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Background: The elderly is characterized by a gradual decline in body function, which represents the clinical situation called "frailty". Prefrailty is the intermediate stage between frailty and the robust condition. L-carnitine (LC) plays an important role in energy production from long-chain fatty acids in mitochondria and its serum level is lower in prefrail and frail subjects. Objective: This study aims to evaluate the effect of Acetyl-L-carnitine (ALCAR) in pre frail older patients. Methods: We scheduled 3 months of treatment and then 3 months of follow-up. 92 subjects were selected from May 2009 to July 2017 in a randomized, observational, double-blind, placebo-controlled study. We scheduled 3 months of treatment and then 3 months of follow-up. ALCAR (oral 1.5 g/bis in die - BID) or placebo group. Results: After the treatment, only the treated group displayed a decrease in C reactive protein (CRP) p Conclusions: ALCAR treatment delays the incidence and severity of onset in prefrail subjects of degenerative disorders of the elderly, with improvement in memory and cognitive processes.

Frailty is an expression that reconciles and condenses loss of autonomy, both physical and cognitive decline and a wide spectrum of adverse outcomes due to aging. The decrease in physical and cognitive activity is associated with altered mitochondrial function, and energy loss and consequently morbidity and mortality. In this cross-sectional study, we evaluated the carnitine levels in frailty status. The mean serum concentrations of total carnitine (TC) were lower in frail elderly subjects than in prefrail ones (p = 0.0006), higher in frail vs. robust subjects (p &lt, 0.0001), and higher in prefrail vs. robust subjects (p &lt, 0.0001). The mean serum concentrations of free carnitine (FC) were lower in frail elderly subjects than in prefrail ones (p &lt, 0.0001), lower in frail vs. robust subjects (p &lt, 0.0001) and lower in prefrail vs. robust subjects (p = 0.0009). The mean serum concentrations of acylcarnitine (AC) were higher in frail elderly subjects than in prefrail ones (p = 0.054) and were higher in pre-frail vs. robust subjects (p = 0.0022). The mean urine concentrations of TC were lower in frail elderly subjects than in prefrail ones (p &lt, 0.05) and lower in frail vs. robust subjects (p &lt, 0.0001). The mean urine concentrations of free carnitine were lower in frail elderly vs. robust subjects (p &lt, 0.05). The mean urine concentrations of acyl carnitines were lower in frail elderly subjects than those in both prefrail (p &lt, 0.0001) and robust subjects (p &lt, 0.0001). Conclusion: high levels of carnitine may have a favorable effect on the functional status and may treat the frailty status in older subjects.

Background Portal vein thrombosis (PVT) occurs frequently in hepatocellular carcinoma (HCC) and is often diagnosed in the course of a routine patient evaluation and surveillance for liver cancer. The purpose of this study is to investigate the relationship between folate status and portal vein thrombosis. Methods HCC with PVT patients were 78, HCC without PVT were 60 and control subjects were 70 randomly selected. We evaluate serum and red blood cellular folate, homocysteine, alpha fetal protein cholesterol, triglycerides, prothrombin time. Results HCC patients with PVT showed lower levels of serum folate, respect HCC patients without PVT, with an average difference of 1.6 nmol/l p p p p p p Conclusion The low folate concentration and higher levels of homocysteine are associated with the loss of antithrombotic function, and with a more aggressive course of HCC and with a higher change of complications related to portal vein thrombosis

Background Portal vein thrombosis (PVT) is reported in 10–40% of hepatocellular carcinoma (HCC) patients. The development of PVT is a multifactorial process, resulting from a reduction in portal blood flow and hypercoagulability. Methods We evaluated 44 HCC patients with PVT, 50 HCC patients without PVT and 50 healthy subjects. Homocysteine (Hcy), Vitamin B6, Vitamin B12 and folate were measured. Results Hcy in HCC patients with PVT is significant higher than the patients without PVT and controls subjects. Conclusion Total Hcy is a sensitive marker of PVT in patients with HCC.

Lipoprotein (a) (Lp (a)) is a plasma lipoprotein consisting of a cholesterol rich LDL particle with one molecule of apolipoprotein B100 and one protein apolipoprotein (a) [apo(a)].

Background: Non-melanoma skin cancers (NMSC), despite having a favourable prognosis, present an increased risk of occult malignancies. The aim of this study was the evaluation of the usefulness of the mucinous marker carbohydrate 19-9 antigen (CA 19-9) in the diagnosis of occult cancers. (1) Patients and Methods: This is a case control study in which 480 patients with NMSC and 480 matched control subjects with dermatitis were enrolled, 208 patients with NMSC showed upper-normal CA 19-9 values, and 272 showed under-normal CA 19-9 values. (2) Results: The 208 patients positive for CA 19-9 included 87 with basal cell carcinoma (BCC) and 121 with squamous cell carcinoma (SCC). The 272 patients negative for CA 19-9 included 107 with BCC and 165 with SCC. For the SCC patients, CA 19-9 serum levels were significant in 121 of the patients (positive), 66 of which were affected by cancer, CA 19-9 was within the normal range in 165 patients, of which 30 were diagnosed with cancer. In the SCC patients, the CA 19-9 sensitivity was 68%, the specificity was 70%, the positive predictive value (PPV) was 54% (95%) and the negative predictive value (NPV) was 81%. In the BCC patients, the CA 19-9 sensitivity was 70%, the specificity was 66%, the PPV was 48% and the NPV was 83%. In the dermatitis patients (controls), we observed 121 patients that were CA 19-9 positive, with 15 malignancies, and 359 CA 19-9-negative patients, with three malignancies. (3) Conclusions: To confirm the association between CA 19-9 and an elevated risk of malignancies in NMSC, prospective cohort studies should be performed.

As natural systems continuously evolve, the human cooperation dilemma represents an increasingly more challenging question. Humans cooperate in natural and social systems, but how it happens and what are the mechanisms which rule the emergence of cooperation, represent an open and fascinating issue. In this work, we investigate the evolution of cooperation through the analysis of the evolutionary dynamics of behaviours within the social network, where nodes can choose to cooperate or defect following the classical social dilemmas represented by Prisoner’s Dilemma and Snowdrift games. To this aim, we introduce a sociological concept and statistical estimator, “Critical Mass”, to detect the minimum initial seed of cooperators able to trigger the diffusion process, and the centrality measure to select within the social network. Selecting different spatial configurations of the Critical Mass nodes, we highlight how the emergence of cooperation can be influenced by this spatial choice of the initial core in the network. Moreover, we target to shed light how the concept of homophily, a social shaping factor for which “birds of a feather flock together”, can affect the evolutionary process. Our findings show that homophily allows speeding up the diffusion process and make quicker the convergence towards human cooperation, while centrality measure and thus the Critical Mass selection, play a key role in the evolution showing how the spatial configurations can create some hidden patterns, partially counterbalancing the impact of homophily.

Background: Portal vein thrombosis (PVT) is a common complication of endstage hepatocellular carcinoma (HCC). : The aim of our study was to evaluate the role of Homocysteine (Hcy) in HCC patient with PVT. Hcy is a sulphur amino-acid involved in two pathways, trans-sulphuration and remethylation, that involve vitamins B6, B12 and folates. Methods: We recruited 54 patients with HCC and PVT, 60 patients with HCC and without PVT and 60 control subjects. We measured serum levels of Hcy, folate, vitamins B6 and B12. Results: The comparison between HCC patients with PVT versus HCC without PVT was shown that mean values of Hcy were 6.4 nmol/L (p Conclusion: High serum levels of Hcy are an established thrombotic risk factor in the general population. We found significantly higher levels of Hcy in HCC patients with PVT versus both HCC patients without PVT and controls.

Michele Malaguarnera,1,2 Saverio Latteri,3 Gaetano Bertino,4 Roberto Madeddu,5 Vito Emanuele Catania,3 Giuseppe Currò,6 Antonio Maria Borzì,2 Filippo Drago,1 Giulia Malaguarnera1 1Department of Biomedical and Biotechnological Science, University of Catania, Catania, Italy; 2Research Center “The Great Senescence”, University of Catania, Catania, Italy; 3Department of Medical, Surgical Sciences and Advanced Technologies “Gian Filippo Ingrassia”, University of Catania, Catania, Italy; 4Department of Experimental and Clinical Medicine, University of Catania, Catania, Italy; 5Department of Biomedical Sciences, University of Sassari, Sassari, Italy; 6Department of Human Pathology, University of Messina, Messina, Italy Purpose: Portal vein thrombosis (PVT) is one of the severe complications of hepatocellular carcinoma (HCC). PVT deteriorates the liver, and its dysfunction increases the risk of bleeding, influencing the prognosis of patients with liver cirrhosis and HCC. The aim of our study was to investigate whether D-dimer testing could be a sensitive marker for the diagnosis and prognosis of HCC patients with PVT.Patients and methods: Between June 2010 and December 2015, 118 HCC patients were admitted to Cannizzaro Hospital, Catania, and 50 controls were recruited from their relatives for health examinations. All enrolled patients were diagnosed and pathologically confirmed as having HCC. D-dimer was measured with an enzyme-linked immunosorbent assay using 2 monoclonal antibodies against nonoverlapping determinants of D-dimer.Results: D-dimer levels in HCC patients with PVT were significantly higher vs HCC patients without PVT, P

Background: Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in the foetal colon, some benign conditions and different malignancies, particularly in colon adenocarcinoma. We focused this study on non-melanoma skin cancer (NMSC). NMSC is a common malignancy and it is an important source of morbidity and death in the world. In this study we evaluated whether CEA level increases in NMSC. Patients and Methods: A total of 566 patients with non-melanoma skin cancer (NMSC) were enrolled; 286 patients with NMSC showed CEA levels above normal values, and 280 showed CEA levels below normal values. Patients with high levels of CEA underwent abdominal ultrasound, gastro endoscopy, colonoscopy, and abdominal CT scans. Results: We studied 566 patients, 286 were positive to CEA and 280 were negative. Of the 286 patients positive to CEA, 132 had basal cell carcinoma (64 patients had an associated cancer) and 154 had squamous cell carcinoma (75 patients were affected by cancer). Of the 280 patients negative to CEA, 130 had basal cell carcinoma (12 were associated with cancer), and 150 had squamous cell carcinoma (18 were associated with cancer). The mean age of the 566 case control subjects were 65–81 years. Of the 10 subjects that were the positive control for CEA, two had cancer. Of the 556 subjects that were the negative control for CEA, three had cancer. Conclusions: In patients that present high serum levels of CEA, we give attention to adenocarcinoma tumour first. The pattern of association may be attributable to bias because the group with NMSC were frequently evaluated than those with no history of NMSC. Our results showed that out of 286 patients that were CEA-positive, 139 had cancer, and of the 280 that were CEA-negative, 30 had cancer. Therefore, 20% of patients do not follow the trend. Other markers should be investigated.

Background Peripheral neuropathy after surgical treatment is an under recognized potential untoward event. Pelvic surgery may be associated with nerve lesions by essentially three main mechanisms: transection, entrapment and pressure-stretching; the latter is the modality most frequently linked to patient's positioning on the operating room table. Presentation of the case A 25 years old woman, after undergoing a laparoscopic gynaecologic procedure lasted >3 hours, on postoperative day one presented with numbness over her lateral right leg and dorsum of the foot, right foot drop and gait instability due to compression-stretching of the right superficial peroneal nerve. Discussion Patient's diagnostic work up, treatment and outcome are reported and measures on how to prevent the occurrence of such type of lesion are outlined together with the importance of an early postoperative diagnosis in order to avoid permanent nerve damage. Conclusion Such lesions are sometimes so unexpected that delayed diagnosis leads to damages which are difficult or impossible to repair. Primary prevention plays a key role and it is realized by adhering to specific protocols. In the occurrence of the lesion a prompt diagnosis is highly recommendable and a comprehensive therapeutic plan is necessary to correctly address the specific pathology., Highlights • After undergoing a laparoscopic gynaecologic procedure lasted >3 hours, a 25 years old woman presented peripheral neuropathy. • Pelvic surgery may be associated with nerve lesions by transection, entrapment and pressure-stretching. • Such lesions are unexpected and diagnosis is delayed to a point when the damage is difficult or impossible to repair. • The treatment should take in account genetical variations of the population and biochemical derangements.

Ultra-dense Networks are attracting significant interest due to their ability to provide the next generation 5G cellular networks with a high data rate, low delay, and seamless coverage. Several factors, such as interferences, energy constraints, and backhaul bottlenecks may limit wireless networks densification. In this paper, we study the effect of mobile node densification, access node densification, and their aggregation into virtual entities, referred to as virtual cells, on location privacy. Simulations show that the number of tracked mobile nodes might be statistically reduced up to 10 percent by implementing virtual cells. Moreover, experiments highlight that success of tracking attacks has an inverse relationship to the number of moving nodes. The present paper is a preliminary attempt to analyse the effectiveness of cell virtualization to mitigate location privacy threats in ultra-dense networks.

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome, caused by germline mutations in the adenomatous polyposis coli (APC) suppressor gene. Patients with colorectal polyps are more likely to develop a malignant condition with poor prognosis. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extra-colonic manifestations; an attenuated form of polyposis (AFAP), presenting less than 100 adenomas and later onset, has been reported.In this study we have examined five Sicilian families affected by FAP syndrome, in order to provide predictive genetic testing for the affected families, as well as to contribute to mutation catalog enrichment.We have detected different APC mutations in these five pedigrees, confirming the remarkable heterogeneity of the mutational spectrum in FAP.

HNPCC is an autosomal inherited cancer syndrome characterized by germinal and somatic mutations of DNA mismatch repair (MMR) genes. The inherited mutation in one allele together with an acquired defect in the other allele of an MMR gene leads to accelerate tumor progression.In this study we analyzed a cohort of 11 subjects belonging to four Sicilian families with HNPCC suspected by molecular analysis of coding regions of hMSH2 (NC_000002) and hMLH1 (NC_000003) genes.Molecular analysis has detected the presence of two mutations in gene MSH2 and one mutation in MHL1 gene. In addition, we found a novel mutation consisting in a G deletion at 914 codon of the exon 16 in the MSH2 gene. This deletion leads to a stop codon due to a frame-shift, resulting in a truncated protein.We extended genetic analysis to the other family members and the same mutation was detected in three sisters and in one of the two healthy daughters.This mutation is correlated with clinical findings revealed in genealogic tree and it represents a novel mutation responsible of HNPCC.

Background This case report describes a spontaneous tumor lysis syndrome due to a rare solid tumor. Case presentation A 65-year-old white woman had tumor lysis syndrome, which represent a dangerous oncological emergency. This syndrome occurs usually with a hematological tumor, but in this case our patient had a solid tumor, which was a rare extraskeletal osteosarcoma, localized in her pelvic region. She also had lung metastases and bilateral hydronephrosis. After spontaneous tumor lysis syndrome, she had acute renal insufficiency, which was treated with hemodialysis and successively with rasburicase, Kayexalate (sodium polystyrene sulfonate), and febuxostat. Conclusion Tumor lysis syndrome represents an oncological emergency, which must be suspected and treated as soon as possible.

Owing to complexity and difficulty regarding evaluation of all the regional lymph nodes, the Sentinel Lymph Node Biopsy (SLNB) has represented in recent years a suitable technique for setting lymph node status; it allows pathologists to focus on a small number of lymph nodes and stage patients with clinically negative lymph nodes; this sort of assessment leads surgeons to a correct approach; on the contrary, the presence of metastases makes advisable to perform Axillary Lymph Node Dissection (ALND).From September 2008 to December 2013, 142 patients suffering from breast cancer were enrolled. Mean age was 54 years (range 37-80), in 88 (62%) patients the lesion was localized to the right breast, while in the remaining 54 (38%) the disease was localized in the left breast. Also in 85 (60%) patients, the tumor involved the upper-outer quadrant, in 24 (17%) the lower external quadrant, in 19 (13%) the upper-inner quadrant and in the remaining 14 (10%) the inferior-internal quadrant.There were neither intra nor post-operative complications. The all removed breast lesions were histologically malignant: 99 (70%) patients had a histological diagnosis of invasive ductal, 30 (21%) of invasive lobular, 9 (6%) ductal in situ and 4 (3%) of mixed invasive cancer. Sentinel Lymph Node (SLN) was always identified and it was extemporaneously positive in 62 cases (44%): 40 cases had macro-metastatic involvement whereas the remaining 22 cases had micro-metastases only. The definitive histological examination confirmed the presence of micro-metastases in 18 cases, while in 2 cases there was a supra-staging to macro-metastases and in other 2 a sub-staging of Isolated Tumor Cells (ITC). None of the patients with micro-metastatic SLN involvement developed recurrence within 24 months, whereas only one patient died after one year owing to at distance dissemination.Lymph node status has increasingly been getting one of the most important prognostic factor. Consequently the bigger the tumor nodal involvement appears the worse the prognosis becomes. Our data confirm the main role of SLNB on managing surgical treatment of breast cancer.Biopsy, Breast cancer, Sentinel lymph node.

Nature shows as human beings live and grow inside social structures. This assumption allows us to explain and explore how it may shape most of our behaviours and choices, and why we are not just blindly driven by instincts: our decisions are based on more complex cognitive reasons, based on our connectedness on different spaces. Thus, human cooperation emerges from this complex nature of social network. Our paper, focusing on the evolutionary dynamics, is intended to explore how and why it happens, and what kind of impact is caused by homophily among people. We investigate the evolution of human cooperation using evolutionary game theory on multiplex. Multiplexity, as an extra dimension of analysis, allows us to unveil the hidden dynamics and observe non-trivial patterns within a population across network layers. More importantly, we find a striking role of homophily, as the higher the homophily between individuals, the quicker is the convergence towards cooperation in the social dilemma. The simulation results, conducted both macroscopically and microscopically across the network layers in the multiplex, show quantitatively the role of homophily in human cooperation.

Background: Since the survival rates of cancer have increased considerably, the long-term side effects of cancer and cancer-related treatments may impact survivors’ capability to regain normal lives. The aim of this study was to evaluate the effects of the breast cancer on the job satisfaction and the quality of life. Methods: We enrolled 130 women divided into four groups: 1) 40 breast cancer survivors (aged 39 - 50); 2) 44 women diagnosed with breast cancer (aged 35 - 49); 3) 46 women in good health status (aged 37 - 48). Job satisfaction was measured with the Warr-Cook-Wall (WCW) Job satisfaction scale that measures overall job satisfaction and satisfaction with nine aspects of work. Results: Compared to healthy subjects, breast cancer survivors reported a poorer number of hours of work (p < 0.05) and a significant amount of variety in job (p < 0.01), opportunity to use abilities (p < 0.001), income (p < 0.01). Compared to patients with breast cancer at diagnosis, breast cancer survivors reported a significant amount of variety in job (p < 0.05), opportunity to use abilities (p < 0.05), amount of responsibility (p < 0.05), income (p < 0.05). In our study, the comparison between breast cancer survivors, breast cancer at diagnosis, and healthy subjects does not differ significantly in overall job satisfaction. Conclusions: Understanding the job problems associated with cancer can provide relevant information regarding potential treatment and psychological support in breast cancer survivors.

Background: Although the majority of breast cancer patients are able to work, lower work ability and reduced job retention have been reported. The aim of the present study was to evaluate the effect of chemotherapy with capecitabine in patients with breast cancer on work productivity and daily activity. Methods: 34 patients with metastatic breast cancer were enrolled for our study. Capecitabine was given twice daily at a cumulative dose of 2500 mg/m2 on days 1 - 14 and repeated on day 22. Work productivity was determined using the WPAI questionnaire. Results: We observed an increase in absenteeism, presenteeism, work productivity loss and daily activity impairment after 1 cycle and 6 cycles of therapy, but we could not find statistically different significances. Conclusions: This study provides some data indicating an association between problems in breast cancer and work. Our results confirm that capecitabine may improve quality of life of patients with metastatic breast cancer.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The main risk factors for HCC are alcoholism, hepatitis B virus, hepatitis C virus, nonalcoholic steatohepatitis, obesity, type 2 diabetes, cirrhosis, aflatoxin, hemochromatosis, Wilson’s disease and hemophilia. Occupational exposure to chemicals is another risk factor for HCC. Often the relationship between occupational risk and HCC is unclear and the reports are fragmented and inconsistent. This review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem.

Malignant skin cancer of the scalp with skull invasion, dural infiltration and brain involvement is a uncommon lesion. This scenario is most often encountered in patients where initial scalp lesions are not appropriately diagnosed or their extent is underestimated by the patient and/or the doctor. Our study is a retrospective review of 25 patients treated using a multidisciplinary approach (combined plastic surgery/neurosurgery procedure and neuro-oncological management). After a mean follow-up of 7 years, 22 patients did not show local recurrence or distant metastases of their primary disease. Overall, these 22 patients had excellent quality of life; however, three patients died from causes not related to their primary pathology. To obtain a complete and definitive cure, prompt diagnosis of scalp cancers followed by appropriate multidisciplinary management is strongly advised.

The influence of ceftriaxone on oral and intestinal flora was investigated in 10 patients undergoing colorectal surgery. Ceftriaxone was given intravenously in one 2g dose before anesthesia. Saliva and feces samples were collected and analyzed on day 0, 3, 5, 14 and 28 after drug administration. All specimens were cultured quantitatively for aerobic and anaerobic microorganisms; representative colonies of each morphologic type of organism cultured were identified. The oral aerobic flora was somewhat affected by the administration of ceftriaxone. In all patients the number of Streptococci, Staphylococci and Neisseria decreased during the 5 days after ceftriaxone administration. No significant changes in the number of anaerobic commensal occurred. The oral microflora of all patients after 14 days had returned to normal. The aerobic fecal flora was considerably affected: in all patients enterobacteria were eliminated or strongly suppressed. Only minor changes in the number of aerobic gram-positive bacteria were observed, and the anaerobic intestinal flora showed only minor alterations. On day 28 the intestinal flora were normalized in all respects. No new colonizing microorganisms were isolated during the investigation period and no colonization with ceftriaxone-resistant bacteria was observed. No postoperative infection occurred and no adverse effects were registered.

The autors pointed out that contamination may be exogenous, as a result of invasive diagnostic techniques, patient preparation, surgery, catheter insertion and wound dressing, or endogenous, especiall

International audience; PURPOSE: Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU). METHODS: Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap). RESULTS: Six hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR\,>\,4), pulmonary embolism (OR\,>\,5) and increased PaCO(2). Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU). CONCLUSION: Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.

Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p

International audience; Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74–0.83) in the overall population, 0.74 (0.62–0.85) at internal validation and 0.71 (0.62–0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance.

Background The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population. Methods and results All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 μm (n = 206) versus 81 μm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint. After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 μm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005). Conclusion In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

International audience; Background: Weaning from mechanical ventilation is a challenging step during recovery from critical illness. Weaning failure or early reintubation are associated with increased morbidity and mortality, exposing patients to life-threatening complications. Cardiac dysfunction represents the most common cause of weaning failure. We conducted a systematic review and meta-analysis to evaluate the association between transthoracic echocardiographic parameters and weaning failure. Methods: We performed a systematic search of MEDLINE and EMBASE screening for prospective studies providing echocardiographic data collected just before the beginning of spontaneous breathing trial and outcome of the weaning attempt. We primarily focused on parameters currently recommended for evaluation of left ventricular (LV) systolic or diastolic dysfunction. Results: We included 11 studies in our primary analysis, which included data on LV ejection fraction (LVEF, n=10 studies) and parameters recommended for the assessment of LV diastolic function (E/e′ ratio n=10; E/A ratio n=9; E wave n=8; and e′ wave n=7). Weaning failure was significantly associated to a higher E/e′ ratio (standardised mean difference [SMD]=1.70, 95% confidence interval [CI; 0.78–2.62]; P

Hypoxaemia is a potential life-threatening yet common complication in the peri-operative and periprocedural patient (e.g. during an invasive procedure at risk of deterioration of gas exchange, such as bronchoscopy). The European Society of Anaesthesiology (ESA) and the European Society of Intensive Care Medicine (ESICM) developed guidelines for the use of noninvasive respiratory support techniques in the hypoxaemic patient in the peri-operative and periprocedural period. The panel outlined five clinical questions regarding treatment with noninvasive respiratory support techniques [conventional oxygen therapy (COT), high flow nasal cannula, noninvasive positive pressure ventilation (NIPPV) and continuous positive airway pressure (CPAP)] for hypoxaemic patients with acute peri-operative/periprocedural respiratory failure. The goal was to assess the available literature on the various noninvasive respiratory support techniques, specifically studies that included adult participants with hypoxaemia in the peri-operative/periprocedural period. The literature search strategy was developed by a Cochrane Anaesthesia and Intensive Care trial search specialist in close collaboration with the panel members and the ESA group methodologist. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the level of evidence and to grade recommendations. The final process was then validated by both ESA and ESICM scientific committees. Among 19 recommendations, the two grade 1B recommendations state that: in the peri-operative/periprocedural hypoxaemic patient, the use of either NIPPV or CPAP (based on local expertise) is preferred to COT for improvement of oxygenation; and that the panel suggests using NIPPV or CPAP immediately post-extubation for hypoxaemic patients at risk of developing acute respiratory failure after abdominal surgery. Electronic supplementary material The online version of this article (10.1007/s00134-020-05948-0) contains supplementary material, which is available to authorized users.

Background: There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. Methods: All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life: The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [

© 2020 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Objective: The present observational cohort study documented the safety of agomelatine in current medical practice in out-patients suffering from major depressive disorder. Method: The 6-month evolution of agomelatine-treated patients was assessed with a focus on safety (emergent adverse events, liver acceptability), severity of depression using the Clinical Global Impression Severity (CGI-S) score, and functioning measured by the Sheehan Disability Scale (SDS). Results: A total of 8453 depressed patients from 761 centres in 6 countries were analysed (female: 67.7%; mean age: 49.1 ± 14.8 years). Adverse events reported were in accordance with the known safety profile of agomelatine. Cutaneous events were reported in 1.7% of the patients and increased hepatic transaminases values were reported in 0.9 % of the patients. The incidence of events related to suicide/self-injury was 1.0%. Two completed suicides, not related to the study drug, were reported. CGI-S total scores and SDS sub-scores improved and numbers of days lost or underproductive decreased over the treatment period. Conclusions: In standard medical practice, agomelatine treatment was associated with a low incidence of side effects. No unexpected events were reported. A decrease in the severity of the depressive episode and improved functioning were observed.

Background There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. Methods In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 μm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed. Results From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12–22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES. Conclusion In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events. Trial registration ClinicalTrials.gov Identifier: NCT03544294. Retrospectively registered June 1, 2018.

Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Chronic graft-versus-host disease (GVHD) is the leading cause of later illness and death after allogeneic hematopoietic stem-cell transplantation. We hypothesized that the inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia would result in a significant reduction in chronic GVHD 2 years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling. METHODS We conducted a prospective, multicenter, open-label, randomized phase 3 study of ATG as part of a conditioning regimen. A total of 168 patients were enrolled at 27 centers. Patients were randomly assigned in a 1:1 ratio to receive ATG or not receive ATG, with stratification according to center and risk of disease. RESULTS After a median follow-up of 24 months, the cumulative incidence of chronic GVHD was 32.2% (95% confidence interval [CI], 22.1 to 46.7) in the ATG group and 68.7% (95% CI, 58.4 to 80.7) in the non-ATG group (P