Clinical and prognostic implications of CD47 and PD-L1 expression in surgically resected small-cell lung cancer.

BACKGROUND: Pharmacological inhibition of the immune-checkpoint molecule CD47 has shown promising results in preclinical small-cell lung cancer (SCLC) models, whereas anti-programmed death-ligand 1 (PD-L1) inhibitors have been recently implemented in the standard of care of advanced-stage SCLC patients. Nevertheless, the expression pattern, clinical relevance and prognostic implication of both CD47 and PD-L1 are rather controversial in surgically treated SCLC patients. MATERIALS AND METHODS: In total, 104 Caucasian SCLC patients from two Central European thoracic centers were included in this study. CD47 and PD-L1 expression as well as the expression of the four major SCLC molecular subtype markers (ASCL1, NEUROD1, YAP1 and POU2F3) were measured by immunohistochemistry. Expression levels were independently evaluated and statistically correlated with clinicopathological data and survival. RESULTS: Positive CD47 and PD-L1 expressions were seen in 84.6% and 9.6% of the samples, respectively. Meanwhile, the tumor-associated stroma was positive for PD-L1 in 59.6% of the cases. Stromal PD-L1 expression correlated with longer overall survival (OS) (versus PD-L1-negative stroma; median OS was 42 versus 14 months, respectively, P = 0.003) and was confirmed as an independent predictor of favorable outcome upon multivariate analysis (hazard ratio 0.530, 95% confidence interval 0.298-0.943, P = 0.031). Notably, neither CD47 nor PD-L1 presence was related to a distinct molecular SCLC subtype. CONCLUSION: CD47 shows a remarkably high expression while tumoral PD-L1 expression is generally low in surgically treated SCLC. Importantly, stromal PD-L1 expression may indicate a favorable clinical outcome and serve as a novel prognostic factor in these patients. Additional studies are warranted to further investigate the clinical impact of CD47 and PD-L1 expression in SCLC.

First Report of Asiatic Brown Rot Caused by Monilinia polystroma on Peach in Italy.

Monilinia spp. are well-known pathogens causing brown rot of fruit trees in many fruit production areas worldwide. In Italy, three Monilinia species are particularly significant with regard to fruit trees, causing blossom and twig blight and brown rot in fruits: Monilinia laxa (Aderhold and Ruhland) Honey, M. fructicola (Winter) Honey, and M. fructigena (Aderhold and Ruhland). In 2009, a new species, M. polystroma, was distinguished from M. fructigena based on morphological and molecular characteristics in Europe (3). M. polystroma is not known to occur in Italy and to date has been reported from the Czech Republic (1), Hungary (3), Poland (4), Serbia (5), and Switzerland (2). In July 2013, during a survey for fungal postharvest pathogens, stored peaches (Prunus persica (L.) Batsch) belonging to different cultivars showing brown rot symptoms were observed in the Emilia Romagna and Sardinia regions of Italy. Typical decay spots were circular and brown, tending toward black, and 5% of peaches presented a large number of yellowish or buff-colored stromata and firm decayed tissues, the symptoms originated by M. polystroma. The pathogen was isolated on V8 agar (V8A) and culture plates were incubated at 25°C in darkness for 5 days. A conidial suspension was spread on malt extract agar (MEA) and single spores were selected. M. polystroma colonies grown on potato dexstrose agar (PDA) were yellowish in color. Irregular black stromatal crusts occurred on the edges of the colonies after 10 to 12 days of incubation and on the margin was present sporogenous tissue slightly elevated above the colony surface, color buff/pale luteous (1). The conidia were one-celled, ovoid or limoniform, smooth and hyaline, and 12 to 20 × 8 to 12 µm in distilled water when grown on V8A at 22°C. The ribosomal ITS1-5.8S-ITS2 region was PCR-amplified from genomic DNA obtained from mycelium using primers ITS1 and ITS4. A BLAST search in GenBank revealed the highest similarity (99%) to M. polystroma sequences (GenBank Accession No. GU067539). Pathogenicity was confirmed using surface-sterilized mature 'Red Heaven' peaches. The fruits were wounded (2 × 2 × 2 mm) twice with a sterile needle and inoculated with 2-mm plugs of 7-day-old mycelia from fungal colony margins. The sample unit was represented by 10 fruits. Control fruits were inoculated with PDA. After 7 days of incubation at 20°C in plastic containers with high humidity, typical symptoms of brown rot developed on both the wounds of all inoculated fruits, while control fruits remained symptomless. By the 14th day, all fruits had rotted and the yellowish exogenous stromata appeared on the surface of infected peaches. The fungus isolated from inoculated fruit exhibited the same morphological and molecular features of the original isolates; the molecular analysis performed using the primers by Petroczy (3) confirmed the result of the PCR with ITS1 and ITS4 primers. To our knowledge, this is the first report of M. polystroma on peach in Italy. This is relevant because the new pathogen could spread into other European countries that are main peach producers (such as Spain), causing economic losses. Bringing it to the attention of the scientific community allows the arrangement of research studies for assessing potential resistances with a significant impact on disease control management. Further studies are necessary to determine geographic distribution, prevalence, and economic importance of this organism in Italy. References: (1) EPPO Reporting Service. 2011/134: First reports of Monilinia polystroma in Hungary and the Czech Republic. No. 6, 2011. (2) M. Hilber-Bodmer et al. Plant Dis. 96:146, 2012. (3) M. Petroczy and L. Palkovics. Eur. J. Plant Pathol. 125:343, 2009. (4) A. Poniatowska et al. Eur. J. Plant Pathol. 135:855, 2013. (5) M. Vasic et al. Plant Dis. 97:145, 2013.

[Rehabilitation of anoxic brain injured patients after reanimation]. / Az anoxiás agykárosodást szenvedett betegek rehabilitációja reanimáció után.

Authors report rehabilitation outcomes of anoxic brain injured patients, following reanimation. In the past 12 years (1988-1999) they treated 54 patients. The patients were selected from other hospitals after successful reanimation, but sustained diffuse anoxic brain injury. The CT and MR examination was generally negative, but small hypodensities were shown rarely (18/54). At the time of admission 21 patients were quadriparetic, 5 patients were hemiparetic, 2 were paraparetic and there were no any paresis in 26 cases. The mean age of the patients was 32 years (7-61). At the time of admission 31 patients were dependent in basic activities of daily living, the mean Barthel Index score was 15 (0-100) but at the time of discharge it was 45 (0-100). 41 patients were discharged into their home and 13 patients had to be transmitted to another hospital for further treating, but later 5 of them died. At the time of discharge only 7 patients had score 100 of the Barthel Index, but they were not able for independent living. Family support, mainly guidance was necessary. Memory deficits, apraxia, attention disturbance, ataxia were the main problems during the rehabilitation process.

Comparison of recoveries of mycobacterium tuberculosis using the automated BACTEC MGIT 960 system, the BACTEC 460 TB system, and Löwenstein-Jensen medium.

Using two different liquid media and one conventional solid medium, a total of 57 mycobacterial isolates (Mycobacterium tuberculosis, n = 55; nontuberculous mycobacteria, n = 2) were recovered from 377 clinical specimens. The rates of recovery of M. tuberculosis were 96. 4% with the BACTEC MGIT 960 liquid medium, 92.7% with BACTEC 12B liquid medium, and 81.8% with the Löwenstein-Jensen (LJ) medium. The mean time to detection of M. tuberculosis in smear-positive specimens was 12.6 days for BACTEC MGIT 960 medium, 13.8 days for BACTEC 12B medium, and 20.1 days for LJ medium, and in smear-negative specimens it was 15.8 days for BACTEC MGIT 960 medium, 17.7 days for BACTEC 12B medium, and 42.2 days for LJ medium. The rates of contamination were 3.7, 2.9, and 1.2% for the BACTEC MGIT 960, BACTEC 12B, and LJ media, respectively. In conclusion, the nonradiometric, fully automated 7-ml BACTEC MGIT 960 system can be considered a viable alternative to the semiautomated, radiometric BACTEC 460 TB system.

[Transbronchial biopsy in diffuse infiltrative lung diseases]. / Transbronchialis biopszia diffúz infiltratív tüdóbetegségekben.

224 transbronchial biopsies were made between 1990 and 1997 in 208 patients suffering diffuse, bilateral, disseminated pulmonary diseases with unidentified origin. The examinations were carried out by flexible bronchoscope with X-ray control after local anaesthesia. The obtained patterns yielded mucous membrane in 15, intact alveoli in 19 percent. In 25 percent of biopsies (57 cases) definitive diagnosis were verifiable. The histological examinations verified the diagnosis of sarcoidosis, hemosiderosis, TB, malignancies, eosinophil pneumonitis etc. In 71 biopsies (62 cases) according to histological opinion were pulmonary fibrosis or some synonyms of these (alveolitis, interstitial fibrosis). From these latter cases the documentation of 18 patients were insufficient, but the data of 44 cases were available. 7/44 carcinosis, 3/44 inactive TB, 8/44 regressive X-ray patterns were verifiable in this group. The idiopathic pulmonary fibrosis as final diagnosis only in 18/44 (41%) cases were established. Further diagnostic procedures are needed if the clinical data, the results of HRCT and histological examinations are not in correlation.

Baclofen, a gamma-aminobutyric acid B agonist, modifies hormonal secretion in pituitary cells from infantile female rats.

Recent work from our laboratory has demonstrated that the activation of GABA B adenohypophyseal receptors by baclofen inhibits pituitary hormone secretion under basal (PRL) or stimulated conditions (PRL and LH) in adult female rats, suggesting a hypophyseal site of action in addition to the central site previously described. Since different patterns of hormone secretion are observed in infantile and adult rats, the purpose of the present study was to determine whether GABA B pituitary receptors were involved in endocrine responses at early stages of development. Pituitary cells of 12 day-old female rats were cultured in vitro and the effect of baclofen was determined in the presence or absence of stimulatory factors. Baclofen (1.10(-9), 1.10(-7) and 1.10(-5) M) did not alter basal LH or FSH secretion but significantly inhibited the LHRH induced gonadotropins release after 30 or 60 minutes of incubation (after 60 minutes of incubation LH (%): control: 100 +/- 5.6; BACL(1.10(-7)): 134.5 +/- 25.8; LHRH(1.10(-7)): 596.7 +/- 85.9; LHRH(1.10(-7))-BACL(1.10(-7)): 374.7 +/- 48.0; p<0.01. FSH (%): control: 100 +/- 6.5; BACL(1.10(-7): 103.7 +/- 6.5; LHRH(1.10(-7)): 283.9 +/- 29.3; LHRH(1.10(-7))-BACL(1.10(-7): 183.0 +/- 20.0; p<0.01). Baclofen did not significantly modify either basal or TRH-stimulated PRL or TSH secretion. These results show that baclofen has direct effects on the of adenohypophyseal cells of immature rats and such effects are different from those observed in adult rats, and depend on the stage of development of the neuroendocrine controls of each cellular type.

In vitro complement activation by ragweed allergen extract in the sera of ragweed allergic and non-allergic persons.

Ragweed allergen (RWA)-induced complement activation in sera of 40 RW allergic patients and of 40 non-allergic controls was investigated. After treatment of the sera with RWA, levels of C3a, C5a, C3bBbP, C1rC1sClinh, SC5b-9 and granulocyte-aggregating activity were determined. Concentration of RW-specific IgG was also measured. After RWA treatment dose-dependent complement activation was detected in sera of RW allergic and non-allergic persons. C3a generation was observed mostly in the sera of RW allergic individuals, while levels of C3bBbP and of RW-specific IgG were significantly higher in sera of allergics, and a strong correlation was found between these two parameters. In a prospective clinical study, a significant positive correlation was observed between the extent of RWA-induced alternative pathway (AP) activation and the severity of symptoms of allergic rhinoconjunctivitis that were developed in a 4-week period subsequent to blood sampling. These observations suggest that complement activation has a role in the development of the symptoms of RW allergy.

[Non-malignant cells in pleural fluid]. / A pleurafolyadék-punctatum nem malignus eredetü sejtjei.

Insufficient attention has been paid to the cytological examination of cellular elements of the pleural fluid besides or in the absence of tumour cells. 108 cases studied due to pleural fluid were selected. They were characterized by the following: 1. each had histological diagnosis established by either pleuroscopy or by pleural needle biopsy and 2. neither of the samples contained tumour cells. Relationship of the dominant cell type and the ethiology of the pleural fluid was analysed. In case of punctates rich in lymphocytes further cytopathological differentiation is possible, e.g. in case of tuberculotic origin the absence of large mesothelial cells with Giemsa-basophilic cytoplasm is rather characteristic. The use of bioptic methods in the clarification of the origin of pleural fluid is still indispensible.

Longitudinal lung function study in heterozygous PiMZ phenotype subjects.

It is a matter of controversy whether subjects who are heterozygous (PiMZ) for alpha 1-antitrypsin deficiency are at risk of developing pulmonary emphysema. To assess the role of MZ phenotype in the development of abnormal lung function the authors performed a 10 year follow-up study of 28 PiMZ subjects, compared to 28 matched-paired normal PiMM subjects. Maximal expiratory flows and mechanical properties of the lungs were studied, in order to determine the changes of the lung function parameters characteristic of pulmonary emphysema. Total lung capacity and residual volume increased, whereas forced expiratory volume in one second, expiratory flows, diffusing capacity of the lungs for carbon monoxide, and static transpulmonary pressures decreased in the PiMZ patients. The majority of the controlled functional parameters were found to deteriorate significantly in PiMZ patients during the 10 year period. Trypsin inhibitory capacity in the PiMZ group (mean +/- SD) was 0.65 +/- 0.17 mg.ml-1 as compared to 1.52 +/- 0.3 mg.ml-1 in the PiMM group. These changes exceeded the values expected as physiological changes due to ageing. The findings in the present longitudinal study--especially the decrease in elasticity, which is the primary pathophysiological damage in alpha 1-antitrypsin deficiency--support the concept that the PiMZ phenotype is a risk factor for the development of pulmonary emphysema at younger age than in those without the deficiency.

[Needle biopsy of the pleura]. / A pleura tübiopsziája.

A total of 171 pleural needle biopsies were carried out in 123 patients with pleural effusion. The sensitivity of the method proved to be 51% for malignant diseases and 75% for tuberculotic pleurisy, respectively. Performing biopsy simultaneously with the cytological examination of the pleural fluid, malignancy was proved only by needle biopsy in 20% of the patients, while cytology was found negative in these cases. Simultaneously performed thoracocentesis and pleural needle biopsy is suggested.

[Late post-tracheostomy airway complications in patients with central nervous system injuries]. / Központi idegrendszeri sérültek késöi posttracheostomiás légúti szövödményei.

At decannulation or often weeks later some of the patients undergone long-term mechanical ventilation through tracheostoma reveal symptoms of airway stenosis. Posttracheostomy airway complications detected during the rehabilitation of 34 patients with central nervous system injury are presented. Endoscopic examinations (total 130) were performed with Olympus BF B3 and OES 20-type fiberscopes and Friedel-type rigid bronchoscopes under local or general anaesthesia. Stridor (20 cases) and possible decannulation (10 cases) were the main indications of the first endoscopic examinations. Stridor was caused by tracheal (12 cases) and laryngeal (8 cases) stenosis. With six patients decannulation was possible after the first endoscopy. Removal of granulomas and sutures was successful in 8 cases. Rigid bronchoscopic dilatations were temporarily successful in 7 cases, but in five of them it had to be repeated on emergency. Further therapeutic interventions were: recannulation (3 cases), retracheostomy (4 cases), implantation of silicon T-endoprothesis (5 cases), tracheal resection (4 cases). Three patients are discussed in details. Eliminating airway complications largely contributed to rehabilitation of the nervous and musculoskeletal system, improved the quality of life, and in acute cases it was a life-saving measure. In order to prevent the development of late airway complications or detect them in time, it is recommended to have an endoscopic protocol following every tracheostomy: 1. at the time of decannulation 2. at closing the trachea and 3. 2-3 months after decannulation.

Use of Taleum 1-mg inhalation aerosol in bronchial asthma patients.

The effect of 2 sodium chromoglycate products: Taleum 1-mg aerosol (EGIS) and Intal powder capsule (Fisons) has been examined for 4-4 weeks in 15 extrinsic asthma patients by cross-over self-controlled open method. The patients measured peak expiratory flow (PEF) 5 times daily and recorded the time of dyspneic periods in a diary as well as the amount of bronchodilator spray (Berodual, Boehringer) used as adjuvant therapy during dyspnea. The results of the weekly evaluation of the complaints and PEF values proved that both drugs are similarly effective in the prevention of dyspnea caused by bronchial asthma. The adjuvant inhalation betamimetic and anticholinergic drug requirement was lowered, the number, intensity and total time of dyspneic episodes decreased. In the course of the examinations Taleum 1-mg inhalation aerosol proved to be of identical value with Intal powder capsule. Some patients who do not like powder inhalation found the Taleum aerosol drug form to be more advantageous. Side-effect of drug was not observed.

[Cobalt-induced asthma in workers exposed to hard metal dust]. / Kobalt asthma keményfém porkohászati üzemben.

A case of 39 years old woman with asthma bronchiale associated with cobalt exposure is reported. Specific bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible. The relevant literature data are reviewed.

[Current methods in the diagnosis of adult-age cystic fibrosis]. / Korszerü vizsgálóeljárások alkalmazása felnöttkori cysticus fibrosisban.

An 19 year old male patient with cystic fibrosis is reported. The clinical, pathogenetic, anatomical features and literature data are reviewed. Attention is called to recent diagnostic facilities.

[Five-year follow-up pulmonary function studies in patients with anti-trypsin deficient pulmonary emphysema]. / Otéves tüdöfunkciós utánvizsgálatok részleges antitripszinhiányos pulmonális emphysemás betegeken.

Five-year follow-up study was carried out in pulmonary emphysematous patients with intermediate antitrypsin deficiency. The examinations showed no deterioration in the clinical state of the patients but in some parts of the controlled functional parameters a statistically significant worsening was found in this period of study.

Loderix (setastine) tablets in the treatment of allergic rhinoconjunctivitis.

The effect of a 3-week treatment with Loderix is examined in an open study in 40 patients suffering from allergic rhinoconjunctivitis. Side-effects, mainly sleepiness, fatigue, weakness, were observed in nearly half of the patients. These were, in general, mild and of a transient character. Treatment had to be stopped in 2 patients due to developed adverse effects. Safety parameters as blood picture, liver function tests, renal function parameters showed no alterations during the study course. During the treatment periods rhinoconjunctivitis symptoms disappeared or significantly decreased in 22 patients out of 40. Moderate effect was registered in 14 patients, and treatment was ineffective in 4 cases. In 6 patients the doses were doubled from the 2nd week of treatment causing an increase in effectivity without a change in side-effect profile.

Hyperaldosteronism in the sodium depleted rat: effect of a low sodium diet or diuretic treatment on steroid output by the superfused adrenal zona glomerulosa.

The effect of chronic and acute sodium depletion on the function of the adrenal zona glomerulosa was examined by means of superfusion of adrenal capsular glands. The glands were removed from rats kept on a low sodium diet for 7 days or from dexamethasone-pretreated rats 30 min after administration of the diuretic drug furosemide. Chronic sodium depletion brought about a high initial output of aldosterone followed by a rapid fall in output. The initial rate of corticosterone output did not differ significantly from that by control glands but exhibited a more rapid decline with time. Aldosterone: corticosterone ratio, an indicator of the rate of conversion of corticosterone to aldosterone, was much higher in the sodium depleted group throughout the whole superfusion period. Acute sodium depletion was followed by high initial and rapidly falling aldosterone and corticosterone output, without any significant change in the ratio of aldosterone to corticosterone output rate. The above dynamic patterns of steroid output indicate that a sodium deficient diet evokes hyperaldosteronism by increasing the formation of aldosterone from corticosterone (not excluding the possibility of increasing the formation of corticosterone as well) while diuretic treatment stimulates aldosterone secretion by acting on the formation of corticosterone only.