Polysomnography in stable COPD under non-invasive ventilation to reduce patient-ventilator asynchrony and morning breathlessness

Background: Stable severe chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure treated by nocturnal bi-level positive pressure non-invasive ventilation (NIV) may experience severe morning deventilation dyspnea. We hypothesised that in these patients, progressive hyperinflation, resulting from inappropriate ventilator settings, leads to patient-ventilator asynchrony (PVA) with a high rate of unrewarded inspiratory efforts and morning discomfort. Methods: Polysomnography (PSG), diaphragm electromyogram and transcutaneous capnography (PtcCO2) under NIV during two consecutive nights using baseline ventilator settings on the first night, then, during the second night, adjustment of ventilator parameters under PSG with assessment of impact of settings changes on sleep, patient-ventilator synchronisation, morning arterial blood gases and morning dyspnea. Results: Eight patients (61 ± 8years, FEV1 30 ± 8% predicted, residual volume 210 ± 30% predicted) were included. In all patients, pressure support was decreased during setting adjustments, as well as tidal volume, while respiratory rate increased without any deleterious effect on nocturnal PtcCO2 or morning PaCO2. PVA index, initially high (40 ± 30%) during the baseline night, decreased significantly after adjusting ventilator settings (p = 0.0009), as well as subjective perception of PVA leaks, and morning dyspnea while quality of sleep improved. Conclusion: The subgroup of COPD patients treated by home NIV, who present marked deventilation dyspnea and unrewarded efforts may benefit from adjustment of ventilator settings under PSG or polygraph

Inflammatory Syndrome as the Initial Manifestation of Retroperitoneal Tuberculosis in a Pregnant Woman

A 20-year-old asylum seeker presented with vomiting and left thigh pain, with a biological inflammatory syndrome. Pregnancy was diagnosed. Investigations revealed a pseudo-cystic, 20-cm-long retroperitoneal abscess, biopsy of which confirmed the diagnosis of tuberculosis. Evolution after cyst drainage and under conventional anti-tuberculosis treatment was favourable. An abdominal location of tuberculosis is rare and its diagnosis is difficult especially in countries with a low incidence of the disease. Unexplained abdominal manifestations and/or persistent biological inflammatory syndrome, especially in high-risk groups, should raise the suspicion of tuberculosis

Tuberculous Cutaneous Ulcers Associated with Miliary Tuberculosis in an Elderly Woman

Skin localizations in disseminated tuberculosis may present a clinical resistant evolution. An 81-year-old woman, treated by long-term steroids and methotrexate for rheumatoid polyarthritis, developed a disseminated tuberculosis in chest, bones and skin. While pulmonary symptoms quickly improved under conventional tuberculostatic drugs, skin ulcers showed positive cultures for 5 months and healed after 12 months of treatment

Recollection of participating in a trial: A qualitative study of patients with severe and very severe chronic obstructive pulmonary disease

<div><p>Background</p><p>Despite having similar palliative needs to patients with lung cancer, advanced chronic obstructive pulmonary disease (COPD) patients are less likely to receive palliative care. To evaluate the effect of introducing specialized palliative care with severe to very severe COPD patients, a randomized controlled trial (RCT) was conducted in Switzerland.</p><p>Aim</p><p>To explore COPD patients’ recollection of the trial, their needs and the usefulness of the palliative care interventions.</p><p>Design and setting</p><p>Qualitative study with advanced COPD patients who participated in a specialized palliative care intervention, conducted in a general hospital.</p><p>Method</p><p>Eighteen patients with severe to very severe COPD were interviewed about their experiences. Interviews were transcribed and thematic content analysis was performed.</p><p>Results</p><p>Patients had poor recollection of the trial and difficulties understanding the palliative care intervention. No major differences were observed between patients who received the specialized intervention and those who did not. Content analysis emphasized that although they experienced disabling symptoms, participants tended to attribute their limitations to problems other than COPD and some declared that they were not sick. Patients reported restrictions due to oxygen therapy, and the burden of becoming dependent on it. This dependence resulted in intense anxiety, leading participants to focus on the present only. A strong feeling of perceived helplessness emerged from the patients’ interviews.</p><p>Conclusions</p><p>Our findings suggest that poor recollection and understanding of the palliative care intervention act as barriers to the conduct of clinical trials with severe and very severe COPD patients. Their cognitive difficulties, perception of COPD, functional limitations, overwhelming anxiety, focus on the present and perceived helplessness also seem to hinder the implementation of such care.</p></div

Interferon-gamma release assays versus tuberculin skin testing for detection of latent tuberculosis in chronic haemodialysis patients

Background. End stage renal disease increases the risk of reactivating latent tuberculosis (LTBI). Interferon-γ release assays (IGRA) are an alternative to the tuberculin skin test (TST) for detecting LTBI. Methods. Sixty-two hemodialysis patients (46 male, 16 female, aged 65 ± 15 years) from 3 hemodialysis facilities in the Geneva area were submitted to a TST, 2 IGRA (T-SPOT.TB and QuantiFERON Gold in tube: QFT), a chest radiography, and a questionnaire to record social status, country of birth, history of prior TST, tuberculosis (TB), BCG (Bacillus of Calmette-Guérin vaccine), and any cause of immuno-suppression. LTBI was defined as prior "at risk” contact with a case of contagious TB and/or a chest X-ray suggestive of prior TB infection. Results. Positivity rate was 19% for TST, 21% for QFT and 29% for T-SPOT-TB; 8% of QFT and 11% of T-SPOT-TB were indeterminate. Agreement between IGRA was fair (κ= 0.60). After adjusting for age and BCG, OR (Odds Ratio) of having a positive QFT was 4.6-fold (p = 0.029) higher in patients with LTBI vs. those without LTBI. In contrast, no association was found between LTBI and having a positive T-SPOT.TB or a positive TST. As expected, there was a strong association between prior BCG vaccination and having a positive TST (OR 5.3, p = 0.017). QFT was the only test with a significant OR of having LTBI (adjusted OR: 4.4; 95%CI: 1.1 − 17.6; p = 0.034). Among 5 patients with definite prior TB, TST and T-SPOT.TB were positive in 1 and QFT, in 2. Conclusions. In this population, QFT was superior to TST for detecting LTBI, but both IGRAs and TST have important limitations, and are unreliable for screening for LTB

Dominant-Negative Tumor Necrosis Factor Protects from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and Endotoxin-Induced Liver Injury without Compromising Host Immunity to BCG and Mycobacterium tuberculosis

BackgroundTumor necrosis factor (TNF) is associated with the development of inflammatory pathologies. Antibodies and soluble TNF (solTNF) receptors that neutralize excessive TNF are effective therapies for inflammatory and autoimmune diseases. However, clinical use of TNF inhibitors is associated with an increased risk of infections MethodsA novel dominant-negative (DN) strategy of selective TNF neutralization, consisting of blocking solTNF while sparing transmembrane TNF (tmTNF), was tested in mouse models of mycobacterial infection and acute liver inflammation. XENP1595, a DN-TNF biologic, was compared with etanercept, a TNF receptor 2 (TNFR2)-IgG1 Fc fusion protein that inhibits murine solTNF and tmTNF ResultsXENP1595 protected mice from acute liver inflammation induced by endotoxin challenge in Mycobacterium bovis bacillus Calmette-Guérin (BCG)-infected mice, but, in contrast to etanercept, it did not compromise host immunity to acute M. bovis BCG and Mycobacterium tuberculosis infections in terms of bacterial burden, granuloma formation, and innate immune responses ConclusionsA selective inhibitor of solTNF efficiently protected mice from acute liver inflammation yet maintained immunity to mycobacterial infections. In contrast, nonselective inhibition of solTNF and tmTNF suppressed immunity to M. bovis BCG and M. tuberculosis. Therefore, selective inhibition of solTNF by DN-TNF biologics may represent a new therapeutic strategy for the treatment of inflammatory diseases without compromising host immunit

Repeatability, and Intra-Observer and Interobserver Agreement of Two Dimensional Perfusion Angiography in Patients with Chronic Limb Threatening Ischaemia

Objective. Two dimensional (2D) perfusion angiography is a method that provides quantitative foot perfusion information from standard digital subtraction angiography acquisitions. The aim of this study was to test the reliability of this method in patients with chronic limb threatening ischaemia (CLTI) by investigating repeatability, and intra-observer and interobserver agreement. Methods: Twenty patients with CLTI and a below the knee endovascular revascularisation were included in a prospective clinical study. Prior to treatment two perfusion angiography runs were acquired with a five minute interval without performing an intervention. In these recordings, regions of interest were selected and time density curves and perfusion parameters were determined. To investigate intra-observer agreement one observer performed five measurements on the same acquisition for each patient. To investigate interobserver agreement three observers performed measurements on the same acquisition for each patient. Results were presented in Bland-Altman plots and as the intraclass correlation coefficient per parameter. Results: Two patients were excluded from repeatability analyses because of major motion artefacts. Repeatability analyses of the 18 remaining patients showed excellent correlation for every parameter (> .96). Intra-observer and interobserver agreement for all 20 patients were excellent for all parameters (1.00). Conclusion: Repeatability and intra-observer and interobserver agreement of 2D perfusion angiography in patients with CLTI were found to be excellent. It is therefore a reliable tool when used according to the standardised methods described in this study

Few multiyear precipitation-reduction experiments find a shift in the productivity-precipitation relationship

Well-defined productivity–precipitation relationships of ecosystems are needed as benchmarks for the validation of land models used for future projections. The productivity–precipitation relationship may be studied in two ways: the spatial approach relates differences in productivity to those in precipitation among sites along a precipitation gradient (the spatial fit, with a steeper slope); the temporal approach relates interannual productivity changes to variation in precipitation within sites (the temporal fits, with flatter slopes). Precipitation–reduction experiments in natural ecosystems represent a complement to the fits, because they can reduce precipitation below the natural range and are thus well suited to study potential effects of climate drying. Here, we analyse the effects of dry treatments in eleven multiyear precipitation–manipulation experiments, focusing on changes in the temporal fit. We expected that structural changes in the dry treatments would occur in some experiments, thereby reducing the intercept of the temporal fit and displacing the productivity–precipitation relationship downward the spatial fit. The majority of experiments (72%) showed that dry treatments did not alter the temporal fit. This implies that current temporal fits are to be preferred over the spatial fit to benchmark land-model projections of productivity under future climate within the precipitation ranges covered by the experiments. Moreover, in two experiments, the intercept of the temporal fit unexpectedly increased due to mechanisms that reduced either water loss or nutrient loss. The expected decrease of the intercept was observed in only one experiment, and only when distinguishing between the late and the early phases of the experiment. This implies that we currently do not know at which precipitation–reduction level or at which experimental duration structural changes will start to alter ecosystem productivity. Our study highlights the need for experiments with multiple, including more extreme, dry treatments, to identify the precipitation boundaries within which the current temporal fits remain valid