Oxidative Stress in Sepsis: A Focus on Cardiac Pathology.

This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.

Is It Still Time for Safety Walkaround? Pilot Project Proposing a New Model and a Review of the Methodology.

Background and Objectives: Healthcare facilities are complex systems due to the interaction between different factors (human, environmental, management, and technological). As complexity increases, it is known that the possibility of error increases; therefore, it becomes essential to be able to analyze the processes that occur within these contexts to prevent their occurrence, which is the task of risk management. For this purpose, in this feasibility study, we chose to evaluate the application of a new safety walkaround (SWA) model. Materials and Methods: A multidisciplinary working group made up of experts was established and then the subsequent phases of the activity were divided into three stages, namely the initial meeting, the operational phase, and the final meeting, to investigate knowledge regarding patient safety before and subsequently through visits to the department: the correct compilation of the medical record, adherence to evidence-based medicine (EBM) practices, the overall health and the degree of burnout of the various healthcare professionals, as well as the perception of empathy of staff by patients. Results: This working group chose to start this pilot project in the vascular surgery ward, demonstrating the ability of the tool used to capture the different aspects it set out to collect. In detail, the new version of SWA proposed in this work has made it possible to identify risk situations and system vulnerabilities that have allowed the introduction of corrective tools; detect adherence to existing company procedures, reschedule training on these specific topics after reviewing, and possibly update the same procedures; record the patient experience about the doctor-patient relationship and communication to hypothesize thematic courses on the subject; evaluate workers' perception of their health conditions about work, and above all reassure operators that their well-being is in the interest of the management of the healthcare company, which is maintained. Conclusions: Therefore, the outcome of the present study demonstrates the versatility and ever-present usefulness of the SWA tool.

Cervical spine injury: clinical and medico-legal overview.

Spinal trauma is an important cause of disability worldwide. Injury to the cervical spine (CS) occurs frequently after major trauma. 5-10% of patients with blunt trauma have a cervical spine injury. The cervical spine accounts for ~ 50% of all spinal injuries. Determination of CS stability is a common challenge in the acute care setting of patients with trauma. Several issues, indeed, are of particular concern: who needs CS imaging; what imaging should be obtained; when should computed tomography (CT), magnetic resonance imaging (MRI), or flexion/extension (F/E) radiographs be obtained; and how is significant ligamentous injury excluded in the comatose patient. CT and MRI both have roles to play. This article aims to present the different imaging to frame techniques to be used with greater precision in the acute event also for the purpose of planning the next therapeutic process. An overview of the applicability of the same methods in forensic pathology is also provided highlighting possible future biomarker to ease in diagnosis of acute TBI.

Glymphatic System a Window on TBI Pathophysiology: A Systematic Review.

BACKGROUND: In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its similarity to the lymphatic system in peripheral tissue and the relevant role of the AQP4 glial channels and described for the first time in 2012. Consequently, numerous studies focused on its role in organ damage in cases of neuropathologies, including TBI. METHODS: To evaluate the role that the glymphatic system has in the pathogenesis of TBI, on 23 March 2022, a systematic review of the literature according to PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, resulting in 12 articles after the selection process. DISCUSSION AND CONCLUSION: The present review demonstrated that an alteration of AQP4 is associated with the accumulation of substances S100b, GFAP, and NSE, known markers of TBI in the forensic field. In addition, the alteration of the functionality of AQP4 favors edema, which, as already described, constitutes alterations of secondary brain injuries. Moreover, specific areas of the brain were demonstrated to be prone to alterations of the glymphatic pathway, suggesting their involvement in post-TBI damage. Therefore, further studies are mandatory. In this regard, a study protocol on cadavers is also proposed, based on the analyzed evidence.

Mapping brain morphological and functional conversion patterns in predementia late-onset bvFTD.

PURPOSE: The diagnosis of behavioural variant frontotemporal dementia (bvFTD) is challenging during the predementia stage when symptoms are subtle and confounding. Morphological and functional neuroimaging can be particularly helpful during this stage but few data are available. METHODS: We retrospectively selected 25 patients with late-onset probable bvFTD. Brain structural MRI and FDG PET were performed during the predementia stage (mean MMSE score 27.1 ± 2.5) on average 2 years before. The findings with the two imaging modalities were compared (SPM8) with those in a group of 20 healthy subjects. The bvFTD patients were divided into two subgroups: those with predominant disinhibition (bvFTD+) and those with apathy (bvFTD-). RESULTS: Hypometabolism exceeded grey matter (GM) density reduction in terms of both extension and statistical significance in all comparisons. In the whole bvFTD group, hypometabolism involved the bilateral medial, inferior and superior lateral frontal cortex, anterior cingulate, left temporal and right parietal cortices and the caudate nuclei. GM density reduction was limited to the right frontal cortex and the left medial temporal lobe. In bvFTD+ patients hypometabolism was found in the bilateral medial and basal frontal cortex, while GM reduction involved the left anterior cingulate and left inferior frontal cortices, and the right insula. In bvFTD- patients, atrophy and mainly hypometabolism involved the lateral frontal cortex and the inferior parietal lobule. CONCLUSION: These findings suggest that hypometabolism is more extensive than, and thus probably precedes, atrophy in predementia late-onset bvFTD, underscoring different topographic involvement in disinhibited and apathetic presentations. If confirmed in a larger series, these results should prompt biomarker operationalization in bvFTD, especially for patient selection in therapeutic clinical trials.

Parkinson's Disease Sleep Scale 2: application in an Italian population.

Sleep disturbances and nocturnal disabilities are common in Parkinson's Disease (PD). The PD sleep scale, second version (PDSS-2), has been proposed as a helpful tool for measuring sleep disorders in PD. We aimed to validate the Italian version of the PDSS-2. One hundred and twenty-three consecutive PD outpatients (76 males) were evaluated by means of PDSS-2, Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Parkinson's Disease Quality of Life Questionnaire (self-administered scales), Unified Parkinson's Disease Rating (motor section) and Hoehn and Yahr Scales, and Mini Mental State Examination. PDSS-2 internal consistency was satisfactory (Cronbach's α: 0.77) with significant item to total score correlation and high intra-class correlation coefficient for test-retest reliability (0.943). Total PDSS-2 score was correlated with the scores on all other clinical scales. The factor analysis identified five factors, related to five areas of nocturnal disturbances, similarly as the original PDSS-2. The five factors mainly reflected: (1) nocturnal movement-related problems, (2) quality of sleep, (3) dreaming distress, (4) fragmentation of sleep and (5) insomnia symptoms. The PDSS-2 scale has confirmed its usefulness in evaluating sleep problems in Italian PD patients.

Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints.

PURPOSE: The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain(18)F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. METHODS: The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. RESULTS: Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. CONCLUSION: These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities.

Risk Management and Patient Safety in the Artificial Intelligence Era: A Systematic Review.

BACKGROUND: Healthcare systems represent complex organizations within which multiple factors (physical environment, human factor, technological devices, quality of care) interconnect to form a dense network whose imbalance is potentially able to compromise patient safety. In this scenario, the need for hospitals to expand reactive and proactive clinical risk management programs is easily understood, and artificial intelligence fits well in this context. This systematic review aims to investigate the state of the art regarding the impact of AI on clinical risk management processes. To simplify the analysis of the review outcomes and to motivate future standardized comparisons with any subsequent studies, the findings of the present review will be grouped according to the possibility of applying AI in the prevention of the different incident type groups as defined by the ICPS. MATERIALS AND METHODS: On 3 November 2023, a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out using the SCOPUS and Medline (via PubMed) databases. A total of 297 articles were identified. After the selection process, 36 articles were included in the present systematic review. RESULTS AND DISCUSSION: The studies included in this review allowed for the identification of three main "incident type" domains: clinical process, healthcare-associated infection, and medication. Another relevant application of AI in clinical risk management concerns the topic of incident reporting. CONCLUSIONS: This review highlighted that AI can be applied transversely in various clinical contexts to enhance patient safety and facilitate the identification of errors. It appears to be a promising tool to improve clinical risk management, although its use requires human supervision and cannot completely replace human skills. To facilitate the analysis of the present review outcome and to enable comparison with future systematic reviews, it was deemed useful to refer to a pre-existing taxonomy for the identification of adverse events. However, the results of the present study highlighted the usefulness of AI not only for risk prevention in clinical practice, but also in improving the use of an essential risk identification tool, which is incident reporting. For this reason, the taxonomy of the areas of application of AI to clinical risk processes should include an additional class relating to risk identification and analysis tools. For this purpose, it was considered convenient to use ICPS classification.

Learning from the Past to Improve the Future-Vaccine Hesitancy Determinants in the Italian Population: A Systematic Review.

WHO identifies vaccine hesitancy (VH) as one of the ten threats to global health. The authors bring to the international scientific community an Italian episode that offers the opportunity to renew the discussion on the extent of the VH matter. The purpose of this systematic review is to analyze the factors determining vaccine hesitancy in the Italian population, to understand its roots, and suggest potential strategies to mitigate it. A systematic review of the literature according to the PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, using the following strategy: (COVID-19 vaccines) AND (vaccination hesitancy) AND (Italy). After the selection process, 36 articles were included in this systematic review. The most frequently detected factors associated with VH in the Italian population can be grouped as vaccine-related factors, socio-cultural factors, and demographic factors. Currently, we are facing a gap between the population and science, governments, and institutions. To heal this breach, it is necessary to strengthen the trust of the population through the implementation of health communication and public education strategies, while scientific literacy must continue to support families and individuals in discerning evidence from opinions to recognize the real risks and balance them with the benefits.

The role of SARS-COV-2 infection in promoting abnormal immune response and sepsis: A comparison between SARS-COV-2-related sepsis and sepsis from other causes.

Background: COVID-19 caused by SARS-CoV-2 virus is characterized by respiratory compromise and immune system involvement, even leading to serious disorders, such as cytokine storm. Methods: We then conducted a literature review on the topic of sepsis and covid-19, and in parallel conducted an experimental study on the histological finding of patients who died from SARS-Covid 19 infection and a control group. Results: Sepsis associated with covid-19 infection has some similarities and differences from that from other causes. Conclusion: In this paper the complex interplay between the 2 disorders was discussed, focusing on the similarities and on the effect that one could have on the other. A preliminary experimental section that demonstrates the multisystemic involvement in subjects who die from SARS-CoV-2 is also proposed.

A repository based on a dynamically extensible data model supporting multidisciplinary research in neuroscience.

BACKGROUND: Robust, extensible and distributed databases integrating clinical, imaging and molecular data represent a substantial challenge for modern neuroscience. It is even more difficult to provide extensible software environments able to effectively target the rapidly changing data requirements and structures of research experiments. There is an increasing request from the neuroscience community for software tools addressing technical challenges about: (i) supporting researchers in the medical field to carry out data analysis using integrated bioinformatics services and tools; (ii) handling multimodal/multiscale data and metadata, enabling the injection of several different data types according to structured schemas; (iii) providing high extensibility, in order to address different requirements deriving from a large variety of applications simply through a user runtime configuration. METHODS: A dynamically extensible data structure supporting collaborative multidisciplinary research projects in neuroscience has been defined and implemented. We have considered extensibility issues from two different points of view. First, the improvement of data flexibility has been taken into account. This has been done through the development of a methodology for the dynamic creation and use of data types and related metadata, based on the definition of "meta" data model. This way, users are not constrainted to a set of predefined data and the model can be easily extensible and applicable to different contexts. Second, users have been enabled to easily customize and extend the experimental procedures in order to track each step of acquisition or analysis. This has been achieved through a process-event data structure, a multipurpose taxonomic schema composed by two generic main objects: events and processes. Then, a repository has been built based on such data model and structure, and deployed on distributed resources thanks to a Grid-based approach. Finally, data integration aspects have been addressed by providing the repository application with an efficient dynamic interface designed to enable the user to both easily query the data depending on defined datatypes and view all the data of every patient in an integrated and simple way. RESULTS: The results of our work have been twofold. First, a dynamically extensible data model has been implemented and tested based on a "meta" data-model enabling users to define their own data types independently from the application context. This data model has allowed users to dynamically include additional data types without the need of rebuilding the underlying database. Then a complex process-event data structure has been built, based on this data model, describing patient-centered diagnostic processes and merging information from data and metadata. Second, a repository implementing such a data structure has been deployed on a distributed Data Grid in order to provide scalability both in terms of data input and data storage and to exploit distributed data and computational approaches in order to share resources more efficiently. Moreover, data managing has been made possible through a friendly web interface. The driving principle of not being forced to preconfigured data types has been satisfied. It is up to users to dynamically configure the data model for the given experiment or data acquisition program, thus making it potentially suitable for customized applications. CONCLUSIONS: Based on such repository, data managing has been made possible through a friendly web interface. The driving principle of not being forced to preconfigured data types has been satisfied. It is up to users to dynamically configure the data model for the given experiment or data acquisition program, thus making it potentially suitable for customized applications.

Penetrating cardiac injuries: literature review and analysis of the forensic approach.

Penetrating cardiac injuries represent an increasingly frequent type of trauma in clinical and autopsy practice. The present study aims to review the specialist literature of the last decade (2010-2020) to assess whether the main features of these lesions have changed compared to previous years. The following characteristics were considered: sex, age, cardiac structure involved, execution or not of surgery and postoperative survival, hemodynamic stability, circumstances and mechanism of production, injury and cause of death. Furthermore, the authors propose a practical appraisal of penetrating heart injury in which death was due to a delay in rescue. In line with the data obtained from the practical case, the review showed that compared to the past, the differences concern especially the mortality rate. This paper highlights that the forensic pathologist who approaches a case of transcardiac injury must consider that the circumstances of death are not always attributable to accidental events, attacks or suicides, but may also be due to clinical malpractice or failure to rescue.

Proactive Risk Assessment through Failure Mode and Effect Analysis (FMEA) for Perioperative Management Model of Oral Anticoagulant Therapy: A Pilot Project.

INTRODUCTION: Correct perioperative management of anticoagulant therapy is essential to prevent thromboembolic events and reduce the risk of bleeding. The lack of universally accepted guidelines makes perioperative anticoagulant therapy management difficult. The present study aims to identify the perioperative risks of oral anticoagulant therapy and to reduce adverse events through Failure Mode and Effect Analysis (FMEA). MATERIALS AND METHODS: A multidisciplinary working group was set up, and four main phases of the process were identified. Each of these phases was divided into micro-activities to identify the related possible failure modes and their potential consequences. The Risk Priority Number was calculated for each failure mode. RESULTS AND DISCUSSION: Seventeen failure modes were identified in the entire perioperative period; those with a higher priority of intervention concern the incorrect timing between therapy suspension and surgery, and the incorrect assessment of the bleeding risk related to the invasive procedure. CONCLUSION: The FMEA method can help identify anticoagulant therapy perioperative failures and implement the management and patient safety of surgical procedures.

Sudden Cardiac Death and Ex-Situ Post-Mortem Cardiac Magnetic Resonance Imaging: A Morphological Study Based on Diagnostic Correlation Methodology.

During the last years, post-mortem imaging has gradually been assumed within research in the field of forensic pathology. This role appears to be clearly and simply applied in the trauma field with the use of conventional radiography or Post Mortem Computed Tomography (PMCT). Recently, particular attention was paid to cardiovascular imaging using Post Mortem Magnetic Resonance Imaging (PMMRI). The present experimental study aims to: (i) confirm the efficacy of a Post Mortem Cardiac Resonance Imaging (PMCRI) study protocol for the study of human hearts collected during the autopsy; (ii) apply the defined protocol on subjects who died of "SCD (sudden cardiac death)", to identify alterations that could guide subsequent sampling. Two hearts of healthy subjects (A: male 22 years; B: female 26 years), who died from causes other than SCD were collected and compared to hearts that belonged to SCD individuals (C: male, 47 years old; D: female, 44 years old; E: male; 72 years old). The exams were performed on a 1.5 T scanner (Philips Intera Achieva, Best, the Netherlands) on hearts collected during autopsy and after a 30-day formalin fixation. Two readers analyzed the obtained images blindly and after randomization. From the comparison between the data from imaging and the macroscopic and histological investigations carried out, the present study proved the effectiveness of a PMMRI protocol to study ex-situ hearts. Moreover, it suggested the following semeiology in post-mortem SCD cases: the hyperintense area with indistinct margins in the Short Tau Inversion Recovery (STIR) sequence was linked to edema or area of pathological fibers, whereas the hypointense area in the T2-FFE sequences was linked to fibrosis. PMMRI can provide a valuable benefit to post-mortem investigations, helping to distinctly improve the success rate of histological sampling and investigations, which remains the gold standard in the diagnosis of sudden death.

Liver Trauma: Management in the Emergency Setting and Medico-Legal Implications.

Traumatic abdominal injuries are life-threatening emergencies frequently seen in the Emergency Department (ED). The most common is liver trauma, which accounts for approximately 5% of all ED admissions for trauma. The management of blunt liver trauma has evolved significantly over the past few decades and, according to the injury's severity, it may require massive resuscitation, radiological procedures, endoscopy, or surgery. Patients admitted to the ED with blunt abdominal trauma require a multidisciplinary evaluation, including emergency physicians, surgeons, radiologists, and anesthetists, who must promptly identify the extent of the injury to prevent serious complications. In case of a patient's death, the execution of a forensic examination carried out with a multidisciplinary approach (radiological, macroscopic, and histological) is essential to understand the cause of death and to correlate the extent of the injuries to the possibility of survival to be able to manage any medico-legal disputes. This manuscript aims to collect the most up-to-date evidence regarding the management of hepatic trauma in the emergency room and to explore radiological findings and medico-legal implications.

COVID-19 and H1N1-09: A Systematic Review of Two Pandemics with a Focus on the Lung at Autopsy.

BACKGROUND: The purpose of this manuscript is to provide a comparative overview of the two global pandemics: the first on June 11th 2009 due to influenza A H1N1 (H1N1-09); the second and current pandemic caused by coronavirus 2019 (COVID-19) on March 11th 2020, focusing on how autopsy can contribute to the definition of cellular pathology, to clinical pathology and, more generally, to public health. METHODS: A systematic literature search selection was conducted on PubMed database on June 5, 2021, with this search strategy: (COVID-19) AND (H1N1 influenza) showing 101 results. The following inclusion criteria were selected: English language; published in a scholarly peer-reviewed journal; full-length articles were further elected. To further refine the research was to focus on the type of manuscript: review, systematic review, and meta-analysis. A critical appraisal of the collected studies was conducted, analyzing titles and abstracts, excluding the following topics: treatment, public health measures and perception of the general population or healthcare personnel about their quality of life. According to these procedures, 54 eligible studies were included in the present review. RESULTS: Histopathological findings play a key role in understanding the pathophysiological mechanisms of diseases and, thus possible therapeutic approaches. The evidence on the thrombo-inflammatory mechanism underlying COVID-19 is growing to a much greater magnitude than the diffuse alveolar damage in common with H1N1-09; our study appears to be in line with these results. The prevailing scientific thinking to explain the morbidity and mortality of COVID-19 patients is that it elicits an exuberant immune reaction characterized by dysregulated cytokine production, known as a "cytokine storm". CONCLUSIONS: The histological and immunohistochemical pattern demonstrated similarities and differences between the infectious manifestations of the two pathogens, which justify empirical therapeutic approaches, in the first phase of the COVID-19 pandemic. Therefore, the previous pandemic should have taught us to promote a culture of clinical and forensic autopsies in order to provide timely evidence from integration among autopsy and clinical data for early adopting adequate therapies.

Traumatic Brain Injury and Gut Brain Axis: The Disruption of an Alliance.

BACKGROUND: Traumatic brain injury (TBI) can be considered a "silent epidemic", causing morbidity, disability, and mortality in all age cohorts. Therefore, a greater understanding of the underlying pathophysiological intricate mechanisms and interactions with other organs and systems is necessary to intervene not only in the treatment but also in the prevention of complications. In this complex of reciprocal interactions, the complex brain-gut axis has captured a growing interest. SCOPE: The purpose of this manuscript is to examine and systematize existing evidence regarding the pathophysiological processes that occur following TBI and the influences exerted on these by the brain-gut axis. LITERATURE REVIEW: A systematic review of the literature was conducted according to the PRISMA methodology. On the 8th of October 2021, two independent databases were searched: PubMed and Scopus. Following the inclusion and exclusion criteria selected, 24 (12 from PubMed and 12 from Scopus) eligible manuscripts were included in the present review. Moreover, references from the selected articles were also updated following the criteria mentioned above, yielding 91 included manuscripts. DISCUSSION: Published evidence suggests that the brain and gut are mutually influenced through four main pathways: microbiota, inflammatory, nervous, and endocrine. CONCLUSION: These pathways are bidirectional and interact with each other. However, the studies conducted so far mainly involve animals. An autopsy methodological approach to corpses affected by traumatic brain injury or intestinal pathology could represent the keystone for future studies to clarify the complex pathophysiological processes underlying the interaction between these two main systems.

Proactive Risk Assessment Through Failure Mode and Effect Analysis (FMEA) for Haemodialysis Facilities: A Pilot Project.

Haemodialysis (HD) is one of the methods for renal replacement therapy in the management of advanced chronic kidney disease through an osmosis process that allows purification of blood in the dialysis machine. The complexity of the dialytic procedure often requires the presence of a multi-specialist, multi-disciplinary team. The dialysis process is an important target for clinical risk management. Failure Mode and Effect Analysis (FMEA) is a proactive technique, considered a purposeful and dynamic tool for clinical risk management. FMEA is noted in five phases that allow a preliminary assessment of a definite process through identification and classification of risk priorities. This study represents the first of a two-phase project where FMEA is applied to HD in the setting of San Feliciano Hospital. The dialysis center performs ~12,000 dialysis sessions per year. The dialysis process is divided into different stages. A total of 31 failure modes were identified in the whole dialysis stages; more than 2/3 of the failure modes were related to the only connecting of the patient to the dialysis machine. The first phase of the study clearly remarked that the most critical step of the dialytic process is represented by the connection between the patient and the machine, as expected. Indeed, in order to have the dialysis set up, an arteriovenous fistula must be surgically created prior to the procedure and it is one of the most important issues in the HD process because of the necessity of a constant revision of it. FMEA application to HD is a useful tool, easy to be implemented and it is likely to nimbly reveal the practical and potential solutions to the critical steps of the procedure.

Brain perfusion correlates of cognitive and nigrostriatal functions in de novo Parkinson's disease.

PURPOSE: Subtle cognitive impairment is recognized in the first stages of Parkinson's disease (PD), including executive, memory and visuospatial dysfunction, but its pathophysiological basis is still debated. METHODS: Twenty-six consecutive, drug-naïve, de novo PD patients underwent an extended neuropsychological battery, dopamine transporter (DAT) and brain perfusion single photon emission computed tomography (SPECT). We previously reported that nigrocaudate impairment correlates with executive functions, and nigroputaminal impairment with visuospatial abilities. Here perfusion SPECT was first compared between the PD group and age-matched controls (CTR). Then, perfusion SPECT was correlated with both DAT SPECT and four neuropsychological factors by means of voxel-based analysis (SPM8) with a height threshold of p < 0.005 at peak level and p < 0.05 false discovery rate-corrected at cluster level. Both perfusion and DAT SPECT images were flipped in order to have the more affected hemisphere (MAH), defined clinically, on the same side. RESULTS: Significant hypoperfusion was found in an occipital area of the MAH in PD patients as compared to CTR. Executive functions directly correlated with brain perfusion in bilateral posterior cingulate cortex and precuneus in the less affected hemisphere (LAH), while verbal memory directly correlated with perfusion in the precuneus, inferior parietal lobule and superior temporal gyrus in the LAH. Furthermore, positive correlation was highlighted between nigrocaudate and nigroputaminal impairment and brain perfusion in the precuneus, posterior cingulate and parahippocampal gyri of the LAH. CONCLUSION: These data support the evidence showing an early involvement of the cholinergic system in the early cognitive dysfunction and point to a more relevant role of parietal lobes and posterior cingulate in executive functions in PD.