Validation of the ALK-Brain Prognostic Index for patients with ALK-rearranged lung cancer and brain metastases.

BACKGROUND: Brain metastases (BMs) are a key challenge in the management of anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK+ NSCLC), but prognostic scores are complicated or rely on data before the era of tyrosine kinase inhibitors (TKIs). This study aimed to validate the novel ALK-Brain Prognostic Index (ALK-BPI), which was originally proposed based on 44 TKI-treated ALK+ NSCLC patients from Karolinska University Hospital, using an external clinical cohort. PATIENTS AND METHODS: TKI-treated ALK+ NSCLC patients with BM from Heidelberg (n = 82, cohort 1) were retrospectively analyzed alone and together with the original Karolinska cohort (n = 126, cohort 2). Cox regression models were used to determine the association of clinical variables and scores with overall survival (OS) after BM diagnosis (BM-related OS). RESULTS: Both cohorts showed a similar median age (58 years), roughly balanced sex distributions (52%-56% females), and Eastern Cooperative Oncology Group performance status (PS) 0-2 for most patients (87%-92%) at the time of BM development, which were present already at initial diagnosis in 36%-38% of the patients. Most patients had received next-generation ALK inhibitors (54%-63%), while 55%-56% of patients did not receive any radiotherapy. The ALK-BPI identified poor-risk patients (i.e. featuring ≥ 2/3 risk factors: PS > 2, male sex, development of BM after initial diagnosis) with a significantly shorter BM-related OS than other patients in both cohorts: 32/82 in cohort 1 with 21.3 versus 62.2 months in median [hazard ratio (HR) = 2.5, P < 0.001]; 59/126 in cohort 2 with 23.1 versus 67.2 months in median (HR = 2.6, P < 0.001). The five-parameter Lung-molGPA score did not achieve statistical significance and/or clear prognostic separation in all four groups, while the Disease-Specific Graded Prognostic Assessment score did not show consistent results. CONCLUSIONS: The ALK-BPI is a reliable tool for easy prognostic dichotomization of TKI-treated ALK+ NSCLC patients with BM in daily clinical practice, without the complexity of previous models.

Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) technique and analgesic efficacy in patients with pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN) for the treatment of abdominal pain in pancreatic cancer can be administered in three different ways, depending on the site of needle insertion: central injection (CI), bilateral injection (BI) and celiac ganglia neurolysis (CGN). This meta-analysis aimed to (1) estimate the overall efficacy of the EUS-CPN; (2) compare the efficacy of each of the three techniques; and (3) investigate demographic and disease characteristics as potential predictors of treatment response. METHODS: We searched MEDLINE and EMBASE for studies that reported the proportion of treatment responders to EUS-CPN overall, and according to the technique used. We performed a random effects meta-analysis of proportions, and meta-regression was used to estimate the association between technique and clinical characteristics on treatment response. The safety profile was reviewed through narrative synthesis. RESULTS: Overall response rate to EUS-CPN was 68% (95% CI 61%-74%) at week two and 53% (95% CI 45%-62%) at week four. There was no evidence of a significant difference in the response rates between the three techniques. Demographics and disease characteristics were not associated with treatment response. Serious complications have been reported for BI and CGN but not for CI. Moderate to high risk of bias was observed. DISCUSSION: EUS-CPN is a useful adjunct to opioids in the management of pain. There is no evidence of a difference in the efficacy among the three techniques, however, CI is the only one for which serious complications have not been reported. Future research should focus on the appropriate timing of EUS-CPN (early versus on demand) and randomised comparison to establish the comparative efficacy of each technique.

Chemical-mineralogical characterisation of coarse recycled concrete aggregate.

The construction industry is now putting greater emphasis than ever before on increasing recycling and promoting more sustainable waste management practices. In keeping with this approach, many sectors of the industry have actively sought to encourage the use of recycled concrete aggregate (RCA) as an alternative to primary aggregates in concrete production. The results of a laboratory experimental programme aimed at establishing chemical and mineralogical characteristics of coarse RCA and its likely influence on concrete performance are reported in this paper. Commercially produced coarse RCA and natural aggregates (16-4 mm size fraction) were tested. Results of X-ray fluorescence (XRF) analyses showed that original source of RCA had a negligible effect on the major elements and a comparable chemical composition between recycled and natural aggregates. X-ray diffraction (XRD) analyses results indicated the presence of calcite, portlandite and minor peaks of muscovite/illite in recycled aggregates, although they were directly proportioned to their original composition. The influence of 30%, 50%, and 100% coarse RCA on the chemical composition of equal design strength concrete has been established, and its suitability for use in a concrete application has been assessed. In this work, coarse RCA was used as a direct replacement for natural gravel in concrete production. Test results indicated that up to 30% coarse RCA had no effect on the main three oxides (SiO2, Al2O3 and CaO) of concrete, but thereafter there was a marginal decrease in SiO2 and increase in Al2O3 and CaO contents with increase in RCA content in the mix, reflecting the original constituent's composition.

A decentralized multichannel length transformation algorithm and its parallel implementation for real-time ECG monitoring.

Multichannel algorithms have been developed for more accurate analysis of electrocardiograms (ECGs). Their benefit is the ability to use the information contained in all simultaneously acquired channels. In this paper we present a multichannel version of a nonsyntactic algorithm, based on length transformation. The proposed algorithm uses a decentralized schema for combining the results derived from each individual lead, instead of a global/centralized one (a spatial vector approach). Its performance was evaluated using the CSE database and real ECGs acquired by a 12-lead cardiograph. The results are also compared with previous-single-channel and multichannel-versions of the algorithm, showing a better performance. Since a multichannel algorithm is always a time-consuming task, it is rarely used in real-time monitoring systems. Motivated by this observation, we designed a parallel implementation of the proposed algorithm and tested its ability to be used in such systems.

ECG handling on a telemedicine platform.

In this paper we present the principles of a new platform developed for handling ECG signals in a telemedicine setting. We focus on three basic services: an ECG file management system (acquisition, storage, transmission); ECG-oriented teleconferencing; and realtime transmission of ECGs over the telephone network. This work has been carried out in the context of national and EU-sponsored projects. Its main purpose was to help patients from remote or isolated areas, like small islands, with insufficient health-care services, to get appropriate and experienced medical care directly from large central hospitals. We present the design and the basic operations of the ECG handling system.

Development of thyrotropin circadian rhythm in infancy.

Normal children and adults show a similar pattern of diurnal variation of TSH secretion with lower values at 1100 h and higher around 2300 h. The purpose of this study was to investigate the age of appearance of TSH circadian rhythm. In 57 fullterm infants 0-6 months old and in 37 premature infants 1-4 weeks old TSH was measured at 1030, 1100, 1130 h and 2230, 2300, and 2330 h. No diurnal rhythm was detected in both premature and fullterm infants less than 4 weeks of life. After the first month of life a significant difference between AM and PM values was observed in fullterm infants. In infants 1-2 months old mean +/- SEM AM and PM values were 2.8 +/- 0.2 and 3.5 +/- 0.4 mU/L, respectively (P less than 0.025), in infants 3-4 months old 3.0 +/- 0.6 and 4.1 +/- 0.8 (P less than 0.01) and in infants 5-6 months old 1.8 +/- 0.2 and 2.6 +/- 0.3 (P less than 0.0005). These data clearly indicate that the development of TSH circadian rhythm starts after the first month of life.

A simple stress test for the evaluation of hypothalamic-pituitary-adrenal axis during the first 6 months of life.

In 33 normal infants, divided into 3 age groups (less than 1 month, 1-3 months, and 3-6 months) plasma cortisol was measured at 2230, 2300, and 2330 h. Baseline plasma cortisol at 2230 h. was, as expected, low in all infants, with mean +/- SEM values of 41 +/- 5, 72 +/- 14, and 97 +/- 17 nmol/L in each group, respectively. Thirty and 60 min after the painful stimulus of the venipuncture, plasma cortisol increased significantly (P less than 0.0005), reaching a maximum increase up to 458 +/- 50, 392 +/- 66, and 455 +/- 97 nmol/L in each age group, respectively. We conclude that in these infants the hypothalamic-pituitary-adrenal axis was functionally intact and responded to the painful stimulus of the venipuncture by a significant increase in plasma cortisol. This test may be used as a simple procedure for the evaluation of the integrity of the hypothalamic-pituitary-adrenal axis without the administration of pharmacological agents. Its usefulness, however, should be validated with patients having a disorder of the system.