Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients' overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis

Frequency and determinants for hemorrhagic transformation of posterior cerebral stroke : Posterior ischemic stroke and hemorrhagic transformation.

BACKGROUND: hemorrhagic transformation is a threatening ischemic stroke complication. Frequency of hemorrhagic transformation differs greatly among studies, and its risk factors have been usually studied in patients with anterior ischemic stroke who received thrombolytic therapy. We evaluated, in a hospital-based series of patients with posterior ischemic stroke not treated with thrombolysis, frequency and risk factors of hemorrhagic transformation. Patients with posterior circulation stroke were seen in our Department during the period January 2004 to December 2009. Demographic and clinical information were collected. We estimated risk for spontaneous hemorrhagic transformation by means of uni- and multivariate logistic regression analyses. RESULTS: 119 consecutive patients were included (73 males, 61.3%). Hemorrhagic transformation was observed in 7 patients (5.9%). Only clinical worsening was significantly associated with hemorrhagic transformation (OR 6.8, 95% CI 1.3-34.5). CONCLUSIONS: Our findings indicate that patients with posterior have a low risk of spontaneous hemorrhagic transformation, suggesting that these patients might have greater advantage from intravenous thrombolysis

The prognostic role of KRAS and BRAF in patients undergoing surgical resection of colorectal cancer liver metastasis: a systematic review and meta-analysis

Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of liver metastasis (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Materials and Methods: Data from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for both the OS and/or RFS. Results: Seven eligible trials (1403 patients) were included. Pooled analysis showed that KRAS mutations predicted a significant worse both RFS (HR: 1.65; 95% CI: 1.23 \u2013 2.21) and OS (HR: 1.86; 95% CI: 1.51 \u2013 2.30) in patients who underwent surgical resection of CLM. BRAF mutations were also associated with a significant worse OS (HR: 3.90; 95% CI: 1.96 \u2013 7.73) in this subgroup of patients. Conclusion: This meta-analysis suggests both KRAS and BRAF mutations as negative prognostic biomarkers associated with worse survival outcomes in patients undergoing hepatic resection of CLM. Such evidences support the introduction of new treatment decision models, taking into account the tumor molecular profile in order to individualize both systemic and loco-regional treatment strategies

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Abstract Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77). Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability

Clinical Features of Patients with Cervical Artery Dissection and Fibromuscular Dysplasia

Background and Purpose: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. Methods: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD-). Results: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13-2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06-18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26-0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58-7.31] and 2.07 [95% CI, 1.06-4.03], respectively) in multivariable Cox proportional hazards analysis. Conclusions: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence

Empowering Deafblind Communication Capabilities by Means of AI-Based Body Parts Tracking and Remotely Controlled Robotic Arm for Sign Language Speakers

Deafblind people face remarkable challenges in communicating, because of their severe disability. The only way to interact with other people is the usage of the tactile sign language, which consists in understanding the sign language putting their hands on the signer’s hands. But this approach works only when the signers are in the same place. The aim of this project is to reduce the gap between deafblind people and the other ones, giving them the capability to communicate remotely. By collecting images with two cameras, the signer’s body is tracked with a deep neural network. The extracted coordinates of the body parts (chest, shoulders, elbows, wrists, palms and fingers) are used to move one or more robotic arms. The deafblind person can put his hands on the robots to understand the message delivered by the person on the other side. The entire system is based on a cloud architecture

Soft large area FBG tactile sensors for exteroception and proprioception in a collaborative robotic manipulator

Interest in tactile sensing technologies is advancing due to the growing adoption of robots in daily life activities. Human-machine interaction has thus to be safe, and collaborative robotics is becoming increasingly important. The present work features the design, development and preliminary validation of a soft large area sensor for tactile and proprioceptive sensing in a collaborative robotic manipulator. Such a manipulator is shaped to resemble the human hand and within this paper we focused on the index finger. The finger architecture has a design which allows setting up a structured 3D model, with flexible parametrization and fast prototyping. An optical fiber embedding 12 Fiber Bragg Gratings (FBGs) has been integrated in a soft polymeric matrix to mimic human sense of touch abilities of a whole finger. In order to assess the sensorized robotic manipulator, a mechatronic validation platform has been developed and employed. Preliminary results show a mechanical decoupling between exteroceptive and proprioceptive functions, and among the spatially distributed outputs of the sensor array. These results demonstrate the potential of the proposed approach towards achieving dexterous and fine capabilities in the manipulation of objects

Design and Development of Large-Area FBG-Based Sensing Skin for Collaborative Robotics

Advancements in the field of collaborative robotics have led to a closer cooperation between humans and machines. Sharing the same environment, safety and adaptive control becomes of paramount importance in human-robot interaction. Thus, tactile feedback technologies are crucial to perceive contacts. This work presents the design and development of a polymeric artificial skin, mimicking the human sense of touch in perceiving and localizing pressure over a large area, and its integration on a custom human-like robotic forearm. The sensing system consisted of a curved soft matrix embedding an optical fiber equipped with 16 distributed Fiber Bragg Gratings (FBGs). To estimate the sensitivity of the tactile sensor array, a preliminary mechanical characterization was performed by means of force-controlled indentations. Results show a high correlation between the applied load and the corresponding output of the sensors. In particular, the median value of the sensitivity resulted in 0.26 nm.N-1, with 0.08 nm.N-1 interquartile range. These promising results call for further investigation on spatial sensitivity and force range, contact localization and calibration of the presented artificial skin