosis and treatment options. First, the development of non-invasive diagnostic methods, predominantly cardiac scintigraphy with bone tracers, has dramatically changed the epidemiology of the disease, revealing the real prevalence of the transthyretin-related form (ATTR), and has consistently reduced the need for histological amyloid confirmation by endomyocardial biopsy. Second, the availability of new specific therapies, such as tafamidis, has made CA early recognition a clinical need with major impact on patients' management and natural history. Since the demonstration of the essential role of bone tracer scintigraphy to non-invasively differentiate ATTR from immunoglobulin light-chain amyloidosis (AL), this imaging technique has become part of the vocabulary and clinical practice of physicians of many specialties, including cardiologists managing patients with cardiomyopathies.In this paper, we address the main questions regarding cardiac scintigraphy with bone tracers and CA, providing cardiologists with the knowledge to guide clinical indications, evaluation and clinical interpretation of images.

Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC-TIVE study, an Italian nationwide survey.

AIM: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. METHODS AND RESULTS: This is an Italian prospective multicentre study, involving a clinical and instrumental work-up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non-dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%-35%). Transthyretin-related AC (ATTR-AC) was diagnosed in 51 and light chain-related AC (AL-AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. CONCLUSION: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.

Detection Rate and Clinical Impact of PET/CT with 18F-FACBC in Patients with Biochemical Recurrence of Prostate Cancer: A Retrospective Bicentric Study.

Our aim was to assess the detection rate (DR) of positron emission computed tomography (PET/CT) with anti-1-amino-3-[18F]-flurocyclobutane-1-carboxylic acid (18F-FACBC) in patients with biochemical recurrence (BCR) from prostate cancer (PC). As a secondary endpoint, we evaluated 18F-FACBC PET/CT's impact on patients management. Clinical records of 81 patients submitted to 18F-FACBC PET/CT due to PC BCR in two Italian Nuclear Medicine Units were retrospectively assessed. DR was gauged in the whole cohort and stratifying patients by discrete intervals of PSA levels. PET/CT's impact on clinical management was scored as (1) major if it entailed an intermodality change (e.g., from systemic to loco-regional therapy); (2) minor if it led to an intramodality change (e.g., modified radiotherapy field). PET/CT's DR resulted in 76.9% in the whole cohort, with a positive predictive value of 96.7%. Stratified by PSA quartile intervals, PET/CT's DR was 66.7%, 71.4%, 78.9% and 90% for PSA 0.2-0.57 ng/mL, 0.58-0.99 ng/mL, 1-1.5 ng/mL and >1.5 ng/mL without significant difference among groups (p = 0.81). The most common sites of relapse were prostate bed and pelvic lymph nodes (59.3%). PET/CT impacted on clinical management in 33/81 cases (40.7%), leading to a major change in 30 subjects (90.9%). 18F-FACBC PET/CT localized recurrence in patients with BCR, with meaningful DR also at low PSA levels and significantly impacted on clinical management.

123I-Metaiodobenzylguanidine Myocardial Scintigraphy in Discriminating Degenerative Parkinsonisms.

BACKGROUND: 123I-Metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy is a useful technique to differentiate Parkinson's disease (PD) from atypical parkinsonisms, since it is generally abnormal in PD and normal in the latter. Reduction of myocardial MIBG uptake is a supportive feature in the latest PD diagnostic criteria. OBJECTIVES: To explore the clinical contribution of myocardial scintigraphy in discriminating different forms of parkinsonisms, especially when atypical features are present. METHODS: Forty-one patients with parkinsonism underwent a 123I-MIBG myocardial scintigraphy in our Movement Disorders Center. Disease evolution was reviewed by applying the latest disease criteria for PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as appropriate. Three diagnostic times were defined: T1 (before scintigraphy execution), T2 (immediately after the exam) and T3 (two years later). Early and delayed heart/mediastinum (H/M) ratios and washout rate (WR) were analyzed. RESULTS: Myocardial scintigraphy showed impaired MIBG uptake in 12 out of 15 patients with a definite PD diagnosis, while normal uptake was found in 20 of 26 patients with no-PD. Early and delayed H/M ratios were significantly lower in PD compared to overall no-PD patients and MSA patients. 123I-MIBG myocardial scintigraphy was abnormal in all PD patients with dysautonomia. After 123I-MIBG myocardial scintigraphy (T2), in 9 patients (22%) an improvement of diagnostic accuracy was reached. CONCLUSIONS: Diagnostic accuracy of myocardial scintigraphy in distinguishing PD from atypical parkinsonism was suboptimal. Nevertheless, this study confirmed the relevance of 123I-MIBG myocardial scintigraphy for the discrimination of PD from atypical parkinsonism, especially when dysautonomic symptoms are present.

A case of primary cardiac sarcoma with an acute presentation: The role of multimodality imaging.

The case highlights the value of contrast echocardiography in raising clinical suspicion of malignancy, allowing a diagnostic work-up and the treatment of the primitive heart tumors.

ASL MRI and 18F-FDG-PET in autoimmune limbic encephalitis: clues from two paradigmatic cases.

BACKGROUND: Autoimmune limbic encephalitis (LE) is a neurological condition characterized by seizures and cognitive dysfunction. Fluorine-18 fluorodeoxyglucose (18F-FDG-PET) has recently proved to be an important diagnostic tool in this condition since it may highlight brain metabolism abnormalities in a very early stage of the disease. Two main 18F-FDG-PET patterns have been described: the mixed hypermetabolic/hypometabolic and the neurodegenerative one. Arterial spin labeling (ASL) is an MRI technique showing brain perfusion, rarely used in autoimmune neurological conditions. The aim of the present study was to study patients with LE with both techniques, in order to compare their results. METHODS: Two patients with LE underwent to 18F-FDG-PET and ASL MRI scans using the pseudo-continuous arterial spin labeling (PCASL) technique. Areas of altered perfusion and metabolism were analyzed by visual inspection, and findings were compared between the two techniques. RESULTS: In the first patient, a relapsing LGI-1 LE, right hippocampal hypermetabolism was detected by 18F-FDG-PET (mixed hypermetabolic/hypometabolic pattern), while ASL MRI showed right hippocampal increased perfusion. In the second patient, a seronegative LE, 18F-FDG-PET scan detected a left hemispheric hypoperfusion (neurodegenerative pattern) and ASL MRI yielded similar results. The two 18F-FDG-PET patterns of altered metabolism were similarly detected by ASL imaging. CONCLUSION: ASL and 18F-FDG-PET findings are strongly concordant in LE. ASL imaging was able to detect the two main 18F-FDG-PET patterns previously described in patients with LE.

Management of abdominal aortic prosthetic graft and endograft infections. A multidisciplinary update.

Abdominal aortic graft infections (AGIs) occur in 1-5% of aortic prosthetic placements. It can result in limb amputation, pseudo-aneurysm formation, septic emboli, aorto-enteric fistulae, septic shock and death. The most frequently involved pathogens are methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci, followed by Enterobacteriaceae and uncommon bacteria. In case of gut involvement the presence of fungi has to be considered. Computed tomography angiography is actually the gold standard diagnostic imaging but magnetic resonance is a valid alternative. Nuclear medicine imaging is commonly used to improve sensitivity and specificity. Signs and symptoms are often aspecific and blood cultures can be negative, requiring alternative ways to detect the microorganism responsible for infection, such as 16S rRNA gene sequencing and molecular rapid diagnostic tests. Curative surgical intervention is the first choice approach, with in-situ reconstruction providing by far the best outcome and xenopericardial bovine patch as a promising option. For patients unable to undergo major surgery, the outcome of conservative approach remains uncertain but usually provides for life-long suppressive therapy. However, in selected cases an attempt of stopping antibiotic treatment after 3-6 months can be done. Given the difficulty in their management, we performed a review of AGIs, in order to raise awareness on clinical presentation, current available diagnostic tools, prophylaxis, surgical and anti-infective treatment of AGIs.

Connected Speech Deficit as an Early Hallmark of CSF-defined Alzheimer's Disease and Correlation with Cerebral Hypoperfusion Pattern.

BACKGROUND: Diagnosis of prodromal Alzheimer's disease (AD) still represents a hot topic and there is a growing interest for the detection of early and non-invasive biomarkers. Although progressive episodic memory impairment is the typical predominant feature of AD, communicative difficulties can be already present at the early stages of the disease. OBJECTIVE: This study investigated the narrative discourse production deficit as a hallmark of CSFdefined prodromal AD and its correlation with cerebral hypoperfusion pattern. METHODS: Narrative assessment with a multilevel procedure for discourse analysis was conducted on 28 subjects with Mild Cognitive Impairment (15 MCI due to AD; 13 MCI non-AD) and 28 healthy controls. The diagnostic workup included CSF AD biomarkers. Cerebral hypoperfusion pattern was identified by SPECT image processing. RESULTS: The results showed that the discourse analysis of global coherence and lexical informativeness indexes allowed to identify MCI due to AD from MCI non-AD and healthy subjects. These findings allow to hypothesize that the loss of narrative efficacy could be a possible early clinical hallmark of Alzheimer's disease. Furthermore, a significant correlation of global coherence and lexical informativeness reduction with the SPECT hypoperfusion was found in the dorsal aspect of the anterior part of the left inferior frontal gyrus, supporting the hypothesis that this area has a significant role in communicative efficacy, and in particular, in semantic selection executive control. CONCLUSION: This study contributes to the understanding of the neural networks for language processing and their involvement in prodromal Alzheimer's disease. It also suggests an easy and sensitive tool for clinical practice that can help identifying individuals with prodromal Alzheimer's disease.