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Interferon (IFN)-β has been classified as a drug that is possibly associated with development of pulmonary arterial hypertension (PAH), a devastating disease that can lead to right heart failure and premature death [1]., The possible causal relationship between interferon-β exposure and pulmonary arterial hypertension development requires close follow-up of patients on treatment with interferon-β http://bit.ly/2OPGSVP

Introduction: Patients recovering from pneumonia and ARDS may develop fibrotic changes. Concerning COVID-19, there is evidence that residual persistent ground glass opacities and/or reticular infiltrates could be related with the development of diffuse parenchymal lung disease. Aim: The detection of interstitial lung disease post COVID-19 pneumonia. Methods: Patients were prospectively assessed 3 months after hospital discharge with high resolution computerized tomography of the chest (HRCT), pulmonary lung function tests (PFTs), SpO2, 6minute walk test (6MWT) and Saint George Respiratory Questionnaire (SGRQ). Patients were classified according to acute phase pneumonia extent as: mild ( 50%). Results: 23 patients (6 women, mean age 55 yrs) were included. 2 patients had a history of mechanical ventilation and 3 of pulmonary embolism. Mild (8), moderate (9) and severe (6) disease patients had no significant differences in age, gender and smoking history. Fifteen (65%) had at least one comorbidity including chronic obstructive respiratory disease. At 3 months patients presented mean values (SD) of FEV1%pred of 98,4±20,3, FVC%pred 104,3±18,3, DLCO%pred 89,2±10,3, Sp02 97,7±0,7%, 6MWT 571,4±87m and SGRQ 4,56(0-8,14). Follow-up HRCT was evaluated as normal or near-normal in all with no significant differences among the three severity groups. 20 patients had normal PFTs, 2 an obstructive pattern (underlying lung disease) and 1 a restrictive pattern with normal DLCO. Conclusion: The results of the present study do not support the hypothesis of the development of diffuse parenchymal lung disease after COVID-19 pneumonia in this study group. The study is ongoing.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment, specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p &lt, 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).

Recently, a lower mean pulmonary arterial pressure (PAP) cutoff of >20 mmHg for pulmonary hypertension (PH) definition has been proposed. We examined whether exercise Doppler echocardiography (EDE) can unmask PA hypertension (PAH) in systemic sclerosis (SSc) patients whose baseline echocardiography for PH is equivocal. We enrolled 49 patients with SSc who underwent treadmill EDE. Tricuspid regurgitation (TR) velocity was recorded immediately after EDE. Inotropic reserve of right ventricle (RV) was assessed by the change (post-prior to exercise) of tissue Doppler imaging-derived peak systolic velocity (S) of tricuspid annulus. Inclusion criteria comprised preserved left and RV function, and baseline TR velocity between 2.7 and 3.2 m/s. All patients had right-heart catheterization (RHC) within 48 h after EDE. From 46 patients with good quality of post-exercise TR velocity, RHC confirmed PAH in 21 (45.6%). Post-exercise TR velocity >3.4 m/s had a sensitivity of 90.5%, a specificity of 80% and an accuracy of 84.8% in detecting PAH. Inotropic reserve of RV was positively correlated with maximum achieved workload in METs (r = 0.571, p < 0.001). EDE has a good diagnostic accuracy for the identification of PAH in selected SSc patients whose baseline echocardiographic measurements for PH lie in the gray zone, and it is also potentially useful in assessing RV contractile reserve. ispartof: DIAGNOSTICS vol:11 issue:7 ispartof: location:Switzerland status: published

Patient: Male, 73-year-old Final Diagnosis: Severe COVID-19 pneumonia complicated by right atrium thrombus Symptoms: Fever • dyspnea • cough Medication:— Clinical Procedure: — Specialty: Critical Care Medicine Objective: Educational purpose Background: Recent studies demonstrated evidence of coagulation dysfunction in hospitalized patients with severe coronavirus disease 2019 (COVID-19) due to excessive inflammation, hypoxia, platelet activation, endothelial dysfunction, and stasis. Effective anticoagulation therapy may play a dominant role in the management of severe COVID-19 cases. Case Report: A 73-year-old man with a 6-day history of fever up to 38.5°C, dyspnea, cough, and fatigue was diagnosed with COVID-19. He had a past medical history significant for hypertension and coronary artery bypass grafting. Two days after hospital admission, the patient developed acute respiratory failure, requiring intubation, mechanical ventilation, and transfer to the intensive care unit (ICU). He received treatment including antibiotics, hydroxychloroquine, tocilizumab, vasopressors, prone positioning, and anticoagulation with enoxaparin at a prophylactic dose. After a 15-day ICU stay, the patient was hemodynamically stable but still hypoxemic; a transthoracic echocardiogram at that time, followed by a transesophageal echocardiogram for better evaluation, revealed the presence of a right atrium thrombus without signs of acute right ventricular dilatation and impaired systolic function. Since the patient was hemodynamically stable, we decided to treat him with conventional anticoagulation under close monitoring for signs of hemodynamic deterioration; thus, the prophylactic dose of enoxaparin was replaced by therapeutic dosing, which was a key component of the patient’s successful outcome. Over the next few days he showed significant clinical improvement. The follow-up transesophageal echo-cardiogram 3 weeks after effective therapeutic anticoagulation revealed no signs of right heart thrombus. Conclusions: The presented COVID-19 case, one of the first reported cases with evidence of right heart thrombus by transesophageal echocardiography, highlights the central role of diagnostic imaging strategies and the importance of adequate anticoagulation therapy in the management of severe COVID-19 cases in the ICU.

Introduction: Antineutrophil cytoplasmic autoantibody–associated vasculitis is an immune-mediated necrotizing vasculitis, affecting small- and medium-sized vessels. Case report: A 22-year-old female patient with free medical history presented with life-threatening pulmonary hemorrhage due to antineutrophil cytoplasmic autoantibody–associated vasculitis, temporarily associated with influenza A H1N1 infection. Due to rapidly worsening respiratory failure, despite conventional management, veno-venous peripheral extracorporeal membrane oxygenation was initiated and continued for 26 days, with subsequent renal replacement therapy. Discussion: We present a case of severe antineutrophil cytoplasmic autoantibody–associated pulmonary vasculitis, managed with veno-venous extracorporeal membrane oxygenation at the initial phase. Despite the significant challenges raised with the use of extracorporeal membrane oxygenation in pulmonary hemorrhage cases, extracorporeal membrane oxygenation may have a significant impact on outcome in this setting, by providing adequate time for a successful immunosuppressive treatment.

BACKGROUND: Although ceramic brackets have been extensively used for decades in orthodontics there is not till today any study focusing on the possible deterioration of mechanical properties after in vivo ageing. OBJECTIVES: To determine whether the mechanical properties of alumina orthodontic brackets change after intraoral ageing thereby assessing the validity of a theoretical model established for the performance of ceramics in wet environments. MATERIALS AND METHODS: Two alumina brackets, one single crystal (Radiance, American Orthodontics, Sheboygan, WI) and one polycrystalline (Clarity, 3M, St. Paul, MN) were included in this study. Ten brackets for each group were collected from different patients after a minimum of 3-month intraoral exposure, whereas as-received brackets of the same manufacturers were used as controls. The specimens were subjected to Raman spectroscopy and were then embedded in epoxy resin and metallographic ground and polished. The mechanical properties of four groups (radiance control: RAC, radiance-retrieved RAR, clarity control: CLC and clarity-retrieved CLR) were determined using instrumented indentation testing according to ISO 14577-2002. The mechanical properties tested were Martens hardness (HM), indentation modulus (EIT), the ratio of elastic to total work, commonly known as elastic index (ηIT), and fracture toughness (KIC). The numerical results were statistically analysed employing two-way analysis of variance (ANOVA) and Tukey multiple comparison test at a = 0.05. RESULTS: Raman analysis revealed that both brackets are made of a-Al2O3 (corundum). No statistically significant differences were found for HM (N/mm2): RAC = 7249 (1507), RAR = 6926 (1144), CLC = 8052 (1360), CLR = 7390 (2393), or for EIT (GPa): RAC = 141 (27), RAR = 139 (23), CLC = 139 (28), CLR = 131 (47). However, significant differences were identified between the two alumina brackets tested for ηIT (%): RAC = 55.7 (4.2), RAR = 54.0 (3.5), CLC = 62.5 (4.4), CLR = 61.8 (4.7), while KIC was measured only for the polycrystalline bracket (Clarity) because of the complicated fractured pattern of the single-crystal bracket. Both brackets share equal HM and EIT before and after orthodontic intraoral ageing. LIMITATIONS: Whereas the study assessed the changes after intraoral exposure per theoretical model, which describes the reduction of critical stress to induce fracture after wetting, long-term intraoral ageing could have induced more pronounced effects. CONCLUSIONS/IMPLICATIONS: The results of this study indicate that 3 months of intraoral ageing do not change the mechanical properties of single-crystal and polycrystalline orthodontic brackets tested, thus indicating that the Griffith theory may not be applied to the case of manufactured ceramic brackets owing possibly to internal defects.

Standard echocardiography is important for pulmonary arterial hypertension (PAH) screening in patients with connective tissue disease (CTD), but PAH diagnosis and monitoring require cardiac catheterization. Herein, using cardiac catheterization as reference, we tested the hypothesis that follow-up echocardiography is adequate for clinical decision-making in these patients. We prospectively studied 69 consecutive patients with CTD-associated PAH. Invasive baseline pulmonary artery systolic pressure (PASP) was 60.19 &plusmn, 16.33 mmHg (mean &plusmn, SD) and pulmonary vascular resistance (PVR) was 6.44 &plusmn, 2.95WU. All patients underwent hemodynamic and echocardiographic follow-up after 9.47 &plusmn, 7.29 months, 27 patients had a third follow-up after 17.2 &plusmn, 7.4 months from baseline. We examined whether clinically meaningful hemodynamic deterioration of follow-up catheterization-derived PASP (i.e., &gt, 10% increase) could be predicted by simultaneous echocardiography. Echocardiography predicted hemodynamic PASP deterioration with 59% sensitivity, 85% specificity, and 63/83% positive/negative predictive value, respectively. In multivariate analysis, successful echocardiographic prediction correlated only with higher PVR in previous catheterization (p = 0.05, OR = 1.235). Notably, in patients having baseline PVR &gt, 5.45 WU, echocardiography had both sensitivity and positive predictive values of 73%, and both specificity and negative predictive value of 91% for detecting hemodynamic PASP deterioration. In selected patients with CTD-PAH echocardiography can predict PASP deterioration with high specificity and negative predictive value. Additional prospective studies are needed to confirm that better patient selection can increase the ability of standard echocardiography to replace repeat catheterization.

OBJECTIVES To evaluate the hard tissue and facial profile changes in matched extraction and non-extraction Class I patients by the use of geometric morphometrics. SUBJECTS AND METHODS From a parent sample of 542 Class I patients, previously subjected to discriminant analysis, a subsample of 68 borderline cases was obtained, 34 treated with extraction and 34 without extraction of 4 first premolars. Geometric morphometric methods (Procrustes superimposition and Principal Component Analysis) were applied on cephalometric tracings to assess the validity of the discriminant analysis in successfully identifying a morphologically homogeneous group and to evaluate inter- and intra-group skeletal and facial profile shape changes. RESULTS No significant pre-treatment shape difference between the two groups was found, thus validating the discriminant analysis. The non-extraction group showed increase in hard tissue facial height (P < 0.001), with slight lower lip retrusion and upper lip protrusion (P = 0.027). The extraction group showed retraction of the hard tissue and facial profile outline (P < 0.001). Permutation tests for post-treatment inter-group differences resulted in P = 0.054 for the soft tissue outline and P = 0.078 for the hard tissue skeletal component. CONCLUSIONS The evidence indicates that borderline cases treated with four premolar extractions will exhibit lip retrusion compared to non-extraction treatment.

Spacing between the maxillary anterior teeth is a common concern for young patients and their parents. Patients often consider a diastema to be an annoying but minor problem; they might consult their general dentists for help, or try to address the issue themselves by applying elastic "gap bands." Moreover, parents, without any informed consent, sometimes accept this erroneous method as an easy and inexpensive treatment approach. A 9-year-old boy had severe acute periodontitis involving the maxillary central incisors caused by the placement of an elastic band and its apical migration. Despite periodontal and surgical interventions, the maxillary central incisors were finally extracted, and the patient started orthodontic treatment. The orthodontic treatment plan included maxillary lateral incisor substitution to replace the lost central incisors and mesialization of the maxillary posterior dentition. An interdisciplinary approach with excellent cooperation among the orthodontist, general dentist, and other dental specialists obtained an esthetically pleasing and optimized functional result. Treating the diastema between the anterior teeth with elastic gap bands and without fixed orthodontic appliances should be avoided. Patients should seek proper orthodontic advice for even small-scale orthodontic problems to prevent catastrophic outcomes, as exhibited in this case report.

The aim of this systematic review was to assess the effect of systematic extraction protocols during orthodontic fixed appliance treatment on the soft tissue profile of human patients. Nine databases were searched until December 2016 for controlled clinical studies including premolar extraction or nonextraction treatment. After elimination of duplicate studies, data extraction, and risk-of-bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MD) or standardized mean differences (SMD) and their 95% CIs were performed, followed by subgroup, meta-regression, and sensitivity analyses. Extraction treatment was associated with increased lower lip retraction (24 studies; 1,456 patients; MD = 1.96 mm), upper lip retraction (21 studies; 1,149 patients; MD = 1.26 mm), nasolabial angle (21 studies; 1,089 patients; MD = 4.21°), soft-tissue profile convexity (six studies; 408 patients; MD = 1.24°), and profile pleasantness (three studies; 249 patients; SMD = 0.41). Patient age, extraction protocol, and amount of upper incisor retraction during treatment were significantly associated with the observed extraction effects, while the quality of evidence was very low in all cases due to risk of bias, baseline confounding, inconsistency, and imprecision. Although tooth extractions seem to affect patient profile, existing studies are heterogenous and no consistent predictions of profile response can be made.

There is a complex and not fully elucidated association between pulmonary arterial hypertension (PAH) and coagulation disorders. The goal of this study was to evaluate platelet function, coagulation and fibrinolysis in PAH patients at diagnosis, before PAH-specific treatment initiation. We enrolled 20 healthy controls and 30 PAH patients (20 with connective tissue disease (CTD-PAH) and 10 idiopathic (iPAH)). None of the participants was on any antiplatelet or anticoagulation therapy. Blood samples from PAH patients were collected during the initial right heart catheterization. All subjects were assessed with platelet function analyzer-100 (PFA-100), epinephrine (Epi) and ADP-induced light transmission aggregometry (LTA), thromboelastometry (ROTEM) and endogenous thrombin potential (ETP). Our results showed that Epi and ADP-LTA values were significantly lower in newly diagnosed PAH patients compared to controls. Disaggregation was present in 73% of patients, a characteristic not seen in healthy individuals. In ROTEM assay, CT and CFT measurements were significantly higher and a angle lower compared to controls. ETP testing revealed significantly reduced outcomes in AUC, Cmax and Tmax. When CTD-PAH and iPAH patient groups were compared, iPAH ADP-LTA values were significantly decreased compared to CTD-PAH. In conclusion, newly diagnosed PAH patients presented with decreased platelet aggregation, clot propagation and thrombin generation, along with delayed initiation of the coagulation process. These hemostatic deficits could indicate an "exhaustion" of the coagulation process that could be caused by endothelial dysfunction and chronic activation of the procoagulant pathways. Further studies are warranted to confirm these laboratory findings and assess their potential clinical significance.

Introduction A controversy exists regarding better treatment outcomes when patients treated with extractions and without extractions are evaluated. The aims of this study were to use the American Board of Orthodontics objective grading system (ABO-OGS) to evaluate and compare treatment outcomes in extraction vs nonextraction Class I patients and to determine whether the treatment choice was a significant predictor of success according to the ABO examination. Methods Discriminant analysis was applied to a sample of 542 patients, and a borderline sample of 55 patients was obtained. Of these patients, 25 were treated with extractions and 30 without extraction of the 4 first premolars. Treatment results were then assessed using the 8 variables of the ABO-OGS. Results The total scores ranged from 11 to 41 (mean, 27.04; SD, 6.3) for the extraction group and from 16 to 44 (mean, 29.07; SD, 7.1) for the nonextraction group. The variable of buccolingual inclination had the highest scores in both groups (8.44 [SD, 3.3] for the extraction group; 8.90 [SD, 3.8] for the nonextraction group; mean difference, 0.46; 95% CI, −1.44, 2.37; P = 0.63). However, no statistically significant intergroup differences were found, either between the scores of the 8 ABO-OGS variables or between the total ABO-OGS scores. Regarding the success rates of the ABO examination, no significant difference was found between the 2 treatment groups (odds ratio, 2.55; 95% CI, 0.74, 0.85; P = 0.14). Conclusions For a patient with a borderline Class I malocclusion, extraction and nonextraction treatment can achieve the same quality of results as assessed by the ABO-OGS. Additionally, in these Class I patients, the treatment modality (extraction or nonextraction) is not a significant predictor of passing the ABO examination.

Background In the long-lasting debate of extraction versus non-extraction treatment, the impact of extractions on the skeletal vertical dimension remains rather unclear. The aim of this retrospective research study was to obtain a bias-free sample of morphologically similar borderline patients treated with or without extraction of the four first premolars and to retrospectively evaluate the vertical changes that occurred. Methods A borderline sample of 83 patients, 41 treated with four first premolar extractions and 42 treated without, was obtained by means of discriminant analysis applied to a previously investigated parent sample of 542 class I patients. The pretreatment and posttreatment cephalometric radiographs were analyzed digitally, and seven measurements were assessed for vertical skeletal changes. Also, average tracings between the two treatment groups were evaluated using the Procrustes superimposition method. Results The variables of SN to Go-Gn and Y-axis showed adjusted intergroup differences of − 0.91° and − 1.11° (P = 0.04). Comparing the mean intra-group differences of all the variables simultaneously, a significant difference was found between the two treatment groups (overall P value = 0.04). In the extraction group, only the gonial angle showed a significant decrease (P = 0.01) while the overall P value evaluating the intra-group differences between pre- and posttreatment was significant (overall P value

Background: Although CTEPH is a thromboembolic disorder, the effect of the coagulation process in the pathogenesis and progression of the disease has not been fully elucidated. Aims: To assess coagulation in CTEPH and to evaluate differences after the initiation of PH-specific treatment. Methods: We studied 20 CTEPH patients (not on anticoagulation therapy at the time of tests) and 20 controls. CTEPH patients were reevaluated 1 year after therapy initiation. We performed Platelet- Function Analyzer/PFA-100 testing, ADP and epinephrine/EPI induced Light Transmission Aggregometry/LTA, Thrombelastometry/ROTEM (na-TEM) and Endogenous Thrombin Potential/ETP essay. Results: Before treatment and when compared to controls, CTEPH patients presented prolonged PFA-100 closure times (174.8sec±27.3, p=0.003), lower EPI and ADP-LTA (43.9%±11.2, p Conclusions: Our data suggest that the observed coagulation defects in CTEPH persist even after PH treatment initiation. EPI-LTA was the only index displaying significant increase after treatment.

Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular and alveolar compartments as outcome predictors in ARDS. Fifty-three consecutive ARDS patients were studied. The primary outcome was 28-day mortality. Secondary endpoints were days of unassisted ventilation and days with organ failure other than ARDS, during the 28-day study period. Nonsurvivors presented higher lung injury scores and epithelial lining fluid (ELF) Ang-2 levels compared to survivors, with no significant differences in plasma Ang-2, endocan, and protein C concentrations between the two groups. In logistic regression analysis, ELF Ang-2 levels > 705 pg/ml were the only independent variable for 28-day mortality among the previous four. Plasma endocan values > 13 ng/pg were the only parameter predictive against days of unassisted ventilation during the 28-day study period. Finally, lung injury score > 2.25 and ELF Ang-2 levels > 705 pg/ml were associated with increased number of days with organ failure, other than ARDS. Our findings suggest that Ang-2 levels are increased in the alveolar compartment of ARDS patients, and this may be associated both with increased mortality and organ failure besides lung.

Background Transthoracic echocardiography (TTE) is well validated for initial assessment of connective tissue disease patients with suspected pulmonary arterial hypertension (PAH). However, in patients with PAH confirmed by the gold-standard method of right heart catheterization (RHC) the role of TTE in their follow-up is less known. Objectives To test the hypothesis that TTE can replace follow-up RHC in connective tissue disease-associated PAH. Methods This retrospective study included 30 consecutive patients with systemic sclerosis (n=24) and mixed connective tissue disease (n=6) (mean age±SD: 60±12 years, 87% women), in whom PAH was suggested by TTE and further confirmed by a baseline RHC [pulmonary artery systolic pressure (PASP): 56.8±19.1, range 25–90mmHg; pulmonary vascular resistance (PVR): 5.9±3.8, range 0.7–14.5 Wood units; cardiac output: 4.4±1.3, range 2–7.8 L/min). All 30 patients underwent a second RHC and TTE at follow-up, after 11±6 (range 4–29) months. Ten patients had a 3rd follow-up RHC and TTE 22±7 (range 15–37) months from baseline, thus producing in all 50 pairs of baseline and follow-up measurements. By considering follow-up RHC as the gold-standard, we examined whether clinically meaningful hemodynamic changes (i.e.>15% change from baseline) in either RHC-derived PASP or PVR could be predicted by the corresponding changes from baseline in follow-up TTE. RHC and TTE were always performed, each, by the same examiner. Results In 68% of comparisons between baseline and follow-up, the latter TTE measurements could safely replace RHC in terms of PASP estimation. Using Mc Nemars test we confirmed that the two methods did not differ significantly (Table 1). When in addition to changes in PASP, PVR changes were also considered, follow-up TTE could again safely replace the second RHC in 70% patient retests (Table 2). Of note, baseline hemodynamic values or TTE measurements did not differ between patients in whom TTE could replace RHC and those in whom the results of the two methods at follow-up were divergent. Conclusions In a study where operator-dependent methodological errors are limited we found that the majority of connective tissue disease patients with PAH can be safely monitored in the long-term by TTE. Further studies to help identify those patients at need for follow-up RHC are warranted. Disclosure of Interest None declared

INTRODUCTION: The aims of this study were to identify a sample of borderline Class I extraction and nonextraction patients and to investigate posttreatment changes in arch-width and perimeter measurements. METHODS: A parent sample of 580 Class I patients was subjected to discriminant analysis, and a borderline subsample of 62 patients, 31 treated with extraction of 4 first premolars and 31 treated without extractions, was obtained. The patients' plaster casts were digitally scanned, and the maxillary and mandibular intercanine and intermolar widths and perimeters were assessed. RESULTS: The extraction group showed increases in maxillary and mandibular intercanine widths (P

Mechanical loading is considered to be a major parameter of the periodontal ligament (PDL) remodeling and differentiation. However, the molecular mechanisms that translate these forces to cellular responses are not fully elucidated. Especially, although aging affects PDL homeostasis, the role of cellular senescence on the activation of signaling pathways in periodontal ligament fibroblasts (PDLF) in response to mechanical stimulation has not been studied yet. Here, we present evidence showing that cyclic mechanical stimulation activates ERK, JNK and p38 MAPK in young (early-passage) human PDLF, in a RhoK-dependent manner. This response was found to be independent of the substratum (i.e. fibronectin or collagen) on which these cells grow. Stretching up-regulates also c-fos, a classical cellular response to mechanical deformation. Inhibition of ERK and JNK reduces, while that of p38 enhances stress-mediated c-fos expression. In addition, cyclic stretching stimulates the expression and activity of alkaline phosphatase (ALP), an early marker of osteoblastic differentiation. We have recently shown that senescent human PDLF have a significantly decreased expression of ALP, linked to an inability towards osteoblastic differentiation. Here, we found that senescent PDLF are able to respond to cyclic mechanical stretching by activating ERK, JNK and p38 MAPK, with similar kinetics compared to young cells, and by up-regulating c-fos and ALP expression and activity. However, even after stimulation, ALP levels in senescent cells are still much lower compared to the basal levels of their young counterparts, suggesting that senescence impairs the differentiation of human PDLF when subjected to cyclic mechanical deformation.

Background The aim of this study was to investigate the prevalence of tooth agenesis, microdontia, and tooth malformation among non-syndromic oral cleft patients and their potential association with cleft type and gender. Methods Intraoral records and radiographs of 154 patients (97 males and 57 females) were examined. The variables assessed were tooth agenesis, microdontia, dental malformations, and cleft types. The statistics included chi-square and Fisher’s exact tests as well as logistic regression to assess any mutual effects of gender and cleft type on the dental variables. Results Tooth agenesis occurred in 50% of the sample and microdontia in 18%. Non-statistically significant odds ratios for the association of gender and cleft type with tooth agenesis were obtained. Tooth agenesis was substantially higher at the unilateral right CL + P and the bilateral CL + P in quadrant 1 and at the unilateral left CL + P and bilateral CL + P in quadrant 2. It was also higher, at the isolated cleft palate (CP) in quadrants 3 and 4. These results were attributed to teeth 22 (31.8%) and 12 (21.6%) in the maxilla and to teeth 35 (6.1%) and 45 (5.4%) in the mandible. In unilateral CL + P patients, the cleft quadrant that presented tooth agenesis was associated with the side of the cleft. Conclusions Interdisciplinary treatment of the oral cleft patients should take into consideration the high prevalence of tooth agenesis and their association with the different cleft types. The most frequently affected teeth by cleft are by far the upper lateral incisors. Results indicate that tooth agenesis appears to be a genetically controlled anomaly related to the orofacial cleft development through various genetic links and not caused by the cleft disruptive process.

Diaphragmatic ultrasonography has been recently considered as a new weaning predictor method. Previous studies checked diaphragmatic excursion and thickness during quiet or deep breathing in unselected populations of critically ill patients. Our study aimed to investigate diaphragmatic excursion during quiet and unassisted breathing, in comparison to standard predictor tools, such as Rapid Shallow Breathing Index (RSBI) and Maximal Inspiratory Pressure (Pimax), in patients with difficult and/or prolonged weaning.Patients with difficult and/or prolonged weaning, who met the criteria for spontaneous breathing trial, were assessed. The excursion of each hemidiaphragm (DEx) was evaluated by B-mode and M-mode ultrasonography while patient was on quiet breathing and at supine position. RSBI and Pimax were simultaneously recorded and weaning outcome was recorded.Thirteen male and fourteen female patients were included. DEx [median and interquartile range, mm] was 14 (8.5-22) for the right hemidiaphragm (RDEx) and 12 (7-23) for the left (LDEx). We found no difference in DEx between sexes. Among the four weaning predictor tools, LDEx at a cut-off 10 mm was the best index to predict weaning success (sensitivity 86%, specificity 85%, Negative Predictive Value 94%). The optimal cut-off values, as determined by the area under the receiver operating characteristic curve, were 10 mm for RDEx, 7 mm for LDEx, 57 breaths/min/L for RSBI and -20 cmH2O for Pimax.Our results suggest that DEx threshold of 10 mm and 7 mm for right and left hemidiaphragms respectively could be used as adjunct tool in the predictive algorithm of weaning in difficult to wean patients.

We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O2, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R(2) = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs' physiologic derangement will be addressed in future studies.

Introduction The aim of this study was to compare treatment outcomes in university vs private practice settings with Class I patients using the American Board of Orthodontics Objective Grading System. Methods A parent sample of 580 Class I patients treated with and without extractions of 4 first premolars was subjected to discriminant analysis to identify a borderline spectrum of 66 patients regarding the extraction modality. Of these patients, 34 were treated in private orthodontic practices, and 32 were treated in a university graduate orthodontic clinic. The treatment outcomes were evaluated using the 8 variables of the American Board of Orthodontics Objective Grading System. Results The total scores ranged from 10 to 47 (mean, 25.44; SD, 9.8) for the university group and from 14 to 45 (mean, 25.94; SD, 7.7) for the private practice group. The university group achieved better scores for the variables of buccolingual inclination (mean difference, 2.28; 95% confidence interval [CI], 0.59, 3.98; P = 0.01) and marginal ridges (mean difference, 1.32; 95% CI, 0.28, 2.36; P = 0.01), and the private practice group achieved a better score for the variable of root angulation (mean difference, −0.65; 95% CI, −1.26, −0.03; P = 0.04). However, no statistically intergroup differences were found between the total American Board of Orthodontics Objective Grading System scores (mean difference, −0.5; 95% CI, −3.82, 4.82; P = 0.82). Conclusions Patients can receive similar quality of orthodontic treatment in a private practice and a university clinic. The orthodontists in the private practices were more successful in angulating the roots properly, whereas the orthodontic residents accomplished better torque control of the posterior segments and better marginal ridges.

Background The extraction rate in orthodontics varies throughout the years. While the extraction decision is easily made or excluded in clear-cut cases, it still remains controversial what makes an orthodontist decide to extract in borderline cases. The aim of this retrospective study was to identify the percentage of extraction cases in a large group of Class I malocclusions and to clarify which variables contributed most to the extraction decision. Methods The sample consisted of 542 randomly selected records of Class I patients treated in a university graduate program and in five private orthodontic offices. Of these patients, 331 were female and 211 male. The mean age was 14.55 (standard deviation (SD) 5.36) for the non-extraction group and 14.52 (SD 4.86) for the extraction group. The extensive series of 32 linear and angular measurements derived from the cephalometric analysis and the dental casts, along with the variables of age and gender, fueled a stepwise discriminant analysis. Results The percentage of the patients treated with four first premolar extractions was 26.8%. The results showed that the variables of lower crowding, lower lip to E-plane, upper crowding, and overjet accounted most for the decision to extract at a very significant level (Sig. 0.000). The discriminant analysis assigned a classification power of 83.9% to the predictive model (p

The role of the D allele of the angiotensin-converting enzyme (ACE) gene I/D polymorphism in the clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains controversial. We assessed simultaneously the effect of the ACE I/D polymorphisms as well as the serum and BALF ACE levels on prognosis of ARDS patients.

Loss of teeth increases with age or after genotoxic treatments, like head and neck radiotherapy, due to periodontium breakdown. Periodontal ligament fibroblasts represent the main cell type in this tissue and are crucial for the maintenance of homeodynamics and for its regeneration. Here, we have studied the characteristics of human periodontal ligament fibroblasts (hPDLF) that became senescent after replicative exhaustion or after exposure to ionizing radiation, as well as their ability for osteoblastic differentiation. We found that senescent hPDLF express classical markers of senescence, as well as a catabolic phenotype, as shown by the decrease in collagen type I and the increase of MMP-2 expression. In addition, we observed a considerably decreased expression of the major transcription factor for osteoblastic differentiation, i.e. Runx2, a down-regulation which was found to be p53-dependent. In accordance to the above, senescent cells have a significantly decreased alkaline phosphatase gene expression and activity, as well as a reduced ability for osteoblastic differentiation, as found by Alizarin Red staining. Interestingly, cells from both type of senescence express similar characteristics, implying analogous functions in vivo. In conclusion, senescent hPDLF express a catabolic phenotype and express a significantly decreased ability towards an osteoblastic differentiation, thus probably affecting tissue development and integrity.

Objective: To obtain through the use of discriminant analysis a relatively bias-free sample of extraction and nonextraction, Class I, equally susceptible to both treatments' malocclusions and to analyze retrospectively the soft tissue changes between the two different treatment groups. Materials and Methods: The cephalometric, model, and demographic data of 215 patients (females and males) fueled a stepwise discriminant analysis that provided the borderline homogenous subsample (30 extraction and 32 nonextraction cases). The pretreatment and postreatment cephalograms of the borderline sample were then subjected to a thorough soft tissue cephalometric analysis. Results: The results indicated that the three variables that played the most important role in the clinician's treatment decision were indicators of lower crowding, soft tissue convexity, and lower incisor protrusion. Significant differences (P

Acute respiratory distress syndrome (ARDS) is characterized by the presence of fibrin-rich inflammatory exudates in the intra-alveolar spaces and the extensive migration of neutrophils into alveoli of the lungs. Tissue factor (TF)-dependent procoagulant properties of bronchoalveaolar lavage fluid (BALF) obtained from ARDS patients favor fibrin deposition, and are likely the result of cross-talk between inflammatory mediators and hemostatic mechanisms. However, the regulation of these interactions remains elusive. Prompted by previous findings suggesting that neutrophils, under certain inflammatory conditions, can express functional TF, we investigated the contribution of intra-alveolar neutrophils to the procoagulant properties of BALF from patients with ARDS. Our results confirm that the procoagulant properties of BALF from ARDS patients are the result of TF induction, and further indicate that BALF neutrophils are a main source of TF in intra-alveolar fluid. We also found that BALF neutrophils in these patients express significantly higher levels of TF than peripheral blood neutrophils. These results suggest that the alveolar microenvironment contributes to TF induction in ARDS. Additional experiments indicated that the ability of BALF to induce TF expression in neutrophils from healthy donors can be abolished by inhibiting C5a or TNF-α signaling, suggesting a primary role for these inflammatory mediators in the up-regulation of TF in alveolar neutrophils in ARDS. This cross-talk between inflammatory mediators and the induction of TF expression in intra-alveolar neutrophils may be a potential target for novel therapeutic strategies to limit ARDS-associated disturbances of coagulation.

Introduction Respiratory failure may develop during the later stages of pregnancy and is usually associated with tocolysis or other co-existing conditions such as pneumonia, sepsis, pre-eclampsia or amniotic fluid embolism syndrome. Case presentation We present the case of a 34-year-old healthy woman with a twin pregnancy at 31 weeks and 6 days who experienced acute respiratory failure, a few hours after administration of tocolysis (ritodrine), due to preterm premature rupture of the membranes. Her chest discomfort was significantly ameliorated after the ritodrine infusion was stopped and a Cesarean section was performed 48 hours later under spinal anesthesia; however, 2 hours after surgery she developed severe hypoxemia, hypotension, fever and mild coagulopathy. The patient was intubated and transferred to the intensive care unit where she made a quick and uneventful recovery within 3 days. As there was no evidence for drug- or infection-related thromboembolic or myocardial causes of respiratory failure, we conclude that our patient experienced a rare type of non-fatal amniotic fluid embolism. Conclusion In spite of the lack of solid scientific support for our diagnosis, we conclude that our patient suffered an uncommon type of amniotic fluid embolism syndrome and we believe that this report highlights the need for extreme vigilance and a high index of suspicion for such a diagnosis in any pregnant individual.

We investigated the efficacy of locally applied nasal decongestant agents and corticosteroids for preventing nosocomial maxillary sinusitis in mechanically ventilated patients with multiple trauma. A prospective, open-label randomized study in two intensive care units (ICUs). 79 consecutive multiple trauma patients admitted to the ICU who were expected to be mechanically ventilated for more than 3 days. Patients were randomly assigned to receive either a combination of a locally applied nasal decongestant agents: 2 drops twice/day of xylometazoline nasal solution 0.1% and 100 μg budesonide (NDCA group, n = 39) or placebo (control group, n = 40). For the diagnosis of radiological maxillary sinusitis patients underwent paranasal computed tomography within 48 h of admission and thereafter every 4–7 days. Infectious maxillary sinusitis was diagnosed by microbiological analysis of fluid aspirated after transnasal puncture of maxillary sinuses. Radiological maxillary sinusitis was detected in 54% of patients in the NDCA group (n = 21) but in 82% of controls (p

Several studies of critically ill patients have suggested an association of the D/D genotype of the insertion/deletion (I/D) angiotensin-converting enzyme (ACE) polymorphism with poor outcome probably by enhancing the inflammatory response and leading to a procoagulant state. Our aim was to evaluate the effect of both the ACE I/D polymorphism and its gene product, on the clinical outcome of critically ill septic patients.

BackgroundAmiodarone is a widely used antiarrythmic drug, which may produce secondary effects on the thyroid. In 14–18% of amiodarone-treated patients, there is overt thyroid dysfunction, usually in the form of amiodarone-induced thyrotoxicosis, which can be difficult to manage with standard medical treatment.Case presentationPresented is the case of a 65-year-old man, under chronic treatment of atrial fibrillation with amiodarone, who was admitted to the Intensive Care Unit with acute cardio-respiratory failure and fever. He was recently hospitalized with respiratory distress, attributed to amiodarone-induced pulmonary fibrosis. Clinical and laboratory investigation revealed thyrotoxicosis due to amiodarone treatment. He was begun on thionamide, prednisone and beta-blockers. After a short term improvement of his clinical status the patient underwent percutaneous tracheotomy due to weaning failure from mechanical ventilation, which led to the development of recurrent thyrotoxicosis, unresponsive to medical treatment. Finally, the patient developed multiple organ failure and died, seven days later.ConclusionWe suggest that percutaneous tracheotomy could precipitate a thyrotoxic crisis, particularly in non-euthyroid patients suffering from concurrent severe illness and should be performed only in parallel with emergency thyroid surgery, when indicated.