Complex chromosomal rearrangements are rare events compatible with survival, consisting of an imbalance and/or position effect of one or more genes, that contribute to a range of clinical ...presentations. The investigation and diagnosis of these cases are often difficult. The interpretation of the pattern of pairing and segregation of these chromosomes during meiosis is important for the assessment of the risk and the type of imbalance in the offspring. Here, we investigated two unrelated pediatric carriers of complex rearrangements of chromosome 7. The first case was a 2-year-old girl with a severe phenotype. Conventional cytogenetics evidenced a duplication of part of the short arm of chromosome 7. By array-CGH analysis, we found a complex rearrangement with three discontinuous trisomy regions (7p22.1p21.3, 7p21.3, and 7p21.3p15.3). The second case was a newborn investigated for hypodevelopment and dimorphisms. The karyotype analysis promptly revealed a structurally altered chromosome 7. The array-CGH analysis identified an even more complex rearrangement consisting of a trisomic region at 7q11.23q22 and a tetrasomic region of 4.5 Mb spanning 7q21.3 to q22.1. The mother’s karyotype examination revealed a complex rearrangement of chromosome 7: the 7q11.23q22 region was inserted in the short arm at 7p15.3. Finally, array-CGH analysis showed a trisomic region that corresponds to the tetrasomic region of the son. Our work proved that the integration of several technical solutions is often required to appropriately analyze complex chromosomal rearrangements in order to understand their implications and offer appropriate genetic counseling.
Acutely decompensated heart failure (HF) in patients with diuretic resistance is often treated with extracorporeal ultrafiltration. Peritoneal ultrafiltration (PUF) has been proposed for the ...long-term management of severe HF after resolution of the acute episode. The aim of the present study was to evaluate the use of PUF in the treatment of chronic refractory HF in patients without end-stage renal disease. ♢
This multicenter (10 nephrology departments throughout Italy) retrospective observational study included patients with severe HF refractory to maximized drug treatment. The patients were proposed for PUF because they had experienced at least 3 hospital admissions in the preceding year for acutely decompensated HF requiring extracorporeal ultrafiltration. ♢
Of the 48 study patients (39 men, 9 women; mean age 74 ± 9 years), 30 received 1 nocturnal icodextrin exchange, 5 required 2 daily exchanges, and 13 received 2 - 4 sessions per week of automated peritoneal dialysis. During the first year, renal function remained stable (initial: 20.8 ± 10.0 mL/min/1.73 m(2); end: 22.0 ± 13.6 mL/min/1.73 m(2)), while pulmonary artery systolic pressure declined to 40 ± 6.09 mmHg from 45.5 ± 9.18 mmHg (p = 0.03), with a significant concomitant improvement in New York Heart Association functional status. Hospitalizations decreased to 11 ± 17 days/patient-year from 43 ± 33 days/patient-year before the start of PUF (p < 0.001). The incidence of peritonitis was 1 episode in 45 patient-months. Patient survival was 85% at 1 year and 56% at 2 years. ♢
This study confirms the satisfactory results of using PUF for chronic HF in elderly patients.
Psoriasis is a chronic inflammatory skin disease associated with increased cardiovascular morbidity and mortality. The Framingham risk score is a validated and composite measurement that predicts the ...absolute risk of developing major cardiovascular events at 5 and 10 years. The objective of this study was to estimate the Framingham cardiovascular risk score in patients with psoriasis. A cross-sectional study in 234 adult patients with psoriasis and 234 age- and gender-matched patients with skin diseases other than psoriasis was performed. The Framingham risk score includes age, gender, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, smoking status, and diabetes mellitus. Framingham risk score was significantly higher in patients with psoriasis than in controls at 5 years (mean ± SD 5.3 ± 4.4 vs 3.4 ± 3.3, p <0.001) and at 10 years (11.2 ± 8.1 vs 7.3 ± 6.3, p <0.001). The risk was higher for patients >50 years of age. Patients with psoriasis were more frequently smokers and diabetics and had more commonly atherogenic dyslipidemia than controls (p <0.05). Presence of psoriasis was independently associated with a higher Framingham score (coefficient 1.6, 95% confidence interval CI 0.6 to 2.5, p = 0.001). There was no correlation between severity or duration of psoriasis and Framingham risk score (coefficient 0.009, 95% CI −0.02 to 0.04, p = 0.6; coefficient 0.02, 95% CI 0.007 to 0.04, p = 0.7, respectively). In conclusion, patients with psoriasis have an intermediate risk of developing major cardiovascular events and thus interventions aimed to correct modifiable cardiovascular risk factors are warranted.
Several studies have investigated the efficacy of balneotherapy in atopic dermatitis (AD), including a pediatric open randomized clinical trial conducted at the Comano thermal spring water center, ...which showed a significant reduction in AD severity and an improvement of the quality of life. However, so far many studies on balneotherapy in pediatric AD have included relatively small populations without identifying patients' characteristics associated with their response. The aim of the present study was to identify any features associated with the clinical response to the Comano thermal spring water balneotherapy in a large cohort of pediatric AD patients.
An observational study was conducted on 867 children aged ≤16 years (females 50.5%, mean patient's age 5.9 years, standard deviation ±3.6 years) with mild to severe AD who underwent balneotherapy at the Comano thermal spring water center (Comano, Trentino, Italy) from April to October 2014. Patients were stratified according to their disease severity, which was evaluated using five SCORing Atopic Dermatitis (SCORAD) categories before and immediately after a thermal spring water balneotherapy course. Potential characteristics associated with the patients' clinical response to Comano thermal spring water balneotherapy were investigated.
A statistically significant improvement in AD severity was observed after Comano thermal spring water balneotherapy (p < 0.0001). A significantly higher percentage of patients achieving improvement in AD severity was reported among children ≤4 years old (p < 0.0001) with early-onset AD (p < 0.0001), severe AD (p < 0.0001) or coexistent reported food allergies (p < 0.01). The therapy was well tolerated, and no relevant adverse effects were reported during the treatment course.
Comano thermal spring water balneotherapy is a safe complementary treatment for pediatric patients with AD, as it was able to reduce the disease severity, especially in children ≤4 years old, with early onset AD, severe AD or concomitant food allergies.
Aims
Changes in peak exercise oxygen uptake (VO2) and cardiac output (CO) 6 months after successful percutaneous edge‐to‐edge mitral valve repair (pMVR) in severe primary (PMR) and functional mitral ...regurgitation (FMR) patients are unknown.
The aim of the study was to assess the efficacy of pMVR at rest by echocardiography, VO2 and CO (inert gas rebreathing) measurement and during cardiopulmonary exercise test with CO measurement.
Methods and results
We evaluated 145 and 115 patients at rest and 98 and 66 during exercise before and after pMVR, respectively.
After successful pMVR, significant reductions in MR and NYHA class were observed in FMR and PMR patients. Cardiac ultrasound showed reverse remodelling (left ventricular end‐diastolic volume from 158 ± 63 mL to 147 ± 64, P < 0.001; ejection fraction from 51 ± 15 to 48 ± 14, P < 0.001; pulmonary artery systolic pressure (PASP) from 43 ± 13 to 38 ± 8 mmHg, P < 0.001) in the entire population. These changes were significant in PMR (n = 62) and a trend in FMR (n = 53), except for PASP, which decreased in both groups. At rest, CO and stroke volume (SV) increased in FMR with a concomitant reduction in arteriovenous O2 content difference ΔC(a‐v)O2. Peak exercise, CO and SV increased significantly in both groups (CO from 5.5 ± 1.4 L/min to 6.3 ± 1.5 and from 6.2 ± 2.4 to 6.7 ± 2.0, SV from 57 ± 19 mL to 66 ± 20 and from 62 ± 20 to 69 ± 20, in FMR and PMR, respectively), whereas peak VO2 was unchanged and ΔC(a‐v)O2 decreased.
Conclusions
These data confirm pMVR‐induced clinical improvement and reverse ventricular remodelling at a 6‐month analysis and show, in spite of an increase in CO, an unchanged exercise performance, which is achieved through a ‘more physiological’ blood flow distribution and O2 extraction behaviour. Direct rest and exercise CO should be measured to assess pMVR efficacy.
Aims
Peak exercise oxygen uptake (VO2) and cardiac output (CO) are strong prognostic indexes in heart failure (HF) but unrelated to real‐life physical activity, which is associated to submaximal ...effort.
Methods and results
We analysed maximal cardiopulmonary exercise test with rest, mid‐exercise, and peak exercise non‐invasive CO measurements (inert gas rebreathing) of 231 HF patients and 265 healthy volunteers. HF patients were grouped according to exercise capacity (peak VO2 < 50% and ≥50% pred, Groups 1 and 2). To account for observed differences, data regarding VO2, CO, stroke volume (SV), and artero‐venous O2 content difference ΔC(a‐v)O2 were adjusted by age, gender, and body mass index. A multiple regression analysis was performed to predict peak VO2 from mid‐exercise cardiopulmonary exercise test and CO parameters among HF patients. Rest VO2 was lower in HF compared with healthy subjects; meanwhile, Group 1 patients had the lowest CO and highest ΔC(a‐v)O2. At mid‐exercise, Group 1 patients achieved a lower VO2, CO, and SV 0.69 (interquartile range 0.57–0.80) L/min; 5.59 (4.83–6.67) L/min; 62 (51–73) mL than Group 2 0.94 (0.83–1.1) L/min; 7.6 (6.56–9.01) L/min; 77 (66–92) mL and healthy subjects 1.15 (0.93–1.30) L/min; 9.33 (8.07–10.81) L/min; 87 (77–102) mL. Rest to mid‐exercise SV increase was lower in Group 1 than Group 2 (P = 0.001) and healthy subjects (P < 0.001). At mid‐exercise, ΔC(a‐v)O2 was higher in Group 2 13.6 (11.8–15.4) mL/100 mL vs. healthy patients 11.6 (10.4–13.2) mL/100 mL (P = 0.002) but not different from Group 1 13.6 (12.0–14.9) mL/100 mL. At peak exercise, Group 1 patients achieved a lower VO2, CO, and SV than Group 2 and healthy subjects. ΔC(a‐v)O2 was the highest in Group 2. At multivariate analysis, a model comprising mid‐exercise VO2, carbon dioxide production (VCO2), CO, haemoglobin, and weight predicted peak VO2, P < 0.001. Mid‐exercise VO2 and CO, haemoglobin, and weight added statistically significantly to the prediction, P < 0.050.
Conclusions
Mid‐exercise VO2 and CO portend peak exercise values and identify severe HF patients. Their evaluation could be clinically useful.
Cardiopulmonary exercise testing allows the assessment of the integrative cardiopulmonary response to exercise and is a useful tool to assess the underlying pathophysiologic mechanisms leading to ...exercise intolerance. Patients with pulmonary hypertension often face a considerable delay in diagnosis due to the rarity of the disease and nonspecific symptoms of dyspnea, fatigue, and exercise limitation. Cardiopulmonary exercise testing may be suggestive of pulmonary hypertension in patients with evidence of both circulatory impairment and ventilatory inefficiency. Other factors, such as mechanical ventilatory constraints from dynamic hyperinflation and peripheral muscle dysfunction, contribute to the profound dyspnea during exercise experienced by many patients with pulmonary hypertension. In patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension, several exercise variables, such as low peak Formula: see texto
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, have proven to be useful in establishing the severity of functional impairment, predicting prognosis, and assessing the efficacy of interventions.
Subcellular compartmentalization contributes to the organization of a plethora of molecular events occurring within cells. This can be achieved in membraneless organelles generated through ...liquid–liquid phase separation (LLPS), a demixing process that separates and concentrates cellular reactions. RNA is often a critical factor in mediating LLPS. Recent evidence indicates that DNA damage response foci are membraneless structures formed via LLPS and modulated by noncoding transcripts synthesized at DNA damage sites. Neurodegeneration is often associated with DNA damage, and dysfunctional LLPS events can lead to the formation of toxic aggregates. In this review, we discuss those gene products involved in neurodegeneration that undergo LLPS and their involvement in the DNA damage response.
Intracellular compartments can assemble as membraneless organelles through a demixing process known as ‘liquid–liquid phase separation’ (LLPS).DNA damage response foci are membraneless structures fueled by LLPS of some DNA damage response factors and are modulated by noncoding transcripts synthesized at DNA damage sites.Several forms of neurodegeneration are associated with, and possibly caused by, dysfunctional LLPS events, ultimately leading to the accumulation of toxic solid-like structures.Emerging evidence links factors involved in LLPS events and neurodegeneration with the cellular response to DNA damage.
Background: Traditionally, ventilatory limitation to exercise is assessed by measuring the breathing reserve (BRR) ie , the difference between minute ventilation at peak exercise and maximum ...voluntary ventilation measured at rest. Recent studies
have however, documented important abnormalities in ventilatory adaptation with a remarkable potential to limit exercise even
in the presence of a normal BRR. Among these abnormalities is lung hyperinflation and expiratory flow limitation. This was
documented by comparing tidal to maximum flow-volume loops (FVLs) collected throughout the test. In the present study, we
wondered whether the advantages of using such a technique within the classic cardiopulmonary exercise test (CPET) might be
obscured by the maneuvers interfering with the main functional parameters of the test, and eventually with interpretation
of the CPET.
Methods: We studied 18 healthy subjects, 19 patients affected by COPD, and 19 patients with chronic heart failure during a maximum
exercise test on three different study days in a random order. On one occasion, the CPET was conducted with no FVLs (control
test CTRL), whereas on the other occasions FVLs were incorporated every 1 min during exercise (FVL 1 -min) or every 2 min during exercise (FVL 2 -min).
Results: None of the classic cardiovascular parameters recorded at ventilatory anaerobic threshold or at peak exercise differed between
the study days (by analysis of variance). Furthermore, the coefficients of variation of the main parameters between FVL 1 -min and FVL 2 -min days vs CTRL day were well within the natural variability thresholds reported in the literature.
Conclusions: The FVLs appear to not interfere with the main functional parameters used for the interpretation of CPET.
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