Cardiac complications in patients with COVID-19: a systematic review.

Cardiac complications in patients with COVID-19 have been described in the literature with an important impact on outcome. The primary objective of our systematic review was to describe the kind of cardiac complications observed in COVID-19 patients and to identify potential predictors of cardiovascular events. The secondary aim was to analyze the effect of cardiac complications on outcome.We performed this systematic review according to PRISMA guidelines using several databases for studies evaluating the type of cardiac complications and risk factors in COVID-19 patients. We also calculated the risk ratio (RR) and 95% CI. A random-effects model was applied to analyze the data. The heterogeneity of the retrieved trials was evaluated through the I2 statistic. Our systematic review included 49 studies. Acute cardiac injury was evaluated in 20 articles. Heart failure and cardiogenic shock were reported in 10 articles. Myocardial infarction was evaluated in seven of the papers retrieved. Takotsubo, myocarditis, and pericardial effusion were reported in six, twelve, and five articles, respectively. Arrhythmic complications were evaluated in thirteen studies. Right ventricular dysfunction was evaluated in six articles. We included 7 studies investigating 2115 patients in the meta-analysis. The RR was 0.20 (95% CI: 0.17 to 0.24; P < 0.00001, I2 = 0.75). Acute cardiac injury represented the prevalent cardiac complications observed in COVID-19 patients (from 20 to 45% of the patients). Patients with acute cardiac injury seemed to be significantly older, with comorbidities, more likely to develop complications, and with higher mortality rates. Acute cardiac injury was found to be an independent risk factor for severe forms of SARS-CoV-2 infection and an independent predictor of mortality. Due to the scarce evidence, it was not possible to draw any conclusion regarding Takotsubo, myocarditis, pleural effusion, and right ventricular dysfunction in COVID-19 patients. Noteworthy, possible arrhythmic alterations (incidence rate of arrhythmia from 3 to 60%) in COVID-19 patients have to be taken into account for the possible complications and the consequent hemodynamic instabilities. Hypertension seemed to represent the most common comorbidities in COVID-19 patients (from 30 to 59.8%). The prevalence of cardiovascular disease (CVD) was high in this group of patients (up to 57%), with coronary artery disease in around 10% of the cases. In the majority of the studies retrieved, patients with CVD had a higher prevalence of severe form, ICU admission, and higher mortality rates.

Elucidation of the role of the lamina cribrosa in glaucoma using optical coherence tomography.

Glaucoma is a chronic and progressive optic neuropathy characterized by the death of retinal ganglion cells and corresponding visual field loss. Despite the growing number of studies on the subject, the pathogenesis of the disease remains unclear. Notwithstanding, several studies have shown that the lamina cribrosa (LC) is considered an anatomic site of glaucomatous optic nerve injury, thus having a key role in the pathophysiology of glaucoma development and progression. Different morphological alterations of the LC have been described in vivo in glaucomatous eyes after the evolution of optical coherence tomography (OCT) devices. The most relevant findings were the reduction of laminar thickness, the presence of localized defects, and the posterior LC displacement. These new laminar parameters documented through OCT are not only promising as possible additional tools for glaucoma diagnosis and monitoring, but also as predictors of disease progression. In spite of the advance of technology, however, proper evaluation of the LC is not yet viable in all eyes. We describe OCT-identified LC changes related to the development and progression of glaucoma and provide future directions based on a critical data analysis, focusing on its clinical relevance and applicability.

Comparison of diuretic strategies in diuretic-resistant acute heart failure: a systematic review and network meta-analysis.

OBJECTIVE: Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a higher risk of death. This review aimed to investigate whether a diuretic therapeutic approach more effective than furosemide alone exists for patients with diuretic-resistant AHF. MATERIALS AND METHODS: We identified all randomized controlled trials (RCTs) evaluating diuretic therapy in patients with diuretic-resistant AHF. We searched Pubmed, BioMed Central, and Cochrane CENTRAL databases. RESULTS: Six RCTs were identified, involving a total of 845 patients. The P-score ranges from 0.6663 for furosemide to 0.2294 for the tolvaptan-furosemide. We found no significant differences in efficacy for any drug comparison. CONCLUSIONS: None of the diuretics considered in RCTs performed to date (tolvaptan, metolazone, hydrochlorothiazide, indapamide) appear to be more effective than furosemide therapy alone for the treatment of patients with diuretic-resistant AHF.

Ultrasound-guided vascular access in critical illness.

Over the past two decades, ultrasound (US) has become widely accepted to guide safe and accurate insertion of vascular devices in critically ill patients. We emphasize central venous catheter insertion, given its broad application in critically ill patients, but also review the use of US for accessing peripheral veins, arteries, the medullary canal, and vessels for institution of extracorporeal life support. To ensure procedural safety and high cannulation success rates we recommend using a systematic protocolized approach for US-guided vascular access in elective clinical situations. A standardized approach minimizes variability in clinical practice, provides a framework for education and training, facilitates implementation, and enables quality analysis. This review will address the state of US-guided vascular access, including current practice and future directions.

Molecular Regulation of the Spindle Assembly Checkpoint by Kinases and Phosphatases.

The spindle assembly checkpoint (SAC) is a surveillance mechanism contributing to the preservation of genomic stability by monitoring the microtubule attachment to, and/or the tension status of, each kinetochore during mitosis. The SAC halts metaphase to anaphase transition in the presence of unattached and/or untensed kinetochore(s) by releasing the mitotic checkpoint complex (MCC) from these improperly-oriented kinetochores to inhibit the anaphase-promoting complex/cyclosome (APC/C). The reversible phosphorylation of a variety of substrates at the kinetochore by antagonistic kinases and phosphatases is one major signaling mechanism for promptly turning on or turning off the SAC. In such a complex network, some kinases act at the apex of the SAC cascade by either generating (monopolar spindle 1, MPS1/TTK and likely polo-like kinase 1, PLK1), or contributing to generate (Aurora kinase B) kinetochore phospho-docking sites for the hierarchical recruitment of the SAC proteins. Aurora kinase B, MPS1 and budding uninhibited by benzimidazoles 1 (BUB1) also promote sister chromatid biorientation by modulating kinetochore microtubule stability. Moreover, MPS1, BUB1, and PLK1 seem to play key roles in APC/C inhibition by mechanisms dependent and/or independent on MCC assembly. The protein phosphatase 1 and 2A (PP1 and PP2A) are recruited to kinetochores to oppose kinase activity. These phosphatases reverse the phosphorylation of kinetochore targets promoting the microtubule attachment stabilization, sister kinetochore biorientation and SAC silencing. The kinase-phosphatase network is crucial as it renders the SAC a dynamic, graded-signaling, high responsive, and robust process thereby ensuring timely anaphase onset and preventing the generation of proneoplastic aneuploidy.

Assessment of liver fibrosis in transplant recipients with recurrent HCV infection: usefulness of transient elastography.

BACKGROUND: Progression of recurrent hepatitis C is accelerated in liver transplant recipients, leading to special need of non-invasive validated methods to estimate liver fibrosis. AIM: To assess the efficacy of liver stiffness measurement by transient elastography (Fibroscan) and serum parameters in predicting fibrosis stage in HCV-infected transplant recipients. METHODS: The correlation between liver fibrosis, assessed at liver histology on bioptic specimens obtained for clinical indications, and stiffness or clinico-serological indexes (Benlloch, APRI, Forns, Fibrotest and Doppler resistance index), was investigated in transplant recipients with recurrence of HCV chronic hepatitis. A total of 56 patients (of which 36 with all clinico-serological indexes), presenting with the following METAVIR fibrosis stage F1=38, F2=9, F3=8, F4=1, were enrolled in the study population. Differences between fibrosis stages were calculated by non-parametric analysis. The best cut-off for identifying significant fibrosis (F2-F4) was assessed by ROC curve analysis. RESULTS: Stiffness (median and range) was 7.7 KPa (range 4.2-13.9) in F1 and 17.0KPa (range 6.8-36.3) in >or=F2 (p<0.001). A stiffness cut-off of 10.1 KPa revealed 94% Sensitivity, 89% Specificity, 81% PPV and 94% NPV in differentiating F1 from F2-F4. The area under the receiver operator curve in the assessment of fibrosis was significantly higher for Liver stiffness (AUROC 0.943) than for any of the other non-invasive indexes (AUROCs ranging 0.591-0.815). CONCLUSIONS: Transient elastography of the liver provides good accuracy in identifying patients with significant fibrosis and performs better than non-invasive indexes based on clinico-serological parameters in transplant recipients.

[Hypertransaminasemia greater than 400 U/l in adults seen at a tertiary hospital. Prospective study of etiology]. / Hipertransaminasemia superior a 400 U/l en adultos atendidos en un hospital terciario. Estudio prospectivo de su etiología.

AIM: To investigate the frequency of distinct causes of elevated transaminase levels in the range of acute viral hepatitides in patients attended in a hospital. PATIENTS AND METHOD: Patients attended in a tertiary hospital over a 3-month period who had elevation of transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) above 400 U/l were identified and their medical records were reviewed to determine etiology. RESULTS: A total of 106 patients were studied, of which 22 had undergone liver transplantation. In these patients, the causes of hypertransaminasemia were ischemic/reperfusion injury in 6 (27%), ischemic hepatitis in 4 (18%), acute hepatitis in 2 (9%), cellular rejection in 3 (14%), chronic hepatitis C in 4 (18%) and cholestasis in 3 (14%). In the 84 patients who did not undergo transplantation, the causes were hepatic ischemia in 24 (28%), chronic viral hepatitis in 19 (22%), toxic hepatitis in 12 (14%), pancreatico-biliary disease in 11 (13%), acute viral or bacterial hepatitis in 10 (12%), liver tumor in 3 (4%), cholestasis of pregnancy in one and unknown in 4 (5%). Ischemic lesions and pancreatico-biliary disease were more frequent in hospitalized patients while acute and chronic hepatitides were more frequent in outpatients. The worst outcomes were found in ischemic lesions and pancreatico-biliary disease. CONCLUSION: Marked elevation of transaminase levels has multiple causes. Acute viral hepatitides were a relatively infrequent cause. In transplant recipients, the most frequent causes were ischemia/reperfusion injury, while in non-transplanted patients the most frequent causes were ischemic hepatitides and acute episodes of chronic viral hepatitides. The AST/ALT ratio did not contribute to etiologic diagnosis.

Clinical implications of the reduced activity of the GH-IGF-I axis in older men.

During the last decade, a significant body of evidence has accumulated, indicating that IGF-I might play a role in several pathological conditions commonly seen during aging, such as atherosclerosis and cardiovascular disease (CVD), cognitive decline, dementia, sarcopenia and frailty. A vascular protective role for IGF-I has been suggested because of its ability to stimulate nitric oxide production from endothelial and vascular smooth muscle cells. In cross sectional studies, low IGF-I levels have been associated with unfavorable CVD risk factors profile, such as atherosclerosis, abnormal lipoprotein levels and hypertension, while in prospective studies, lower IGF-I levels predict future development of ischemic heart disease. The fall in IGF-I levels with aging correlates with cognitive decline and it has been suggested that IGF-I plays a role in the development of dementia. IGF-I is highly expressed within the brain and is essential for normal brain development. IGF-I has anti-apoptotic and neuroprotective effects and promotes projection neuron growth, dendritic arborization and synaptogenesis. Collectively, these data are consistent with a causal link between the age-related decline in GH and IGF-I levels and cognitive deficits in older persons. Finally, there is evidence of a relationship between declining GH and IGF-I levels and age-related changes in body composition and physical function. However, few studies have documented a precise role of IGF-I in the development of sarcopenia, frailty and poor mobility. We have recently documented that serum IGF-I is significantly associated with measures of muscle strength and physical performance in men and to a lesser extent in women. In conclusion, IGF-I is a pleiotropic hormone that in older persons may positively affect the cardiovascular system, the central nervous system and physical function.

Coeliac disease associated with Sjögren's syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism.

Although coeliac disease may occur in patients affected by another immune-mediated disorder, its coexistence with multiple autoimmune diseases is not frequently described. We report here the case of a 45-year-old woman referred to our centre because of diarrhoea and weight loss, who had already received a diagnosis of primary biliary cirrhosis, Sjögren's syndrome and renal tubular acidosis. Following the development of diarrhoea we established the diagnosis of coeliac disease, based on the presence of anti-endomysium antibodies and a compatible duodenal biopsy. Despite gluten withdrawal she went on to develop an autoimmune hyperthyroidism. The patient tested positive for HLA DRB1*03 and DQB1*02. The association is unlikely to be casual and may be explained by autoimmune mechanisms, genetic susceptibility and favouring environmental factors commonly shared by the diseases of our patient.

Effect of inhalation aspirin challenge on exhaled nitric oxide in patients with aspirin-inducible asthma.

BACKGROUND: A complex relationship between arachidonic acid metabolites and nitric oxide (NO) synthesis has been reported in asthma. The effects of inhaled aspirin on fractional exhaled NO (FENO) in patients with aspirin-tolerant (ATA) and aspirin-inducible (AIA) asthma compared with normal controls have been investigated. METHODS: The FENO was measured baseline, after saline and lysine-aspirin (L-ASA) bronchial challenge in 10 patients with ATA and in 10 patients with AIA [mean (PD(20)FEV(1) L-ASA): 14.7 +/- 12.7 mg], who had comparable age and baseline FEV(1). Ten healthy subjects served as controls. Sputum eosinophils were counted after saline and after L-ASA challenge in the two groups of asthmatics. RESULTS: Asthmatic patients had baseline FENO significantly higher than controls (29.7 +/- 6.8 vs 9.8 +/- 2.05 p.p.b. respectively, P < 0.0001). No difference was observed in methacholine PD(20)FEV(1) and baseline FENO between ATA and AIA patients. After L-ASA inhalation, FENO increased significantly only in patients with AIA, reaching the peak value 4 h after bronchoconstriction (from 31.1 +/- 6 to 43 +/- 4.8 p.p.b., P < 0.001), while no change was observed in patients with ATA and in controls. Sputum eosinophils increased significantly after L-ASA inhalation only in patients with AIA (from 8.1 +/- 2.7 to 11.1 +/- 2.8%, P < 0.005) and there was a significant relationship between the increase in sputum eosinophils and the increase in FENO after ASA challenge. CONCLUSION: Exhaled NO may indicate eosinophilic airway inflammation during ASA exposure in patients with ASA inducible asthma.

Pituitary function in chronic heart failure in the elderly.

Heart failure is a complex syndrome characterized by the activation of hemodynamic, immunologic and neurohormonal systems, which have beneficial effects in the short run, but will ultimately lead to secondary end-organ damage with worsening of LV remodeling and subsequent cardiac decompensation. A very important role seems to be played by modifications of the pituitary hormone systems. Due to the neurohormonal activation there is an increase in the activity in the renin angiotensin system, in the adrenergic nervous system, and in the cytokine system. In heart failure there is a decrease in many anabolic hormones, such as a decrease of GH and IGF-I, of DHEA/DHEAS with normal or increased F, and a decrease of LH and sex steroids, resulting in an important catabolic drive, capable of contributing to the development of cardiac failure and to sarcopenia and/or cachexia, frequently observed in the advanced stages of the disease. However, these hormone alterations have been described in relatively young patients with chronic heart failure, since the mean age of all the subjects studied was of about 60 yr and none of the studies have specifically addressed this issue in the very old patients, who represent the largest portion of population affected by this pathological condition. The role of hormone replacement therapy needs to be verified in a population of elderly patients with heart failure.

Role of antibiotic therapy on long-term germ excretion in faeces and digestive symptoms after Salmonella infection.

BACKGROUND: The role of antibiotic therapy on Salmonella faecal excretion is controversial. Acute Salmonella gastroenteritis induces long-lasting digestive symptoms in up to one-third of subjects. The role of antimicrobial therapy on persistent post-infectious symptoms is unknown. AIM: To investigate the role of antibiotic therapy on long-term germ faecal excretion and digestive symptoms after Salmonella infection. SUBJECTS AND METHODS: 1543 subjects [518 aged between 3 and 5 years (35.3%); 950 between 6 and 10 years (64.7%) and 75 adults (4.9%)] involved in a single outbreak of Salmonella enteritis fulfilled the study criteria by repeating stool cultures and answering a symptom questionnaire 3 months post-infection. RESULTS: 327 subjects (21.2%) were treated with antibiotics during the acute infection [121 children aged 3-5 years (23.4%), 175 children aged 6-10 years (18.4%) and 31 adults (41.3%)]. Antibiotic treatment did not affect Salmonella excretion at any of the time points studied up to three months post-infection in any age group as compared to age-matched untreated controls. Persistent digestive symptoms were more common among the patients treated with antibiotics (9.5% vs. 2.9%; P=0.003). CONCLUSIONS: Antibiotic therapy does not affect Salmonella enteritis excretion. Digestive symptoms after clearance of the infectious agent are significantly higher in patients treated with antibiotics during acute gastroenteritis.

[Hypertension as a function of age]. / L'ipertensione in funzione dell'età.

Hypertension is one of the main risk factors for cerebrovascular disease (stroke), coronary artery disease (acute myocardial infarction), congestive heart failure (both systolic and diastolic dysfunction), and renal dysfunction. The risk is related to blood pressure level and to the presence of target organ damage. Together with hypertension, other cardiovascular risk factors, such as hyperlipidemia and/or diabetes, also contribute to the chain of events leading to atherosclerosis, vascular complications and death. Three-quarters of middle-aged, urban population show at least one cardiovascular risk factor and 91.3% of all hypertensives show at least one cardiovascular risk factor in addition to hypertension itself. In most populations, the risk of cardiovascular disease rises steeply with age. This powerful effect of age on disease risk has important consequences for the risk of cardiovascular disease related to blood pressure and other risk factors. At most ages the risk for cardiovascular diseases is higher in men than in women, although this difference declines with increasing age and is greater for coronary heart disease than for stroke; in the United States from age 34 to 74 the risk of death from coronary heart disease is 2- to 3-fold greater in men; the risk of death from stroke is 30% higher in men than in women; after age 75 the risk of death from stroke and from coronary heart disease is similar in men and women. Postmenopausal women share the same risk with men for cardiovascular disease. For many years the study and treatment of hypertension has been largely directed toward diastolic blood pressure; the importance of elevated systolic blood pressure in the management of cardiovascular disease is being largely underrecognized. Convincing evidence is presently available indicating that elevated systolic blood pressure is even a stronger predictor than diastolic blood pressure for progression of cardiovascular disease and adverse outcomes. The clinical and laboratory evaluation and drug treatment of the hypertension is related to age. The elderly benefit from treatment of elevated systolic blood pressure as much or even more than middle-aged hypertensive subjects. Two large clinical trials on treatment of isolated systolic hypertension, the Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe Study (Syst-Eur), have demonstrated that antihypertensive drug therapy in elderly patients with isolated systolic hypertension effectively reduces the risk of stroke and other major cardiovascular events.