Evaluation of Tooth Movement Accuracy with Aligners: A Prospective Study.

Background. Clear aligners treatment (CAT) is a common solution in orthodontics to treat both simple and complex malocclusions. This study aimed to evaluate the predictability of CAT, comparing the virtually planned and the achieved tooth movement at the end of stage 15, which is often the time of first refinement. Methods. Seventeen patients (mean age: 28.3 years) were enrolled in the study. Torque, tip and rotation were analyzed in 238 maxillary teeth on digital models at Pre-treatment (T0), at the end of stage 15 (T15) and at virtually planned stage 15 (T15i). Prescription, Achieved movement and performance values were calculated to compare the virtually planned and the clinical tooth position. Data were analyzed by means of Student's t test with a level of significance set at p < 0.05. Results. The largest iper-performance was the torque correction of the second molars (+2.3° ± 3.1°), the greatest under-performance was the tip correction of the first molars (−2.3° ± 3.3°), while rotation corrections of all the teeth showed more accurate performance. No significant differences were found between mean Prescription and mean Achieved movement for all the assessed movements (p < 0.05). Conclusions. An accurate evaluation of CAT after the 15th aligner is fundamental in order to individuate the movements that are not matching the digital set-up.

Home Monitoring trends during COVID-19 infection.

BACKGROUND: Cardiac implantable electronic device (CIED) recipients could have an unfavorable prognosis if infected with the novel coronavirus (COVID-19). We aimed to analyze the data daily transmitted by the Home Monitoring (HM) system (BIOTRONIK, Berlin, Germany) of CIEDs during the infection. METHODS: We identified CIED patients followed with the HM who experienced COVID-19 clinical manifestations. The daily trends of the following HM variables were analyzed: mean heart rate (HR), physical activity, thoracic impedance (TI), ventricular and atrial arrhythmic burden. RESULTS: The study cohort included 10 CIED patients (median age 90 [84-92] years, male 90%) with acute respiratory syndrome. The HR showed an increase of a value ranging from 10 to 30 bpm well in advance of the severe clinical manifestations. The physical activity was generally low during the entire infection course. The TI decreased in patients presented with pulmonary edema, but increased significantly (8 to 25 Ω) in most COVID-19 patients (8 out of 10) suggesting an association with pulmonary fibrosis. Arrhythmic complications were also found in half of the patients. CONCLUSION: The trends of HR and TI in CIEDs recipients infected by the COVID-19 often showed early recurrent patterns before adverse clinical manifestations.

Telecardiology during the Covid-19 pandemic: past mistakes and future hopes.

Covid-19 has caused a striking global impact on public health services. The inevitable suspension of all scheduled visits without urgency and non-urgent hospitalizations has resulted in relevant modifications in our management of cardiac patients. Our goal should be to maintain high standards in the treatment of cardiovascular diseases, reducing the risk of esposure to Covid-19 for patients and healthcare professionals. Our Division of Cardiology follows 300 patients in a Heart Failure Ambulatory and almost all of these, as CIEDs' carriers, are monitored by remote monitoring; in addition, we follow more than 2000 CIEDs' carriers using remote monitoring. The purpose of telemedicine, using telecommunications technology, must be to optimize the clinical management of heart failure patients at home, in order to improve their quality of life, reducing hospitalization and emergency department access, also promoting self-management. The evolution of technology has led to the development and refinement of telemedicine and remote monitoring and even more in pandemic times these methods are to be considered a cornerstone. So that telemedicine can really become a well-structured reality, the following are fundamental: the uniform recognition of a reimbursement for this type of medical service, the creation of an organizational model with an adequately structured team, a valid integration with the territorial reality.

Direct oral anticoagulants for patients aged over 80 years in nonvalvular atrial fibrillation: the impact of frailty.

AIMS: In patients aged at least 80 years, atrial fibrillation is responsible for significant morbidity and mortality, with a high incidence of stroke. Four new direct oral anticoagulants (DOACs) have been introduced in Italy for the prevention of thromboembolism. Their safety and efficacy in the elderly have already been confirmed. Frailty is frequently associated with aging, but only a few studies have paid attention to interactions between frailty and anticoagulation therapy. METHODS: We retrospectively evaluated the effectiveness and safety of DOACs in a population aged at least 80 years. Frailty was appraised using an adaptation of the Reported Edmonton Frail Scale, considering a value at least 8 (on a scale from 0 to 18). RESULTS: The majority (644/731) of patients remained on DOACs for more than 1 year. A total of 19 patients experienced a thrombotic event while on anticoagulation (1.11 events per 100 person-years) and 26 patients a major bleeding episode (1.52 events per 100 person-years). The probability of interrupting therapy increased significantly with frailty [hazard ratio 2.91 with confidence interval (CI) 2.15-3.92 at univariate analysis, hazard ratio 2.80 with CI 2.03-3.86 at multivariate]; frailty showed a significant impact also on major bleeding (hazard ratio 3.28 with CI 1.45-7.37 at univariate analysis, hazard ratio 3.56 with CI 1.58-8.01 at multivariate). CONCLUSION: Our study highlights how DOACs are a safe and effective option for anticoagulation, even in frail elderly people; the introduction of these drugs is leading to an increased use of anticoagulation therapy in this population. Prospective trials will be needed to reinforce these results and to consider new variables in the thrombotic and hemorrhagic risk scores underlying the prescription of DOACs.

Reduction in pulmonary artery pressures with use of sacubitril/valsartan.

Pulmonary hypertension due to left heart disease (PH-LHD) frequently complicates heart failure with reduced ejection fraction (HFrEF). Specific therapies for PH have not offered an advantage in patients with PH-LHD. The combined angiotensin receptor blocker-neprilysin inhibitor (ARNI), sacubitril/valsartan, is a novel therapy that can increase levels of natriuretic peptides (NPs). The resulting action on natriuresis and vasodilation may play an important role in the reduction of pulmonary pressures. Here, we report how the use of ARNI in two patients with HFrEF has resulted in an improvement in PH and, consequently, in clinical status and prognosis. .

Effects of remote monitoring of cardiac implantable electronic devices after stroke or transient ischemic attack.

AIMS: Cardiac implantable electronic device (CIED) recipients who experienced an ischemic cerebral event may particularly benefit from continuous remote monitoring. We aimed to assess the effect of remote monitoring on the occurrence of 1-year serious adverse events in CIED recipients after ischemic stroke or transient ischemic attack (TIA). METHODS: Patients were eligible if they suffered a TIA/stroke. Study endpoints were all-cause mortality, all-cause hospitalization, and TIA/stroke recurrence. Patients were retrospectively divided according to the presence of remote monitoring for CIED follow-up. RESULTS: From January 2011 to December 2017, 71 CIED recipients were hospitalized in our institution for TIA/stroke: pacemaker (76%), cardiac resynchronization therapy device (17%), or implantable cardioverter defibrillator (7%). Among them, 26 (37%) were remotely monitored (RM-ON), whereas 45 (63%) were followed with conventional in-hospital visits (RM-OFF). No significant differences were found in baseline characteristics between groups. The all-cause mortality and hospitalization rates were significantly lower in the RM-ON group [2.2; 95% confidence interval (CI) 0.8-4.8, and 5.8; 95% CI 3.3-9.4 per 100 patient-months] as compared with the RM-OFF group (8.1; 95% CI 5.2-11.9, and 9.7; 95% CI 6.5-13.9 per 100 patient-months). Despite a similar incidence of new diagnosis of atrial fibrillation, the median time from the arrhythmic episode to the physician evaluation was dramatically lower in the RM-ON as compared with the RM-OFF group [2 (1-3) vs. 78 (64-92) days; P = 0.002]. CONCLUSION: We found that remote monitoring as compared with conventional in-hospital visits may contribute to a better outcome in CIED recipients who had suffered from an ischemic cerebral event.

Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated state.

BACKGROUND: A growing body of evidence has shown that Krüppel-like transcription factors play a crucial role in maintaining embryonic stem cell (ESC) pluripotency and in governing ESC fate decisions. Krüppel-like factor 5 (Klf5) appears to play a critical role in these processes, but detailed knowledge of the molecular mechanisms of this function is still not completely addressed. RESULTS: By combining genome-wide chromatin immunoprecipitation and microarray analysis, we have identified 161 putative primary targets of Klf5 in ESCs. We address three main points: (1) the relevance of the pathways governed by Klf5, demonstrating that suppression or constitutive expression of single Klf5 targets robustly affect the ESC undifferentiated phenotype; (2) the specificity of Klf5 compared to factors belonging to the same family, demonstrating that many Klf5 targets are not regulated by Klf2 and Klf4; and (3) the specificity of Klf5 function in ESCs, demonstrated by the significant differences between Klf5 targets in ESCs compared to adult cells, such as keratinocytes. CONCLUSIONS: Taken together, these results, through the definition of a detailed list of Klf5 transcriptional targets in mouse ESCs, support the important and specific functional role of Klf5 in the maintenance of the undifferentiated ESC phenotype. See: http://www.biomedcental.com/1741-7007/8/125.

RIFLE criteria for acute kidney injury in valvular surgery.

BACKGROUND AND AIM OF THE STUDY: The RIFLE classification, which defines three grades of increasing severity of acute kidney injury--risk (RIFLE R), injury (RIFLE I) and failure (RIFLE F), and two outcome classes (L, loss) and E (end-stage kidney disease)--represents a valuable method for evaluating acute renal failure. Risk factors for acute kidney injury (AKI) according to the RIFLE criteria and for operative mortality were identified in patients undergoing valvular procedures. METHODS: A single-center prospective cohort study of 1424 patients who were not receiving renal replacement therapy preoperatively was conducted between January 2004 and December 2007. A total of 100 variables was collected from each patient. RESULTS: The main features were: mean age 61.9 +/- 12.9 years (range: 15-88 years), 47% females, 6% endocarditis, 11% redo surgery, 8% urgent/emergent surgery, 30% combined procedures, 5% complex, and 16% associated coronary artery bypass grafting (CABG). The overall AKI prevalence was 10%, with RIFLE scores of I or F being detected in 8% and continuous veno-venous hemofiltration being required in 5%. Risk factors for AKI were age (OR 1.03; 95% CI 1.14-4.15), time of extracorporeal circulation (ECC) (OR 1.09; 95% CI 1.005-1.013), redo procedure (OR 2.35; 95% CI 1.42-3.8), chronic kidney disease (OR 3.2; 95% CI 1.6-6.1), and blood transfusion (OR 3.8; 95% CI 2.5-6.5). The transfusion of leukodepleted blood exerted a protective effect on AKI development (OR 0.6; 95% CI 0.4-0.9). The average overall hospital mortality was 4.8%. Risk factors for operative mortality included: ECC time (OR 1; 95% CI 1.002-1.014), age (OR 1.043; 95% CI 1.01-1.07), chronic kidney disease (OR 4.8; 95% CI 2.2-10.6), blood transfusion (OR 6.43; 95% CI 2.8-14.7), surgical priority (OR 6.5; 95% CI 2.8-14.7), RIFLE class I (OR 11.9; 95% CI 5.5-25.7), and RIFLE class F (OR 30; 95% CI 8.1-111.7). Mortality increased with each RIFLE stratification (Normal 1.7%, RIFLE R = 4.1%, RR = 2.5; RIFLE I = 27.6%, RR = 16.2; and RIFLE F = 43.8% RR = 25.8). CONCLUSION: AKI is a highly prevalent and prognostically important complication, for which the majority of risk factors that have been identified are not modifiable. The transfusion of leukodepleted blood products was seen to exert a preventive effect.

Preoperative anemia in patients undergoing coronary artery bypass grafting predicts acute kidney injury.

OBJECTIVES: Recent authoritative studies suggested that low preoperative hemoglobin concentration may affect cardiac surgery outcomes. This study aimed, primarily, to investigate whether preoperative anemia is an independent determinant of adverse events after coronary artery bypass grafting and, secondarily, to evaluate the potential dose responsiveness between anemia severity and primary end points. METHODS: This single-center prospective study investigated 1214 consecutive patients undergoing coronary artery bypass grafting between January 2004 and June 2007, collecting 100 variables per patient. In 1047 patients (median age 64 years, 18.8% female, 38.9% diabetic, 31.9% urgent/emergency, 15.3% with low preoperative left ventricular ejection fraction) who underwent on-pump procedures and received no preoperative transfusion, the prevalence of preoperative anemia (according to World Health Organization definition) and its unadjusted and adjusted relationships with in-hospital death, cardiac morbidity, and acute kidney injury (AKI-RIFLE [Risk, Injury, Failure, Loss, End-stage kidney disease] criteria) were obtained. RESULTS: The prevalence of preoperative anemia was 28%. In-hospital death averaged 3.9%, cardiac morbidity 7.3%, and acute kidney injury 4%. Unadjusted odds ratios (Ors) for in-hospital death, cardiac morbidity, and acute kidney injury were 3.8 (95% confidence interval [CI] 2.0-7.3), 1.7 (95% CI 1.1-2.8), and 4.0 (95% CI 2.1-7.6), respectively. Adjusting for anemia in confounders proved an independent predictor of acute kidney injury (OR 2.06; 95% CI 1.14-3.70), whereas the cardiac morbidity and in-hospital mortality were independently predicted by kidney function. No dose-response relationship emerged between anemia severity and acute kidney injury. CONCLUSIONS: Preoperative anemia is independently associated with acute kidney injury after coronary artery bypass grafting. Further studies are warranted to determine whether preoperative low hemoglobin concentration is a marker of severity of illness or a modifiable risk factor.

Visceral adiposity and arterial stiffness: echocardiographic epicardial fat thickness reflects, better than waist circumference, carotid arterial stiffness in a large population of hypertensives.

AIMS: Relationship between obesity and cardiovascular (CV) disease depends not only on the amount of body fat, but also on its distribution. For example, individuals with increased fat accumulation in the abdominal region have atherogenic lipid profiles and are at increased CV risk. The loss of elasticity in medium and large arteries is an early manifestation of atherosclerosis. The aim of this study was to evaluate whether echocardiographic epicardial adipose tissue, an index of cardiac adiposity, is related to carotid stiffness and carotid intima-media thickness (IMT), indexes of subclinical atherosclerosis, better than waist circumference in hypertensive patients. METHODS AND RESULTS: We studied 459 patients with Grade I and II essential hypertension who were referred to our outpatient clinic over a period from May 2007 to March 2008. The population was first sorted by waist circumference and then by epicardial fat < or = 7 or >7 mm. We measured epicardial fat thickness, waist circumference, carotid artery stiffness, and carotid IMT in all patients. Patients divided according to waist circumference showed no statistical differences in carotid artery stiffness between the two groups. Subjects with epicardial fat >7 mm were older, had higher systolic, diastolic, and pulse pressure, increased left ventricular mass index, carotid IMT, diastolic parameters, and stiffness parameters compared with those with epicardial fat < or = 7 mm (P < 0.001). A positive correlation was found between epicardial fat and age, pulse pressure, stiffness parameters, carotid IMT, systolic blood pressure, and duration of hypertension, and a negative correlation was found with diastolic parameters. Age, carotid IMT, and stiffness parameters were independently related to epicardial fat. CONCLUSION: Our findings indicate that epicardial fat reflects carotid artery stiffness in hypertension-induced organ damage.

Feasibility, accuracy, and clinical relevance of a rapid thyroid evaluation during carotid duplex ultrasonography in hypertensive patients.

Carotid ultrasonography can detect thyroid nodules without increasing examination duration. The authors analyzed whether management is influenced by reporting such findings during routine carotid ultrasonography in hypertensive patients vs waiting for 6 months to repeat them. This is a population-based study of 1216 hypertensive patients. During carotid ultrasonography, nodule cystic/solid characteristics and size of thyroid changes were recorded. Patients with nodules were divided into those with nodules reported at the moment of diagnosis (group A) and those reported 6 months after diagnosis (group B). The authors monitored patients who underwent thyroid treatment 12 months after carotid ultrasonography. A total of 255 participants had thyroid nodules detected on screening and 99 patients started therapy after discovery. Six months later, as expected, there were more patients undergoing thyroid treatment in the group with nodules reported at time of diagnosis. This difference between groups was not significant, however, 6 months after reporting the nodules, in group B, because the number of patients on therapy significantly increased. Thyroid nodules cannot be ignored during carotid ultrasonography, and reporting their presence is valuable to general practitioners. Thyroid screening during carotid ultrasonography is cost-effective, rapid, sensitive, and specific and may affect the patient's diagnostic and therapeutic management.

Short and highly efficient synthetic promoters for melanoma-specific gene expression.

Here, we report the construction and functional analysis of synthetic promoters designed for gene therapy applications requiring strong and specific gene expression in melanoma cell lines. We have analysed the transcriptional activity of different combinations of two transcriptional regulatory modules, a melanocyte-specific element from the human tyrosinase promoter and a cell-cycle-specific element from the human alpha-fetoprotein promoter. Transient expression assays in different cell lines show that several of these composite synthetic promoters can drive a strong and selective expression of a reporter gene in melanoma cell, providing us with a new powerful tool for gene therapy of melanomas.

High prevalence of non-HFE gene-associated haemochromatosis in patients from southern Italy.

Hereditary haemochromatosis is an autosomal recessive disorder of iron regulation that results in abnormal intestinal iron absorption with progressive iron overloading of parenchymal cells. Two specific, single point mutations of the HFE gene (C282Y and H63D) have been described in haemochromatosis patients. Epidemiological studies have revealed a strict association between hereditary haemochromatosis and C282Y homozygosis or C282Y/H63D compound heterozygosis, suggesting that these mutations may provide a useful tool for diagnosis. However, recent investigations from southern Europe have reported lower allelic frequencies of the C282Y mutation among haemochromatosis patients, apparently depending on the geographical area of the population analysed. To assess the predictive value of the detection of the C282Y and H63D HFE mutations in our geographical area, we have evaluated their occurrence in 46 haemochromatosis patients from southern Italy. We found that only 19.6% of our patients were homozygous for the C282Y mutation and 21.7% were compound C282Y/H63D heterozygotes. Among the remaining 59%, approximately 40% did not display any of the known HFE mutations. We conclude that, in southern Italy, another genetic determinant/s must be responsible for many haemochromatosis cases and that a genetic screening for the C282Y and H63D HFE mutations is not sufficient for hereditary haemochromatosis diagnosis.

Increased carotid artery intima-media thickness is associated with a novel mutation of low-density lipoprotein receptor independently of major cardiovascular risk factors.

The current study sought to investigate the role of low-density lipoprotein receptor (LDLr) mutations in assessing the risk profile of familial hypercholesterolemia (FH) patients, independently of major cardiovascular risk factors. FH due to LDLr mutations is associated with premature atherosclerosis. The variable clinical severity of the disease in heterozygotes has been related to cholesterol levels and the coexistence of other cardiovascular risk factors, but the independent role of different LDLr mutations is still unclear. cDNA of LDL gene was sequenced in 102 patients with clinical features of heterozygous FH. Carotid artery intima-media thickness (IMT) was measured by B-mode ultrasound imaging in all patients. Sixteen different mutations (5 never described) were found in 82 patients (49 families; mean age, 39 years; 53% women). One of the newly described mutations, the 2312-3 C-->A, was found in 24 patients (13 families). The mean of maximum thicknesses was significantly higher in the 2312-3 C-->A group than in patients with other LDLr mutations (P=.004 after adjustment for major cardiovascular risk factors). Similar results (P=.001) were obtained in the adjusted comparisons of probands only, and of the patients with similar baseline cholesterol (P=.002). This study indicates that the identification of an LDLr mutation can help to assess the risk profile of FH patients independently of the major cardiovascular risk factors.