Carfilzomib, lenalidomide, dexamethasone (KRD) in BTKi relapsed or refractory mantle cell lymphoma: A phase II study from Fondazione Italiana Linfomi.

Mantle cell lymphoma (MCL) is a rare lymphoproliferative neoplasm considered incurable, with a median survival of 3-5 years. In recent years, Bruton's tyrosine kinase inhibitors (BTKi) have been introduced, demonstrating high therapeutic activity. However, the prognosis for MCL patients failing ibrutinib therapy is particularly poor, with a survival expectation of a few months. In this phase II trial, we assessed the efficacy and safety of the carfilzomib-lenalidomide-dexamethasone (KRD) combination in MCL patients who were relapsed/refractory (R/R) or intolerant to BTKi and in need of treatment. The primary objective of the study was to evaluate the antitumor efficacy of the KRD combination in terms of 12-month overall survival (12-month OS). From September 2019 to December 2020, 16 patients were enrolled from 11 Italian centers. After a median follow-up of 2.37 months (95% CI 0.92-6.47), the 12-month OS was 13%. The rate of grade 3-4 adverse events (AEs) was 35%, and the overall response rate (ORR) was 19%. These results led to the premature termination of enrollment, as defined in the protocol stopping rules. The efficacy of the KRD combination in advanced-stage MCL patients who are R/R to BTKi is unsatisfactory and too toxic.

Implementing Enhanced Recovery After Surgery for hysterectomy in a hospital network with audit and feedback: A stepped-wedge cluster randomised trial.

OBJECTIVE: To evaluate the effectiveness of implementing the Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing elective hysterectomy in a network of regional hospitals, supported by an intensive audit-and-feedback (A&F) approach. DESIGN: A multi-centre, stepped-wedge cluster randomised trial (ClinicalTrials.gov NCT04063072). SETTING: Gynaecological units in the Piemonte region, Italy. POPULATION: Patients undergoing elective hysterectomy, either for cancer or for benign conditions. METHODS: Twenty-three units (clusters), stratified by surgical volume, were randomised into four sequences. At baseline (first 3 months), standard care was continued in all units. Subsequently, the four sequences implemented the ERAS protocol successively every 3 months, after specific training. By the end of the study, each unit had a period in which standard care was maintained (control) and a period in which the protocol, supported by feedback, was applied (experimental). MAIN OUTCOME MEASURES: Length of hospital stay (LOS), without outliers (>98th percentile). RESULTS: Between September 2019 and May 2021, 2086 patients were included in the main analysis with an intention-to-treat approach: 1104 (53%) in the control period and 982 (47%) in the ERAS period. Compliance with the ERAS protocol increased from 60% in the control period to 76% in the experimental period, with an adjusted absolute difference of +13.3% (95% CI 11.6% to 15.0%). LOS, moving from 3.5 to 3.2 days, did not show a significant reduction (-0.12 days; 95% CI -0.30 to 0.07 days). No difference was observed in the occurrence of complications. CONCLUSIONS: Implementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance, but without meaningful effects on LOS and complications. This study confirms the effectiveness of A&F in promoting important innovations in an entire hospital network and suggests the need of a higher compliance with the ERAS protocol to obtain valuable improvements in clinical outcomes.

Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial.

BACKGROUND: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. METHODS: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. RESULTS: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. CONCLUSIONS: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020.

Unwanted Memory Intrusions Recruit Broad Motor Suppression.

Quickly preventing the retrieval of (inappropriate) long-term memories might recruit a similar control mechanism as rapid action-stopping. A very specific characteristic of rapid action-stopping is "global motor suppression": When a single response is rapidly stopped, there is a broad skeletomotor suppression. This is shown by the technique of TMS placed over a task-irrelevant part of the primary motor cortex (M1) to measure motor-evoked potentials. Here, we used this same TMS method to test if rapidly preventing long-term memory retrieval also shows this broad skeletomotor suppression effect. Twenty human participants underwent a Think/No-Think task. In the first phase, they learned word pairs. In the second phase, they received the left-hand word as a cue and had to either retrieve the associated right-hand word ("Think") or stop retrieval ("No-Think"). At the end of each trial, they reported whether they had experienced an intrusion of the associated memory. Behaviorally, on No-Think trials, they reported fewer intrusions than Think trials, and the reporting of intrusions decreased with practice. Physiologically, we observed that the motor-evoked potential, measured from the hand (which was irrelevant to the task), was reduced on No-Think trials in the time frame of 300-500 msec, especially on trials where they did report an intrusion. This unexpected result contradicted our preregistered prediction that we would find such a decrease on No-Think trials where the intrusion was not reported. These data suggest that one form of executive control over (inappropriate) long-term memory retrieval is a rapid and broad stop, akin to action-stopping, that is triggered by the intrusion itself.

Effects of treatments on gonadal function in long-term survivors of pediatric hematologic malignancies: A cohort study.

BACKGROUND: Potentially gonadotoxic protocols are currently used for the treatment of childhood hematologic malignancies. This study aims to evaluate the prevalence of gonadal dysfunction and the most important associated risk factors in a cohort of hematologic malignancy survivors. PROCEDURE: We considered all patients referred to our long-term follow-up clinic for childhood cancer survivors, between November 2001 and December 2017. Inclusion criteria were: (a) previous diagnosis of hematologic malignancy; (b) age at hematologic malignancy diagnosis < 18 years; (c) at least five years after the end of anticancer treatments; (d) at least one evaluation of gonadal function after the 18th birthday. Patients diagnosed before January 1, 1990, were excluded. RESULTS: Three hundred twenty-seven survivors (males = 196) were included. Isolated spermatogenesis damage was found in 58/196 (29.6%) of males, whereas 18/196 (9.2%) had Leydig cell failure. In females, 35/131 (26.7%) experienced premature ovarian insufficiency. In both sexes, abdominopelvic irradiation and hematopoietic stem cell transplantation were strongly associated with the risk of gonadal dysfunction. For every 1000 mg/m2 increase in cyclophosphamide-equivalent dose exposure, the risk of spermatogenesis damage increased 1.52-fold and that of Leydig cell failure increased 1.34-fold, whereas the risk of premature ovarian insufficiency increased 1.80-fold. About 30% of those males who developed Leydig cell failure did so more than five years after the end of treatments. CONCLUSIONS: Gonadal dysfunction is still a significant late effect of therapies for pediatric hematologic malignancies. In males, the reevaluation of Leydig cell function may be useful even several years after the exposure to gonadotoxic treatments.

Preventing a Thought from Coming to Mind Elicits Increased Right Frontal Beta Just as Stopping Action Does.

In the stop-signal task, an electrophysiological signature of action-stopping is increased early right frontal beta band power for successful vs. failed stop trials. Here we tested whether the requirement to stop an unwanted thought from coming to mind also elicits this signature. We recorded scalp EEG during a Think/No-Think task and a subsequent stop signal task in 42 participants. In the Think/No-Think task, participants first learned word pairs. In a second phase, they received the left-hand word as a reminder and were cued either to retrieve the associated right-hand word ("Think") or to stop retrieval ("No-Think"). At the end of each trial, participants reported whether they had experienced an intrusion of the associated memory. Finally, they received the left-hand reminder word and were asked to recall its associated target. Behaviorally, there was worse final recall for items in the No-Think condition, and decreased intrusions with practice for No-Think trials. For EEG, we reproduced increased early right frontal beta power for successful vs. failed action stopping. Critically, No-Think trials also elicited increased early right frontal beta power and this was stronger for trials without intrusion. These results suggest that preventing a thought from coming to mind also recruits fast prefrontal stopping.

[Covid-19 and clinical-epidemiological research in Italy: proposal of a research agenda on priority topics by the Italian association of epidemiology]. / Covid-19 e ricerca clinico-epidemiologica in Italia: proposta di un'agenda di ricerca su temi prioritari da parte dell'Associazione italiana di epidemiologia.

BACKGROUND: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts or case-control studies). OBJECTIVES: in response to the fragmented and uncoordinated research production on Covid-19, the   italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology. METHODS: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges. RESULTS: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis, interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography. CONCLUSIONS: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.

Clinical and epidemiological characteristics associated with pneumonia at disease onset in patients admitted for COVID-19 to the Emergency Department of a large Hospital in Piedmont (North-Western Italy).

OBJECTIVES: to explore clinical and epidemiological characteristics associated with an imaging feature of COVID-19 pneumonia at disease onset, in order to identify factors that may be evaluable by general practitioners at patient's home, and which may lead to identify a more severe disease, needing hospitalization. DESIGN: this is a retrospective/prospective observational hospital cohort. SETTING AND PARTICIPANTS: the study population includes all patients consecutively admitted to the emergency department of Città della salute e della scienza University Hospital from 01.03 to 31.05.2020 with a confirmed diagnosis of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: patients were classified in two groups according to the findings of X-ray imaging, lung ultrasound and chest computer tomography, as pneumonia or not pneumonia patients. RESULTS: in multivariable analysis, factors most strongly associated with emergency department admission with pneumonia were age, oxygen saturation <90% (adj OR 4.16 ;95%CI 1.44-12.07), respiratory rate >24 breaths/min (adj OR 6.50; 95%CI 2.36-17.87), fever ≥38° (adj OR 3.05; 95%CI 1.53-6.08) and the presence of gastroenteric symptoms (vomiting and diarrhea). A delay (> 7 days) between the appearance of the initial lung symptoms (cough and dyspnea) and the admission to the emergency department was also related to a higher probability of receiving a positive imaging report (OR 4.99; 95%CI 2,02-12,34). CONCLUSIONS: in order to reorganize the management of COVID-19 patients in Italy, in view of the risk of a second wave of epidemic or of local outbreaks, it would be desirable to relocate the triage, and possibly the patient's care, from hospital to home. In this scenario it is important to identify all symptoms and signs associated with COVID-19 pneumonia that would facilitate the decision-making process of GPs leading to patients hospitalization.

Prevalence of periodontitis: misclassification, under-recognition or over-diagnosis using partial and full-mouth periodontal examination protocols.

OBJECTIVE: The aim of this cross-sectional study was to assess the bias in estimating the prevalence of periodontitis due to partial-mouth periodontal examination protocols (PMPE) and to relate the severity and extent of periodontal damage to periodontitis misclassification when applying case definitions by Centres of Disease Control and Prevention and American Academy of Periodontology (CDC/AAP). MATERIALS AND METHODS: A full-mouth periodontal examination (FMPE) was performed in 721 adults living in North Italy to identify moderate and severe periodontitis. These results were compared with those obtained with two PMPE protocols analyzing two interproximal sites on all teeth (fMB-DL) or four interproximal sites in two random diagonal quadrants (pMDB-MDL). RESULTS: Both PMPE systems estimated the prevalence of moderate periodontitis with limited bias (-2.79% for pMDB-MDL and -3.49% for fMB-DL), whereas produced larger relative biases for severe periodontitis (-28.74% versus - 14.55%). The percentage of under-recognition of existing periodontal disease was 8.9% under fMB-DL and 15.5% under pMDB-MDL. The diagnosis of moderate and severe periodontal disease was correctly assigned to individuals with on average 8% and 30% of pathological sites, respectively. CONCLUSION: These findings suggest that PMPE systems provide high level of bias when using CDC/AAP case definitions.

Prevalence estimation of halitosis and its association with oral health-related parameters in an adult population of a city in North Italy.

AIM: No epidemiological data on halitosis are available from Italy. Thus, the aim of this population-based cross-sectional study was to estimate the prevalence of halitosis in an urban adult population from North Italy and to explore related oral risk indicators. MATERIALS AND METHODS: The survey used a two-stage probability sampling method to collect a representative sample of inhabitants, aged between 20 and 75 years, in the city of Turin. Seven hundred and forty-four adults were clinically examined (47% of sampled subjects) for oral malodor and periodontal conditions. Using a standardized questionnaire social, health and halitosis-related parameters were collected. Logistic models with interaction terms between tongue coating scores (TCS) and periodontal status were used to explore halitosis risk indicators. RESULTS: The prevalence estimate of halitosis according to the organoleptic assessment was 53.51% (95% CI: 48.55-58.50). A statistically significant correlation was found between organoleptic and gas chromatography measurements (p < 0.0001). Stronger associations between halitosis and periodontitis were observed in people having higher TCS: adjusted odds ratio considering low and high TCS in individuals with severe periodontitis were 2.95 and 20.77 (p ≤ 0.003). CONCLUSIONS: Due to the high prevalence of halitosis in the Turin population, its diagnosis and management should be incorporated in comprehensive dental care.

Prevalence of periodontitis in an adult population from an urban area in North Italy: findings from a cross-sectional population-based epidemiological survey.

AIM: There is a paucity of up-to-date data regarding prevalence and risk indicators of periodontitis in Italy. Therefore, the aim of this study was to evaluate the prevalence of periodontitis and its risk indicators among adults from an urban area in North Italy. MATERIAL AND METHODS: This cross-sectional survey used a stratified two-stage probability sampling method to draw a representative sample of the adult population of the city of Turin. About 1600 individuals, 20-75 years old, were randomly selected and 736 subjects agreed to participate (47% of the sampled subjects). Clinical parameters were assessed using a full-mouth protocol. Logistic models were applied to assess associations between periodontitis and its putative risk indicators. Age was included as restricted cubic spline. RESULTS: Based on CDC/AAP case definition, the prevalence estimates of severe and moderate periodontitis were 34.94% (95% CI: 31.23-38.74) and 40.78% (95% CI: 36.89-44.79). The probability of periodontitis increased in smokers (adjusted OR 2.06, 95% IC: 1.26-3.37, p = 0.004) and with age but leveled off in the 50+ year-old group (p < 0.001). CONCLUSION: Periodontitis was highly prevalent in the Turin population. The present data will enable development of appropriate public health programs and allocation of resources.

X-ray, CT and DXA study of bone loss on medieval remains from North-West Italy.

PURPOSE: The aim of this study was to investigate whether the population differences in osteoporosis observed nowadays is a reflection of the times and modern lifestyle factors, or whether they were also present in the past. MATERIALS AND METHODS: The study was performed on the skeletal remains of medieval and post-medieval populations from a burial ground in the North-West of Italy. Some individuals had been buried inside the church (privileged subjects), others outside in the parvis (members of rural population), and others still to the north of the church. X-ray, computed tomography and dual-energy X-ray absorptiometry studies were carried out on the lumbar spines and/or femurs of 27 male and 28 female individuals to determine any associations between cortical index, bone mineral density (BMD), gender, age and social status. RESULTS: No statistically significant differences were observed in cortical index values according to gender, age or place of burial. Conversely, statistically significant differences in average BMD values were observed according to place of burial; in particular, among those buried inside the church, a lower BMD was observed compared to the parvis group (1.09 vs. 1.42, p < 0.001) and the north group (1.09 vs. 1.49, p < 0.001). CONCLUSIONS: The differences observed in the BMD values may be related to the different lifestyle of the rural population, i.e. more dietary calcium intake, more sun exposure and vigorous physical activity, compared to that of the privileged individuals.

Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology).

The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM were enrolled. The authors observed a 6-month PFS rate of 42.6% (95% CI 29.3-55.2) and a median PFS of 5.2 months (95% CI 3.8-6.6). The median OS was 9.1 months (95% CI 7.3-10.3). Twenty-eight patients (52%) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60%). MGMT promoter methylation was significantly associated with improved PFS in univariate analysis. Most unifocal tumors at baseline had a focal enhancing progression (76%), while the diffuse non-enhancing progression accounted for 9.5%. Response or survival were not associated with any pattern of progression. Survival after failure of treatment was short. Twelve out of 54 patients (22%) discontinued fotemustine for grade 3/4 myelotoxicity, while 4/54 (7.4%) discontinued bevacizumab. This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs.

MGMT promoter methylation in plasma of glioma patients receiving temozolomide.

Promoter methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene plays a role in cellular response to alkylating agents. In the present study aimed to: (i) evaluate the concordance between MGMT promoter methylation status in tumor tissue and plasma; (ii) monitor MGMT promoter methylation status in plasma taken before and during temozolomide treatment; (iii) explore the value of MGMT promoter methylation status in plasma as a prognostic/predictive biomarker in glioma patients. We enrolled 58 patients with histologically confirmed glioma at different grades of malignancy. All patients underwent surgical resection and temozolomide treatment. Paraffin-embedded tumor tissue was available for 48 patients. Blood samples were collected from all patients before temozolomide treatment (baseline) and at each MRI examination for a 12-month period. MGMT promoter methylation status was assessed in both sample types by real time PCR with a specific probe. The frequency of MGMT promoter methylation was 60.4 % in tumor tissue and 41.38 % in plasma. MGMT promoter methylation status was concordant in the two sample types (Kappa = 0.75, 95 % confidence interval (CI) 0.57-0.93; p value <0.001). Overall and progression-free survival were longer in patients with methylated MGMT promoter. Mortality was higher in patients with unmethylated MGMT promoter, whether in tumor tissue [hazard ratio (HR) 2.21; 95 % CI 0.99-4.95] or plasma (HR 2.19; 95 % CI 1.02-4.68). Progression-free survival was shorter in patients with unmethylated MGMT promoter, whether in tissue (HR 2.30; 95 % CI 1.19-4.45) or plasma (HR 1.77; 95 % CI 0.95-3.30). The cumulative incidence of unmethylated MGMT promoter in plasma at baseline was 58 %, and reached virtually 100 % at 12 months. In conclusion MGMT promoter methylation status in tumor tissue and plasma was highly concordant, and both were associated with longer survival, supporting the role of the detection of methylated MGMT promoter in predicting treatment response. However we suggest caution in using plasma as a surrogate of tumor tissue due to possible false-negative results.

Implementation of an enhanced recovery after surgery protocol for colorectal cancer in a regional hospital network supported by audit and feedback: a stepped wedge, cluster randomised trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are known to potentially improve the management and outcomes of patients undergoing colorectal surgery, with limited evidence of their implementation in hospital networks and in a large population. We aimed to assess the impact of the implementation of an ERAS protocol in colorectal cancer surgery in the entire region of Piemonte, Italy, supported by an audit and feedback (A&F) intervention. METHODS: A large, stepped wedge, cluster randomised trial enrolled patients scheduled for elective surgery at 29 general surgery units (clusters). At baseline (first 3 months), standard care was continued in all units. Thereafter, four groups of clusters began to adopt the ERAS protocol successively. By the end of the study, each cluster had a period in which standard care was maintained (control) and a period in which the protocol was applied (experimental). ERAS implementation was supported by initial training and A&F initiatives. The primary endpoint was length of stay (LOS) without outliers (>94th percentile), and the secondary endpoints were outliers for LOS, postoperative medical and surgical complications, quality of recovery and compliance with ERAS items. RESULTS: Of 2626 randomised patients, 2397 were included in the LOS analysis (1060 in the control period and 1337 in the experimental period). The mean LOS without outliers was 8.5 days during the control period (SD 3.9) and 7.5 (SD 3.5) during the experimental one. The adjusted difference between the two periods was a reduction of -0.58 days (95% CI -1.07, -0.09; p=0.021). The compliance with ERAS items increased from 52.4% to 67.3% (estimated absolute difference +13%; 95% CI 11.4%, 14.7%). No difference in the occurrence of complications was evidenced (OR 1.22; 95% CI 0.89, 1.68). CONCLUSION: Implementation of the ERAS protocol for colorectal cancer, supported by A&F approach, led to a substantial improvement in compliance and a reduction in LOS, without meaningful effects on complications. Trial registration number NCT04037787.

Persistent type II endoleak: two cases of successful sacotomy.

Endovascular treatment of persistent type II endoleak may not resolve the complication. We report two cases of sacotomy performed to treat this problem: the first case was in an emergency setting for aneurismal sac rupture, and the second occurred in an elective surgery setting after several unsuccessful endovascular procedures. In both cases, sacotomy allowed us identify the bleeding sources without aortic cross-clamping and endograft explantation. By minimizing hemodynamic modifications and reducing operative time, this procedure can be carried out even in patients considered unfit for surgery. Sacotomy could be considered as an alternative in selected cases of persistent type II endoleak with aneurysm sac enlargement.

Carotid artery free-floating thrombus caused by paradoxical embolization from greater saphenous vein ascending thrombophlebitis.

Stroke of unknown origin in young patients is seen to be closely correlated with patent foramen ovale (PFO) than stroke in patients with established stroke mechanisms. We report a case of a young woman without cardiovascular risk factors who was admitted to our emergency department with listlessness and altered mental status. The clinical examination revealed right lower limb swelling. Magnetic resonance imaging and contrast-enhanced computed tomographic scans revealed a free floating thrombus of the left internal carotid artery (ICA) with a large bilateral frontal ischemic lesion. The diagnosis of a medium-sized PFO with moderate right-to-left contrast shunting was made after transesophageal echocardiography. No other cardiac sources for embolization were detected, while an ascending thrombophlebitis of the right greater saphenous vein was detected by venous Doppler ultrasonography. These findings support the diagnosis of ICA free-floating thrombus caused by paradoxical embolization (via the PFO) of clot from the greater saphenous vein. The patient underwent emergency saphenofemoral disconnection with femoral vein thrombectomy and subsequently carotid artery thrombectomy under general anesthesia. No carotid atheromatous wall lesions were detected at surgical exploration; no immunologic pathology, hypercoagulable status, or malignancy were recorded. No hemorrhagic cerebral complications were observed in the postoperative period, and the patient had an improvement of her neurologic status (a reduction of the National Institutes of Health Stroke Scale score from 7 to 3). Her recovery was uneventful. The patient was transferred for rehabilitation on postoperative day 5 with oral anticoagulation. Six-month ultrasound follow-up revealed deep and superficial venous system and carotid artery patency. The patient was asymptomatic and anticoagulation was discontinued. Paradoxical cerebral embolization through a PFO is a rare phenomenon that, in our patient, appeared to have resulted in stroke caused by a free-floating thrombus in the ICA. Accurate evaluation of carotid and lower limb veins by duplex scan is mandatory in cases of stroke of unknown origin, and urgent surgical repair can be useful in order to improve the clinical outcome.

Large aortic pseudoaneurysm and subsequent spondylodiscitis as a complication of endovascular treatment of iliac arteries.

Both aortic pseudoaneurysm following endovascular aortoiliac reconstruction and spondylodiscitis subsequent to endograft infections are rare complications. We present a case of aortic false aneurysm following iliac arteries treatment complicated by spondylodiscitis after its endovascular repair. In this patient, a huge aortic pseudoaneurysm was diagnosed and treated in an emergency setting a few days after the procedure. A left aortomonoiliac endograft was placed and a femoro-femoral crossover bypass was performed. Afterward, the patient developed a stent graft infection and a lumbar spondylodiscitis. The patient was managed with a conservative treatment and, after 4 years, he continues to live. Analyzing this case, we would like to point out the following aspects: any procedure, although well established and technically simple, can cause life-threatening complications; hematomas resulting from endovascular exclusion of large pseudoaneurysms could be drained, to prevent bacterial infections.

Light Scattering Technology and MALDI-TOF MS in the microbiological fast-track of bloodstream infections: potential impact on antimicrobial treatment choices in a real-life setting.

Introduction. Rapid identification (ID) and antimicrobial susceptibility testing (AST) of bloodstream infections (BSI) pathogens are fundamental to switch from empirical to targeted antibiotic therapy improving patients outcome and reducing antimicrobial resistance spreading.Hypothesis. The adoption of a rapid microbiological protocol (RP) based on Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS) and Light Scattering Technology (LST) for rapid diagnosis of BSI could positively impact on patients' antimicrobial management.Aim. The study aim was to evaluate a RP for BSI microbiological diagnosis in terms of accuracy, turnaround time (TAT) and potential therapeutic impact.Methodology. A prospective observational study was conducted: monomicrobial bacterial blood cultures of septic patients were analysed in parallel by RP and standard protocol (SP). In RP the combination of MALDI-TOF MS and LST was used for rapid ID and AST assessments, respectively. To determine the potential impact of RP on antimicrobial therapy management, clinicians were interviewed on therapeutic decisions based on RP and SP results. RP accuracy, TAT and impact were evaluated in comparison to SP results.Results. A total of 97 patients were enrolled. ID and AST concordance between RP and SP were 96.9 and 94.7 %, respectively. RP technical and real-life TAT were lower than SP (6.4 h vs. 18.4 h; 9.5 vs. 27.1 h). The agreement between RP- and SP-based therapeutic decisions was 90.7 (90 % CI 84.4-95.1). RP results could produce 24/97 correct antibiotic changes with 18/97 possible de-escalations and 25/97 prompt applications of infection control precautions.Conclusion. With the application of RP in BSI management, about one-fourth of patients may safely benefit from early targeted antibiotic therapy and infection control policies with one working day in advance in comparison to conventional methods. This protocol is feasible for clinical use in microbiology laboratories and potentially helpful for Antimicrobial Stewardship.