Heme Oxygenase-1/High Mobility Group Box 1 Pathway May Have a Possible Role in COVID-19 ARDS (Acute Respiratory Distress Syndrome): A Pilot Histological Study.

COVID-19 is a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The persistent and excessive inflammatory response can build up a clinical picture that is difficult to manage and potentially fatal. Potent activators of inflammatory phenomena are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). HMGB1 is an intranuclear protein that is either passively released during hypoxia-related necrosis or actively released by macrophages. Heme oxygenase (HO-1) has an anti-inflammatory effect by inhibiting HMGB1, which could be a therapeutic target to reduce COVID-19 inflammation. In our study, we evaluated CD3, CD4, CD8, HMGB1 and HO-1 in the COVID-19 lung and correlated it to clinical data.

Morphological and morphometric analysis of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa: a retrospective study.

BACKGROUND: Recessive dystrophic epidermolysis bullosa is a highly disabling genodermatosis characterized by skin and mucosal fragility and blistering. Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications, having a high morbidity and mortality rate. Patients with recessive dystrophic epidermolysis bullosa were reported to have up to a 70-fold higher risk of developing cSCC than unaffected individuals. Immune cells play a role in cancer evolution. OBJECTIVE: The aim of our study was to evaluate immunohistological differences between cSCC in patients with and without recessive dystrophic epidermolysis bullosa. METHODS: A retrospective study of 25 consecutive cases was performed; five were biopsies of cSCC taken from five patients with recessive dystrophic epidermolysis bullosa; as controls we analysed 10 cSCC in subjects without recessive dystrophic epidermolysis bullosa (5 primitive, 3 postburns and 2 postradiotherapy), 5 cSCC in renal transplant recipients and 5 cutaneous pseudoepitheliomatous hyperplasia in patients with recessive dystrophic epidermolysis bullosa. RESULTS: A significant reduction of CD3+, CD4+ and CD68+ between the cSCC in patients with recessive dystrophic epidermolysis bullosa compared to primary cSCC and a significant reduction of CD3+, CD4+, CD8+ and CD20+ were observed in cSCC in patients with recessive dystrophic epidermolysis bullosa compared to secondary cSCC. On the contrary, there was no difference in CD3+, CD8+, CD20+ and CD68+ expression when comparing cSCC in patients with recessive dystrophic epidermolysis bullosa to cSCC in renal transplant recipients. No significant difference was found in size, histopathology, grading, number of mitoses and EGFR expression between the different groups. CONCLUSIONS: Our data show a reduction in immune cell peritumoral infiltration. Considering the well-known evolution of cSCC in patients with recessive dystrophic epidermolysis bullosa, as well as the younger age at diagnosis, it can be assumed that immune dysfunction might contribute to the cSCC aggressiveness in these patients.

Aortic valve stenosis and lipid-lowering therapy: the state of the art.

Aortic valve stenosis is the most common native valve disease and its most common cause in the United States and Europe is the calcification of a normal trileaflet. Recently, there is increasing evidence indicating that valve calcification has common underlying mechanisms with atherosclerosis. This connection raises interest in the potential efficacy of antiatherosclerosis medications in calcific valve stenosis (AS) therapy. Among them statins, are one of the most promising candidates, because of their pleiotropic effects. The aim of this review is to summarize and analyze the findings of contemporary studies and to discuss the rationale for statin usage in AS populations.

Stem cells and repair of the heart: cell-releasing epicardial scaffolds.

Cell transplantation represents the last frontier within the treatment of cardiac diseases. From the first paper published in 1992 that has documented the potentials of the transplantation of autologous skeletal muscle cells to treat the damage induced by acute myocardial infarction, innumerable techniques of implantation and types of cells used has been reported, greatly expanding this innovative and appealing field of search in cardiovascular medicine. Despite original promises and expectations, current evidences of stem cell transplantation are still weak and controversial. Therefore, alternative line of research are being explored, particularly in the field of techniques of cell implantation and engraftment. Besides direct implantation or myocardial colonization by bone marrow stimulation, epicardial application of cell-delivering systems (scaffold and patches) have gained popularity due to the possibility to apply selectively a cell-containing device which may gradually release the chosen cell type, alone or in combination with trophic substances. The scaffolds have proven to be successful in this respect and may represent a valid alternative to coronary, intra-myocardial, or venous injection of stem cells, or to stem cell stimulating factors. Finally these systems may be applied through minimally invasive procedures and act as external constraint to enhance ventricular reverse remodelling or limit further cardiac dilatation.

The effects of weight loss due to gastric banding and lifestyle modification on red blood cell aggregation and deformability in severe obese subjects.

OBJECTIVE: To investigate the changes in the aggregation index (AI) and the elongation index (EI), in severe obese subjects (MbObS) undergoing laparoscopic adjustable gastric banding (LAGB). AI and EI are measured by Laser assisted Optical Rotational Red Cell Analyzer (LORCA) and are markers of erythrocyte aggregation and deformability, respectively. DESIGN AND SUBJECTS: Before, 3 and 6 months after LAGB plus lifestyle changes (Mediterranean diet plus daily moderate exercise), we evaluated AI, EI, body mass index (BMI), total (ToT) cholesterol (Chol), high-density lipoprotein (HDL)-Chol, low-density lipoprotein (LDL)-Chol, triglycerides and fasting glucose and insulin levels in 20 MbObS. The Student's t-test was used for comparisons between independent groups and the analysis of variance to assess differences in AI and EI at the 3 time points. Pearson's correlation coefficient was used to assess correlation among continuous variables and multiple linear regression analysis to assess predictive factors for AI and EI changes. RESULTS: BMI and all blood parameters showed a statistically significant decline 3 and 6 months after LAGB as compared with basal, except for EI and HDL-Chol that significantly increased. Stepwise selection of predictors shows that at 3 and 6 months, EI values depended on HDL-Chol values at the same time point. In the EI model, blood glucose was also statistically significant at 6 months. CONCLUSION: Our data show a significant improvement in EI after LAGB-induced weight loss, which correlates with an improved lipid pattern and support the idea that the rapid weight loss induced by LAGB plus lifestyle changes might reduce the thromboembolic risk and the high mortality risk found in MbObS.

[Hemorheology and microcirculation in some pathologies of internal medicine]. / Alterazioni emoreologiche e microcircolatorie in alcune patologie di interesse internistico.

AIM: It is very interesting in physiopathology to evaluate the blood flow in the microvasculature of patients affected by diabetes, arterial hypertension, lipoproteinosis, peripheral occlusive arterial disease (POAD) and liver failure. METHODS: We studied 4 groups. Group 1: controls formed by 25 healthy subjects (15 males and 10 females aged 36+/-3 years); group 2: diabetes, including 32 patients (group 2A, 20 subjects with diabetes type 1: 12 males and 8 females aged 43+/-4 years and group 2B, 12 subjects with diabetes type 2: 6 males and 6 females aged 45+/-3 years); group 3: liver failure, formed by 6 subjects (3 males and 3 females aged 44+/-5 years); group 4: hypertensives, 50 subjects (group 4A, 28 smokers 12 males and 16 females aged 40+/-4 years and group 4B, 22 non-smokers: 12 males and 10 females aged 38+/-3 years). We evaluated the capillary morphology using computerized videocapillaroscopy, the hemorheology (red blood cell RBC deformability and aggregability) using LORCA (Laser assisted Optical Rotational Red Cell Analyzer) and tissue oxygenation using transcutaneous oxymeter (Periflux 5000 Perimed). Statistical analysis were performed using the Student t-test. RESULTS: The capillary loops in patients with diabetic microangiopathy had in 50% of the patients studied an image such as ''deer horns'', as ''elephant nose'' in 72% and as ''cork screw'' in 44%. In diabetics we found also a capillary rarefaction in 28% of them. An improvement in perfusion was observed in patients with liver failure one week after liver transplantation from cadaver in 83% of them. Morphological alterations were present in hypertensives (27% in non-smokers, 46% in smokers). The RBC deformability evaluated as elongation index (EI) and RBC aggregability (t1/2 expressed in seconds) were detected using LORCA. Group 1: EI 0.59+/-0.02, t1/2 3+/-1 s; group 2A: EI 0.55+/-0.01; t1/2 2+/-0.5 s p<0.05 vs controls; group 2B: EI 0.56+/-0.01; t1/2 2+/-0.2 s p<0.04 vs controls; group 3: EI 0.56+/-0.02, t1/2 2+/-0.4 s p<0.04; group 4A: EI 0.56+/-0.02, t1/2 2+/-0.6 s p<0.03; group 4B: 0.57+/-0.02, t1/2 2+/-0.6 s p<0.04. We evaluated also the TcpO2 at the dorsum of the right foot expressed in mmHg: group 1, 96+/-11 mmHg; group 2A, 74+/-9 p<0.05 vs controls; group 2B, 76+/-8 mmHg p<0.05; group 3, 69+/-6 mmHg p<0.05; group 4A, 70+/-5 mmHg p<0.05; group 4B, 77+/-9 mmHg p<0.05. CONCLUSION: This study indicates an interesting and complete methodology in order to evaluate the microcirculation condition in different pathologies inducing microvasculature alterations.

Acute changes in circulating hormones in older patients with impaired ventricular function undergoing on-pump coronary artery bypass grafting.

OBJECTIVES: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) causes an acute stress response characterized by changes in the levels of several hormones, which might play a role in the high complication rate experienced by older patients after CABG. Thus, the aim of the study was to investigate changes in the circulating levels of anabolic and catabolic hormones in old people undergoing CABG with CPB. DESIGN: Intervention case study. METHODS: 19 patients (12 males, 7 females) aged 70.1 +/- 6.1 yr (age range 62-80) with coronary artery disease and an ejection fraction <40% who underwent cardiac surgery. Cortisol (Cort), DHEA, DHEAS, LH, estradiol (E2), total testosterone (Te), SHBG, IGF-I were measured the day before, on the day of the procedure and 1, 2, 3, 4, and 30 days after CABG. RESULTS: After surgery, serum IGF-I levels decreased (p<0.001), while levels of Cort, DHEAS and E2 significantly increased in both men and women. Alterations in Te levels differed between the two sexes with a significant decline in men and a significant increment in women. CONCLUSION: CABG with CPB resulted in a dramatic drop in Te levels in old men and a significant decline in IGF-I in both sexes. Serum Cort levels also significantly increased in both sexes. These hormonal changes may, at least partially, explain why the elderly need prolonged rehabilitation after CABG.

Solutions for organ perfusion and storage: haemorheologic aspects.

BACKGROUND: The hydroxyethyl starch (HES) contained in University of Wisconsin (UW) solution causes erythrocyte aggregation. The effect of UW on red blood cell (RBC) deformability is still unclear. HES-free preservation solutions, Celsior (CS) and Custodiol (CU) are available. In this study we evaluated whether they really showed a reduced aggregating and stiffening effect on RBCs when compared with UW. We was also evaluated the effect of these solutions on cellular membranes by measuring acetylcholinesterase (AChE), which is a marker of RBC membrane integrity. METHODS: The determination of RBC aggregation and deformability was performed by a laser-assisted optical rotation cell analyzer (LORCA). AChE measurement was performed with a spectrophotometric technique. RESULTS: The mean RBC aggregation index (AI) measured in pure blood control samples was 28.00 +/- 0.73%. The AI measured samples containing UW was 38.82 +/- 1.58%. In samples with CS, it was 13.307 +/- 0.64% and in samples with CU the mean AI was 12.47 +/- 0.42%. Also the RBC aggregating time was quicker in presence of UW compared with controls. AChE concentration in blood was 3.043 +/- 0.4 nmol. CS and UW did not produce any significant change; a significant reduction was found when CU was added to blood, namely 1.975 +/- 0.1 nmol (P < .05). The use of UW or CS or CU did not result in any significant change in RBC deformability. DISCUSSION: CS and CU solutions do not aggregate erythrocytes, whereas Wisconsin does massively. CU causes an alteration of RBC cellular membrane as demonstrated by depletion of AChE.

MELD predictive value of alterations of brain perfusion during liver transplantation.

INTRODUCTION: The systemic circulation of patients with liver failure is characterized by low vascular resistance and a compensatorily increased cardiac output. In addition, some patients show functional loss of the autoregulation system for cerebral blood flow, creating enhanced risk during orthotopic liver transplantation (OLT), a possible cause of the high incidence of central nervous system complications after OLT. PATIENTS AND METHODS: Sixteen consecutive patients undergoing OLT were enrolled and characterized by the Child-Pugh (CTP), the MELD, and the HCC-adjusted-MELD score before surgery. OLT was performed with the "piggyback" technique. Brain perfusion and oxygenation was monitored by NIRO300 by Hamamatsu. This instrument detects concentration changes in oxygenated hemoglobin (DeltaHbO(2)), deoxygenated hemoglobin (DeltaHHb), and total volume of hemoglobin (DeltaHbT). It also calculates the tissue oxygenation index (TOI), namely HbO(2)/HbT expressed as a percentage, and the tissue hemoglobin index (THI). RESULTS: The lowest levels of brain perfusion were recorded at the washout, DeltaHbO(2) = -13.95 (-20/-5.3) micromol L(-1) and TOI = 51.5 (35.2/70.7)%, while immediately after, at reperfusion, the highest peaks were observed: DeltaHbO(2) was 0.16 (16.9/13) micromol L(-1); DeltaHbT was 1.1 (22.3/11.8) mumol L(-1); and TOI was 73.6 (78.1/65.3)%. CONCLUSIONS: Patients with more severe liver deficiency scores showed higher levels of brain perfusion and oxygenation during surgery. Both the MELD and the CTP score predict alterations in brain perfusion.

Surgical repair of thoracic aortic aneurysms: results and complications.

Between January 1990 and February 2001 a total of 323 patients underwent following operations at our Institution: respectively 256 on the ascending aorta, 13 on the transverse arch and 54 on thoracic descending aorta. Sixteen patients with thoracic aortic aneurysms underwent endovascular stent graft implantation. The overall in-hospital mortality was respectively: 7% for ascending aortic aneurysms, 7.7% in the aortic arch aneurysms group and 5.5% for descending aortic aneurysms. The mortality was greater in case of emergency surgery and in the subgroup of patients with acute type A dissection. Stroke with permanent dysfunction occurred in 1.5% of ascending aneurysms, 7.7% of arch aneurysms and in 3.7% of thoracic descending aneurysms. In the latter group, all the major neurological events were related to conventional surgical procedures only: really no mortality or neurological morbidity occurred with endovascular stent graft implantation. Even if modern physiologic monitoring devices and new surgical techniques have been developed in the last years, the treatment of thoracic aortic aneurysms remains challenging. Endoluminal placement of stent grafts has developed as an alternative procedure for the treatment of thoracic aortic aneurysms, even if longer term follow-up is still necessary to fully define the efficacy of this approach.

Cytosolic calcium and hemorheological patterns during arterial hypertension.

Hypertension can be considered as a progressive ischaemic syndrome interesting micro- and macrovasculature. In hypertensives it is possible to observe a link between an increase in peripheral resistance and blood viscosity, and a decrease in red blood cell (RBC) deformability. It is important to underline the link between the increase of blood viscosity, the decrease of RBC deformability and the cytosolic calcium level, which is related to the ischaemic syndrome in hypertension. The aim of this study was to evaluate the level of Ca++ and its possible correlation with hemorheological patterns during arterial hypertension. Two groups were studied: Group 1 consisted of 18 mild hypertensives (11 males and 7 pre-menopausal females, aged 39 +/- 3 years). This group was of medium risk according to WHO and ISH (1999) with no other pathologies apart from peripheral occlusive arterial disease II stage type A. Group 2 was made up of 14 healthy subjects (9 males and 5 females, aged 34 +/- 4 years). The intraerythrocytic cytosolic calcium was evaluated using a fluorescent marker FURA 2/AM (Calbiochem). The following hemorheological parameters were also assessed using the new Laser assisted Optical Rotational Red Cell Analyzer (LORCA) according to the Hardeman method (1994): RBC deformability-Elongation Index (EI), RBC aggregability- aggregation half time (t 1/2). The data obtained showed that compared to the control group the hypertensives had a significantly higher level of intraerythrocytic cytosolic calcium (p < 0.01), plus a significant decrease in EI and t 1/2 evaluated using LORCA. We also observed a significant correlation (p < 0.01) between an increase in Ca++ and a decrease in EI in the hypertensive patients. Moreover our study revealed a significant correlation between the increase in intraerythrocytic Ca++ and the t 1/2 decrease. The evaluation of the hemorheological patterns and cytosolic calcium could explain the impairment in peripheral perfusion and oxygenation in hypertensive patients and could provide a good model for a better evaluation and treatment of microvasculature perfusion in subjects with essential and complicated hypertension.

Pericardial drainage for pericardial tamponade: surgical management criteria.

Aim of this study is the review of our experience in 82 patients treated by pericardial drainage for cardiac tamponade, to assess the efficacy and safety of different techniques and the related indications. The causes of pericardial effusion were: malignancy in 8 patients (9.7%), post-cardiac surgery in 12 (14.6%), while the others patients were admitted at our Institution with no identified preoperative diagnosis. Thirty-eight patients (46%) underwent subxiphoid pericardial drainage and 44 (54%) were operated on by catheter pericardiocentesis. There were no perioperative deaths. Two patients, who initially underwent pericardiocentesis, needed urgent sternotomy: the first patient developed a severe hypotension and bradicardia related to a vagal reaction and the other one because of accidental right ventricle puncture. Our experience indicates that subxiphoid pericardiocentesis provides expeditious, effective and durable treatment, with low morbidity, in case of pericardial effusions related to all causes. We believe that echocardiography is a powerful tool in the diagnosis and management of pericardial effusion. We conclude that pericardiocentesis seems to be the procedure of choice for patients with pericardial tamponade requiring an emergency treatment.

Ischaemic mitral valve regurgitation: a surgical approach.

UNLABELLED: The aim of this study IS to determine surgical results after surgical mitral valve repair in ischaemic mitral regurgitation. MATERIALS AND METHODS: Between January 1999 and June 2000, 64 patients (5.1% of overall patients) underwent myocardial revascularization and mitral valve surgery. A Cosgrove-Edwards mitral annuloplasty ring was used in 59 cases (92.2%). Average patient age was 64.3 +/- 12.4 years (38 males, 21 females). Average degree of mitral regurgitation was 2.8 +/- 0.6. Average NYHA class was 3.5 +/- 0.5. Average ejection fraction (EF) was 40 +/- 12.5 percent. RESULTS: Post-operative 30-day mortality was 3.4% (2 patients). The follow-up was complete for 95 percent (mean 20.4 +/- 4.8 months for patients) and data showed an improvement of NYHA class (mean value 1.8 +/- 0.2) (p = 0.01) and ejection fraction (mean value 51.7 +/- 10.2) (p = 0.05) with residual mitral regurgitation value of 0.6 +/- 0.7. CONCLUSIONS: Mitral valve repair in coronary artery disease improves left ventricular function, quality of life and survival rate with low operative risk. Perioperative transesophageal echocardiography has a central role in surgical decision making.

[Endoluminal repair of aortic aneurysms. Our experience]. / Correzione endoluminale degli aneurismi aortici. Nostra esperienza.

From February 1998 and March 2000 fourteen patients underwent "custom made" aortic self-expanding endoprostheses implantation (World Medical Talent Sunrise): nine of them for dilative pathology of thoracic aorta and 5 for abdominal aortic aneurysm below renal arteries. The etiology was degenerative in 8 patients, false aneurysm in 2, chronic dissection in 2 cases, acute dissection in one patient and post traumatic in the last one. All patients underwent preoperative Computed Tomography and Substraction Angiography studies. Stent-graft implantation was successful in all cases but one who required the conversion of the endovascular procedure in traditional surgery for technical problems. There were no perioperative deaths or major complications. We registered 2 cases of dissection of the femoral artery used to introduce the stent-graft, and treated with an iliac-femoral prosthetic bypass. There were no cases of paraplegia or renal failure or bowel ischemia. With the exception of one patient, died for a car accident, the others are alive and continue their scheduled follow-up controls. Our experience shows that this procedure is safe, allowing favorable results, if compared to traditional surgery, even if it requires further long-term evaluations.

Red blood cell (RBC) deformability, RBC aggregability and tissue oxygenation in hypertension.

Arterial hypertension could be considered a progressive ischaemic syndrome interesting the macro and the microcirculation. In order to improve the clinical and therapeutic approach to the treatment of arterial hypertension, research has centered on blood flow to evaluate the different components and their very intricate relationships influencing the micro- and the macrocirculation. Of course the main problem is to study the link between the blood flow and the peripheral tissue oxygenation. During hypertension very important alterations in rheological, mechanical and biochemical characteristics of erythrocytes and of blood flow have been shown. It is very relevant the increase in blood viscosity, the decrease in red blood cell (RBC) deformability, the formation of RBC "rouleaux" and RBC aggregates. These hemorheological determinants can favour an increase of peripheral resistances and of arterial blood pressure, causing or worsening hypertension, a decrease in oxygen transport to tissue and peripheral perfusion, a decrease of the active exchange surface area in the microvasculature, especially in complicated hypertension. We have studied 320 patients: 123 with Essential Hypertension (EH) (M 59, F 64 aged 50 +/- 25 years); 81 with Secondary Hypertension (SH) without associated other pathologies influencing hemorheology (M 42, F 39 aged 48 +/- 20 years); 116 SH with other pathologies or conditions associated influencing hemorheology such as: diabetes, lipoidoproteinosis, obesity, smoking, HD, elderly, etc. (M 48, F 68 aged 46 +/- 20 years). Using a Laser-assisted Optical Rotational Red Cell Analyzer (LORCA) acc. to Hardeman (1994) we studied Elongation Index (EI) and aggregation kinetics of red blood cells in these patients. We also evaluated TcpO2 and TcpCO2 using a transcutaneous oxymeter (Microgas 7650, Kontron Instruments). In hypertensives we found a decrease in erythrocyte deformability (evaluated with EI), in erythrocyte aggregation time, a fibrinogenaemia increase, an increase of shear rate to disaggregate erythrocytes, a decrease in cellular oxygen delivery and tissue oxygenation, an impairment of microcirculation. These changes may be involved in the development of arterial hypertension and in its pathogenesis. These patterns also are more impaired in hypertensives with diabetes, lipoidoproteinosis, etc. These patterns are not related with the age of the patients but they are significantly and directly related (p < 0.01) with the patient hypertension-age. This could be a new way to realize a better treatment in hypertensives and a prevention of cardiovascular complications (i.e.: myocardial infarction, TIA, etc.).

Microvascular changes during laboratory stimuli and structural haemodynamic indices: the role of pulse pressure.

Office and ambulatory pulse pressure have been recognized as independent predictors of cardiovascular mortality and atherosclerosis in hypertensives as well as in normotensives. On the other hand, the vascular reactivity, in subjects with high pulsatile component of blood pressure, has not been studied yet. The purpose of our study was to identify the regional muscular hemodynamics and the cutaneous microvascular changes during laboratory stimuli in young adult very mild hypertensives with high pulse pressure. The cardiovascular (Finapres), the forearm vascular (plethysmography) and the microvascular cutaneous (laser-Doppler flowmetry and transcutaneous oximetry) responses to psychophysiological stimuli were measured. In addition, the hyperemic forearm vascular response to the ischaemic test was measured as haemodynamic index of vascular damage. We studied 15 very mild hypertensives with higher office pulse pressure and 15 patients with similar age, history of hypertension, metabolic parameters and systodiastolic blood pressure but lower pulse pressure values. Patients with high pulse pressure demonstrated reduced hyperemic response and increased residual vascular resistance at the forearm ischaemic test. They did not vary for all the parameters, except pulse pressure, during the baseline period but the total stress response, as residualized area-under-the-curve, was notably different. Patients with higher office pulse pressure demonstrated a significant increased heart rate, systolic and pulsatile blood pressure reactivity. On the contrary, they showed a reduced forearm and cutaneous blood flow response combined to a reduced transcutaneous tissutal oxygenation. The findings suggest that the increased pulsatile component of blood pressure might be associated to structural and functional vascular impairments since the very early stages of hypertension in young adults without metabolic disorders.