Obtaining tissue diagnosis in lung cancer patients with poor performance status and its influence on treatment and survival

Introduction: 25% of patients with lung cancer have performance status 3 or 4. A pragmatic approach to investigative procedures is often adopted based on the risks and benefits in these patients and whether tissue diagnosis is necessary for anticipated future treatment. This cohort study investigated factors influencing a clinician's decision to pursue a tissue diagnosis in patients with lung cancer and performance status 3 and 4 and to examine the association of tissue diagnosis with subsequent management and survival. Methods: All patients with lung cancer diagnosed in North Glasgow from 2009 to 2012 were prospectively recorded in a registry. We investigated the relationships between achieving a tissue diagnosis, treatment and survival. Results: Of 2493 patients diagnosed with lung cancer, 490 patients (20%) were PS 3 and 122 patients (5%) were PS 4. Tissue diagnosis was attempted in 60% and 35% patients with PS 3 and PS 4 respectively. Younger age, better performance status and having stage 4 disease were independently associated with a diagnostic procedure being performed. Only 5% of patients with poor performance status received treatment conventionally requiring a tissue diagnosis. Age, stage and performance status were independent predictors of mortality. Achieving a tissue diagnosis was not associated with mortality. Receiving treatment requiring tissue diagnosis is associated with survival benefit. Conclusions: The majority of patients with poor fitness undergo a diagnostic procedure which does not influence further treatment or affect survival. However, the cohort of patients who do undergo therapy determined by tissue diagnosis have improved survival

Model for Entangled States with Spin-Spin Interaction

A system consisting of two neutral spin 1/2 particles is analyzed for two magnetic field perturbations: 1) an inhomogeneous magnetic field over all space, and 2) external fields over a half space containing only one of the particles. The field is chosen to point from one particle to the other, which results in essentially a one-dimensional problem. A number of interesting features are revealed for the first case: the singlet, which has zero potential energy in the unperturbed case, remains unstable in the perturbing field. The spin zero component of the triplet evolves into a bound state with a double well potential, with the possibility of tunneling. Superposition states can be constructed which oscillate between entangled and unentangled states. For the second case, we show that changes in the magnetic field around one particle affect measurements of the spin of the entangled particle not in the magnetic field nonlocally. By using protective measurements, we show it is possible in principle to establish a nonlocal interaction using the two particles, provided the dipole-dipole potential energy does not vanish and is comparable to the potential energy of the particle in the external field

Effect of quantum and thermal jitter on the feasibility of Bekenstein’s proposed experiment to search for Planck-scale signals

A proposed experiment to test whether space is discretized [J. D. Bekenstein, Phys. Rev. D 86, 124040 (2012); Found. Phys. 44, 452 (2014)] is based on the supposed impossibility of an incident photon causing a displacement of a transparent block by less than the Planck length. An analysis of the quantum and thermal jitter of the block shows that it greatly diminishes the possibility that the experiment could reveal Planck-scale signals

Filled pauses in Hungarian: Their phonetic form and function

Filled pauses are natural occurrences in spontaneous speech and they may turn up at any level of the speech planning process and in a number of functions. The aim of this paper is to find out whether the diverse functions of filled pauses correlate with diverse articulations resulting in diverse acoustic structures. Spontaneous narratives are used as research material. The duration of the filled pauses and the frequency values of their first two formants are analyzed. The most frequent form, schwa, shows function-dependent realizations as confirmed by the durational values and by the second formant values of these vowel-like sounds

Speaker- versus listener-oriented disfluency: A re-examination of arguments and assumptions from autism spectrum disorder

We re-evaluate conclusions about disfluency production in high-functioning forms of autism spectrum disorder (HFA). Previous studies examined individuals with HFA to address a theoretical question regarding speaker- and listener-oriented disfluencies. Individuals with HFA tend to be self-centric and have poor pragmatic language skills, and should be less likely to produce listener-oriented disfluency. However, previous studies did not account for individual differences variables that affect disfluency. We show that both matched and unmatched controls produce fewer repairs than individuals with HFA. For silent pauses, there was no difference between matched controls and HFA, but both groups produced more than unmatched controls. These results identify limitations in prior research and shed light on the relationship between autism spectrum disorders and disfluent speech

The relationship between 18F-FDG-PETCT-derived tumour metabolic activity, nutritional risk, body composition, systemic inflammation and survival in patients with lung cancer

The aim of this study was to examine the relationship between PET-CT derived tumour glucose uptake as measured by maximum standard glucose uptake (SUVmax) and total lesion glycolysis (TLG), nutritional risk as measured by the malnutrition universal screening tool (MUST), CT derived body composition as measured by skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), the systemic inflammatory response as measured by the modified Glasgow prognostic score (mGPS) and the neutrophil to lymphocyte ratio (NLR) and survival in patients with lung cancer, treated with radiotherapy. In a retrospective cohort study, 119 patients were included in final analyses. The majority of patients were over 65 (86%), female (52%), had a performance status (ECOG-PS) of 0 or 1 (57%), were at nutritional risk (57%), were overweight (53%), had visceral obesity (62%), had a normal SMI (51%), had a low SMD (62%) and were systemically inflammed (mGPS 1/2, 51%). An elevated TLG was associated with sex (p < 0.05), TNM stage (p < 0.001), MUST (p < 0.01) and mGPS (p < 0.01). An elevated mGPS was associated with age (p < 0.05), NLR (p < 0.01), MUST (p < 0.01), and TLG (p < 0.01). On univariate survival analysis, TNM stage (p < 0.01), mGPS (p < 0.05), NLR (p < 0.01), MUST (p ≤ 0.001), Low SMD (p < 0.05), SUVmax (p ≤ 0.001) and TLG (p < 0.001) were associated with overall survival. On multivariate survival analysis MUST (HR: 1.49 95%CI 1.12–01.98 p < 0.01) and TLG (HR: 2.02 95%CI 1.34–3.04 p = 0.001) remained independently associated with survival. In conclusion, elevated tumour metabolic activity was associated with more advanced stage, greater nutritional risk, the systemic inflammatory response and poorer survival but not body composition analysis in patients with lung cancer. These results suggest that detrimental body composition is not directly determined by tumour metabolic activity but rather an ongoing systemic inflammatory response

Reference standard methodology in the clinical evaluation of AI chest X-ray algorithms for lung cancer detection: A systematic review

Background: Lung cancer remains the leading cause of cancer death worldwide, with early diagnosis linked to improved survival. Artificial intelligence (AI) holds promise for augmenting radiologists’ workflows in chest X-ray (CXR) interpretation, particularly for detecting thoracic malignancies. However, clinical implementation of this technology relies on robust and standardised reference standard methodology at the patient-level. Purpose: This systematic review aims to describe reference standard methodology in the clinical evaluation of CXR algorithms for lung cancer detection. Materials and Methods Searches targeted studies on AI CXR analysis across MEDLINE, Embase, CENTRAL, and trial registries. 2 reviewers independently screened titles and abstracts, with disagreements resolved by a 3rd reviewer. Studies lacking external validation in real-world cohorts were excluded. Bias was assessed using a modified QUADAS-2 tool, and data synthesis followed SWiM guidelines. Results: 1,679 papers were screened with 46 papers included for full paper review. 24 different AI solutions were evaluated across a broad range of research questions. We identified significant heterogeneity in reference standard methodology, including variations in target abnormalities, reference standard modality, expert panel composition, and arbitration techniques. 25 % of reference standard parameters were inadequately reported. 66% of included studies demonstrated high risk of bias in at least one domain. Discussion: To our knowledge, this is the first systematic description of patient-level reference standard methodology in CXR AI analysis of thoracic malignancy. To facilitate translational progress in this field, researchers undertaking evaluations of diagnostic algorithms at the patient-level should ensure that reference standards are aligned with clinical workflows and adhere to reporting guidelines. Limitations include a lack of prospective studies

The prevalence and prognostic value of systemic inflammation in good performance status patients with advanced, inoperable non-small cell lung cancer receiving palliative radiotherapy: comparison of composite ratios and cumulative scores

Introduction: The present study sought to examine the relationships between systemic inflammatory composite ratios/cumulative scores, magnitude of systemic inflammatory response (SIR) and survival in good performance status patients (ECOG-PS 0/1) with advanced NSCLC receiving palliative radiotherapy. Methods: Systemic inflammatory composite ratios/cumulative scores included the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), C-reactive protein, (CRP)-albumin ratio (CAR), neutrophil- lymphocyte score (NLS), platelet-lymphocyte score (PLS), lymphocyte-monocyte score (LMS), neutrophil-platelet score (NPS), modified Glasgow prognostic score (mGPS). The magnitude of SIR was determined by serum CRP concentration, with a median CRP concentration of >10 m mg/L considered to be systemically inflamed. Relationships between systemic inflammatory composite ratios/ cumulative scores and clinicopathological characteristics were examined using chi-square analysis. Relationships between overall survival (OS) and systemic inflammatory composite ratios/ cumulative scores were examined using cox regression analysis. Results: 479 patients were included. 48% (n = 231) of patients were male and 70% (n = 338) were ≥65 years of age. 29% (n = 140) patients were ECOG-PS 0 and 71% (n = 339) were ECOG-PS 1. 98% (n = 469) of patients died during follow-up. The median survival was 5 months (2–11). A similar prevalence of systemic inflammation was noted across the various ratios/scores (NLR >3 68%; LMR <2.4 65%; PLR >150 70%; CAR >0.20 83%; NLS ≥1 66%; LMS ≥1 71%; NPS≥1 50%; PLS≥1 60% and mGPS≥1 75%). Despite not considered to be systemically inflamed, an NLR <3, LMR ≥2.4, PLR ≤150, NLS 0, LMS 0, NPS 0 and PLS 0 all had a median CRP concentration of >10 mg/L. When adjusted for ECOG-PS, CAR>0.40 (p < 0.001) and mGPS 2 (p < 0.05) remained significantly associated with OS. Conclusion: Liver-based measures of systemic inflammation (CAR and mGPS) appear more reliable for the quantification of the magnitude of SIR and have prognostic value in patients with advanced NSCLC