A Case of Osteonecrosis of the Jaw in a Patient with Crohn's Disease Treated with Infliximab

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse drug reaction, occurring in patients undergoing treatments with antiresorptive or antiangiogenic agents, such as bisphosphonates, denosumab, or bevacizumab, for different oncologic and non-oncologic diseases. The aim of this study was to report a case of MRONJ in a patient taking infliximab, an anti-TNF-alpha antibody used to treat Crohn's disease, rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Case Report: A 49-year-old female patient affected by Crohn's disease, who had been undergoing 250 mg intravenous infliximab every six weeks for 12 years, with no history of antiresorptive or antiangiogenic agent administration, came to our attention for post-surgical MRONJ, associated with a wide cutaneous necrotic area of her anterior mandible. Following antibiotic cycles, the patient underwent surgical treatment with wide bone resection and debridement of necrotic tissues; after prolonged follow-up (16 months), the patient completely healed without signs of recurrence. Conclusions: Prevention of MRONJ by dental check-up before and during treatments with antiresorptive treatments (bisphosphonates or denosumab) is a well-established procedure. Although further studies are required to confirm the role of infliximab in MRONJ, based on the results of this study, we propose that patients who are going to be treated with infliximab should also undergo dental check-up before starting therapy, to possibly avoid MRONJ onset

Methods for control over learning individual trajectory

The article discusses models, methods and algorithms of determining student's optimal individual educational trajectory. A new method of controlling the learning trajectory has been developed as a dynamic model of learning trajectory control, which uses score assessment to construct a sequence of studied subjects

Sampling protein motion and solvent effect during ligand binding.

An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is of great value because it provides the opportunity for an exogenous control of the related process. Very often this aim can be pursued using high resolution structures of the complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, in many other cases a number of factors, like protein flexibility or solvent effects, increase the degree of complexity of ligand/protein interaction and these standard techniques are no longer sufficient to describe the binding event. We have experienced and tested these limits in the present study in which we have developed and revealed the mechanism of binding of a new series of potent inhibitors of Adenosine Deaminase. We have first performed a large number of docking calculations, which unfortunately failed to yield reliable results due to the dynamical character of the enzyme and the complex role of the solvent. Thus, we have stepped up the computational strategy using a protocol based on metadynamics. Our approach has allowed dealing with protein motion and solvation during ligand binding and finally identifying the lowest energy binding modes of the most potent compound of the series, 4-decyl-pyrazolo[1,5-a]pyrimidin-7-one

Left atrial volume during stress is associated with increased risk of arrhythmias in patients with hypertrophic cardiomyopathy

Introduction: In patients affected by hypertrophic cardiomyopathy (HCM), left atrial volume index (LAVi) is associated with an increased risk of tachyarrhythmias and major clinical events. To date, the clinical meaning of LAVi measured during exercise (stress LAVi [sLAVi]) has not yet been investigated in HCM. This study sought to evaluate the correlation between LAVi/sLAVi and clinical outcome (risk of arrhythmias and heart failure [HF]) in patients with HCM. Methods and Results: We enrolled a total of 51 consecutive patients with HCM (39 men; mean age: 39.41 ± 17.9 years) who underwent standard and stress echocardiography, following a common protocol. During follow-up (median follow-up was 1.82 years), the following composite endpoints were collected: ARRHYT endpoint (atrial fibrillation, paroxysmal supraventricular tachycardia, nonsustained ventricular tachycardia (VT), sustained VT, ventricular fibrillation, syncope of likely cardiogenic nature, and sudden cardiac death) and HF endpoint (worsening of functional class and left ventricular ejection fraction, hospitalization, and death for end-stage HF). Eight patients were lost at follow-up. ARRHYT endpoint occurred in 13 (30.2%) patients (8, 18.6%, supraventricular and 10, 23.2%, ventricular arrhythmias), whereas HF endpoint occurred in 5 (11.6%) patients. sLAVi (mean value of 31.16 ± 10.15 mL/m2) performed better than rLAVi as a predictor of ARRHYT endpoint (Akaike Information Criterion: 48.37 vs. 50.37, if dichotomized according to the median values). A sLAVi value of 30 mL/m2 showed a predictive accuracy of 72.1% (C-statistics of 0.7346), with a high negative predictive value (87.5%). Conclusion: These findings encourage future studies on sLAVi, as a potential predictor of arrhythmias and adverse outcome in patients with HCM

The Biological Role of Vitamins in Athletes’ Muscle, Heart and Microbiota

Physical activity, combined with adequate nutrition, is considered a protective factor against cardiovascular disease, musculoskeletal disorders, and intestinal dysbiosis. Achieving optimal performance requires a significantly high energy expenditure, which must be correctly supplied to avoid the occurrence of diseases such as muscle injuries, oxidative stress, and heart pathologies, and a decrease in physical performance during competition. Moreover, in sports activities, the replenishment of water, vitamins, and minerals consumed during training is essential for safeguarding athletes’ health. In this scenario, vitamins play a pivotal role in numerous metabolic reactions and some muscle biochemical adaptation processes induced by sports activity. Vitamins are introduced to the diet because the human body is unable to produce these micronutrients. The aim of this review is to highlight the fundamental role of vitamin supplementation in physical activity. Above all, we focus on the roles of vitamins A, B6, D, E, and K in the prevention and treatment of cardiovascular disorders, muscle injuries, and regulation of the microbiome

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

The T.O.S.C.A. Project: Research, Education and Care

Despite recent and exponential improvements in diagnostic- therapeutic pathways, an existing “GAP” has been revealed between the “real world care” and the “optimal care” of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF “metabolic pathophysiological model” and to improve the quality of care of HF patients through research and continuing medical education

Water-peptide dynamics during conformational transitions

Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that the water molecules represent an integral part of the molecular system during the conformational changes, in contrast to the metastable periods when water and peptide dynamics are essentially decoupled

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET)

Background. Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E’ and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. Methods. EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. Results. Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E’ that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E’ but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E’ and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E’, p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E’ of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. Conclusion. Age and HTN have a synergic negative effect on E/E’ and TAPSE at peak exercise in hypertensive subjects

Prognostic Value of Indeterminable Anaerobic Threshold in Heart Failure.

Background In patients with heart failure (HF), during maximal cardiopulmonary exercise test, anaerobic threshold (AT) is not always identified. We evaluated whether this finding has a prognostic meaning. Methods and Results We recruited and prospectively followed up, in 14 dedicated HF units, 3058 patients with systolic (left ventricular ejection fraction <40%) HF in stable clinical conditions, New York Heart Association class I to III, who underwent clinical, laboratory, echocardiographic, and cardiopulmonary exercise test investigations at study enrollment. We excluded 921 patients who did not perform a maximal exercise, based on lack of achievement of anaerobic metabolism (peak respiratory quotient 1.05). Primary study end point was a composite of cardiovascular death and urgent cardiac transplant, and secondary end point was all-cause death. Median follow-up was 3.01 (1.39-4.98) years. AT was identified in 1935 out of 2137 patients (90.54%). At multivariable logistic analysis, failure in detecting AT resulted significantly in reduced peak oxygen uptake and higher metabolic exercise and cardiac and kidney index score value, a powerful prognostic composite HF index (P<0.001). At multivariable analysis, the following variables were significantly associated with primary study end point: peak oxygen uptake (% pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97-0.98), ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01-1.03), hemoglobin (P<0.05; HR=0.931; CI=0.87-1.00), left ventricular ejection fraction (P<0.001; HR=0.948; CI=0.94-0.96), renal function (modification of diet in renal disease; P<0.001; HR=0.990; CI=0.98-0.99), sodium (P<0.05; HR=0.967; CI=0.94-0.99), and AT nonidentification (P<0.05; HR=1.41; CI=1.06-1.89). Nonidentification of AT remained associated to prognosis also when compared with metabolic exercise and cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09-1.10). Similar results were obtained for the secondary study end point. Conclusions The inability to identify AT most often occurs in patients with severe HF, and it has an independent prognostic role in HF