Feasibility and reproducibility of spleen transient elastography and its role in combination with liver transient elastography for predicting the severity of chronic viral hepatitis.

Liver transient elastography (L-TE) is a reliable, noninvasive predictor of disease severity in chronic liver disease of viral aetiology (CLD). Owing to the relationships among severity of CLD, portal hypertension and spleen involvement, the assessment of splenic stiffness (S-TE) may have an added value in staging CLD. Of 132 CLD patients of viral aetiology, 48 with myeloproliferative disorders (MD) and 64 healthy volunteers (HV), were concurrently investigated by both L-TE and S-TE. Liver disease severity was staged by liver biopsy (LB; Metavir) taken concurrently with TE examination and upper gastrointestinal tract endoscopy for gastro-oesophageal varices. The S-TE inter-observer agreement was analysed by an intra-class correlation coefficient (ICC); L-TE and S-TE accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis assessed the independent effect of L-TE and S-TE as predictors of hepatic fibrosis stage. S-TE failed in 22 CLD (16.6%), 12 (25%) MD and 12 (18%) HV. In the three groups, the ICC was 0.89 (0.84-0.92), 0.90 (0.85-0.94) and 0.86(0.80-0.91), respectively. In the CLD group, L-TE and S-TE independently predicted significant fibrosis (OR 5.2 and 4.6) and cirrhosis (OR 7.8 and 9.1), but at variance from L-TE, S-TE was independent from liver necroinflammation and steatosis. The NPV of S-TE for gastro-oesophageal varices was 100% using a 48 kPa cut-off. In CLD, spleen stiffness alone or in combination with hepatic stiffness can be reliably and reproducibly assessed by TE with the added value of improving the noninvasive diagnosis of severe liver disease and excluding the presence of oesophageal varices.

Predicting depression from illness severity in cardiovascular disease patients: self-efficacy beliefs, illness perception, and perceived social support as mediators.

BACKGROUND: Many studies have investigated the relationships between cardiovascular diseases and patients' depression; nevertheless, few is still known as regard the impact of illness severity on depression and whether psychosocial variables mediate this association. PURPOSE: The aim of this study is to investigate the putative mediating role of illness representations, self-efficacy beliefs, and perceived social support on the relationship between illness severity and depression. METHODS: A total of 75 consecutive patients with cardiovascular disease (80 % men; mean age = 65.44, SD = 10.20) were enrolled in an Italian hospital. Illness severity was measured in terms of left ventricular ejection fraction, whereas psychological factors were assessed using self-report questionnaires. RESULTS: The relationship between left ventricular ejection fraction and depression was mediated by identity illness perception, self-efficacy beliefs in managing cardiac risk factors, and perceived social support. CONCLUSION: The treatment of depression in cardiovascular disease patients may therefore benefit from a psychological intervention focused on patients' illness representations, self-efficacy beliefs, and their perceived social support.

COVID-19 therapies and their impact on QT interval prolongation: A multicentre retrospective study on 196 patients.

BACKGROUND: SARS-CoV-2 infection has caused a global pandemic. Many of the medications identified to treat COVID-19 could be connected with QTc prolongation and its consequences. METHODS: Non-ICU hospitalized patients of the three centres involved in the study from the 19th of March to the 1st of May were included in this retrospective multicentre study. Relevant clinical data were digitally collected. The primary outcome was the incidence of QTc prolongation ≥ 500 ms, the main secondary outcomes were the Tisdale score ability to predict QTc prolongation and the incidence of ventricular arrhythmias and sudden deaths. RESULTS: 196 patients were analysed. 20 patients (10.2%) reached a QTc ≥ 500 ms. Patients with QTc ≥ 500 ms were significantly older (66.7 ± 14.65 vs 76.6 ± 8.77 years p: 0.004), with higher Tisdale score (low 56 (31.8%) vs 0; intermediate 95 (54.0%) vs 14 (70.0%); high 25 (14.2%) vs 6 (30.0%); p: 0.007) and with higher prognostic lab values (d-dimer 1819 ± 2815 vs 11486 ± 38554 ng/ml p: 0.010; BNP 212.5 ± 288.4 vs 951.3 ± 816.7 pg/ml p < 0.001; procalcitonin 0.27 ± 0.74 vs 1.33 ± 4.04 ng/ml p: 0.003). After a multivariate analysis the Tisdale score was able to predict a QTc prolongation ≥ 500 ms (OR 1,358 95% CI 1,076-1,714p: 0,010). 27 patients died because of COVID-19 (13.7%), none experienced ventricular arrhythmias, and 2 (1.02%) patients with concomitant cardiovascular condition died of sudden death. CONCLUSIONS: In our population, a QTc prolongation ≥ 500 ms was observed in a minority of patients, no suspected fatal arrhythmias have been observed. Tisdale score can help in predicting QTc prolongation.

Expression of natriuretic peptide in ventricular myocardium of failing human hearts and its correlation with the severity of clinical and hemodynamic impairment.

Atrial natriuretic peptide (ANP) was immunohistochemically investigated in (1) right ventricular endomyocardial biopsy specimens from 87 apparently healthy donor hearts taken from victims of cerebral accidents; (2) 1 normal heart not suitable for transplantation (HBsAg carrier); (3) right ventricular endomyocardial biopsy specimens from 151 patients with dilated cardiomyopathy (DC); and (4) 57 explanted hearts, 26 with DC and 31 with ischemic heart disease. No ANP immunoreactivity was found in normal ventricles. Failing hearts showed ventricular positivity in 31% of the DC biopsy series, in 61% of the left ventricles, and in 30% of the right ventricles of the explanted heart series. An endoepicardial gradient was observed, because ANP positivity was greater and more extensive in the subendocardial layers. Ultrastructural studies were performed on biopsy specimens from 10 normal hearts and 132 DC biopsy samples. No ANP-storing granules were found in biopsy samples of normal ventricles, whereas ANP granules were seen in 15 of 132 (11.4%) DC cases. In parallel immunoblotting, investigation showed the same 13 kDa band protein in 1 normal atrium as well as in 8 failing atria and ventricles. ANP immunoreactivity was positively correlated with higher New York Heart Association functional classes as well as with higher left ventricular end-diastolic pressure (p less than 0.005), end-diastolic volume (p less than 0.005) and end-diastolic volume index (p less than 0.005). In conclusion, apparently healthy ventricles do not show ANP immunoreactivity, whereas failing ventricles do. ANP expression seems to be independent of the underlying disease, but positively related to the clinical status and the degree of left ventricular impairment and dilatation.

The morphologic spectrum of dilated cardiomyopathy and its relation to immune-response genes.

Endomyocardial biopsies from 174 patients with dilated cardiomyopathy (DC) were examined. Eight patients with histologically proven myocarditis were excluded from the study. A peculiar pattern of oversized and bizarre nuclei was observed in only some of the remaining patients. Two groups were identified: those with and without this feature (groups A and B, respectively). Myocyte width, nuclear diameter and nuclear/sarcoplasmic ratio were significantly higher in group A. The mean respective values were 36 +/- 5 mu, 14 +/- 3 mu and 0.41 +/- 0.08 for group A versus 20 +/- 8 mu, 7 +/- 2 mu and 0.37 +/- 0.08 for group B. Interstitial fibrosis was similarly present in groups A and B. Endocardial thickness was significantly increased in all patients, with group A showing the highest mean value. The morphologic features showed no correlation with the clinical condition of the patients at time of presentation. HLA typing was performed in 50 consecutive patients, 38 from group A and 12 from group B. DR4 and DR5 antigens were significantly more frequent in DC patients than in a normal population control (400 blood donors), while DR3 was less frequent. Group A was more strongly associated with the DR5 antigen than group B (55.3 vs 25.0%, respectively). It was less strongly associated with the DR4 antigen compared with group B (21.5 vs 41.7%, respectively). No difference was observed between the 2 groups concerning negative association with the DR3 antigen. Endomyocardial biopsies from DC patients reveal marked morphologic changes from patient to patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment and prevention of osteoporosis in juvenile chronic arthritis with disodium clodronate.

Osteoporosis is one of the most difficult problems in the management of Chronic Juvenile Arthritis (JCA). The available data suggest that bone loss results from multifactorial processes which lead to bone degradation through the activation of osteoclasts. Biphosphonates are synthetic factors that, once localized on the surface of hydroxyapatite crystals, do not allow either the production or destruction of the crystals. This activity seems to be due to cytotoxicity against osteoclasts and to inhibition of prostaglandin E2 synthesis. There is some evidence that these drugs are effective in the treatment of osteoporosis in several diseases. In an attempt to reduce or prevent osteoporosis in children affected by JCA we started a trial with disodium clodronate, a type of biphosphonate. Thirteen patients were enrolled in the study: 7 received disodium clodronate and 6 acted as control subjects. Before starting the therapy and after one year we performed a CT scan to evaluate the mineral bone density in all patients. The mean bone density increased from a bone mineral content of 129 mg/cc before treatment to 134 mg/cc after treatment (8% increase); control patients passed from 123 mg/cc to 115 mg/cc (7% decrease) in the same period. Only one child stopped treatment because of gastrointestinal side effects. The small number of patients enrolled in the trial does not allow any definite conclusions to be drawn, but the data are interesting and worthy of further study.

Phototoxic effect of fluoroquinolones on two human cell lines.

Photosensitization induced by the fluoroquinolone ofloxacin (OFLX) has been studied using two human cell lines, HL60 and K562, two UV wavelengths, 290 and 330 nm, and two different exposure protocols, acute and protracted. The examined endpoints are the cellular lethality and recovery and the membrane changes produced by the oxidative damage, studied using cloning and counting techniques and the measurement of the generalized polarization (GP) of the fluorescent membrane probe 2-dimethylamino-6-lauroyl-naphthalene (Laurdan). The results show that: (i) the photosensitizing effect is detectable at concentrations similar to those found in patients treated with OFLX only when the cells are irradiated with 330 nm; (ii) the amount of photodamage is a function of the drug concentration and of UV dose and persists also after the removal of the drug; (iii) during the first 24 h after OFLX treatment, a large decrease of the cell number can be observed due to cell lysis; (iv) the OFLX is inserted in the cell membranes at concentrations directly related with the drug concentration and incubation time; (v) the OFLX produces an increase in the GP values similar to that produced by membrane lipid oxidation which persists for hours after the removal of the drug. The overall results suggest the cell membrane as the main target of the OFLX adverse action, with a possible mechanism involving the formation of reactive oxygen species (ROS), which triggers, in turn, the lipid peroxidation chain reaction.

Ultrafiltration in the treatment of refractory congestive heart failure.

Artificial subtraction of fluids and solutes was evaluated in the course of acute and chronic heart failure when it became refractory to standard intensive medical treatment. A group of 19 patients (mean age 57 years), 9 with ischemic, 2 amyloidotic, 4 valvular, and 4 idiopathic cardiomyopathy, were treated. In 17 patients extracorporeal ultrafiltration (UF) by means of a polysulfonate ultrafilter was adopted along 125 sessions (105 assisted by a roller pump and 20 as a slow continuous ultrafiltrate). In two patients continuous peritoneal dialysis was adopted. In every case UF was well tolerated. Ultrafiltrate volumes ranged from 1680 to 3500 ml for every session with corresponding Na losses ranging from 194 to 434 mEq/session. Improved clinical and functional status with reduction of edema was observed in 17 of 19 patients. In 12 patients UF could be discontinued due to restored response to diuretics; 5 of these patients could subsequently undergo heart surgery (1 transplant, 3 valve replacement, 1 coronary bypass). The remaining 7 patients survived on medical therapy alone for an average of 228 days. In 7 of 19 cases, UF could not be discontinued, and these patients died after an average of 23 days of treatment. In conclusion, UF proved to be effective in eliminating salt-fluid overload and restoring response to medical treatment. Patients who are potential surgical candidates seem to be the most suitable for UF.

[Change in ventricular repolarization associated with acute spontaneous pneumothorax]. / Modificazioni della ripolarizzazione ventricolare associate a pneumotorace spontaneo acuto.

Cases of acute pneumothorax admitted in the period 1975-1978 were examined to determine the presence of changes in ventricular repolarization. A significant elongation of the QT segment was noted in 23/126 cases. The series did not include subjects with chronic heart and /or bronchopulmonary disease, or other clinical features that might explain such elongation. The ECG changes bore no relation to the site and extent of the pneumothorax. Agreement is expressed with the view that their explanation lies in the existence of a reflex mechanism acting on the autonomous nervous system.

[Aneurysm of the sinus of Valsalva and late rupture of the interventricular septum due to infective endocarditis. Is the two-dimensional echocardiography of endocarditic extension into the interventricular septum possible?]. / Aneurisma del seno di Valsalva e rottura tardiva del setto interventricolare per endocardite infettiva. E possibile la diagnosi ecocardiografica bidimensionale di estensione endocarditica al setto interventricolare?

In a 54 year old woman affected by infective endocarditis, with bicuspid aortic valve and aneurysm of sinus of Valsalva protruding into the right atrium, two-dimensional echocardiography helped to identify altered myocardial echo patterns of the interventricular septum at basal level. Because of the proximity with valvular lesions due to endocarditis, we could interpret these appearances as produced by invasion of the infective process into the septum. The autopsy report of septum rupture in the same area further supports our interpretation of the echocardiographic finding.

Gas exchange threshold as a predictor of severe postoperative complications after lung resection in mild-to-moderate chronic obstructive pulmonary disease.

Low exercise capacity is considered predictive for postoperative complications or death after thoracic and general surgery. However, in recent literature no agreement has been found about the predictive cut-off values for preoperative exercise parameters. The aim of this work was to investigate whether peak oxygen consumption (V'o2) and noninvasive anaerobic threshold (AT) determined by gas exchange threshold (GET) can be reliable preoperative predictors of mortality and morbidity after lung resection in patients with mild-to-moderate (forced expiratory volume in one second (FEV1) > 50% predicted) chronic obstructive pulmonary disease (COPD). Fifty tour COPD patients were studied before lung surgery: 12 had severe complications, 16 had mild and 26 had no complications. Peak V'O2 sensitivity and specificity in predicting severe postoperative complications were 41.6% and 95.5% respectively (using 75% of the predicted value as cut-off), while for GET they were 91.6% and 97.6% respectively (using 14.5 mL.kg-1.min-1 as cut-off value). Only one patient (3.5%) with a peak V'O2 > 20 mL.kg-1.min-1 suffered severe complications. On the other hand 11 out of the 26 patients (42.3%) with peak V'O2 < 20 mL.kg-1.min-1 had serve complications. In patients with peak V'O2 < 20 mL.kg-1.min-1, 11 out of 12 (91.6%) with a GET < or = 14.5 mL.kg-1.min-1 suffered severe complications, whereas 15 out of 15 (100%) with a GET > 14.5 mL.kg-1.min-1 showed no or mild complications. In conclusion, peak oxygen consumption values > 20 mL.kg-1.min-1 can be considered a safe upper cut-off limit for pulmonary resection. In patients with a peak oxygen consumption value < 20 mL.kg-1.min-1, gas exchange threshold determination can improve significantly the predictivity of a cardiopulmonary test for severe complications and must be routinely considered.

[True and presumed contraindications of beta blockers. Peripheral vascular disease, diabetes mellitus, chronic bronchopneumopathy]. / Controindicazioni vere o presunte dei betabloccanti. Vasculopatie periferiche, diabete mellito, broncopneumopatie croniche.

Traditional contraindications to beta-blockers are peripheral vascular diseases, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and asthma. Recent data seem to show that rigorous application of these rules are not completely justified and indicate that many patients would be inappropriately excluded from the beneficial effects of this therapy. Appraisal of clear guidelines for a safe use of beta-blockers is thus mandatory for the clinician. A brief review of the effects of beta-adrenergic receptor blockade is offered. The therapy is aimed at blocking beta 1-receptors. On the other hand, the block of beta 2-receptors causes the well known side effects, i.e. vasoconstriction, delayed response to hypoglycemia in diabetic patients, bronchoconstriction. From the first compound, propranolol, with uniform action on beta 1 and beta 2-receptors, further generation of beta-blockers were subsequently developed: beta 1-selective, with intrinsic sympathomimetic activity, and with associated vasodilating "ancillary" property. Some favorable reduction in collateral effects has thus been obtained with new compounds, without reaching complete safety. Examination of exclusion criteria applied in clinical trials offers no useful indications because of their imprecise definition. Examination of the literature and a more accurate understanding of the diseases, traditionally considered contraindications, may help setting up a uniform and clear path: peripheral vascular disease: beta-blockers should be avoided only in those patients with vasospastic disorders, rest pain with severe peripheral vascular disease or nonhealing lesions. In patients with mild to moderate disease, beta-blockers can be prescribed, but careful surveillance for any changes in symptoms related to intermittent claudicatio should be achieved; diabetes mellitus: previous apprehension for the lessening reaction to hypoglycemia in patients treated with insulin has been retracted. Beta-blockers are not contraindicated in these patients. Some caution should be addressed when signs of autonomic disease are present or in patients with difficult glycemic control. Patients on oral long-acting antidiabetic drugs should not be neglected. The risk of prolonged and paucisymptomatic hypoglycemia while taking beta-blocker agents is somewhat more relevant than in patients treated regularly with insulin; COPD and asthma: confusion may arise if rigorous definition of these diseases and their severity is not applied following the guidelines of the American Thoracic Society. Because bronchial hyperreactivity seems the crucial factor in determining collateral effects to beta-blocker agents, agreement can be reached on the following statements. Beta-blockers are contraindicated a) when history of asthma is present, b) when COPD is moderate to severe, i.e. with FEV1 reduction < 50% of the predicted value, c) in patients on chronic bronchodilator treatment, d) in chronic airflow limitation with evidence of > or = 20% reversibility in airway obstruction in response to inhaled salbutamol. When FEV1 is > 50% of the predicted value, beta-blockers can be given, providing adequate control of stability of ventilatory conditions.

[Aortic dissection. A diagnostic hypothesis that is frequently discussed]. / La dissezione aortica. Un'ipotesi diagnostica che fa spesso discutere.

Aortic dissection is a dramatic event which too often carries an ominous prognosis. The characteristic clinical presentation has been well described in medical texts and cannot be misdiagnosed. However, in some not infrequent cases, symptoms and signs may be so misleading and subtle that a subsequent catastrophic evolution then seems unexpected. The diagnosis may be easily confirmed or excluded by modern diagnostic tools such as transesophageal echocardiography, magnetic resonance imaging or spiral computed tomography, which all offer such accurate anatomic images of the aortic wall that nowadays it is possible to diagnose even those minimal lesions that can precede dissection, such as intramural hemorrhages or penetrating ulcers. However, these techniques are complex, costly and require experienced operators for optimum sensitivity and accuracy. Their use in patients with suspected acute aortic syndromes is of proven necessity. However, how often is all this feasible in a crowded Emergency Department where hundreds of patients with aspecific and overlapping symptoms and signs all require immediate attention? Furthermore, how often is a subtle intriguing initial presentation then followed by fatality, which might also come about some days later? Can failing to make an early diagnosis be cause for prosecution for having given a faulty diagnosis or might it be accepted as a risk related to the imprecise, probabilistic nature of the medical approach to the diagnosis? How can an Emergency Department doctor produce a reliable document of his way of proceeding in order to offer verifiable legal proof of his methodological integrity and thus be able to avoid misinterpretation of guilt? It is all too easy to judge overlooked clinical recognition when the clear and "simple" pathological diagnosis is available, if one does not consider the complexity of the disease and its possible manifestations in the single patient. In order to answer these questions it is necessary to collect the experience of doctors and others involved in this field. It is the aim of this paper and the clinical case presented to stimulate discussion and initiate the task in hand.

[Effect of thermal mud baths on normal, dry and seborrheic skin]. / Effetti dell'uso di un fango termale su cute normale, secca e seborroica.

PURPOSE: To investigate the curative effects of thermal water and thermal muds in various cutaneous pathologies. PATIENTS AND METHODS: Modifications of phmetry and sebometry using sulphur thermal muds in normal, dry and seborrheic skin have been studied. The three groups of patients have been submitted to a 14 day treatment with thermal muds. RESULT: The application of thermal mud normalized the value of cutaneous pH and sebometry. CONCLUSIONS: These beneficial effects are long-lasting in individuals who have a prolonged treatment with thermal muds.

Point-of-care multiorgan ultrasonography for the evaluation of undifferentiated hypotension in the emergency department.

PURPOSE: We analyzed the efficacy of a point-of-care ultrasonographic protocol, based on a focused multiorgan examination, for the diagnostic process of symptomatic, non-traumatic hypotensive patients in the emergency department. METHODS: We prospectively enrolled 108 adult patients complaining of non-traumatic symptomatic hypotension of uncertain etiology. Patients received immediate point-of-care ultrasonography to determine cardiac function and right/left ventricle diameter rate, inferior vena cava diameter and collapsibility, pulmonary congestion, consolidations and sliding, abdominal free fluid and aortic aneurysm, and leg vein thrombosis. The organ-oriented diagnoses were combined to formulate an ultrasonographic hypothesis of the cause of hemodynamic instability. The ultrasonographic diagnosis was then compared with a final clinical diagnosis obtained by agreement of three independent expert physicians who performed a retrospective hospital chart review of each case. RESULTS: Considering the whole population, concordance between the point-of-care ultrasonography diagnosis and the final clinical diagnosis was interpreted as good, with Cohen's k = 0.710 (95 % CI, 0.614-0.806), p < 0.0001 and raw agreement (Ra) = 0.768. By eliminating the 13 cases where the final clinical diagnosis was not agreed upon (indefinite), the concordance increased to almost perfect, with k = 0.971 (95 % CI, 0.932-1.000), p < 0.0001 and Ra = 0.978. CONCLUSIONS: Emergency diagnostic judgments guided by point-of-care multiorgan ultrasonography in patients presenting with undifferentiated hypotension significantly agreed with a final clinical diagnosis obtained by retrospective chart review. The integration of an ultrasonographic multiorgan protocol in the diagnostic process of undifferentiated hypotension has great potential in guiding the first-line therapeutic approach.

Mutagenicity and cytotoxicity assessment in patients undergoing orthodontic radiographs.

OBJECTIVES: The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated buccal mucosa cells from individuals following radiography. METHODS: Lateral and frontal cephalometric X-ray and panoramic dental X-rays were taken of a total of 18 healthy patients (6 male and 12 female) referred for orthodontic therapy. Exfoliated oral mucosa cells were collected immediately before X-ray exposure and after 10 days. RESULTS: The results revealed no statistically significant difference (P > 0.05) in the frequency micronucleated oral mucosa cells after X-ray exposure. However, X-ray was able to increase other nuclear alterations closely related to cytotoxicity, such as karyorrhexis, pyknosis and karyolysis. CONCLUSIONS: Data indicated that exposure to certain radiography may not be a factor in inducing chromosomal damage, but it does promote cytotoxicity.