•This is the first reports addressing the imbalance of the Treg/Th17 axis in IPF patients.•Expansion of the Treg compartment is associated with preserved turn-over and ability to express ...TGF-beta.•Th17 impairment along with NK depletion suggests the existence of an immune perturbation with similarities with cancer.
The immune response plays an unsettled role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the contribution of inflammation being controversial as well. Emerging novel T cell sub-populations including regulatory T lymphocytes (Treg) and interleukin (IL)-17 secreting T helper cells (Th17) may exert antithetical actions in this scenario. Phenotype and frequency of circulating immune cell subsets were assessed by multi-parametric flow cytometry in 29 clinically stable IPF patients and 17 healthy controls. The interplay between Treg lymphocytes expressing transforming growth factor (TGF)-β and Th17 cells was also investigated. Proportion and absolute number of natural killer (NK) cells were significantly reduced in IPF patients in comparison with controls (p<0.001). Conversely, the proportion and absolute number of CD3+CD4+CD25highFoxp-3+ cells were significantly increased in IPF patients (p=0.000). As in controls, almost the totality of cells (>90%) expressed TGF-β upon stimulation. Interestingly, the frequency of Th17 cells was significantly compromised in IPF patients (p=0.000) leading to an increased TGF-β/IL-17 ratio (4.2±2.3 vs 0.5±0.3 in controls, p=0.000). Depletion of NK and Th17 cells along with a not compromised Treg compartment delineate the existence of an “immune profile” that argue against the recent hypothesis of IPF as an autoimmune disease. Our findings along with the imbalance of the Treg/Th17 axis more closely suggest these immune perturbations to be similar to those observed in cancer. Clinical relevance, limitations and perspectives for future research are discussed.
Background and aims
Anorexia nervosa is an eating disorder characterized by food restriction, irrational fear of gaining weight and consequent weight loss. High mortality rates have been reported, ...mostly due to suicide and malnutrition. Good outcomes largely vary between 18 and 42 %. We aimed to assess outcome and prognostic factors of a large group of patients with anorexia nervosa. Moreover we aimed to identify clusters of prognostic factors related to specific outcomes.
Methods
We retrospectively reviewed data of 100 patients diagnosed with anorexia nervosa previously hospitalized in a tertiary level structure. Then we performed follow-up structured telephone interviews.
Results
We identified four dead patients, while 34 % were clinically recovered. In univariate analysis, short duration of inpatient treatment (
p
= 0.003), short duration of disorder (
p
= 0.001), early age at first inpatient treatment (
p
= 0.025) and preserved insight (
p
= 0.029) were significantly associated with clinical recovery at follow-up. In multiple logistic regression analysis, duration of first inpatient treatment, duration of disorder and preserved insight maintained their association with outcome. Moreover multiple correspondence analysis and cluster analysis allowed to identify different typologies of patients with specific features. Notably, group 1 was characterized by two or more inpatient treatments, BMI ≤ 14, absence of insight, history of long-term inpatient treatments, first inpatient treatment ≥30 days. While group 4 was characterized by preserved insight, BMI ≥ 16, first inpatient treatment ≤14 days, no more than one inpatient treatment, no psychotropic drugs intake, duration of illness ≤4 years.
Conclusions
We confirmed the association between short duration of inpatient treatment, short duration of disorder, early age at first inpatient treatment, preserved insight and clinical recovery. We also differentiated patients with anorexia nervosa in well-defined outcome groups according to specific clusters of prognostic factors. Our study might help clinicians to evaluate prognosis of patients with anorexia nervosa.
We reviewed the shoulder arthroplasty (SA) literature to correlate citations, methodological characteristics and quality of most-cited articles in this field. We hypothesized that a greater number of ...citations would be found for high-quality clinical studies.
We searched the Web of Knowledge database for the 50 most-cited articles about SA and collected author name, publication year, country of origin, journal, article type, level of evidence (LoE), subject of paper, type of arthroplasty and metrics (number of citations and citation rate). Coleman Methodology Score (CMS) was computed for clinical articles. Statistical analysis of variance and correlation coefficients were used to investigate the relationship between different variables.
Out of the selected 50 studies on SA, 26% were nonclinical. There were 15,393 citations overall (mean 307.8), with a mean 19.5 citations per year (range 48.3-6.7). Thirty or 60% of all articles were LoE IV. All studies were published between 1984 and 2011 in 8 journals. Reverse SA (RSA) was the most common subject (36% of studies). The United States was the country responsible for most contributions (50% of studies). CMS ranged from 81 to 38 (mean 59.6). RSA received the highest number of citations (
< .001), independently from country of origin (
= .137) and LoE (
= .723). CMS correlated with citation rate (
= 0.397;
= .013) and publication year (tau = 0.397;
= .013), but not with LoE (
= .204).
In SA literature, citation rate positively correlates with methodological quality of a study, independently from publication country and LoE. Among most-cited papers, RSA is the most common standalone subject.
Interleukin-1beta (IL-1β) is crucially involved in the pathogenesis of coronary atherosclerotic diseases (CAD) and its inhibition has proven cardiovascular benefits. Epicardial adipose tissue (EAT) ...is a local source of inflammatory mediators which may negatively affect the surrounding coronary arteries. In the present study, we explored the relationship between serum and EAT levels of IL-1β and IL-1 receptor antagonist (IL-1ra) in patients with chronic coronary syndrome (CCS) and recent acute coronary syndrome (ACS).
We obtained EAT biopsies in 54 CCS (Group 1) and 33 ACS (Group 2) patients undergoing coronary artery bypass grafting. Serum and EAT levels of IL-1β and IL-1ra were measured in all patients. An immunophenotypic study was carried out on EAT biopsies and the CD86 events were studied as markers of M1 macrophages.
Circulating levels of IL-1β were significantly higher in the overall CAD population compared to a control group 7.64 pg/ml (6.86; 8.57) vs. 1.89 pg/ml (1.81; 2.29);
< 0.001. In contrast, no differences were observed for serum IL-1ra levels between CAD and controls. Comparable levels of serum IL-1β were found between Groups 1 and 2 7.6 pg/ml (6.9; 8.7) vs. 7.9 pg/ml (7.2; 8.6);
= 0.618. In contrast, significantly lower levels of serum IL-1ra were found in Group 2 compared to Group 1 274 pg/ml (220; 577) vs. 603 pg/ml (334; 1022);
= 0.035. No differences of EAT levels of IL-1β were found between Group 2 and Group 1 3.4 pg/ml (2.3; 8.4) vs. 2.4 pg/ml (1.9; 8.0);
= 0.176. In contrast, significantly lower EAT levels of IL-1ra were found in Group 2 compared to Group 1 101 pg/ml (40; 577) vs. 1344 pg/ml (155; 5327);
= 0.002. No correlation was found between EAT levels of IL-1β and CD86 and CD64 events.
The present study explores the levels of IL-1β and IL-1ra in the serum and in EAT of CCS and ACS patients. ACS seems to be associated to a loss of the counter-regulatory activity of IL-1ra against the pro-inflammatory effects related to IL-1β activation.
The Prostate Health Index (PHI) and Proclarix (PCLX) have been proposed as blood-based tests for prostate cancer (PCa). In this study, we evaluated the feasibility of an artificial neural network ...(ANN)-based approach to develop a combinatorial model including PHI and PCLX biomarkers to recognize clinically significant PCa (csPCa) at initial diagnosis.
To this aim, we prospectively enrolled 344 men from two different centres. All patients underwent radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/mL. We used an artificial neural network to develop models that can identify csPCa efficiently. As inputs, the model uses -2proPSA, freePSA, total PSA, cathepsin D, thrombospondin, and age.
The output of the model is an estimate of the presence of a low or high Gleason score PCa defined at RP. After training on a dataset of up to 220 samples and optimization of the variables, the model achieved values as high as 78% for sensitivity and 62% for specificity for all-cancer detection compared with those of PHI and PCLX alone. For csPCa detection, the model showed 66% (95% CI 66-68%) for sensitivity and 68% (95% CI 66-68%) for specificity. These values were significantly different compared with those of PHI (
< 0.0001 and 0.0001, respectively) and PCLX (
= 0.0003 and 0.0006, respectively) alone.
Our preliminary study suggests that combining PHI and PCLX biomarkers may help to estimate, with higher accuracy, the presence of csPCa at initial diagnosis, allowing a personalized treatment approach. Further studies training the model on larger datasets are strongly encouraged to support the efficiency of this approach.
Epicardial adipose tissue (EAT) has been shown to be involved in the pathogenesis and progression of heart failure (HF). In this study we aimed to explore the predictive value of echocardiographic ...EAT thickness on prognosis of a selected population of HF patients.
The patient population included n. 69 consecutive patients with systolic HF referred to implantable cardioverter defibrillator (ICD) implantation for primary or secondary prevention. At the time of enrolment, echocardiographic EAT thickness was assessed in all patients along with demographic and clinical data. The study had a median follow-up time of 49.8 months. We assessed the prognostic predictive value of EAT thickness on a composite clinical and arrhythmic outcome including HF related deaths, new hospital admissions for HF worsening, and atrial and life threatening ventricular arrhythmic events. Clinical and arrhythmic outcomes were also evaluated separately.
At univariate analysis, EAT thickness significantly predicted all the three outcomes considered. Of interest, at multivariate analysis, after adjusting for known risk factor, EAT remained significantly associated to the composite HR 1.18 (1.09-1.28);
< 0.001, arrhythmic HR 1.14 (1.03-1.25);
= 0.008, and clinical HR 1.14 (1.03-1.27);
= 0.010 outcomes.
Echocardiographic assessment of EAT can predict outcome of HF patients and it is significantly associated with both arrhythmic and clinical events. These preliminary findings pave the way for future and larger studies aimed to definitively recognize the prognostic value of this novel risk marker in HF.
Introduction
In Charcot-Marie-Tooth type 1A (CMT1A) patients, daily life is mainly influenced by mobility and ambulation dysfunctions. The aim of our work was to evaluate the perception of ...disturbances that mostly impact on daily life in CMT1A patients and its difference on the basis of age, gender, disability, and quality of life.
Methods
Forty-one CMT1A patients underwent neurological assessment focused on establishing clinical disability through the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and quality of life through the Short Form-36 (SF-36) questionnaire. We identified from CMT disturbances 5 categories weakness in lower limbs (WLL), weakness in upper limbs (WUL), skeletal deformities (SD), sensory symptoms (SS), balance (B) and patients classified the categories from the highest to the lowest impact on daily life (1: highest; 5: lowest). Ranking of the 5 categories, in the overall sample and in the different subgroups (dividing by gender, median of age and disease duration, CMTNS, domains of SF-36), was obtained and differences among subgroups were assessed using a bootstrap approach.
Results
Rank analysis showed that WLL was the most important disturbance on daily life whereas WUL had the lowest impact. In the older CMT1A group, the most important disturbance on daily life was B that was also the most relevant disturbance in patients with a greater disability. SD influenced daily life in younger patients. SS had less impact on daily life, with the exception of patients with a milder disability.
Discussion
Our findings demonstrated that the perception of disturbances that mostly impact on CMT1A patients’ daily life changes over the lifetime and with degree of disability.
Weight gain and metabolic changes have been related to survival of early breast cancer patients (EBC). ‘’However, factors influencing metabolism post-diagnosis are not fully understood. We measured ...anthropometric body mass index (BMI), body weight, waist and hip circumferences, and waist-to-hip ratio and metabolic (levels of insulin, glucose, H1Ac, total, HDL, and LDL cholesterol, triglycerides, and the homeostasis model assessment score HOMA) parameters in 433 pre- and post-menopausal women with EBC at diagnosis and 3, 6, 9, 12, and 24 months thereafter. At diagnosis, compared with post-menopausal women, pre-menopausal patients were more likely to be leaner and to have a lower BMI, smaller waist and hip circumferences, and waist-to-hip ratio. They had also lower glucose, HbA1c, and triglyceride levels and a lower HOMA score. Furthermore, they were more likely to have an estrogen- and/or progesterone-positive tumor and a higher proliferating breast cancer. During the first two post-diagnosis years, all women showed a significant increase of weight (+0.72 kg/year,
P
< 0.001), waist circumference (+1.53 cm/year,
P
< 0.001), and plasma levels of LDL cholesterol (+5.4 mg/dl per year,
P
= 0.045) and triglycerides (+10.73 mg/dl per year,
P
= 0.017). In patients receiving chemotherapy only, there was a significant increase in hip circumference (+3.16 cm/year,
P
< 0.001) and plasma cholesterol levels (+21.26 mg/dl per year,
P
< 0.001). We showed that weight, body fat distribution, and lipid profile changed in EBC patients receiving adjuvant therapy. These changes occurred during the first 2 years after diagnosis and were not specifically related to chemotherapy, menopausal status, or initial body weight.
Objectives
We designed a multicentre open prospective randomized trial to evaluate the risk-benefit profile of two different initial treatment schemes with levothyroxine (L-T4), 10-12.5 μg/kg/day vs ...12.6-15 μg/kg/day, on growth and neurodevelopmental outcomes in children with congenital hypothyroidism (CH) detected by neonatal screening to identify the best range dose to achieve optimal neurocognitive development.
Design, patients and methods
Children detected by neonatal screening were randomly assigned to receive an initial L-T4 dose of 10-12.5 μg/kg/day (Low) or 12.6-15 μg/kg/day (High). All patients underwent periodical clinical examination with measurement of growth parameters and measurement of TSH and FT4. Neurocognitive development was evaluated at the age of 24 months using Griffiths Mental Development Scales (GMDS) and cognitive and behavioral assessment was performed at 48 months of age using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The study was registered with clinicaltrials.gov (NCT05371262).
Results
Treatment schemes below or above 12.5 μg/kg/day were both associated with rapid normalization of TSH and thyroid hormone levels in most patients with no differences in the risk of over- and under-treatment episodes in the first months of life. Growth parameters were normal and comparable between the two groups. Developmental quotients at 24 months of age were normal in both groups (Low 100.6 ± 15.5 vs High 96.9 ± 16.6). Likewise, at 4 years of age IQ and subtest scores were comparable between patients from Low and High (Total IQ 104.2 ± 11.4 vs 101.0 ± 20.3, Verbal IQ 103.9 ± 11.5 vs 98.7 ± 15.1, Performance IQ 105.3 ± 10.4 vs 100.3 ± 19.8). 6/45 CH patients (13.3%) showed a total IQ below 85 (73.7 ± 5.9) regardless of age at diagnosis, L-T4 starting dose, time of FT4 and TSH normalization and episodes of over and undertreatment. Worse socioeconomic status and delayed bone age at diagnosis were the only predictors of an increased risk of having suboptimal IQ at 24 and IQ at 48 months.
Conclusions
Our results indicate that initial treatment with L-T4, 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, are both associated with normal growth and neurodevelopmental outcomes in children with CH detected by neonatal screening. Further studies with a long-term follow-up on a larger number of patients are needed to confirm these results.
Clinical trial registration
https://clinicaltrials.gov/ct2/show/NCT05371262?term=NCT05371262&draw=2&rank=1
identifer NCT05371262.
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