Impaired diffusing capacity for carbon monoxide in children with type 1 diabetes: is this the first sign of long-term complications?

We assessed the presence of lung dysfunction in children with type 1 diabetes, evaluated as reduced diffusing capacity of the lung for carbon monoxide (DLCO), and its components: membrane diffusing capacity (DM) and pulmonary capillary blood volume (Vc). A total of 42 children, aged 15.6 ± 3.8 years, with type 1 diabetes for 8.3 ± 5.5 years, and 30 healthy age and sex-matched peers were recruited for the study. Lung volumes and spirometric dynamic parameters were assessed by plethysmography. Single-breath DLCO was measured according to international recommendation. DM and Vc volume were calculated. Lung volumes were significantly reduced in young patients with type 1 diabetes when compared to controls. Moreover, DLCO was reduced in patients compared to controls (78% ± 16% vs. 120% ± 1%, P = 0.0001). However, when differentiating DM and Vc compartments, we observed a significant impairment only about Vc (34 ± 20 ml vs. 88 ± 18 ml; P = 0.0001), while no difference was observed about DM compartment (23 ± 4 vs. 26 ± 3 ml/min/mmHg, P = 0.798). Whether this might be seen as the “first” sign of microangiopathic involvement in patients with type 1 diabetes has to be confirmed on larger groups but is still fascinating. Meanwhile, we suggest to screen DLCO in all patients with type 1 diabetes.     

Modern Morbidity following Pulmonary Resection for Postprimary Tuberculosis

n = 8), multidrug resistance or noncompliance to the medical treatment ( n = 11), parenchymal sequelae ( n = 3), suspected cancer ( n = 5), and for the correction of postpneumonectomy bronchopleural fistula and empyema ( n = 1). On admission, eight patients presented with sputum positivity (28.6%). Similar to previous series, tubercular predilection for upper lobes was confirmed (21/28, 75%); accordingly, upper lobectomy through an extrapleural approach was the most common procedure (16/28, 57.1%). Atypical segmental resections or segmentectomies were performed in seven patients (25%), whereas a bilobectomy was necessary in another three patients (10.7%) and a completion pneumonectomy in one (3.6%). Additional procedures were an open-window thoracostomy with transpericardial closure of the main bronchus and a tailored thoracoplasty. No operative mortality was reported. Healing was achieved in 26 patients (93%). Bleeding, either from the chest wall or hilar dissection, was the only reported intraoperative complication. Median blood loss, inclusive of early postoperative collections from chest tubes, reached 1330 ml (range 100–3700 ml). Major postoperative complications included recurrent disease (2/28, 7%) in sputum-positive patients and segmental pulmonary embolism (3.5%). Causes of minor morbidity were air leaks resulting in residual space undergoing spontaneous resolution (18%), wound breakdown (14%), and, fever (11%). This limited series confirms the therapeutic value of the surgical treatment of postprimary tuberculosis, provided that correct indications, adequate pre- and postoperative medical coverage, and meticulous technique are applied.     

Correlations between Oxidative DNA Damage, Oxidative Stress and Coenzyme Q10 in Patients with Coronary Artery Disease

The correlation of coronary artery disease (CAD) with pro-oxidant/antioxidant balance and oxidative DNA damage was investigated.Seventy-seven patients with CAD and 44 healthy individuals as control were included in this study. The comparative ratios of ubiquinol-10/ubiquinone-10, 8-hydroxy-2^''-deoxyguanosine/deoxyguanosine and the level of MDA measured by HPLC and the activities of GPX and SOD by colorimetric approach in blood samples obtained from patients with CAD were unraveled.8-OHdG/dG ratios, serum MDA level and GPX activity were found significantly elevated level in serum of CAD patients compared to control group. The SOD activity was observed in stable levels in CAD patients. Ubiquinol-10/ubiquinone-10 ratio was significantly lower in patients with CAD than the controls.The positive correlation was observed between 8-OHdG/dG ratios in both MDA levels and GPX activity, while the significant negative correlation was seemed between the ratio of 8-OHdG/dG and ubiquinol-10/ ubiquinone-10 as well as MDA levels and ubiquinol-10/ ubiquinone-10 ratio.We conclude that, both the disruption of pro-oxidant/antioxidant balance and oxidative stress in DNA may play an important role in the pathogenesis of coronary artery disease.     

Self-Coding of Fidelity as a Potential Active Ingredient of Consultation to Improve Clinicians’ Fidelity

A key goal for implementation science is the identification of evidence-based consultation protocols and the active ingredients within these protocols that drive clinician behavior change. The current study examined clinicians’ self-coding of fidelity as a potential active ingredient of consultation for the Attachment and Biobehavioral Catch-up (ABC) intervention. It also examined two other potential predictors of clinician fidelity in response to consultation: dosage of consultation and working alliance. Twenty-nine clinicians (97% female, 62% White, M age?=?34 years) participated in a year of weekly fidelity-focused ABC consultation sessions, for which clinicians self-coded fidelity and received consultant feedback on both their coding and their fidelity. Data from the ABC fidelity measure were available for 1067 sessions coded by consultants, and clinicians’ self-coding accuracy was calculated from 1044 sessions coded by both clinicians and consultants. Alliance was measured with the Working Alliance Inventory—Trainee and Supervisor Versions. The study was observational, and fidelity and self-coding accuracy were modeled across time using hierarchical linear modeling. Clinicians’ ABC fidelity, as well as their self-coding accuracy, increased over the course of consultation. Clinicians’ self-coding accuracy predicted their initial fidelity and growth in fidelity. Working alliance was also linked to fidelity and self-coding accuracy. These results suggest that clinician self-coding should be further examined as an active ingredient of consultation. The study has important implications for the design of consultation procedures and fidelity assessments.

     

CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Granular Computing Techniques for Classification and Semantic Characterization of Structured Data

We propose a system able to synthesize automatically a classification model and a set of interpretable decision rules defined over a set of symbols, corresponding to frequent substructures of the input dataset. Given a preprocessing procedure which maps every input element into a fully labeled graph, the system solves the classification problem in the graph domain. The extracted rules are then able to characterize semantically the classes of the problem at hand. The structured data that we consider in this paper are images coming from classification datasets: they represent an effective proving ground for studying the ability of the system to extract interpretable classification rules. For this particular input domain, the preprocessing procedure is based on a flexible segmentation algorithm whose behavior is defined by a set of parameters. The core inference engine uses a parametric graph edit dissimilarity measure. A genetic algorithm is in charge of selecting suitable values for the parameters, in order to synthesize a classification model based on interpretable rules which maximize the generalization capability of the model. Decision rules are defined over a set of information granules in the graph domain, identified by a frequent substructures miner. We compare the system with two other state-of-the-art graph classifiers, evidencing both its main strengths and limits.     

Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting

International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...     

Morphological and Morphometrical Description of Trichostrongylus Species Isolated from Domestic Ruminants in Khuzestan Province,Southwest Iran

Backgrounds

Genus Trichostrongylus (Nematoda: Trichostrongylidae) is one of the most important zoonotic nematodes with wide geographic distribution in the world. The purpose of the present study was to describe morphological and morphometrical characteristics of male Trichostrongylus species, currently prevalent in domestic ruminants of Khuzestan Province, southwest Iran.

Methods

Gastro-intestinal organs of 1600 sheep, goats, cattle, and buffalos, slaughtered in Khuzestan Province, southwest Iran, were examined for infectivity with Trichostrongylus species. For examination and measurements of helminthes, Azo-carmine staining was performed, followed by camera lucida drawings of morphological characters and measurements of morphometrical criteria with a calibrated microscope. Using valid nematodes systematic keys, almost all the parasites were identified at the level of species.

Results

Overall, 114 animals were found infected with at least one species of Trichostrongylus. Considering morphological characteristics of male Trichostrongylus, six species were identified including T. colubriformis, T. vitrinus, T. probolorus, T. capricola, T. longispicularis and Trichostrongylus sp.

Conclusion

Although, compared to the previous decades, currently Trichostrongylus is much less prevalent in the domestic ruminants of the study area, but still different species occur in these animals.     

In vitro effects of bisantrene on fresh clonogenic leukemia cells: a preliminary study on 15 cases

In vitro clonogenic assays may be useful for determining the sensitivity of leukemic cells to chemotherapeutic agents. We evaluated the antileukemic effect of Bisantrene (an anthracene derivative now undergoing phase II clinical trials in relapsed/resistant acute non lymphoid leukemias-ANLL) using the ANLL cell clonogenic assay. Fifteen cases were studied (9 newly diagnosed, 5 relapsed and 1 refractory ANLL). Normal CFU-GM sensitivity was tested in a subset of 10 normal controls. A wide range of concentrations (from 0.01 to 10 micrograms/ml) at 3 durations of exposure (30 min, 120 min, continuous) was employed. Bisantrene proved effective in 12 out of 15 ANLL cases, inhibiting blast colony growth (50% at 1 micrograms/ml; nearly 100% at 10 micrograms/ml) in a dose-dependent, time-independent way. Three cases were unresponsive both in vitro and in vivo. Normal CFU-GM were inhibited at lower doses (50% at 0.5 micrograms/ml; 100% at 5 micrograms/ml). We conclude that: 1) Bisantrene is active in vitro on leukemic clonogenic cells at doses corresponding to plasmatic levels achievable in patients, with a parallel activity in vivo in 3 relapsed cases. It should be tested in vitro before therapeutic use in order to avoid, if possible, improper use in resistant patients. 2) Normal CFU-GM are more sensitive than clonogenic leukemic cells. This must be taken into account, in view of possible prolonged neutropenias after therapy. 3) The time-independent effect of the drug should be evaluated in the design of new therapeutic schedules.