Clusters of individuals recovering from an exacerbation of chronic obstructive pulmonary disease and response to in-hospital pulmonary rehabilitation.

INTRODUCTION AND OBJECTIVES: Due to the present low availability of pulmonary rehabilitation (PR) for individuals recovering from a COPD exacerbation (ECOPD), we need admission priority criteria. We tested the hypothesis that these individuals might be clustered according to baseline characteristics to identify subpopulations with different responses to PR. METHODS: Multicentric retrospective analysis of individuals undergone in-hospital PR. Baseline characteristics and outcome measures (six-minute walking test - 6MWT, Medical Research Council scale for dyspnoea -MRC, COPD assessment test -CAT) were used for clustering analysis. RESULTS: Data analysis of 1159 individuals showed that after program, the proportion of individuals reaching the minimal clinically important difference (MCID) was 85.0%, 86.3%, and 65.6% for CAT, MRC, and 6MWT respectively. Three clusters were found (C1-severe: 10.9%; C2-intermediate: 74.4%; C3-mild: 14.7% of cases respectively). Cluster C1-severe showed the worst conditions with the largest post PR improvements in outcome measures; C3-mild showed the least severe baseline conditions, but the smallest improvements. The proportion of participants reaching the MCID in ALL three outcome measures was significantly different among clusters, with C1-severe having the highest proportion of full success (69.0%) as compared to C2-intermediate (48.3%) and C3-mild (37.4%). Participants in C2-intermediate and C1-severe had 1.7- and 4.6-fold increases in the probability to reach the MCID in all three outcomes as compared to those in C3-mild (OR = 1.72, 95% confidence interval [95% CI] = 1.2 - 2.49, p = 0.0035 and OR = 4.57, 95% CI = 2.68 - 7.91, p < 0.0001 respectively). CONCLUSIONS: Clustering analysis can identify subpopulations of individuals recovering from ECOPD associated with different responses to PR. Our results may help in defining priority criteria based on the probability of success of PR.

Prevalence of exercise-induced oxygen desaturation after recovery from SARS-CoV-2 pneumonia and use of lung ultrasound to predict need for pulmonary rehabilitation.

BACKGROUND: Persistence of breathlessness after recovery from SARS-CoV-2 pneumonia is frequent. Recovery from acute respiratory failure (ARF) is usually determined by normalized arterial blood gases (ABGs), but the prevalence of persistent exercise-induced desaturation (EID) and dyspnea is still unknown. METHODS: We investigated the prevalence of EID in 70 patients with normal arterial oxygen at rest after recovery from ARF due to COVID-19 pneumonia. Patients underwent a 6-min walking test (6MWT) before discharge from hospital. We recorded dyspnea score and heart rate during 6MWT. We also investigated the possible role of lung ultrasound (LU) in predicting EID. Patients underwent a LU scan and scores for each explored area were summed to give a total LU score. RESULTS: In 30 patients (43%), oxygen desaturation was >4% during 6MWT. These patients had significantly higher dyspnea and heart rate compared to non-desaturators. LU score >8.5 was significantly able to discriminate patients with EID. CONCLUSION: In SARS-CoV-2 pneumonia, ABGs at discharge cannot predict the persistence of EID, which is frequent. LU may be useful to identify patients at risk who could benefit from a rehabilitation program.

Reliability of automatic detection of AHI during positive airway pressure treatment in obstructive sleep apnea patients: A "real-life study".

INTRODUCTION: Automatic event detection (AED) of residual apnea-hypopnea index (AHI) by ventilators is a current practice in sleep and mechanical ventilation Units but this methodology has not been validated in an unselected population of OSA patients. Aim of the present study was to assess in a "real-life" condition the reliability of AED during PAP therapy by the in-built software compared to full polysomnography during follow-up. METHODS: We enrolled 300 OSA patients (105 F; AHI 45.3 ± 27.8) already on Positive airway pressure (PAP) therapy: 53% of the patients were on CPAP while other modalities were used in the rest of the sample. RESULTS: Overall, the built-in software identified residual obstructive AHI (AHIPAP) > 5, 10 or 15 in 18.7, 8.6 or 4.6% of patients, respectively. By using AHIPAP, 28.4% of patients were wrongly classified as "well controlled" despite a residual AHIPSG>5 (6% considering a residual AHIVENT >15); 7% of patients were classified as not controlled while AHIPSG was <5 (1.4% considering a residual AHIVENT >15). Type of ventilation, ventilator parameters, adherence to treatment and level of baseline or follow-up Epworth Sleepiness Scale score were similar between groups. The sensitivity and positive predicted values were very low. Positive likelihood ratio appears adequate only for residual AHIPAP ≥10, but negative likelihood ratio was inconclusive for all the cut-off considered. DISCUSSION: The results of the present study suggest a more cautious approach in the follow-up of OSA patients, since a protocol based only on AED detection and symptoms assessment may not be accurate especially for AHIPAP<15.

Comparison of data mining techniques applied to fetal heart rate parameters for the early identification of IUGR fetuses.

The onset of fetal pathologies can be screened during pregnancy by means of Fetal Heart Rate (FHR) monitoring and analysis. Noticeable advances in understanding FHR variations were obtained in the last twenty years, thanks to the introduction of quantitative indices extracted from the FHR signal. This study searches for discriminating Normal and Intra Uterine Growth Restricted (IUGR) fetuses by applying data mining techniques to FHR parameters, obtained from recordings in a population of 122 fetuses (61 healthy and 61 IUGRs), through standard CTG non-stress test. We computed N=12 indices (N=4 related to time domain FHR analysis, N=4 to frequency domain and N=4 to non-linear analysis) and normalized them with respect to the gestational week. We compared, through a 10-fold crossvalidation procedure, 15 data mining techniques in order to select the more reliable approach for identifying IUGR fetuses. The results of this comparison highlight that two techniques (Random Forest and Logistic Regression) show the best classification accuracy and that both outperform the best single parameter in terms of mean AUROC on the test sets.

Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are associated with prolongation of the QTc interval on the electrocardiogram (ECG). The QTc-interval prolongation increases the risk of life-threatening arrhythmias. However, studies evaluating the effects of TKIs on QTc intervals are limited and only consist of small patient numbers. METHODS: In this multicentre trial in four centres in the Netherlands and Italy we screened all patients who were treated with any TKI. To evaluate the effects of TKIs on the QTc interval, we investigated ECGs before and during treatment with erlotinib, gefitinib, imatinib, lapatinib, pazopanib, sorafenib, sunitinib, or vemurafenib. RESULTS: A total of 363 patients were eligible for the analyses. At baseline measurement, QTc intervals were significantly longer in females than in males (QTcfemales=404 ms vs QTcmales=399 ms, P=0.027). A statistically significant increase was observed for the individual TKIs sunitinib, vemurafenib, sorafenib, imatinib, and erlotinib, after the start of treatment (median ΔQTc ranging from +7 to +24 ms, P<0.004). The CTCAE grade for QTc intervals significantly increased after start of treatment (P=0.0003). Especially patients who are treated with vemurafenib are at increased risk of developing a QTc of ⩾470 ms, a threshold associated with an increased risk for arrhythmias. CONCLUSIONS: These observations show that most TKIs significantly increase the QTc interval. Particularly in vemurafenib-treated patients, the incidence of patients at risk for arrhythmias is increased. Therefore, especially in case of combined risk factors, ECG monitoring in patients treated with TKIs is strongly recommended.

Association of rs2200733 at 4q25 with atrial flutter/fibrillation diseases in an Italian population.

BACKGROUND: Atrial fibrillation (AF) and atrial flutter (AFL) are common cardiac conduction disorders affecting many people. Recent studies on sporadic cases of AF/AFL showed a significant association of the single nucleotide polymorphism rs2200733T with the disease, suggesting a genetic factor in the development of the disease. OBJECTIVES: To determine the association of rs2200733 with AF/AFL derived from an Italian population sample. SUBJECTS: 78 patients with AF/AFL and 348 controls took part in the study. DESIGN: Genetic case-control study. RESULTS: The results indicate that there is a positive, significant association between the rs2200733 T allele and patients with AF/AFL of Italian origin (allelic p<0.001 with OR = 2.17). CONCLUSION: These results derived from a sample of the Italian population agree with previously reported findings from an Icelandic study, which also found that the minor allele rs2200733 was associated with AF/AFL disease.

Diagnostic value of PRND gene expression profiles in astrocytomas: relationship to tumor grades of malignancy.

Doppel (PRND) is a paralogue of the mammalian prion (PRNP) gene. It is abundant in testis and, unlike PRNP, it is expressed at low levels in the adult central nervous system (CNS). Besides, doppel overexpression correlates with some prion-disease pathological features, such as ataxia and death of cerebellar neurons. Recently, ectopic expression of doppel was found in two different tumor types, specifically in glial and haematological cancers. In order to address clinical important issues, PRND mRNA expression was investigated in a panel of 111 astrocytoma tissue samples, histologically classified according to the World Health Organization (WHO) criteria (6 grade I pilocytic astrocytomas, 15 grade II low-grade astrocytomas, 26 grade III anaplastic astrocytomas and 64 grade IV glioblastoma multiforme). Real-time PRND gene expression profiling, after normalisation with GAPDH, revealed large differences between low (WHO I and II) and high grade (III and IV) of malignancy (P<0.001). Extensive differences in PRND gene expression were also found within each grade of malignancy, suggesting that PRND mRNA quantitation might be useful to distinguish astrocytoma subtypes, and important in disease stratification and in the assessment of specific treatment strategies.