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The COVID-19 pandemic is a highly dramatic concern for mankind. In Italy, the pandemic exerted its major impact throughout the period of February to June 2020. To date, the awkward amount of more than 134,000 deaths has been reported. Yet, post-mortem autopsy was performed on a very modest number of patients who died from COVID-19 infection, leading to a first confirmation of an immune-thrombosis of the lungs as the major COVID-19 pathogenesis, likewise for SARS. Since then (June-August 2020), no targeted early therapy considering this pathogenetic issue was approached. The patients treated with early anti-inflammatory, anti-platelet, anticoagulant and antibiotic therapy confirmed that COVID-19 was an endothelial inflammation with immuno-thrombosis. Patients not treated or scarcely treated with the most proper and appropriate therapy and in the earliest, increased the hospitalization rate in the intensive care units and also mortality, due to immune-thrombosis from the pulmonary capillary district and alveoli. The disease causes widespread endothelial inflammation, which can induce damage to various organs and systems. Therapy must be targeted in this consideration, and in this review, we demonstrate how early anti-inflammatory therapy may treat endothelia inflammation and immune-thrombosis caused by COVID-19, by using drugs we are going to recommend in this paper.

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

Introduction: Healthcare patterns change during disease outbreaks and pandemics. Identification of modified patterns is important for future preparedness and response. Emergency department (ED) crowding can occur because of the volume of patients waiting to be seen, which results in delays in patient assessment or treatment and impediments to leaving the ED once treatment is complete. Therefore, ED crowding has become a growing problem worldwide and represents a serious barrier to healthcare operations. Methods: This observational study was based on a retrospective review of the epidemiologic and clinical records of patients who presented to the Foundation IRCCS Policlinic San Matteo in Pavia, Italy, during the coronavirus disease 2019 (COVID-19) outbreak (February 21–May 1, 2020, pandemic group). The methods involved an estimation of the changes in epidemiologic and clinical data from the annual baseline data after the start of the COVID-19 pandemic. Results: We identified reduced ED visits (180 per day in the control period vs 96 per day in the pandemic period; P < 0.001) during the COVID-19 pandemic, irrespective of age and gender, especially for low-acuity conditions. However, patients who did present to the ED were more likely to be hemodynamically unstable, exhibit abnormal vital signs, and more frequently required high-intensity care and hospitalization. During the pandemic, ED crowding dramatically increased primarily because of an increased number of visits by patients with high-acuity conditions, changes in patient management that prolonged length of stay, and increased rates of boarding, which led to the inability of patients to gain access to appropriate hospital beds within a reasonable amount of time. During the pandemic, all crowding output indices increased, especially the rates of boarding (36% vs 57%; P < 0.001), “access block” (24% vs 47%; P < 0.001), mean boarding time (640 vs 1,150 minutes [min]; P 0.001), mean “access block” time (718 vs 1,223 min; P < 0.001), and “access block” total time (650,379 vs 1,359,172 min; P < 0.001). Conclusion: Crowding in the ED during the COVID-19 pandemic was due to the inability to access hospital beds. Therefore, solutions to this lack of access are required to prevent a recurrence of crowding due to a new viral wave or epidemic.

The geriatric population constitutes a large slice of the population of Western countries and a class of fragile patients, with greater deaths due to COVID-19. The patterns of healthcare utilization change during pandemic disease outbreaks. Identifying the patterns of changes of this particular fragile subpopulation is important for future preparedness and response. Overcrowding in the emergency department (ED) can occur because of the volume of patients waiting to be seen, delays in patient assessment or treatment in the ED, or impediments to leaving the ED once the treatment has been completed. Overcrowding has become a serious and growing issue globally, which represents a serious impediment to healthcare utilization. To estimate the rate of ED visits attributable to the outbreak and guide the planning of strategies for managing ED access or after the outbreak of transmittable respiratory diseases. This observational study was based on a retrospective review of the epidemiological and clinical records of patients aged > 75 years who visited the Foundation IRCCS Policlinic San Matteo during the first wave of COVID-19 outbreak (February 21 to May 1, 2020; pandemic group). The analysis methods included estimation of the changes in the epidemiological and clinical data from the annual baseline data after the start of the COVID-19 pandemic. Outcome measures and analysis: Primary objective is the evaluation of ED admission rate change and ED overcrowding. Secondary objectives are the evaluation of modes of ED access by reason and triage code, access types, clinical outcomes (such as admission and mortality rates). During the pandemic, ED crowding increased dramatically, although the overall number of patients decreased, in the face of a percentage increase in those with high-acuity conditions, because of changes in patient management that have prolonged length of stay (LOS) and increased rates of access block. Overcrowding during the COVID-19 pandemic can be attributed to the Access Block. Access Block solutions are hence required to prevent a recurrence of crowding to any new viral wave or new epidemic in the future. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02732-w.

Introduction The sudden increase in the number of critically ill patients following a disaster can be overwhelming. Study objective The main objective of this study was to assess the real number of available and readily freeable beds ("bed surge capacity") and the availability of emergency operating rooms (OR) in a maximum emergency using a theoretical simulation. Patients and methods The proportion of dismissible patients in four areas (Medical Area, Surgical Area, Sub-intensive Care Units, Intensive Care Units) and three emergency OR was assessed at 2 and 24 hours after a simulated maximum emergency. Four scenarios were modeled. Hospitalization and surgical capacities were assessed on weekdays and holidays. The creation of new beds was presumed by the possibility of moving patients to a lower level of care than that provided at the time of detection, of dislocation of patients to a discharge room, with care transferred to lower-intensity hospitals, rehabilitation, or discharge facilities. The Phase 1 table-top simulations were conducted during the weekday morning hours. In particular, the 24-hour table-top simulations of a hypothetical event lasted about 150 minutes compared to those conducted at 2 hours, which were found to be longer (about 195 minutes). Phase 2 was conducted on two public holidays and a quick response time was observed within the first 40 minutes of the start of the test (about 45% of departments). Results The availability of simulated beds was greater than that indicated in the maximum emergency plans (which was based solely on the census of beds). Patients admitted to Intensive Care and The Sub-Intensive Area may be more difficult to move than those in low-intensity care. The availability of emergency OR was not problematic. Age influenced the possibility of remitting/transferring patients. Conclusion Simulation in advance of a maximum emergency is helpful in designing an efficient response plan.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as “brain fog”. These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods of physical or mental activity become almost impossible. However, the disease presents heterogeneously with varying severity across patients. Therefore, consensus criteria have been designed to provide a diagnosis based on symptoms. To date, no biomarker-based tests or diagnoses are available, since the molecular changes observed also largely differ from patient to patient. In this review, we discuss the infectious, genetic, and hormonal components that may be involved in CFS pathogenesis, we scrutinize the role of gut microbiota in disease progression, we highlight the potential of non-coding RNA (ncRNA) for the development of diagnostic tools and briefly mention the possibility of SARS-CoV-2 infection causing CFS.

Background: Tetanus infection remains a significant complication of wounds. Because most tetanus treatment guidelines rely on anamnestic data collected directly from patients, the congruence between anamnesis and laboratory evidence must be verified, especially in the elderly population.Aim: Assess, in both the geriatric population (>65) and the non-geriatric one, the reliability of anamnestic data for managing patients with tetanus-risk wounds, identified categories of populations most exposed to non-vaccination coverage, and assessed the agreement of the Tetanos Quick Stick (TQS) results with the therapy performed (administration of tetanus vaccine or immunoglobulin).Methods: In this retrospective single-center observational study, patients were asked their immunization status against tetanus vaccination. The decision to administer a vaccine or immunoglobulin was therefore clinical and based on anamnestic criteria. The TQS test was then given to patients who were unaware of their immunity status. Patients who thought they knew it but were not sure were given the TQS test to determine whether the anamnestic collection was supported by the test. The TQS test results were compared with the anamnestic data.Results: Most patients, geriatric and not geriatric, did not know their immune status. Among those who reported knowing their immune status, there was no agreement between the vaccine coverage declared by patients and the TQS test results (p < 0.001), mainly in geriatric patients but also in the control group. Elderly and women had significantly lower positive TQS test results (p < 0.001). There was a statistically significant discrepancy (p < 0.001) between the therapy based on anamnestic data and the TQS test results.Conclusion: The reliability of anamnestic data for the management of patients with tetanus-risk wounds is low and decreases with age, becoming minimal in geriatric patients. Elderly and women are less likely to have an effective vaccination status against tetanus.

The evaluation of new therapeutic resources against coronavirus disease 2019 (COVID-19) represents a priority in clinical research considering the minimal options currently available. To evaluate the adjuvant use of systemic oxygen-ozone administration in the early control of disease progression in patients with COVID-19 pneumonia. PROBIOZOVID is an ongoing, interventional, randomized, prospective, and double-arm trial enrolling patient with COVID-19 pneumonia. From a total of 85 patients screened, 28 were recruited. Patients were randomly divided into ozone-autohemotherapy group (14) and control group (14). The procedure consisted in a daily double-treatment with systemic Oxygen-ozone administration for 7 days. All patients were treated with ad interim best available therapy. The primary outcome was delta in the number of patients requiring orotracheal-intubation despite treatment. Secondary outcome was the difference of mortality between the two groups. Moreover, hematological parameters were compared before and after treatment. No differences in the characteristics between groups were observed at baseline. As a preliminary report we have observed that one patient for each group needed intubation and was transferred to ITU. No deaths were observed at 7-14 days of follow up. Thirty-day mortality was 8.3% for ozone group and 10% for controls. Ozone therapy did not significantly influence inflammation markers, hematology profile, and lymphocyte subpopulations of patients treated. Ozone therapy had an impact on the need for the ventilatory support, although did not reach statistical significance. Finally, no adverse events related to the use of ozone-autohemotherapy were reported. Preliminary results, although not showing statistically significant benefits of ozone on COVID-19, did not report any toxicity.

The present study discusses about the effects of a combination of probiotics able to stimulate the immune system of patients affected by Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To this purpose, patients diagnosed according to Fukuda’s criteria and treated with probiotics were analyzed by means of clinical and laboratory evaluations, before and after probiotic administrations. Probiotics were selected considering the possible pathogenic mechanisms of ME/CFS syndrome, which has been associated with an impaired immune response, dysregulation of Th1/Th2 ratio, and high oxidative stress with exhaustion of antioxidant reserve due to severe mitochondrial dysfunction. Immune and oxidative dysfunction could be related with the gastrointestinal (GI) chronic low-grade inflammation in the lamina propria and intestinal mucosal surface associated with dysbiosis, leaky gut, bacterial translocation, and immune and oxidative dysfunction. Literature data demonstrate that bacterial species are able to modulate the functions of the immune and oxidative systems and that the administration of some probiotics can improve mucosal barrier function, modulating the release of proinflammatory cytokines, in CFS/ME patients. This study represents a preliminary investigation to verifying the safety and efficacy of a certain combination of probiotics in CFS/ME patients. The results suggest that probiotics can modify the well-being status as well as inflammatory and oxidative indexes in CFS/ME patients. No adverse effects were observed except for one patient, which displayed a flare-up of symptoms, although all inflammatory parameters (i.e., cytokines, fecal calprotectin, ESR, and immunoglobulins) were reduced after probiotic intake. The reactivation of fatigue symptoms in this patient, whose clinical history reported the onset of CFS/ME following mononucleosis, could be related to an abnormal stimulation of the immune system as suggested by a recent study describing an exaggerated immune activation associated with chronic fatigue.

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An increasing amount of reports in the literature is showing that medical ozone (O3) is used, with encouraging results, in treating COVID-19 patients, optimizing pain and symptoms relief, respiratory parameters, inflammatory and coagulation markers and the overall health status, so reducing significantly how much time patients underwent hospitalization and intensive care. To date, aside from mechanisms taking into account the ability of O3 to activate a rapid oxidative stress response, by up-regulating antioxidant and scavenging enzymes, no sound hypothesis was addressed to attempt a synopsis of how O3 should act on COVID-19. The knowledge on how O3 works on inflammation and thrombosis mechanisms is of the utmost importance to make physicians endowed with new guns against SARS-CoV2 pandemic. This review tries to address this issue, so to expand the debate in the scientific community.

Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient’s condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk (p &gt, 0.05), as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%, p &lt, 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%, 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge (p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe.

Coagulopathy induced by major trauma is common, affecting approximately one-third of patients after trauma. It develops independently of iatrogenic, hypothermic, and dilutive causes (such as iatrogenic cause in case of fluid administration), which instead have a pejorative aspect on coagulopathy. Notwithstanding the continuous research conducted over the past decade on Trauma-Induced Coagulopathy (TIC), it remains a life-threatening condition with a significant impact on trauma mortality. We reviewed the current evidence regarding TIC diagnosis and pathophysiological mechanisms and summarized the different iterations of optimal TIC management strategies among which product resuscitation, potential drug administrations, and hemostatis-focused approaches. We have identified areas of ongoing investigation and controversy in TIC management.

Paraneoplastic neurological syndromes (PNS) are a group of rare and severe immune-mediated disorders that affect the nervous system in patients with cancer. The best way to diagnose a paraneoplastic neurological disorder is to identify anti-onconeural protein antibodies that are specifically associated with various cancers. The aim of this multicentric study was to clinically and immunologically characterize patients with PNS and study their association with cancer. Patients suspected to have PNS were enrolled from various clinical centres and were characterized immunologically. This study population consisted of 112 patients. Onset of PNS was mainly subacute (76 %). PNS patients had various neurological disorders and symptoms. PNS developed before the diagnosis of cancer in 28 definite PNS patients and in six suspected PNS patients. The most frequent autoantibodies detected in PNS patients were anti-Hu and anti-Yo. One definite PNS patient with cerebellar syndrome had anti-Tr antibody and seven patients had atypical antibodies. The literature associates these antibodies with various neurological disorders and cancers. Our observations confirm the important role of autoantibodies in PNS and their importance for the early diagnosis of cancer in PNS patients.

Background and Objectives: Adherence to guidelines by physicians of an emergency department (ED) depends on many factors: guideline and environmental factors, patient and practitioner characteristics, the social-political context. We focused on the impact of the environmental influence and of the patients&rsquo, characteristics on adherence to the guidelines. It is our intention to demonstrate how environmental factors such as ED organization more affect adherence to guidelines than the patient&rsquo, s clinical presentation, even in a clinically insidious disease such as pulmonary embolism (PE). Materials and Methods: A single-center observational study was carried out on all patients who were seen at our Department of Emergency and Acceptance from 1 January to 31 December 2017 for PE. For the assessment of adherence to guidelines, we used the European guidelines 2014 and analyzed adherence to the correct use of clinical decision rule (CDR as Wells, Geneva, and YEARS), the correct initiation of heparin therapy, and the management of patients at high risk for short-term mortality. The primary endpoint of our study was to determine whether adherence to the guidelines as a whole depends on patients&rsquo, management in a holding area. The secondary objective was to determine whether adherence to the guidelines depended on patient characteristics such as the presence of typical symptoms or severe clinical features (massive pulmonary embolism, organ damage). Results: There were significant differences between patients who passed through OBI and those who did not, in terms of both administration of heparin therapy alone (p = 0.007) and the composite endpoints of heparin therapy initiation and observation/monitoring (p = 0.004), as indicated by the guidelines. For the subgroups of patients with massive PE, organ damage, and typical symptoms, there was no greater adherence to the decision making, administration of heparin therapy alone, and the endpoints of heparin therapy initiation and guideline-based observation/monitoring. Conclusion: Patients managed in an ED holding area were managed more in accordance with the guidelines than those who were managed only in the visiting ED rooms and directly hospitalized from there.

Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. This study aims to compare the incidence of post-traumatic ICH following mild head injury (MHI) and to assess the need for surgery, mortality rates, emergency department (ED) revisit rates, and the volume of ICH. Materials and Methods: This is a retrospective, single-center observational study on all patients admitted to our emergency department for mild head trauma from 1 January 2016, to 31 December 2018. We enrolled 234 anticoagulated patients, of which 156 were on VKAs and 78 on DOACs. Patients underwent computed tomography (CT) scans on arrival (T0) and after 24 h (T24). The control group consisted of patients not taking anticoagulants, had no clotting disorders, and who reported an MHI in the same period. About 54% in the control group had CTs performed. Results: The anticoagulated groups were comparable in baseline parameters. Patients on VKA developed ICH more frequently than patients on DOACs and the control group at 17%, 5.13%, and 7.5%, respectively. No significant difference between the two groups was noted in terms of surgery, intrahospital mortality rates, ED revisit rates, and the volume of ICH. Conclusions: Patients with mild head trauma on DOAC therapy had a similar prevalence of ICH to that of the control group. Meanwhile, patients on VKA therapy had about twice the ICH prevalence than that on the control group or patients on DOAC, which remained after correcting for age. No significant difference in the need for surgery was determined, however, this result must take into account the very small number of patients needing surgery.

Background and objectives: Acute heart failure (AHF) is one of the main causes of hospitalization in Western countries. Usually, patients cannot be admitted directly to the wards (access block) and stay in the emergency room. Holding units are clinical decision units, or observation units, within the ED that are able to alleviate access block and to contribute to a reduction in hospitalization. Observation units have also been shown to play a role in specific clinical conditions, like the acute exacerbation of heart failure. This study aimed to analyze the impact of a brief intensive observation (OBI) area on the management of acute heart failure (AHF) patients. The OBI is a holding unit dedicated to the stabilization of unstable patients with a team of dedicated physicians. Materials and Methods: We conducted a retrospective and single-centered observational study with retrospective collection of the data of all patients who presented to our emergency department with AHF during 2017. We evaluated and compared two cohorts of patients, those treated in the OBI and those who were not, in terms of the reduction in color codes at discharge, mortality rate within the emergency room (ER), hospitalization rate, rate of transfer to less intensive facilities, and readmission rate at 7, 14, and 30 days after discharge. Results: We enrolled 920 patients from 1st January to 31st December. Of these, 61% were transferred to the OBI for stabilization. No statistically significant difference between the OBI and non-OBI populations in terms of age and gender was observed. OBI patients had worse clinical conditions on arrival. The patients treated in the OBI had longer process times, which would be expected, to allow patient stabilization. The stabilization rate in the OBI was higher, since presumably OBI admission protected patients from &ldquo, worse condition&rdquo, at discharge. Conclusions: Data from our study show that a dedicated area of the ER, such as the OBI, has progressively allowed a change in the treatment path of the patient, where the aim is no longer to admit the patient for processing but to treat the patient first and then, if necessary, admit or refer. This has resulted in very good feedback on patient stabilization and has resulted in a better management of beds, reduced admission rates, and reduced use of high intensity care beds.

Background and Objectives: Trauma coagulopathy begins at the moment of trauma. This study investigated whether coagulopathy upon arrival in the emergency room (ER) is correlated with increased hemotransfusion requirement, more hemodynamic instability, more severe anatomical damage, a greater need for hospitalization, and hospitalization in the intensive care unit (ICU). We also analyzed whether trauma coagulopathy is correlated with unfavorable indices, such as acidemia, lactate increase, and base excess (BE) increase. Material and Methods: We conducted a prospective, monocentric, observational study of all patients (n = 503) referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for major trauma from 1 January 2018 to 30 January 2019. Results: Of the 503 patients, 204 had trauma coagulopathy (group 1), whereas 299 patients (group 2) did not. Group 1 had a higher hemotransfusion rate than group 2. In group 1, 15% of patients showed hemodynamic instability compared with only 8% of group 2. The shock index (SI) distribution was worse in group 1 than in group 2. Group 1 was more often hypotensive, tachycardic, and with low oxygen saturation, and had a more severe injury severity score than group 2. In addition, 47% of group 1 had three or more body districts involved compared with 23% of group 2. The hospitalization rate was higher in group 1 than in group 2 (76% vs. 58%). The length of hospitalization was &gt, 10 days for 45% of group 1 compared with 28% of group 2. The hospitalization rate in the ICU was higher in group 1 than in group 2 (22% vs. 14.8%). The average duration of ICU hospitalization was longer in group 1 than in group 2 (12.5 vs. 9.78 days). Mortality was higher in group 1 than in group 2 (3.92% vs. 0.98%). Group 1 more often had acidemia and high lactates than group 2. Group 1 also more often had BE &lt, &minus, 6. Conclusions: Trauma coagulopathy patients, upon arrival in the ER, have greater hemotransfusion (p = 0.016) requirements and need hospitalization (p = 0.032) more frequently than patients without trauma coagulopathy. Trauma coagulopathy seems to be more present in patients with a higher injury severity score (ISS) (p = 0.000) and a greater number of anatomical districts involved (p = 0.000). Head trauma (p = 0.000) and abdominal trauma (p = 0.057) seem related to the development of trauma coagulopathy. Males seem more exposed than females in developing trauma coagulopathy (p = 0.018). Upon arrival in the ER, the presence of tachycardia or alteration of SI and its derivatives can allow early detection of patients with trauma coagulopathy.

The problems related to the approach to the outbreak of COVID-19 in the world require that all possible effective treatment options be explored. The clinical criterion of the researcher is not to refuse a priori, but to verify and evaluate the proposals that are made. Italian Society of Oxygen Ozone Therapy (SIOOT) proposed to the Italian ISS (Italian Institute of Health) to use oxygen ozone therapy (O2O3) in patients with COVID-19. (...)

The well-known symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are chronic pain, cognitive dysfunction, post-exertional malaise and severe fatigue. Another class of symptoms commonly reported in the context of ME/CFS are gastrointestinal (GI) problems. These may occur due to comorbidities such as Crohn’s disease or irritable bowel syndrome (IBS), or as a symptom of ME/CFS itself due to an interruption of the complex interplay between the gut microbiota (GM) and the host GI tract. An altered composition and overall decrease in diversity of GM has been observed in ME/CFS cases compared to controls. In this review, we reflect on genetics, infections, and other influences that may factor into the alterations seen in the GM of ME/CFS individuals, we discuss consequences arising from these changes, and we contemplate the therapeutic potential of treating the gut to alleviate ME/CFS symptoms holistically.

Delirium is a severe neuropsychiatric syndrome characterized by inattention and global cognitive dysfunction in the setting of an acute medical illness, medical complication, drug intoxication or drug withdrawal. The most important risk factors are advanced age and dementia whereas pain, dehydration, infections, stroke, metabolic disturbances, and surgery are the most common triggering factors. Although delirium is a common clinical syndrome in different setting of care (acute care hospitals, inpatient rehabilitation facilities, nursing homes, and hospices) it often remains under-recognised, poorly understood and not adequately managed then there exists a clear need for improved understanding to overcome cultural stereotypes and for the development and dissemination of a comprehensive model of implementation of general good practice points. A network of Italian national scientific societies was thus convened (1) to develop a collaborative multidisciplinary initiative report on delirium in the elderly hospitalized patients, (2) to focus the attention of health care personnel on prevention, diagnosis and therapy of patients suffering from delirium, and (3) to make the health services research community and policy-makers more aware of the potential risks of this condition providing a reference for training activities and data collection.

Objective This study evaluated the potential efficacy of a novel approach to treat COVID-19 patients, using an oxygen-ozone (O2-O3) mixture, via a process called Oxygen-Ozone- Immunoceutical Therapy. The methodology met the criteria of a novel, promising approach to treat successfully elderly COVID-19 patients, particularly when hospitalized in intensive care units (ICUs) Experimental design: We investigated the therapeutic effect of 4 cycles of O2-O3 in 50 hospitalized COVID-19 subjects suffering from acute respiratory disease syndrome (ARDS), aged more than 60 years, all males and undergoing non invasive mechanical ventilation in ICUs. Results Following O2-O3 treatment a significant improvement in inflammation and oxygenation indexes occurred rapidly and within the first 9 days after the treatment, despite the expected 14–20 days. A significant reduction of inflammatory and thromboembolic markers (CRP, IL-6, D-dimer) was observed. Furthermore, amelioration in the major respiratory indexes, such as respiratory and gas exchange markers (SatO2%, PaO2/FiO2 ratio), was reported. Conclusion Our results show that O2-O3 treatment would be a promising therapy for COVID-19 patients. It leads patients to a fast recovery from ARDS via the improvement of major respiratory indexes and blood gas parameters, following a relatively short time of dispensed forced ventilation (about one to two weeks). This study may encourage the scientific community to further investigate and evaluate the proposed method for the treatment of COVID-19 patients.

The prevention of surgical site infections is a priority within the objectives of the National Health System. The negative consequences of postoperative infections (morbidity, duration of hospitalization, mortality) are particularly serious events for the individual patient and for the community, given both the welfare resources needed to treat them, and the continued growth of the phenomenon of antibiotic resistance. In a global health context in which evidence-based medicine has established itself, all medical interventions must be reconsidered in the light of what can be inferred from the literature evaluated according to strict methodological criteria, all the more so when the evidence is available and unanimously shared. The future objective will be to introduce in the national guidelines a protocol involving the use of ozone therapy alongside antibiotic therapy, both in the prevention and treatment of infections, to avoid the emergence of antibiotic resistance and thus reduce the expenditure of the national health system.

Ozone major autohemotherapy is effective in reducing the symptoms of multiple sclerosis (MS) patients, but its effects on brain are still not clear. In this work, we have monitored the changes in the cerebrovascular pattern of MS patients and normal subjects during major ozone autohemotherapy by using near-infrared spectroscopy (NIRS) as functional and vascular technique. NIRS signals are analyzed using a combination of time, time-frequency analysis and nonlinear analysis of intrinsic mode function signals obtained from empirical mode decomposition technique. Our results show that there is an improvement in the cerebrovascular pattern of all subjects indicated by increasing the entropy of the NIRS signals. Hence, we can conclude that the ozone therapy increases the brain metabolism and helps to recover from the lower activity levels which is predominant in MS patients.

Due to an increasingly aging population, Alzheimer disease (AD) represents a crucial issue for the healthcare system because of its widespread prevalence and the burden of its care needs. Several hypotheses on AD pathogenesis have been proposed and current therapeutical strategies have shown limited effectiveness. In the last decade, more evidence has supported a role for neuroinflammation and immune system dysregulation in AD. It remains unclear whether astrocytes, microglia and immune cells influence disease onset, progression or both. Amyloid-β peptides that aggregate extracellularly in the typical neuritic plaques generate a constant inflammatory environment. This causes a prolonged activation of microglial and astroglial cells that potentiate neuronal damage and provoke the alteration of the blood brain barrier (BBB), damaging the permeability of blood vessels. Recent data support the role of the BBB as a link between neuroinflammation, the immune system and AD. Hence, a thorough investigation of the neuroinflammatory and immune system pathways that impact neurodegeneration and novel exciting findings such as microglia-derived microvesicles, inflammasomes and signalosomes will ultimately enhance our understanding of the pathological process. Eventually, we should proceed with caution in defining a causal or consequential role of neuroinflammation in AD, but rather focus on identifying its exact pathological contribution.

Neuroinflammation is a biological process by which the central nervous system responds to stimuli/injuries affecting its homeostasis. So far as this reactive response becomes exacerbated and uncontrolled, it can lead to neurodegeneration, compromising the cognitive and neuropsychiatric domains. Parallelly, modifications in the hypothalamic signaling of neuroprotective hormones linked also to the inflammatory responses of microglia and astrocytes can exacerbate these processes. To complicate the picture, modulations in the gut microbiota (GM) can induce changes in neuroinflammation, altering cognitive and neuropsychiatric functioning. We conducted a web-based search on PubMed. We described studies regarding the cross-talk among microglia and astrocytes in the neuroinflammation processes, along with the role played by the steroid hormones, and how this can reflect on cognitive decline/neurodegeneration, in particular on Alzheimer’s Disease (AD) and its neuropsychiatric manifestations. We propose and support the huge literature showing the potentiality of complementary/alternative therapeutic approaches (nutraceuticals) targeting the sustained inflammatory response, the dysregulation of hypothalamic system and the GM composition. NF-κB and Keap1/Nrf2 are the main molecular targets on which a list of nutraceuticals can modulate the altered processes. Since there are some limitations, we propose a new intervention natural treatment in terms of Oxygen-ozone (O2-O3) therapy that could be potentially used for AD pathology. Through a meta-analytic approach, we found a significant modulation of O3 on inflammation-NF-κB/NLRP3 inflammasome/Toll-Like Receptor 4 (TLR4)/Interleukin IL-17α signalling, reducing mRNA (p

Introduction: Major trauma is the leading cause of mortality in the world in patients younger than 40 years. However, the proportion of elderly people who suffer trauma has increased significantly. The purpose of this study is to assess the correlation of old age with mortality and other unfavorable outcomes. Methods: We assessed on one hand, anatomical criteria such as ISS values and the number of body regions affected, on the other hand, hemodynamic instability criteria, various shock indices, and Glasgow Coma Scale. Finally, we also evaluated biochemical parameters, such as lactate, BE, and pH values. We conducted a prospective and monocentric observational study of all the patients referred to the Emergency Department of the IRCCS Fondazione Policlinico S. Matteo in Pavia for major trauma in 13 consecutive months: January 1, 2018–January 30, 2019. We compared the elderly population (>75 years) and the younger population (≤75). Results: We included 501 patients, among which 10% were over the age of 75 years. The mortality rate was higher among the older patients than among the younger (4% vs. 1.33%; P = 0.050). Hemodynamic instability was more common in the older patients than in the younger (26% vs. 9%; P < 0.001). More older patients (44%) had an ISS >16, in comparison with 32% of younger patients (P = 0.01). Conclusions: The elderly showed worse outcomes in terms of mortality, hospitalization rate, hemodynamic instability criteria, and anatomical and biochemical parameters.

Introduction We evaluated the risk profile of elderly patients who came to the emergency department for mild head trauma. The primary goal was to determine the difference in the incidence of posttraumatic intracranial hemorrhage (ICH) after minor head injury (MHI). The secondary objective was to assess worse outcome, such as: hospitalization rate, rate of re-admission, need of neurosurgery. We also assess the admission process times and length of hospital stay. The ultimate goal was to optimize the diagnostic-observational management of minor head trauma in elderly patients. Material and methods We evaluated all patients with MHI who came to our emergency department during 2017 and 2018. All patients underwent computed tomography. Results We enrolled 2325 patients, of whom 1094 were 75 years of age or older. The population was divided into two categories according to age: The “elderly population” was 75 or older, and the younger patients were younger than 75. The elderly population, in comparison with the younger patients, had a higher rate of ICH (12.1% versus 5.1%), a higher hospitalization rate (11.7% versus 5.5%), and a higher rate of readmission within 30 days (6.8% versus 3.2%). The elderly population also had longer admission process times (8 h, 25 min, versus 4 h, 09 min) and longer lengths of hospital stay (9 h, 41 min, versus 5 h, 29 min). Of the younger patients, 92% (versus 41% of the elderly population) did not take any drugs, 6% (versus 39%) were receiving antiplatelet therapy, 1% (versus 13%) took vitamin K antagonists, and 1% (versus 7%) took oral direct-acting anticoagulants. Logistic regression models revealed that a 1-year increase in age raised the risk of bleeding by 2% on average; this finding was statistically significant (odds ratio [OR], 1023/year, p < 0.001). The rate of ICH increased significantly after the age of 75, by 180% (OR, 2.82; p < 0.001). Conclusions These data suggest that age is an independent risk factor for ICH, whereby the age of 75 entails a 180% increase in the risk of bleeding., Neurosurgery; Trauma; Emergency medicine; Internal medicine; Clinical research; Brain injury management; Elderly patients; Hemorrhage; Mild traumatic brain injury; Posttraumatic intracranial hemorrhage.

Antimicrobial resistance is one of the most complex global health challenges today. The world has long ignored warnings that antibiotics and other medicines are losing their effectiveness after decades of overuse and misuse in human medicine, animal health and agriculture. Common illnesses like pneumonia, postoperative infections, diarrhoeal and sexually transmitted diseases, as well as the world’s largest infectious disease killers – tuberculosis (TB), HIV and malaria – are increasingly becoming untreatable because of the emergence and spread of drug resistance. Worsening antimicrobial resistance could have serious public health, economic and social implications. The threat of antimicrobial resistance is also becoming a key consideration for programmes addressing maternal and child health, sexual and reproductive health, foodborne diseases, water and sanitation, and infection prevention and control. Although the 21st century is being shaped by technology and innovation, humans could soon find themselves in an era where simple infections once again kill millions every year. The past three years have seen unprecedented global political momentum to address antimicrobial resistance: in 2015, governments adopted a global action plan at the World Health Assembly and in 2016 passed a political declaration at the United Nations General Assembly. Antimicrobial resistance has made it onto the agendas of the G7 and G20 groups and is a core component of the Global Health Security Agenda. WHO is working closely with the Food and Agriculture Organization of the United Nations and the World Organization for Animal Health in leading global efforts against antimicrobial resistance and ensuring that the necessary momentum is consolidated and sustained. These efforts are guided by an ad-hoc interagency coordination group established in 2017. A global development and stewardship framework to combat antimicrobial resistance is being drafted to support the development of new antimicrobial medicines, diagnostics, vaccines and other tools. One of the gravest global concerns about antimicrobial resistance currently is that antibiotic resistance has emerged in so many pathogens, including TB. In 2016, at the high-level meeting of the UN General Assembly on antimicrobial resistance, Heads of State directed an unprecedented level of attention to curbing the spread of infections that are resistant to antimicrobial medicines. They reaffirmed their commitment to stopping the misuse of antimicrobial medicines in human health, animal health and agriculture, and recognized the need for stronger systems to monitor drug-resistant infections and the amounts of antimicrobials used in humans and animals. In the wake of the increasing global awareness of the need for new antibiotics, Member States highlighted market failures, and called for new incentives for investment in research and development of new, effective and affordable medicines, rapid diagnostic tests, and other important therapies to replace those that are losing their effectiveness. In response to this and in line with the Global Action Plan on Antimicrobial Resistance to support the identification of pathogens of greatest concern, WHO developed a priority list of antibiotic resistant bacteria to underpin renewed efforts for the research and development of new antibiotics. The only possible defence against the threat of antimicrobial resistance and the (very real) possibility of a post-antibiotic era is a global and coordinated effort by all stakeholders to support other important therapies such as the Oxygen-Ozone (O2O3) therapy. As a result, the scope and focus of the work underlying this dissertation was to study the application of O2O3 therapy towards several resistant bacteria. Moreover, we evaluated three different framework for gut bacteria, skin and soft tissue infections and mucosal infections.

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This paper presents a step toward the development of a data-centric approach to prevention of Mild Cognitive Impairment and frailty in the elderly population. The scientific literature provides a large number of “indicators” for assessing the quality of behavior for aged individuals, in order to predict possible decaying. On the opposite side, a large variety of sensors and datasets today allows the effective collection of elementary data about actions performed by individuals. This paper proposes to build a bridge between these two sides. In a bottom-up vision, data from sensors and smart cities' datasets are aggregated and interpreted in a way that leads to reliable assessment of the indicators. In a top-down vision, indicators are translated into data analysis. The work described in this paper is part of City4age, a project partially funded by the EU within the H2020 Programme.

The ApoE gene is associated with the risk of Alzheimer or cardiovascular disease but its influence on exceptional longevity (EL) is uncertain. Our primary purpose was to determine, using a case-control design, if the ApoE gene is associated with EL. We compared ApoE allele/genotype frequencies among the following cohorts: cases (centenarians, most with 1+ major disease condition; n=163, 100-111years) and healthy controls (n=1039, 20-85years) from Spain; disease-free cases (centenarians; n=79, 100-104years) and healthy controls (n=597, age 27-81years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1+ major disease condition; n=729, 100-116years) and healthy controls (n=498, 23-59years) from Japan. Our main findings were twofold. First, the ε4-allele was negatively associated with EL in the three cohorts, with the following odds ratio (OR) values (adjusted by sex) having been found: 0.55 (95% confidence interval (CI): 0.33, 0.94), P=0.030 (Spain); 0.41 (95%CI: 0.18, 0.99), P=0.05 (Italy); and 0.35 (95%CI: 0.26, 0.57), P

Introduction. A number of studies suggest that oxygen-ozone therapy may have a role in the treatment of chronic, nonhealing, or ischemic wounds for its disinfectant and antibacterial properties. Nonhealing wounds are a significant cause of morbidity. Here we present a case of subcutaneous oxygen-ozone therapy used to treat a nonhealing postoperative wound in a young man during a period of 5 weeks.Case Presentation. A 46-year-old man had a motorcycle accident and underwent amputation of the right tibia and fibula. At the discharge he came to our attention to start rehabilitation treatment. At that time the wound was ulcerated but it was afebrile with no signs of inflammation and negativity to blood tests. At 2 months from the trauma despite appropriate treatment and dressing, the wound was slowly improving and the patient complained of pain. For this reason in addition to standard dressing he underwent oxygen-ozone therapy. After 5 weeks of treatment the wound had healed.Conclusion. In patients with nonhealing wounds, oxygen-ozone therapy could be helpful in speeding the healing and reducing the pain thanks to its disinfectant property and by the increase of endogenous oxygen free radicals’ scavenging properties. Compared to standard dressing and other treatments reported in the literature it showed a shorter time of action.

Alzheimer's disease (AD) has been recognized as the most common cause of sporadic dementia. It represents both a medical and social problem, as it affects 10% of over-65 population. Even if the elderly are the most involved population, aging alone cannot be considered as the only cause of this disease. In this review we wanted to focus on the last hypotheses on the possible causes of this neuronal affection. We focused in particular on the role of inflammation and alteration of the inflammatory status that is typical of the elderly and may lead to chronic inflammation. The inflammation seems to be a cause of neuronal impairment and loss. Some studies have proposed a protective role of antiinflammatory drugs. Then we analyzed the role of genetic polymorphisms of some pro-inflammatory substances that seem to be linked to some cases of dementia. The complement system seems to have a role too, as some factors have been found in senile plaques, representing a possible involvement of classical complement pathway. One of the latest hypotheses is about the role of blood-brain barrier (BBB), as its loss of integrity may lead to a passage of proteins in cerebro spinal fluid (CSF), causing a compromised role of BBB in preserving the brain as an "immune sanctuary".

HIV-related acute inflammatory leukoencephalopathy of undetermined origin (AIL) has been anecdotally described in literature as being responsible for cognitive and motor deficits. We carried out a review of all the cases of AIL published in literature. Articles were selected according to 2 criteria: acute onset of symptoms; undetermined aetiology and non-fulfilment of multiple sclerosis diagnostic criteria. They were then analyzed in terms of clinical, biological and instrumental features, therapy, diagnostic classification and prognosis. Although rare (21 patients out of about 4,000 publications), AIL is of particular interest, as the comprehension of its mechanisms could give some insight into the direct and immune-mediated actions of HIV within the brain. All the reported patients share several clinical, histopathological, radiological and CSF features, leading to hypothesize a similar aetiopathogenetic mechanism. Conversely, we observed a high heterogeneity of treatment and diagnostic classification, which could have conditioned the broad prognostic variability. The absence of a defined aetiology leads to consider these forms as a particular subgroup of “not determined leucoencephalopathies” (NDLE), with both MRI and histological pattern dominated by inflammation as distinctive feature.

Chronic fatigue syndrome (CFS) is a disease that can seriously impair one's quality of life; patients complain of excessive fatigue and myalgia following physical exertion. This disease may be associated with abnormalities in genes affecting exercise tolerance and physical performance. Adenosine monophosphate deaminase (AMPD1), carnitine palmitoyltransferase II (CPT2), and the muscle isoform of glycogen phosphorylase (PYGM) genes provide instructions for producing enzymes that play major roles in energy production during work. The aim of this study was to look for evidence of genotype-associated excessive muscle fatigue. Three metabolic genes (AMPD1, CPT2, and PYGM) were therefore fully sequenced in 17 Italian patients with CFS. We examined polymorphisms known to alter the function of these metabolic genes, and compared their genotypic distributions in CFS patients and 50 healthy controls using chi-square tests and odds ratios. One-way analysis of variance with F-ratio was carried out to determine the associations between genotypes and disease severity using CF scores. No major genetic variations between patients and controls were found in the three genes studied, and we did not find any association between these genes and CFS. In conclusion, variations in AMPD1, CPT2, and PGYM genes are not associated with the onset, susceptibility, or severity of CFS.

In this study we analyzed the clinical features of a population of Italian patients with chronic fatigue syndrome (CFS) diagnosed according to the CDC-1994 criteria. The aim was to investigate CFS patients and their relatives, in order to search for events related to the onset of the disease and to identify correlations with other diseases. The analysis was carried out by examining medical records belonging to 82 patients suffering from the syndrome. The documentation was collected between 2008 and 2011 and provided by the non-profit Italian organization AMCFS (Associazione Malati di CFS). The influence of gender on the age of onset and association with potential risk factors were investigated in patients and in their relatives. From the results a significant correlation between the age of onset and autoimmunity was observed.

We analyzed soluble vascular adhesion molecules (sVCAM-1), reactive oxygen metabolites (ROMs) level, total antioxidant status (TAS) and telediastolic left ventricular volume (TLW) in patients with myocardial infarction undergoing reperfusion therapy and treated with antioxidant vitamins (AT) or placebo (P) before and for 1 month after reperfusion. After reperfusion, sVCAM-1 serum concentration, reactive oxygen metabolites level, and TLW were significantly higher in patients treated with placebo than in those treated with antioxidant vitamins, while TAS was significantly higher in patients treated with antioxidant supplementation. We observed that 48 hours after reperfusion sVCAM-1 (P) vs sVCAM −1(AT) was 2.03±0.5 vs 1.63±0.7 μg/ml with p

SummaryPlatelet recruitment crucially depends on amplification systems provided by autocrine and paracrine factors such as adenosine diphosphate. In inflammatory states, consumption of coagulation proteins, such as antithrombin aggravates the procoagulant state. In this study, we report that platelets express synde-can-4, an antithrombin-binding cell surface heparan sulphate proteoglycan, whose ligation with antithrombin inhibits activated platelet-dependent superoxide anion release from neut-rophils by the limitation of adenosine diphosphate and adeno-sine triphosphate secretion in activated platelets. Adenosine triphosphate-induced platelet aggregation is reduced after treatment of platelets with antithrombin, which is reversed by blockade of syndecan-4. We further observed that antithrombin limits CD40 ligand expression in adenosine diphosphate-activated platelets and inhibits the shedding of syndecan-4 from activated platelets. Syndecan-4 appears to be directly involved in regulating platelet aggregation as anti-syndecan-4 antibody augments platelet aggregation. We suggest that antithrombin might exert beneficial effects in disseminated intravascular coagulation by reducing platelet activation, observed as inhibited CD40 ligand expression, syndecan-4 shedding, and adenosine diphosphate- and adenosine triphosphate-release from activated platelets with subsequent inhibition of neutrophil respiratory burst. From these data it is concluded that syndecan-4 may play important roles in the regulation of inflammatory effects of platelets.

The problem of a correct fall risk assessment is becoming more and more critical with the ageing of the population. In spite of the available approaches allowing a quantitative analysis of the human movement control system's performance, the clinical assessment and diagnostic approach to fall risk assessment still relies mostly on non-quantitative exams, such as clinical scales. This work documents our current effort to develop a novel method to assess balance control abilities through a system implementing an automatic evaluation of exercises drawn from balance assessment scales. Our aim is to overcome the classical limits characterizing these scales i.e. limited granularity and inter-/intra-examiner reliability, to obtain objective scores and more detailed information allowing to predict fall risk. We used Microsoft Kinect to record subjects' movements while performing challenging exercises drawn from clinical balance scales. We then computed a set of parameters quantifying the execution of the exercises and fed them to a supervised classifier to perform a classification based on the clinical score. We obtained a good accuracy (~82%) and especially a high sensitivity (~83%).

Although the number of centenarians is growing worldwide, the potential factors influencing the aging process remain only partially elucidated. Researchers are increasingly focusing toward biomarkers as tools to shed more light on the pathophysiology of complex phenotypes, including the ability to reach successful aging, i.e., free of major chronic diseases. We therefore conducted a case-control study examining the potential associations of multiple candidate biomarkers in healthy centenarians and sex-matched healthy elderly controls. Using a case-control study of 81 centenarians (aged ≥ 100 years) selected based on the fact that they were disease-free and 46 healthy elderly controls (aged 70-80 years), serum levels of 15 different candidate biomarkers involved in the regulation of metabolism, angiogenesis, inflammation, and bone formation were measured. Of the 15 biomarkers tested, four molecules (chemerin, fetuin-A, and fibroblast growth factors [FGF] 19 and 21) were found to be independently associated with successful aging regardless of sex. Logistic regression analysis confirmed that chemerin, fetuin-A, FGF19, and FGF21 were independently associated with successful aging [predicted probability (PP) = 1 / [1 + 1 / exp (11.832 - 0.027 × (chemerin) - 0.009 × (fetuin-A) + 0.014 × (FGF19) - 0.007 × (FGF21)]. The area under the curve (AUC) of predicted probability values for the four-biomarker panel revealed that it can discriminate between centenarians and elderly controls with excellent accuracy (AUC > 0.94, P

Skin ulcers are a common issue in the elderly, as physiological loss of skin elasticity, alterations in microcirculation, and concomitant chronic diseases typically occur in advanced age, thereby predisposing to these painful lesions. Wound-related pain is often associated with skin ulcers and negatively impacts both the patient’s quality of life and, indirectly, wound healing. Pain management is an ongoing issue in the elderly, and remains underestimated and under-treated in this fragile population. Recent guidelines suggest the use of opioids as the frontline treatment of moderate and severe pain in nononcological pain in the elderly. However, due to the concerns of adverse reactions, drug interactions, and addiction, clinicians frequently hesitate to prescribe opioids. This case report describes an elderly diabetic patient with multiple ulcers of the lower limbs suffering wound-related pain. In our report, oxycodone/naloxone has proved to be an effective and safe drug, providing pain relief as well as increased compliance when redressing wounds and faster healing compared to that in similar patients. Our case provides anecdotal evidence, supported by other studies, to justify future, larger studies on chronic pain using this therapy.

Alzheimer's disease (AD) is widely identified as the most common cause of sporadic dementia. Its aetiology is still debated, as despite several hypotheses, different factors seem to play a role in its establishment and development. Recent studies have proposed a possible preventing role of nutrition. The weight loss typical of earlier phase of disease and the finding of malnutrition as a common trait between patients leads to hypothesize that a supplementation of specific nutrients seems to be useful and effective in terms of improvement of cognitive functions. Malnourished patients show also altered parameters when investigating inflammation markers: for example, hyperhomocysteinemia is a typical finding in elderly affected by dementia, and it can be prevented and corrected by using a proper nutrients supplementation. Pro-inflammatory state can be reduced with supplementation of polyunsaturated fatty acids, vitamins of the group B and phosphatidylserine, that can act reducing IL-1β (pro-inflammatory cytokine) and improving IL-10 (anti-inflammatory cytokine) synthesis. While investigating the role of nutrition, it seems to be deeply linked with genetic; a genetic onset AD-related could be latent and can be influenced by nutritional attitude. AD can be considered a sort of latent clinical condition that would disclose or not, depending also on micro-environment and nutritional parameters. The genetic expression can be influenced by assumptions or not of specific nutrients, with the promotion of different pro- or anti-inflammatory settings. The specific role of each micronutrient (in particular vitamins) and trace elements still needs to be punctuated, as they are involved in a pool of different reactions. Also genes acts not independently but in an interconnected pattern, in which the role of a single gene needs to be cleared, depending on others. This complex system of predisposing conditions and a possible role of nutrition as modulator of the inflammatory state is the object of this review.

Estimation of cardiac morbidity in patients after major surgery is a difficult problem. In addition, infectious complications seriously decrease potential beneficial outcome after cardiovascular surgery. The present study assessed the use of a newer marker of the inflammatory response, procalcitonin, in the field of myocardial infarction, in conjunction with measurements of interleukin-6. Forty-four consecutive cases with acute myocardial infarction were included in the study 4 ± 1.3 h after the onset of symptoms. Plasma levels of procalcitonin and interleukin-6 were obtained at admission, and after 3, 6, 12, 18, 24 and 48 h, using commercially available test kits. The range of levels of interleukin-6 and procalcitonin was about normal at admission. Interleukin-6 levels increased significantly following myocardial infarction, whereas procalcitonin were essentially unchanged, i.e. remained close to the normal level threshold of 0.5 ng/ml; only minor variability occurred with a mean peak level of procalcitonin of 1 ± 0.4 ng/ml. Data demonstrate that, in contrast to the acute phase reactant interleukin-6, plasma levels procalcitonin are not significantly elevated during uncomplicated acute myocardial infarction. This observation may support the role of procalcitonin measurements in the differential diagnosis of infectious and cardiovascular complications after major surgery.

UNLABELLED Background: Metformin is a biguanide antihyperglycemic agent that decreases insulin resistance. It is removed through renal mechanisms and its clearance is reduced in renal failure. Metformin ingestion should always be considered in the differential diagnosis of any patient with metabolic acidosis and increased lactate level. Hemodialysis and continuous veno-venous hemofiltration (CVVH) are both efficient methods to treat metformin intoxication and correct metabolic abnormalities. METHODS Patient 1: A 63-year-old man with type 2 diabetes mellitus presented to emergency department (ED) of Lodi (Italy) for dyspnea. He also reported having diarrhea for 10 days. Initial investigations revealed metabolic acidosis with hyperlactatemia and hypoglycemia (54 mg/dL), metformin concentration was 41 μg/mL (normal value

Objectives.This study sought to evaluate the relation, if any, between clinical and angiographic findings in patients with unstable angina and monocyte and neutrophil CD11b/CD18 receptor density. The expression of HLA-DR molecules on T lymphocytes, an index of activation of these cells, was also investigated.Background.Although activation of neutrophils and monocytes has recently been shown in unstable angina, no studies have correlated activation indexes with clinical and angiographic features of patients with this clinical condition.Methods.Sixty patients underwent diagnostic coronary arteriography and simultaneous blood sampling from the aorta and coronary sinus before injection of contrast medium. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytometry using monoclonal antibodies tagged with fluorescent markers.Results.In 38 patients with unstable angina, neutrophils and monocytes showed a significantly higher expression of CD11b/ CD18 adhesion receptors in coronary sinus than aortic blood (p < 0.0001 and p < 0.001, respectively). When these patients were analyzed according to clinical characteristics or angiographic findings, no difference in CD11b/CD18 receptor expression in coronary sinus blood was found between the various subgroups, except for patients with at least one episode of chest pain at rest within 48 h of coronary arteriography and a higher neutrophil adhesion molecule density than patients who remained asymptomatic (p = 0.04). Lymphocytes in patients with stable and unstable angina showed a similar percent expression of CD2/ CD19 and CD3/HLA-DR antigens, with no difference between aortic and coronary sinus blood.Conclusions.These results in a larger cohort confirm previous data that neutrophil and monocyte CD11b/CD18 adhesion molecules show a higher expression in the coronary sinus blood of patients with unstable angina. Among clinical and angiographic findings in patients with unstable angina, only the occurrence of chest pain within 48 h of coronary angiography was related to significantly higher values of neutrophil fluorescence intensity, suggesting that the degree of neutrophil activation is related to the proximity of rest angina episodes to blood sampling. Finally, our data do not support the concept of systemic or transcardiac lymphocyte activation in unstable angina.

In order to elucidate better the immunological effect of opioid abuse in the absence of HIV infection as a confounding factor, granulocyte function was investigated in three groups of HIV-negative subjects, including 20 active parenteral heroin abusers (H), 20 long-term methadone-maintained former opiate abusers (M) and 20 healthy controls (C). Chemotaxis to N-formyl methionyl-leucyl-phenylalanine (fMLP), casein and activated plasma were markedly and similarly reduced (approx. 50%) in both H and M groups, as was true for superoxide production after fMLP and PMA stimulation, 47% decrease of C values. Polymorphonuclear (PMN) of H and M subjects also exhibited a very marked and similar reduction in the expression of CD11b/CD18 integrin receptors after fMLP treatment, with values that were less than 10% of those in controls, as observed by flow cytometry. In parallel, PMN of H and M individuals presented an approximately four-fold increase in opioid receptors numbers compared to controls, a significant inverse correlation existing between the increase in opiate receptors and defective chemotaxis. The possible mechanism underlying the observed changes in PMN of H and M individuals is discussed.