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The most recent international guidelines regarding recurrent pregnancy loss (RPL) exclude most of the immunological tests recommended for RPL since they do not reach an evidence-based level. Comparisons for metanalysis and systematic reviews are limited by the ambiguity in terms of RPL definition, etiological and risk factors, diagnostic work-up, and treatments applied. Therefore, cohort heterogeneity, the inadequacy of numerosity, and the quality of data confirm a not standardized research quality in the RPL field, especially for immunological background, for which potential research application remains confined in a separate single biological layer. Innovative sequencing technologies and databases have proved to play a significant role in the exploration and validation of cancer research in the context of dataset quality and bioinformatics tools. In this article, we will investigate how bioinformatics tools born for large-scale cancer immunological research could revolutionize RPL immunological research but are limited by the nature of current RPL datasets.

BackgroundCalcineurin inhibitors (CNIs) are associated with nephrotoxicity, endothelial cell dysfunction, and thrombotic microangiopathy (TMA). Evolving evidence suggests an important role for complement dysregulation in the pathogenesis of CNI-induced TMA. However, the exact mechanism(s) of CNI-induced TMA remain(s) unknown.MethodsUsing blood outgrowth endothelial cells (BOECs) from healthy donors, we evaluated the effects of cyclosporine on endothelial cell integrity. Specifically, we determined complement activation (C3c and C9) and regulation (CD46, CD55, CD59, and complement factor H [CFH] deposition) as these occurred on the endothelial cell surface membrane and glycocalyx.ResultsWe found that exposing the endothelium to cyclosporine resulted in a dose- and time-dependent enhancement of complement deposition and cytotoxicity. We, therefore, employed flow cytometry, Western blotting/CFH cofactor assays, and immunofluorescence imaging to determine the expression of complement regulators and the functional activity and localization of CFH. Notably, while cyclosporine led to the upregulation of complement regulators CD46, CD55, and CD59 on the endothelial cell surface, it also diminished the endothelial cell glycocalyx through the shedding of heparan sulfate side chains. The weakened endothelial cell glycocalyx resulted in decreased CFH surface binding and surface cofactor activity.ConclusionOur findings confirm a role for complement in cyclosporine-induced endothelial injury and suggest that decreased glycocalyx density, induced by cyclosporine, is a mechanism that leads to complement alternative pathway dysregulation via decreased CFH surface binding and cofactor activity. This mechanism may apply to other secondary TMAs—in which a role for complement has so far not been recognized—and provide a potential therapeutic target and an important marker for patients on calcineurin inhibitors.

IntroductionElderly endometrial cancer (EEC) patients represent a challenging clinical situation because of the increasing number of clinical morbidities. In this setting of patients, minimally invasive surgery (MIS) has been shown to improve surgical and clinical outcomes. The aim of this study was to evaluate the peri-operative and oncological outcomes of EEC patients who had undergone laparoscopic (LS) or robotic surgery (RS).Materials and MethodsThis is a retrospective multi-institutional study in which endometrial cancer patients of 70 years or older who had undergone MIS for EC from April 2002 to October 2018 were considered. Owing to the non-randomized nature of the study design and the possible allocation biases arising from the retrospective comparison between LS and RS groups, we also performed a propensity score-matched analysis (PSMA).ResultsA total of 537 patients with EC were included in the study: 346 who underwent LS and 191 who underwent RS. No significant statistical differences were found between the two groups in terms of surgical and survival outcomes. 188 were analyzed after PSMA (94 patients in the LS group were matched with 94 patients in the RS group). The median estimated blood loss was higher in the LS group (p=0.001) and the median operative time was higher in the RS group (p=0.0003). No differences emerged between LS and RS in terms of disease free survival (DFS) (p=0.890) and overall survival (OS) (p=0.683).ConclusionsOur study showed that when compared LS and RS, RS showed lower blood losses and higher operative times. However, none of the two approaches demonstrated to be superior in terms of survival outcomes. For this reason, each patient should be evaluated individually to determine the best surgical approach.

Breast reconstruction plays a fundamental role in the therapeutic process of breast cancer treatment and breast implants represents the leading breast reconstruction strategy. Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL), locoregional recurrence in the skin flap, and skin flap necrosis are well-known complications following mastectomy and immediate breast reconstruction (IBR). We report a case of locoregional cancer recurrence in the mastectomy flap mimicking BIA-ALCL, in a patient who underwent 6 breast procedures in four facilities across 15 years including immediate breast reconstruction with macrotextured breast implants. Despite the rate and onset of the disease, clinicians should be aware of BIA-ALCL. Due to the risk of false negative results of fine needle aspiration, clinical suspicion of BIA-ALCL should drive clinicians' choices, aside from cytological results. In the present case, surgical capsulectomy of the abnormal periprosthesic tissue revealed locoregional recurrence.

The clinical effects of the Covid-19 pandemic are now the subject of numerous studies worldwide. But what are the effects of the quarantine imposed by the states that implemented the measures of lockdown? The present research aims to explore, in a preliminary way, the major stress-related symptoms during the lockdown, due to Covid-19, in the Italian population. Subjects were asked to fill out a survey, that traced a line identifying the most relevant psychophysiological symptoms that took into account factors such as perceived stress, body perception, perceived pain, quality of sleep, perceptive variations (i.e., olfactory, gustatory, visual, acoustic, and haptic perception). A network approach formulating a hypothesis-generating exploratory analysis was adopted. Main results of the network analysis showed that the beliefs of having had the Covid-19 was related to individual variables (i.e., gender, working in presence, sleep quality, anxiety symptoms), while the familiarity of Covid-19 disease was related to contextual factors (e.g., number of recorded cases in the Region, working in presence). The self-perception of olfactory and perceptive alterations highlighted a great sensorial cross-modality, additionally, the olfactory impairment was related to the belief of having had the Covid-19. Compared to general network data, BAI, perceived stress, anxiety and chronic pain were in relation to daily sleep disturbance. Main study's results show how the management of the Covid-19 stressful representation, in its cognitive aspects, can modulate the psychophysiological responses.

The immune escape mechanisms at the base of tumor progression in endometrial cancer mimic immune tolerance mechanisms occurring at the maternal–fetal interface. The biological and immunological processes behind the maternal–fetal interface are finely tuned in time and space during embryo implantation and subsequent pregnancy stages; conversely, those behind cancer progression are often aberrant. The environment composition at the maternal–fetal interface parallels the pro-tumor microenvironment identified in many cancers, pointing to the possibility for the use of the maternal–fetal interface as a model to depict immune therapeutic targets in cancer. The framework of cancer environment signatures involved in immune adaptations, precisely timed in cancer progression, could reveal a specific “immune clock” in endometrial cancer, which might guide clinicians in patient risk class assessment, diagnostic workup, management, surgical and therapeutic approach, and surveillance strategies. Here, we review studies approaching this hypothesis, focusing on what is known so far about oncofetal similarities in immunity with the idea to individualize personalized immunotherapy targets, through the downregulation of the immune escape stage or the reactivation of the pro-inflammatory processes suppressed by the tumor.

Previous evidence has shown that tool-use can reshape one’s own body schema, extending peripersonal space and modulating the representation of related body parts. Here, we investigated the role of tool action in shaping the body metric representation, by contrasting two different views. According to a first view, the shaping would rely on the mere execution of tool action, while the second view suggests that the shaping induced by tool action on body representation would primarily depend on the representation of the action goals to be accomplished. To this aim, we contrasted a condition in which participants voluntarily accomplish the movement by representing the program and goal of a tool action (i.e., active tool-use training) with a condition in which the tool-use training was produced without any prior goal representation (i.e., passive tool-use training by means of robotic assistance). If the body metric representation primarily depends on the coexistence between goal representation and bodily movements, we would expect an increase of the perceived forearm length in the post- with respect to the pre-training phase after the active training phase only. Healthy participants were asked to estimate the midpoint of their right forearm before and after 20 min of tool-use training. In the active condition, subjects performed “enfold-and-push” movements using a rake to prolong their arm. In the passive condition, subjects were asked to be completely relaxed while the movements were performed with robotic assistance. Results showed a significant increase in the perceived arm length in the post- with respect to the pre-training phase only in the active task. Interestingly, only in the post-training phase, a significant difference was found between active and passive conditions, with a higher perceived arm length in the former than in the latter. From a theoretical perspective, these findings suggest that tool-use may shape body metric representation only when action programs are motorically represented and not merely produced. From a clinical perspective, these results support the use of robots for the rehabilitation of brain-damaged hemiplegic patients, provided that robot assistance during the exercises is present only “as-needed” and that patients’ motor representation is actively involved.

Pathological embodiment (E+) is a specific contralesional delusion of body ownership, observed following brain damage, in which patients embody someone else’s arm and its movements within their own body schema whenever the contralesional ‘alien’ arm is presented in a body-congruent position (i.e., 1st person perspective and aligned with the patient’s shoulder). This disorder is often associated with spatial neglect, a neurological syndrome in which patients are unaware of stimuli presented in the contralesional (often the left) space. Capitalizing on previous evidence demonstrating that prismatic adaptation of the ipsilesional arm to right-deviating prisms is effective in ameliorating neglect symptoms, here we investigated whether such amelioration also occurs in E+ patients with neglect when prismatic training is performed by the ‘alien’ embodied arm. Four left neglect patients (one with and three without pathological embodiment) underwent visuomotor prismatic training performed by an ‘alien’ arm. Specifically, while patients were wearing prismatic goggles shifting the visual field rightward, a co-experimenter’s left arm presented in a body-congruent perspective was repeatedly moved toward visual targets by another examiner. In a control condition, the co-experimenter’s arm was moved toward the targets from a body-incongruent position (i.e., 3rd person perspective). Neglect symptoms were assessed before and after training through paper-and-pencil tasks. In the E+ patient, neglect improved significantly more in 1st than in 3rd person perspective training, suggesting that prismatic adaptation of the ‘alien’ embodied arm is effective in modulating spatial representation. Conversely, for control E- patients (not embodying the ‘alien’ arm), we observed more limited improvements following training. These findings indicate that the ‘alien’ embodied arm is so deeply embedded in the patient body and motor schema that adaptation to prismatic lenses can affect multiple processing stages, from low level sensory-motor correspondences, to higher level body, motor and spatial maps, similarly as it occurs in normal subjects and neglect patients without pathological embodiment.

The ability to know where our body parts are located in space (proprioception) is fundamental for both successfully interacting with the external world and monitoring potential threats. In this case-control study, we investigated whether the absence of proprioceptive signals may affect physiological defensive responses. To this aim, a right brain-damaged patient with a left upper-limb proprioceptive deficit (P+ patient) and age-matched healthy controls, underwent the recording of the Hand-Blink Reflex (HBR). This defensive response, elicited by electrical stimulation of the median nerve and recorded from the orbicularis oculi, is modulated by the hand position: it is enhanced when the threatened hand is near to the face, inside the defensive peripersonal-space (DPPS). According to the classical neuropsychological perspective, we used P+ patient as a model to investigate the role of proprioception in HBR modulation, by manipulating the congruity/incongruity between the intended and actual positions of the stimulated hand. P+ patient, with his eyes closed, had to voluntarily place his left hand either far from or near to his face and to relieve the arm’s weight over a supporting device. Then, in congruent conditions, the hand was stimulated in the actual (intended) position. In incongruent conditions, the patient’s hand was moved by the examiner from the intended to the opposite (not-intended) position and then stimulated. We observed an inverse response pattern between congruent and incongruent conditions. In congruent conditions, P+ patient showed an HBR enhancement in near compared to far position, comparable to that found in healthy controls. This suggests that, even in absence of proprioceptive and visual information, the HBR modulation was still present. Conversely, in incongruent conditions, P+ patient showed a greater HBR magnitude for far position (when the hand was actually far, but the patient intended it to be near) than for near position (when the hand was actually near, but the patient intended it to be far). This result suggests that proprioceptive signals are not necessary for HBR modulation to occur. It relies more on the intended than on the actual position of the hand. The role of motor intention and planning in shaping the DPPS is discussed.