Robot Assisted Object Manipulation for Minimally Invasive Surgery

Robotic systems have an increasingly important role in facilitating minimally invasive surgical treatments. In robot-assisted minimally invasive surgery, surgeons remotely control instruments from a console to perform operations inside the patient. However, despite the advanced technological status of surgical robots, fully autonomous systems, with decision-making capabilities, are not yet available. In 2017, a structure to classify the research efforts toward autonomy achievable with surgical robots was proposed by Yang et al. Six different levels were identified: no autonomy, robot assistance, task autonomy, conditional autonomy, high autonomy, and full autonomy. All the commercially available platforms in robot-assisted surgery is still in level 0 (no autonomy). Despite increasing the level of autonomy remains an open challenge, its adoption could potentially introduce multiple benefits, such as decreasing surgeons’ workload and fatigue and pursuing a consistent quality of procedures. Ultimately, allowing the surgeons to interpret the ample and intelligent information from the system will enhance the surgical outcome and positively reflect both on patients and society. Three main aspects are required to introduce automation into surgery: the surgical robot must move with high precision, have motion planning capabilities and understand the surgical scene. Besides these main factors, depending on the type of surgery, there could be other aspects that might play a fundamental role, to name some compliance, stiffness, etc. This thesis addresses three technological challenges encountered when trying to achieve the aforementioned goals, in the specific case of robot-object interaction. First, how to overcome the inaccuracy of cable-driven systems when executing fine and precise movements. Second, planning different tasks in dynamically changing environments. Lastly, how the understanding of a surgical scene can be used to solve more than one manipulation task. To address the first challenge, a control scheme relying on accurate calibration is implemented to execute the pick-up of a surgical needle. Regarding the planning of surgical tasks, two approaches are explored: one is learning from demonstration to pick and place a surgical object, and the second is using a gradient-based approach to trigger a smoother object repositioning phase during intraoperative procedures. Finally, to improve scene understanding, this thesis focuses on developing a simulation environment where multiple tasks can be learned based on the surgical scene and then transferred to the real robot. Experiments proved that automation of the pick and place task of different surgical objects is possible. The robot was successfully able to autonomously pick up a suturing needle, position a surgical device for intraoperative ultrasound scanning and manipulate soft tissue for intraoperative organ retraction. Despite automation of surgical subtasks has been demonstrated in this work, several challenges remain open, such as the capabilities of the generated algorithm to generalise over different environment conditions and different patients

Automated pick-up of suturing needles for robotic surgical assistance

Robot-assisted laparoscopic prostatectomy (RALP) is a treatment for prostate cancer that involves complete or nerve sparing removal prostate tissue that contains cancer. After removal the bladder neck is successively sutured directly with the urethra. The procedure is called urethrovesical anastomosis and is one of the most dexterity demanding tasks during RALP. Two suturing instruments and a pair of needles are used in combination to perform a running stitch during urethrovesical anastomosis. While robotic instruments provide enhanced dexterity to perform the anastomosis, it is still highly challenging and difficult to learn. In this paper, we presents a vision-guided needle grasping method for automatically grasping the needle that has been inserted into the patient prior to anastomosis. We aim to automatically grasp the suturing needle in a position that avoids hand-offs and immediately enables the start of suturing. The full grasping process can be broken down into: a needle detection algorithm; an approach phase where the surgical tool moves closer to the needle based on visual feedback; and a grasping phase through path planning based on observed surgical practice. Our experimental results show examples of successful autonomous grasping that has the potential to simplify and decrease the operational time in RALP by assisting a small component of urethrovesical anastomosis

Systemic adipokines, hepatokines and interleukin-6 in HCV-monoinfected and HCV/HIV coinfected patients treated with direct antiviral agents (DAAs)

In this study, we demonstrated that that altered levels ofadipokines/hepatokines in HCV-infected patients, including HIV coinfected, can be restored by treatment with direct antiviral agents (DAAs), thus indicating the important metabolic changes occurring during the eradication of this viral infection

Learning intraoperative organ manipulation with context-based reinforcement learning

PURPOSE: Automation of sub-tasks during robotic surgery is challenging due to the high variability of the surgical scenes intra- and inter-patients. For example, the pick and place task can be executed different times during the same operation and for distinct purposes. Hence, designing automation solutions that can generalise a skill over different contexts becomes hard. All the experiments are conducted using the Pneumatic Attachable Flexible (PAF) rail, a novel surgical tool designed for robotic-assisted intraoperative organ manipulation. METHODS: We build upon previous open-source surgical Reinforcement Learning (RL) training environment to develop a new RL framework for manipulation skills, rlman. In rlman, contextual RL agents are trained to solve different aspects of the pick and place task using the PAF rail system. rlman is implemented to support both low- and high-dimensional state information to solve surgical sub-tasks in a simulation environment. RESULTS: We use rlman to train state of the art RL agents to solve four different surgical sub-tasks involving manipulation skills using the PAF rail. We compare the results with state-of-the-art benchmarks found in the literature. We evaluate the ability of the agent to be able to generalise over different aspects of the targeted surgical environment. CONCLUSION: We have shown that the rlman framework can support the training of different RL algorithms for solving surgical sub-task, analysing the importance of context information for generalisation capabilities. We are aiming to deploy the trained policy on the real da Vinci using the dVRK and show that the generalisation of the trained policy can be transferred to the real world

Higher levels of osteoprotegerin and immune activation/immunosenescence markers are correlated with concomitant bone and endovascular damage in HIV-suppressed patients

HIV-infected patients appear to have a significantly greater risk of non-AIDS comorbidities such as osteoporosis and atherosclerosis. Subjects with osteoporosis are at a higher risk of developing cardiovascular disease than those with normal bone mass, therefore a possible relation between these two conditions can be hypothesized. In the setting of HIV infection, several factors might contribute to bone disease and endothelial dysfunction. The aim of our study was to evaluate the relationship between bone and cardiovascular disease and to investigate the role of traditional factors, T-cell phenotype and osteoprotegerin in HIV positive subjects on effective antiretroviral therapy. We included 94 HIV positive subjects on antiretroviral therapy with virological suppression and 41 healthy subjects matched for age and gender as a control group. Carotid-Intima Media Thickness (c-IMT) and bone mineral density (BMD) were performed by ultrasound and DEXA, respectively. CD4+/CD8+ T-cell activation, senescence and osteoprotegerin plasma levels were measured by flow-cytometry and ELISA, respectively. Among HIV positive patients, 56.4% had osteopenia/osteoporosis and 45.7% had pathological c-IMT (>0.9mm). Subjects with pathological c-IMT and BMD exhibited higher CD4+ and CD8+ activated, CD8+ senescent and osteoprotegerin than subjects with normal c-IMT and BMD. HIV positive subjects with osteopenia/osteoporosis had higher c-IMT than subjects with normal BMD, and linear regression analysis showed a negative correlation between BMD and c-IMT. Several factors are implicated in the pathogenesis of non-AIDS comorbidities in HIV positive patients. Osteoprotegerin together with inflammation and immunosenescence in HIV positive patients could affect bone and vascular system and could be considered as a possible common link between these two diseases

Modulation of tryptophan/serotonin pathway by probiotic supplementation in human immunodeficiency virus-positive patients: preliminary results of a new study approach

Background: To date, no data are available regarding the effects of probiotics on the pathway of tryptophan/serotonin metabolism among human immunodeficiency virus (HIV) 1–infected individuals. Because a condition of dysbiosis might be responsible for the altered use of tryptophan described in this population, the aim of this study was to investigate the link between probiotic supplementation and serotonin levels in combined antiretroviral therapy–treated patients and the subsistence of an interplay with inflammation. Methods: We conducted a pilot study that included 8 HIV-positive subjects. We collected blood and fecal samples before and after 6 months of probiotic supplementation, to measure the level of serotonin in serum and tryptophan in stool, the expression of CD38 and HLADR on peripheral CD4+ T lymphocytes (as immune activation markers), the expression of indoleamine 2,3-dioxygenase 1 messenger RNA (mRNA) and IFN-γ mRNA (as markers of tryptophan metabolism and systemic inflammation). Results: After probiotic supplementation, we observed a significant increase in concentration of serum serotonin (P=.008) and a decreased level of tryptophan in plasma. Moreover, a significant reduction in CD38 and HLA-DR expression on the surface of peripheral CD4+ T cells (P=.008) and a reduced expression of indoleamine 2,3-dioxygenase 1 mRNA on peripheral blood mononuclear cells (P=.04) were observed. Conclusions: Considering that this probiotic (Vivomixx® in EU; Visbiome® in USA) has an influence on tryptophan metabolism, larger studies on this topic are needed

Antibacterial effectiveness of fecal water and in vitro activity of a multi-strain probiotic formulation against multi-drug resistant microorganisms

Introduction: Intestinal colonization with multi-drug resistant (MDR) microorganisms is a consequence of antimicrobial-induced gut dysbiosis. Given the effect of probiotics in modulating gut microbiota, the aim of the study was to investigate whether the ingestion of high concentration multi-strain probiotic formulation would change the antibacterial activity of the feces against clinical strains ofMDRmicroorganisms. The corresponding in vitro antibacterial activity was also investigated. Materials/Methods: The feces of healthy donors (n = 6) were analyzed before and after a 7-day dietary supplementation with a multi-strain probiotic formulation and tested against MDR microorganisms of clinical concern (carbapenem-resistant (CR), Klebsiella pneumoniae (CR-Kp), CR-Acinetobacter baumannii (CR-Ab), CR-Pseudomonas aeruginosa (CR-Pa), and methicillin-resistant Staphylococcus aureus (MRSA)). The tested MDR pathogens were cultured with decreasing concentrations of fecal water obtained before and after the treatment period. Furthermore, to corroborate the results obtained from the feces of healthy donors, the in vitro antibacterial activity of probiotic formulation (both whole probiotic (WP) and probiotic surnatant (PS)) against the same collection of MDR microorganisms was evaluated at different incubation times throughout the minimum bactericidal dilution and the corresponding serial silution number. Results: While before probiotic administration, the fecal water samples did not inhibit MDR microorganism growth, after supplementation, a reduced bacterial growth was shown. Accordingly, a noticeable in vitro activity of WP and PS was observed. Conclusions: Although preliminary, these experiments demonstrated that a specific multi-strain probiotic formulation exhibits in vitro antibacterial activity against MDR microorganisms of clinical concern. If confirmed, these results may justify the administration of probiotics as a decolonization strategy against MDR microorganisms

Targeting microbiome: an alternative strategy for fighting SARS-CoV-2 infection

Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients

Long COVID refers to patients with symptoms as fatigue, “brain fog,” pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB–). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7%of participants reported fatigue while 29.3%were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB– one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways

Parietal resting-state EEG alpha source connectivity is associated with subcortical white matter lesions in HIV-positive people

Objective Parietal resting-state electroencephalographic (rsEEG) alpha (8–10 Hz) source connectivity is abnormal in HIV-positive persons. Here we tested whether this abnormality may be associated with subcortical white matter vascular lesions in the cerebral hemispheres. Methods Clinical, rsEEG, and magnetic resonance imaging (MRI) datasets in 38 HIV-positive persons and clinical and rsEEG datasets in 13 healthy controls were analyzed. Radiologists visually evaluated the subcortical white matter hyperintensities from T2-weighted FLAIR MRIs (i.e., Fazekas scale). In parallel, neurophysiologists estimated the eLORETA rsEEG source lagged linear connectivity from parietal cortical regions of interest. Results Compared to the HIV participants with no/negligible subcortical white matter hyperintensities, the HIV participants with mild/moderate subcortical white matter hyperintensities showed lower parietal interhemispheric rsEEG alpha lagged linear connectivity. This effect was also observed in HIV-positive persons with unimpaired cognition. This rsEEG marker allowed good discrimination (area under the receiver operating characteristic curve > 0.80) between the HIV-positive individuals with different amounts of subcortical white matter hyperintensities. Conclusions The parietal rsEEG alpha source connectivity is associated with subcortical white matter vascular lesions in HIV-positive persons, even without neurocognitive disorders. Significance Those MRI-rsEEG markers may be used to screen HIV-positive persons at risk of neurocognitive disorders