An Overview of the Microbiota of the Human Urinary Tract in Health and Disease: Current Issues and Perspectives.

This article is intended to deepen our knowledge to date regarding the functions of the resident microbiota/microbiome in the urinary system for human health and disease. First, we sought to report the general characteristics (composition and stability) of the normal urinary system microbiota in the different anatomical sites in relation to some factors such as the effect of age, gender and diet, analyzing in detail the functions and the composition of the microbiota in the light of current knowledge. Several pieces of evidence suggest the importance of preserving the micro-ecosystem of the urinary system, and in some cases their relationship with diseases is important for maintaining human health is well understood. The female and male reproductive microbiota have mainly been studied over the past decade. In the past, the arrest was thought to have taken place in a sterile environment. Microorganisms of the microbiota form biofilms, three-dimensional structures, that differ in the reproductive organs and interact with both gametes and the embryo as well as with maternal tissues. These biofilms from the reproductive system also interact with others, such as that of the gastrointestinal tract. Reduction in its diversity intestinal microbiota can disrupt estrogen metabolism and affect the reproductive microbiota. It is therefore understood that its quantitative and qualitative identification is important for microbiota, but also the study of the structures formed by the microorganisms. A dysbiosis with local or systemic causes can lead to serious diseases. The role of probiotics in maintaining microbial population harmony (eubiosis) and preventing certain pathologies of the urinary and reproductive system was also investigated. A negative variation in the qualitative and quantitative composition of certain strains of microorganisms (dysbiosis) due to local or systemic causes can even lead to serious diseases. The role of probiotics in maintaining the healthy balance of microorganism populations (eubiosis), and thus in the prevention of certain pathologies of the urinary and reproductive system, has also been studied.

Cardiac Involvement in COVID-19 Patients: A Contemporary Review.

Background: The widely variable clinical manifestations of SARS-CoV2 disease (COVID-19) range from asymptomatic infections to multiple organ failure and death. Among the organs affected is the heart. This does not only affect people who already have previous cardiovascular problems, but also healthy people. This is a reason not to overlook any symptoms or to perform targeted examinations, even if apparently unrelated to the heart, for quick recognition and timely therapy. Aim of the study: This review recapitulates the current state of knowledge on the potential mechanisms and manifestation of myocarditis in patients with COVID-19 infection. Methods: A web-based search of published data was performed for all relevant studies on patients diagnosed with a COVID-19-induced acute myocarditis, and a total of 50 reports were included. The analysis of the studies evaluated highlights a male predominance, with the average age of patients being 55 years. The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. Finally, we wanted to use a general evaluation without distinguishing between various countries, taking into consideration only the peer or reviewer, regardless of the declared value of the journals that have been published. Results and critical findings: The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. In most patients, elevated levels of cardiac and inflammatory biomarkers were measured. Left ventricular dysfunction and hypokinesis were commonly exhibited symptoms. Cardiac Magnetic Resonance Imaging (CMRI) confirmed the diagnosis of myocarditis with features of cardiac edema and cardiac injury. Nine patients underwent histopathological examination. Treatment with corticosteroids and immunoglobulins was the most applied strategy following the administration of antivirals. Discussion: Despite the exponentially growing knowledge on the management of COVID-19 infection, current available data on SARS-CoV2-correlated myocarditis are still limited, and several difficulties may be encountered in the differential diagnosis of acute myocarditis in the context of COVID-19 disease. Conclusions: While diagnostic criteria and evaluation strategies for myocarditis are well described, no guidelines for the diagnosis and treatment of myocarditis in COVID-19 patients have yet been established. Therefore, further research is needed to advance the understanding of this disease process and define the most appropriate strategic approach in these patients.

The Preoperative Inflammatory Status Affects the Clinical Outcome in Cardiac Surgery.

AIMS: There are many reasons for the increase in post-operative mortality and morbidity in patients undergoing surgery. In fact, an activated inflammatory state before cardiac surgery, can potentially worsen the patient's prognosis and the effects of this preoperative inflammatory state in the medium-term remains unknown. METHODS: There were 470 consecutive patients who underwent cardiac surgery, and were divided in three groups according to the median values of preoperative C-reactive protein (CRP) and fibrinogen (FBG): The first group was the low inflammatory status group (LIS) with 161 patients (CRP < 0.39 mg/dL and FBG < 366 mg/dL); the second was the medium inflammatory status group (MIS) with 150 patients (CRP < 0.39 mg/dL and FBG ≥ 366 mg/dL or CRP ≥ 0.39 mg/dL and FBG < 366 mg/dL,); and the third was the high inflammatory status group (HIS) with 159 patients (CRP ≥ 0.39 mg/dL and FBG ≥ 366 mg/dL,). RESULTS: The parameters to be considered for the patients before surgery were similar between the three groups except, however, for age, left ventricular ejection fraction (LVEF) and the presence of arterial hypertension. The operative mortality was not significantly different between the groups (LIS = 2.5%, MIS = 6%, HIS = 6.9%, p = 0.16) while mortality for sepsis was significantly different (LIS = 0%, MIS = 1.3%, HIS = 3.7%, p = 0.03). The infections were more frequent in the HIS group (p = 0.0002). The HIS group resulted in an independent risk factor for infections (relative risk (RR) = 3.1, confidence interval (CI) = 1.2-7.9, p = 0.02). During the 48-months follow-up, survival was lower for the HIS patients. This HIS group (RR = 2.39, CI = 1.03-5.53, p = 0.05) and LVEF (RR = 0.96, CI = 0.92-0.99, p = 0.04) resulted in independent risk factors for mortality during the follow-up. CONCLUSIONS: The patients undergoing cardiac surgery with a preoperative highly activated inflammatory status are at a higher risk of post-operative infections. Furthermore, during the intermediate follow-up, the preoperative highly activated inflammatory status and LVEF resulted in independent risk factors for mortality.

Current Issues and Perspectives in Patients with Possible Sepsis at Emergency Departments.

In the area of Emergency Room (ER), many patients present criteria compatible with a SIRS, but only some of them have an associated infection. The new definition of sepsis by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine (2016), revolutionizes precedent criteria, overcoming the concept of SIRS and clearly distinguishing the infection with the patient's physiological response from the symptoms of sepsis. Another fundamental change concerns the recognition method: The use of SOFA (Sequential-Sepsis Related-Organ Failure Assessment Score) as reference score for organ damage assessment. Also, the use of the qSOFA is based on the use of three objective parameters: Altered level of consciousness (GCS <15 or AVPU), systolic blood pressure ≤ 100 mmHg, and respiratory rate ≥ 22/min. If patients have at least two of these altered parameters in association with an infection, then there is the suspicion of sepsis. In these patients the risk of death is higher, and it is necessary to implement the appropriate management protocols, indeed the hospital mortality rate of these patients exceeds 40%. Patients with septic shock can be identified by the association of the clinical symptoms of sepsis with persistent hypotension, which requires vasopressors to maintain a MAP of 65 mmHg, and serum lactate levels >18 mg/dL in despite of an adequate volume resuscitation. Then, patient first management is mainly based on: (1) Recognition of the potentially septic patient (sepsis protocol-qSOFA); (2) Laboratory investigations; (3) Empirical antibiotic therapy in patients with sepsis and septic shock. With this in mind, the authors discuss the most important aspects of the sepsis in both adults and infants, and also consider the possible treatment according current guidelines. In addition, the possible role of some nutraceuticals as supportive therapy in septic patient is also discussed.

Philosophy and Hippocratic Ethic in Ancient Greek Society: Evolution of Hospital - Sanctuaries.

The aim of this paper is to offer a new perspective of the Hippocratic thought and how it influenced the evolution of the medical art till now, highlighting the ethical aspects and hospital born from ancient temples and sanctuary. Ethics is defined as a set of values, principles, and rules that regulate human behavior and relate to how human actions can significantly affect not only their own lives but also the lives of others. The essence of a culture can be perceived by the philosophy and the means by which is placed against the illness and its treatment. In this sense, the medical anthropology of every age is an indicator of its culture and help us understand its basic dimensions such as life and death.

Hyperoxia confers myocardial protection in mechanically ventilated rats through the generation of free radicals and opening of mitochondrial ATP-sensitive potassium channels.

1. One hour exposure to hyperoxia has been shown previously to limit a subsequent ischaemia-reperfusion injury in spontaneously breathing rats. We tested the cardioprotective effect of a shorter period of hyperoxia during mechanical ventilation and the possible contribution of reactive oxygen species (ROS) and mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels. 2. Mechanically ventilated rats were exposed to normoxia (Fi O2 = 0.3) or hyperoxia (Fi O2 = 1.0) for 30 min and pH, P CO2, PO2, heart rate, airway and blood pressure were measured at baseline and after 30 min mechanical ventilation. Isolated hearts were subsequently subjected to 30 min ischaemia and 120 min reperfusion. Infarct size and left ventricular end-diastolic pressure (LVEDP), developed pressure (LVDP) and coronary flow (CF) were measured. In order to investigate the role of ROS and KATP channels within the mechanism leading to cardioprotection, the free radical scavenger N-acetylcysteine (NAC; 150 mg/kg) was infused in mechanically ventilated rats and the KATP channel blockers glibenclamide (200 mmol/L) or 5-hydroxydecanoate (10 mmol/L) were infused in isolated hearts immediately before ischaemia. 3. No differences were detected in P CO2, pH, heart rate, airway and blood pressure between the groups. However, the PO2 in hyperoxic groups was significantly higher compared with that in normoxic groups (P < 0.01). After 30 min ischaemia, we found that hyperoxic preconditioning significantly improved CF (P < 0.01), LVDP (P < 0.01) and LVEDP (P < 0.01) and reduced the extent of infarct size in the reperfused heart compared with the normoxic group (P < 0.01). When rats were pretreated either with NAC before hyperoxic ventilation or with K(ATP) channel blockers before ischaemia, myocardial protection was abolished. 4. Hyperoxic mechanical ventilation, prior to ischaemia, reduces myocardial reperfusion injury. This is likely to occur through the induction of oxidative stress, which leads to myocyte mitoKATP channel opening.

Post-traumatic blunt rupture of the aorta: endo-aortic stenting therapy.

With the increased use of the endovascular approach, the management and outcome of traumatic aortic injuries have changed dramatically over the past 10 years. Understanding pathogenic mechanism underlying aortic injury is critical in choosing the kind of stent-graft to be used. The possible mechanisms of non-penetrating blunt trauma of the aorta have been studied for a long time and are not completely clarified yet. The principal hypotheses concern the differential acceleration and deceleration movements exerting in horizontal and/or longitudinal planes, associated with the abrupt increase of endoluminal pressure and direct or indirect compression of the thoracic aorta from the ribcage structures. When blunt chest trauma causes direct compression of the sternum and spine with a sudden increase in endoluminal pressure, the rupture more frequently involves the ascending aorta or the descending thoracic aorta downstream the isthmus area. On the other hand, when the trauma generates differential acceleration and deceleration movements the rupture involves more frequently the isthmus because this region represents one of the points of fixity of the aorta through the junction of the ligamentum arteriosus and the first ribs. The following presentation is aimed at illustrating some of the possible pathophysiological mechanisms of post-traumatic blunt rupture of the aorta and the indications for its endovascular treatment.

Isthmus endoprosthesis stent-graft treatment: implantation of relay dedicated device.

Among the 123 patients treated in our department by endovascular stent graft, 113 (91.8%) were identified as having involvement of the isthmus. Therefore, the incorrectly defined descending aortic disease is essentially a pathology of the isthmus that represents the distal portion of the arch. The key to the treatment of all types of aortic lesions rests on understanding the morphology of this region gifted with a "double S" configuration. Current thoracic devices are noncompliant systems and should be modified greatly, taking into account that the media of the aorta has a semi-compliant behavior. The resultant of power transmission is oriented at 45 degrees and produces a transmural radial force that animal implantation has demonstrated to be a torsional movement. The improvements in new devices actually result in a new generation of endoprostheses that seem to be closely related to the anatomy of the patient by increasing the conformability and, therefore, we expect an increase in durability. To test these features, we have studied a new stent graft in different settings of thoracic aortic disease. The new device should conform to current standards while simultaneously transmitting torsional forces. The dedicated delivery system should be arch-compatible, flexible but sufficiently rigid, and able to be three-dimensionally oriented. Moreover, the new stent graft should follow the three-dimensional anatomy of the "double S" configuration of the isthmus area and thus reduce the mismatch between the aorta and the device itself.

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia-reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion.

Several recent works have shown that a brief ischemia applied during the onset of reperfusion (postconditioning) is cardioprotective in different animal models and that the early minutes of reperfusion are critical to its cardioprotection. This effect has been related to prevention of oxidative stress, but mechanisms have not been clearly demonstrated. The present study tested the hypothesis that mitochondria play a central role in peroxide production and oxidative stress during reperfusion and are responsible for the protective effect of postconditioning. Isolated perfused rat hearts were subjected to complete global ischemia for 45 min and reperfused for 40 min. Normoxic group was reperfused with a Krebs-Henseleit solution with the preischemic pO2 level (600 mmHg); in the "hypoxic group," normoxic reperfusion was preceded by 3 min with 150 mmHg pO2. Reperfusion was stopped at 3 and 40 min. The rate of hydroperoxide production, GSH, GSSG, and carbonyl protein levels were measured in mitochondria at 3 min and at the end of reperfusion. GSH and GSSG were also measured in tissue. Hemodinamic function was monitored during the experiment. LVEDp increased and LVDp decreased in the normoxic group but not in the hypoxic group. The rate of mitochondrial peroxide production was higher in normoxic than in the hypoxic group 3 min after reperfusion and at its conclusion. Accordingly, GSH was oxidized in normoxic but not in hypoxic hearts. Mitochondria carbonyl proteins were significantly higher in normoxic than in the hypoxic group at the end of reperfusion. In this model, 1) hypoxic reperfusion at the onset of reperfusion reduces myocardial injury; 2) the major rate of mitochondrial peroxide production is 3 min after the onset of reperfusion; 3) cardioprotection of postconditioning correlates with reduced mitochondria peroxide production and prevention of GSH oxidation.

Endovascular treatment of thoracic aortic disease: four years of experience.

BACKGROUND: The aim of this retrospective study is to investigate efficacy and middle-term results of the stent graft treatment for diseases of descending thoracic aorta. METHODS AND RESULTS: From March 1999 to October 2003, 132 patients (113 male and 19 female, mean age 62+/-14 years) were enrolled. They were divided into 4 groups: aneurysms (43, group A), post-traumatic lesions (24, group B), and complicated type B dissections (43, group C). Twenty-two further patients, with chronic type B dissection and not suitable for endovascular or surgical or hybrid techniques because of multiple entry tears without difference between the true and false lumen and poor clinical conditions, were obliged to receive medical management only (group D). All patients underwent computed tomography (CT) scan and angiography as preoperative assessment. An optimal deployment with exclusion of the aneurysm and/or closure of the entry tear in dissection was achieved in 96.4% (106/110) of the patients that were discharged in good conditions within 6 days. No spinal cord injuries were observed. The follow-up (average 20.82+/-10.01 months, range 1 to 55 months), performed with serial chest CT scans, was 100% complete. No stent graft-related complications were detected, although only in 1 case, an asymptomatic rupture of the Excluder connecting bar was found with a perforation of the fabric and an intra-aortic exposition of the bar itself. In 2 patients with chronic dissection an asymptomatic type II endoleak was detected. A total of 4 hospital deaths resulted in an overall operative mortality of 3.9%. Seven patients (6.3%) died during the follow-up 5 of them for other diseases (4.5%). However, a 40.9% mortality was observed within the obliged medical treatment group. CONCLUSIONS: Endovascular treatment of thoracic aortic diseases, even in the acute phase, may represent a valid option with a low mortality rate. Moreover, the efficacy is proved in the middle-term whereas the long-term follow-up is still pending.

Stent graft treatment of thoracic aortic disease.

This study was a retrospective analysis of both the efficacy and long-term outcome of endovascular management of thoracic aortic disease. From March 1999 to August 2003, 129 patients (110 males; 19 females) were enrolled. They were divided into four groups: aneurysms (41, 5 of which acutely ruptured, Group A), post-traumatic lesions (24, 14 acute and 10 chronic, Group B) and complicated type B dissections (42, 23 acute and 19 chronic, Group C). Twenty-two of the 129 patients with chronic type B dissection, not suitable for endovascular treatment, received medical management only (Group D). All patients underwent computed tomography (CT) scan and angiography as preoperative assessment. Stent-graft systems were Talent -Medtronic, Excluder-Gore, Zenith-Cook and Endofit-Endomed, deployed by transesophageal echocardiography (TEE) monitoring. An optimal deployment with sealing of the graft was achieved in 95.3% (102/107) of the treated patients discharged in good condition within 6 days. Five patients (3 in Group A and 2 in Group C) underwent endovascular completion of the elephant trunk technique successfully. In 5 patients affected by atherosclerotic aneurysm, in a single-time procedure, we have also treated the abdominal aortic aneurysm by endovascular. No spinal cord injuries were observed. The follow up (average: 20.82+/-10.01 months), performed with serial chest CT scans, was 100% complete. No stent-graft related complications were detected. In 2 patients with chronic dissection, an asymptomatic type II endoleak was detected. A total of 4 hospital deaths resulted in an overall operative mortality rate of 3.7%. Seven patients (6.5%) died during the follow-up period, whereas a 31.8% (7/22) mortality rate (p<0.001) was observed within the medical treatment group. Endovascular treatment of thoracic aortic diseases, even in the acute phase, may represent a valid option, especially when compared to medical therapy.

Immediate versus delayed endovascular treatment of post-traumatic aortic pseudoaneurysms and type B dissections: retrospective analysis and premises to the upcoming European trial.

BACKGROUND: Stent grafting has been reported as a viable therapeutic option for the delayed treatment of traumatic rupture of the aortic isthmus as well as reconstruction of thoracic aortic dissections. We tested the hypothesis of whether immediate endovascular management offers clinical and pathological advantages over a delayed approach in patients with post-traumatic aortic pseudoaneurysms (PAPs) and Stanford type-B dissections (TBDs). METHODS: Thirty-one consecutive patients who were admitted with diagnosis of either PAP (n=10; 33.4+/-8.7 years) or TBD (n=21; 58.2+/-8.4 years) were respectively divided into 2 groups according to the timing of diagnosis and endovascular treatment after the traumatic or pathologic event: immediate ([lteq]2 weeks; PAP=6 and TBD=7) and delayed (>2 weeks; PAP=4 and TBD=14). Excluder-Gore (11 in PAP and 8 in TBD) and Talent-Medtronic (1 in PAP and 7 in TBD) endovascular stent grafts were deployed. Follow-up was performed at 3 months, 6 months, and 1 year and based on laboratory tests; chest angio-computed tomography scans of chest, abdomen, and pelvis; and transesophageal echocardiography. RESULTS: The endovascular procedure proved uneventful in all PAP patients who underwent either immediate or delayed treatment. In 1 PAP patient with delayed treatment, surgical removal of the pseudoaneurysm was still necessary because of further compression of the airway stem. All immediately treated TBD patients were also successful. However, in 8 of 13 TBD patients with delayed treatment (61.5%), a stent graft deployment was not possible because of complicated progression of the false lumen and multiple intimal entry tears: 1 patient benefited by fenestrations of the false lumen and 7 patients underwent medical therapy. One patient (8.3%) died because of retrograde dissection involving the aortic arch. All patients treated with endovascular stent grafts were discharged within 5 days. CONCLUSIONS: An immediate endovascular management of PAP and TBD patients offers important advantages such as avoidance of high-risk surgical procedures and postoperative complications with short hospital stay. Moreover, it has been observed that an immediate endovascular treatment allows a safe management of all patients with complete healing of the aortic wall and regression of the pseudoaneurysm in the PAP group and thrombosis of the false lumen in TBD patients.