T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 ...cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Research on cardiorespiratory fitness (CRF) in relation to physical activity (PA) and fatigue after stroke is limited. Increased knowledge of interrelationships between these factors can help ...optimize rehabilitation strategies and improve health-outcomes.
We aimed to: 1) evaluate CRF, PA, and fatigue, 2) characterize patients with impaired versus non-impaired CRF, and 3) examine associations of CRF with PA and fatigue, three months after first-ever ischemic stroke.
In this cross-sectional study CRF was measured as peak oxygen uptake (VO
) by cardiopulmonary exercise testing. PA was measured using accelerometers. Fatigue was assessed with the 7-item Fatigue Severity Scale (FSS).
The sample (n=74, mean age 64±13 years, 36% women) had a mean VO
of 27.0±8.7 (86% of predicted). Fifty-one percent met the World Health Organization's recommendation of ≥150 min of moderate PA/week. Mean steps-per-day was 9316±4424 (113% of predicted). Thirty-five percent of the sample had moderate-to-high fatigue (FSS≥4), mean FSS score was 3.2±1.8. Patients with impaired CRF (VO
<80% of predicted) had higher body-fat-percent (p<0.01), less moderate-to-vigorous PA (MVPA) (p<0.01) and a trend toward higher fatigue (p=0.053) compared to the non-impaired. Backward regression analysis showed that higher CRF was associated with more MVPA (unstandardized beta 95% CI: 0.38 0.15, 0.63, p=0.002) and less fatigue (unstandardized beta 95% CI: -3.9 -6.4, -1.6, p=0.004).
Stroke patients had lower CRF compared to reference values. Impaired CRF was mainly related to overweight. Higher CRF was associated with more MVPA and less fatigue. Exercise after stroke may be especially beneficial for patients with impaired CRF.
Our study aimed to evaluate perioperative complications following our institutional pre- and intraoperative management in cleft palate repair with Robin sequence (RS).
RS patients who underwent cleft ...palate repair between 2000 and 2020 were retrospectively analysed. RS children with complete documentation and whose initial treatment involved the Tuebingen palatal plate (TPP) were included. Clinical records and operative charts were reviewed with regard to clinical characteristics as well as the neonatal and perioperative course. Results before and after adjustment of the anesthesiology protocol in 2014 were compared.
143 RS patients (41% male, 59% female) were included. Median pretherapeutic mixed-obstructive apnea index (MOAI) after birth was 9.4/hour (IQR 20.0). TPP treatment was associated with normalisation of the MOAI and adequate weight gain until surgery. At surgery, median age was 10 months (IQR 3), MOAI 0.1/h (IQR 0.5), and weight 8.7 kg (IQR 1.7). In 93% of cases (n = 133), the postoperative course was uneventful. Refinement of the anesthesiology protocol showed positive effects on the perioperative course and led to a reduction in perioperative events (10.7% vs. 2.9%). No severe perioperative complications occurred.
We recommend the adoption of TPP treatment in the therapy of RS children. Our favourable results show that early TPP treatment minimizes perioperative complications in cleft palate repair by effectively and sustainably correcting upper airway obstruction.
Highlights • Guided breathing show positive effect on perceived change of breathlessness in COPD. • Guided breathing show positive effect on breathing pattern in COPD. • All groups (i.e. breathing, ...music, relaxation) show positive improvement of COPD symptoms. • All groups may have an efficacy of self-care approaches.
The cancer-associated antigen NY-ESO-1 is expressed in a number of malignancies of different histological type. Patients with NY-ESO-1 expressing tumors have been shown to bear circulating ...autoantibodies against this antigen. In this study, we have assessed the NY-ESO-I autoantibody response in patients with lung cancer by a serum ELISA. Using a serum dilution of 1:400 we detected seroreactivity in 35 of 175 (20%) of patients. Incidence of autoantibodies was significantly higher in patients suffering from non small cell lung cancer (NSCLC, 23%) as compared to those with small cell lung cancer (SCLC, 9%). In the NSCLC group, NY-ESO-I antibody was significantly more frequent in patients with undifferentiated tumors (40%) as compared to patients with either adenocarcinoma or squamous cell carcinoma (15 and 29%). Our observations indicate that induction of NY-ESO-I autoantibodies depends on the histological subtype within a given tumor entity.
T-cell responses towards tuberculin (purified protein derivative; PPD) or the Mycobacterium tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein-10 ...are indicative of prior contact with mycobacterial antigens. In this study, we investigated the exceptional case of a 75-yr-old patient who devoted more than one-third of his CD4 T-cells against PPD and ESAT-6. Antigen-specific T-cells were characterised using flow cytometric intracellular cytokine staining, ELISPOT assay, proliferation assays, and T-cell receptor spectratyping. T-cell frequencies were far above those found in age-matched controls (median 0.33%, range 0.05-6.32%) and remained at high levels for >2 yrs. The patient initially presented with haemoptysis, but active tuberculosis was ruled out by repeated analysis of sputum and bronchoalveolar lavage fluid. Skin testing was negative and haemoptyses did not have a M. tuberculosis-related aetiology. Phenotypical and functional properties of specific T-cells were consistent with a terminally differentiated effector-memory phenotype with capacity to produce interferon-γ, interleukin-2 and tumour necrosis factor-α. Epitope mapping showed that the CD4 T-cells were directed against a single peptide from ESAT-6 (amino acid 5-20) that was presented in context of HLA-DR. T-cell receptor Vβ-spectratyping and sequencing of specific CD4 T-cells revealed a prominent peak fraction of monoclonal origin. In conclusion, similar to monoclonal gammopathies of undetermined significance, this may represent the first T-cell counterpart with known specificity against M. tuberculosis.
Multidrug-resistant/Rifampicin-resistant tuberculosis (TB) is a major obstacle to successful TB control. The recommendation by the World Health Organization to use bedaquiline, pretomanid, linezolid ...and moxifloxacin (BPaL(M)) for 6 months, based on results of three trials with high efficacy and low toxicity, has revolutionized treatment options.
In this study, representatives of the Tuberculosis Network European Trialsgroup (TBnet) in 44/54 countries of the WHO Europe region document the availability of the medicines and drug susceptibility testing (DST) of the BPaL(M) regimen through a structured questionnaire between September to November 2023.
24/44 (54.5%), 42/44 (95.5%), 43/44 (97.7%), and 43/44 (97.7%) had access to pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, 23/44 (52.3%) had access to all the drugs composing the BPaL(M) regimen. 7/44 (15.9%), 28/44 (63.6%), 34/44 (77.3%) and 36/44 (81.8%) had access to DST for pretomanid, bedaquiline, linezolid and moxifloxacin, respectively. DST was available for all medicines composing the BPaL(M) regimen in 6/44 (13.6%) countries.
Only in about half of the countries participating in the survey clinicians have access to all the BPaL(M) regimen drugs. In less than a fifth of countries, a complete DST is possible. Rapid scale up of DST capacity to prevent unnoticed spread of drug resistance and equal access to new regimens are urgently needed in Europe.
Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients.
Identification of latent Mycobacterium tuberculosis infection in hemodialysis ...patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)–specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection.
One hundred and twenty-seven hemodialysis patients and 218 control patients (blood donors, health care workers, and control patients) were analyzed. Specific T cells toward PPD and early secretory antigenic target-6 (ESAT-6), a protein expressed in Mycobacterium tuberculosis but absent from M. bovis bacillus Calmette-Guerin (BCG) vaccine strains, were flow cytometrically quantified from whole blood, and results were compared with skin testing.
Compared to blood donors, a high proportion of both health care workers (48.6%) and hemodialysis patients (53.5%) had PPD-specific Th1-type CD4 T-cell reactivity with similar median frequencies of PPD-specific T cells (0.17%; 0.06–3.75% vs. 0.26%; 0.06–4.12%, respectively). In contrast, skin test reactivity was significantly reduced in hemodialysis patients. Whereas 85.7% of control patients with PPD reactivity in vitro were skin test–positive, the respective percentage among hemodialysis patients was 51.4% (P = 0.007). Among individuals with PPD reactivity in vitro, ∼50% had T cells specific for ESAT-6.
Unlike the skin test, measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was unaffected by uremia-associated immunosuppression. This whole-blood assay may thus be a valuable alternative to skin testing, and detection of ESAT-6–specific T cells could moreover allow distinction of latent M. tuberculosis infection from BCG-induced reactivity to PPD. The assay is well suited for clinical use and may facilitate targeting of preventative therapy in high-risk individuals.
Field experiments over a 3 y period were conducted in a winter wheat‐maize double‐cropping system at the Dongbeiwang Experimental Station, Beijing, China. Three different treatments of irrigation ...(sprinkler “suboptimal” and “optimized”; conventional flood irrigation) and N fertilization (none, according to Nmin soil tests, conventional) were studied with respect to effects on soil water balance, nitrate leaching, and grain yield. Under sprinkler irrigation, evaporation losses were higher due to a more frequent water application. On the other hand, in this treatment nitrate leaching was smaller as compared to flood irrigation, where abundant seepage fluxes >10 mm d–1 along preferential flow paths occurred. For quantifying nitrate leaching, passive samplers filled with ion‐exchange resins appeared to be better suited than a method which combined measurements of suction‐cup concentrations with model‐based soil water fluxes. As a result of the more balanced percolation regime (compared to that under conventional flood irrigation), there was a tendency of higher salt load of the soil solution in the rooting zone. Given a seepage rate of 50 mm, a winter wheat grain production of 5–6 t ha–1 required a total water addition of about 430 mm. Fertilizer treatments >100 kg N ha–1 did not result in any additional yield increase. An even balance between withdrawing and recharge of groundwater cannot be achieved with “optimized” irrigation, but with a reduction of evapotranspiration losses, adapted cropping systems, and/or by tapping water resources from reservoirs in more distant areas with surpluses.
Bodenwasserhaushalt und Nitratauswaschung in Winterweizen‐Sommermais‐Anbausystemen mit unterschiedlicher Bewässerung und N‐Düngung in der nordchinesischen Tiefebene
Feldexperimente mit einer Winterweizen‐Sommermais‐Doppelfruchtfolge erfolgten über einen dreijährigen Zeitraum auf dem Versuchsfeld Dongbeiwang bei Peking, China. Untersucht wurde die Auswirkung von je drei Varianten der Bewässerung (Sprinkler “suboptimal“ und “optimiert“ sowie konventionelle Überstaubewässerung) und der N‐Düngung (ohne, basierend auf Nmin‐Bodenuntersuchungen, konventionell) auf Bodenwasserhaushalt, Nitratauswaschung und Kornertrag. Bei Sprinklerbewässerung entstanden durch die häufigere Wasserzufuhr größere Evaporationsverluste. Andererseits war hier die Nitratauswaschung deutlich geringer als bei Überstaubewässerung, bei der häufig Sickerwasserströme von >10 mm d–1 entlang präferenzieller Fließwege auftraten. Zur Erfassung der N‐Auswaschung erwiesen sich Ionenaustauscher‐Passivsammler als besser geeignet als die Kombination von Saugkerzenlösungen und modellberechneten Sickerraten. Unter dem bei Beregnung im Vergleich zur Überstaubewässerung ausgeglicheneren Sickerungsregime ergaben sich Hinweise auf eine Salzanreicherung im Wurzelraum. Die Erzeugung von 5–6 t ha–1 Winterweizenkornertrag erfordert bei 50 mm Sickerung eine Gesamtwasserzufuhr von ca. 430 mm. Düngergaben >100 kg N ha–1 führten zu keiner weiteren Ertragssteigerung. Eine ausgeglichene Bilanz zwischen Neubildung und Entnahme von Grundwasser ist nicht mit “optimierter“ Bewässerung, sondern nur über eine Reduzierung der Verdunstungsverluste, angepasste Fruchtfolgen und/oder Wasserzufuhr aus weiter entfernten Gebieten mit Wasserüberschuss zu erreichen.
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