Abstract:Patients with Alzheimer's disease (AD) are characterized by an altered sensitivity to cortisol-mediated modulation of circulating lymphocytes. Longitudinal studies are needed to address the clinical applicability of these abnormalities as prognostic factors. Therefore, we designed a longitudinal study to address the clinical applicability of physiologic modulation of Natural Killer (NK) cell activity as a prognostic factor in AD. NK activity was assessed as baseline measurement and in response to modulation by cortisol at 10 -6 M. To verify the immunophysiological integrity of the NK cell population, we tested augmentation of NK cytotoxicity by human recombinant interleukin (IL)-2 (100 IU/ml) as control. The response to modulation by cortisol or by IL-2 was significantly greater in patients with AD. Based on change in the Mini-Mental State score at entry and at 18 months, patients with AD could be assigned to a "fast progression" (Δ > 2 points) or to a "slow progression" group (Δ < 2 points). The change in the response of NK cytotoxic activity to cortisol, and the strength of the association of this parameter with circulating activated T cells in time was greater in patients with Fast Progression vs. Slow Progression AD. These results suggest that changes in the response of NK cells to negative (e.g., cortisol) or positive modifiers (e.g., IL-2) follow progression of AD.
Background Lung ultrasound (LUS) and chest radiography (CXR) are the most used chest imaging tools in the early diagnosis of COVID-19 associated pneumonia. However, the relationship between LUS and CXR is not clearly defined. The aim of our study was to describe the comparison between LUS interpretation and CXR readings in the first approach to patients suspected of COVID-19. Methods In the time of the first COVID-19 pandemic surge, we prospectively evaluated adult patients presenting to an emergency department complaining of symptoms raising suspicion of COVID-19. Patients were studied by LUS and only those performing also CXR were analyzed. All the patients performed viral reverse transcriptase-polymerase chain reaction (RT-PCR). LUS studies were classified in 4 categories of probabilities, based on the presence of typical or alternative signs of COVID-19-associated interstitial pneumonia. Accordingly, the CXR readings were retrospectively adapted by 2 experts in 4 categories following the standard language that describes the computed tomography (CT) findings. Patients were divided in two groups, based on the agreement of the LUS and CXR categories. Results were also compared to RT-PCR and, when available, to CT studies. Results We analyzed 139 cases (55 women, mean age 59.1 ± 15.5 years old). The LUS vs CXR results disagreed in 60 (43.2%) cases. RT-PCR was positive in 88 (63.3%) cases. In 45 cases, a CT scan was also performed and only 4 disagreed with LUS interpretation versus 24 in the comparison between CT and CXR. In 18 cases, LUS detected signs of COVID-19 pneumonia (high and intermediate probabilities) while CXR reading was negative; in 14 of these cases, a CT scan or a RT-PCR-positive result confirmed the LUS interpretation. In 6 cases, LUS detected signs of alternative diagnoses to COVID-19 pneumonia while CXR was negative; in 4 of these cases, CT scan confirmed atypical findings. Conclusion Our study demonstrated a strong disagreement between LUS interpretation and CXR reading in the early approach to patients suspected of COVID-19. Comparison with CT studies and RT-PCR results seems to confirm the superiority of LUS over a second retrospective reading of CXR.
Background Lung ultrasound (LUS) has a role in the diagnosis of pulmonary embolism (PE) mainly based on the visualization of pulmonary infarctions. However, examining the whole chest to detect small peripheral infarctions by LUS may be challenging. Pleuritic pain, a frequent presenting symptom in patients with PE, is usually localized in a restricted chest area identified by the patient itself. Our hypothesis is that sensitivity of LUS for PE in patients with pleuritic chest pain may be higher due to the possibility of focusing the examination in the painful area. We combined data from three prospective studies on LUS in patients suspected of PE and extracted data regarding patients with and without pleuritic pain at presentation to compare the performances of LUS. Results Out of 872 patients suspected of PE, 217 (24.9%) presented with pleuritic pain and 279 patients (32%) were diagnosed with PE. Pooled sensitivity of LUS for PE in patients with and without pleuritic chest pain was 81.5% (95% CI 70–90.1%) and 49.5% (95% CI 42.7–56.4%) (p < 0.001), respectively. Specificity of LUS was similar in the two groups, respectively 95.4% (95% CI 90.7–98.1%) and 94.8% (95% CI 92.3–97.7%) (p = 0.86). In patients with pleuritic pain, a diagnostic strategy combining Wells score with LUS performed better both in terms of sensitivity (93%, 95% CI 80.9–98.5% vs 90.7%, 95% CI 77.9–97.4%) and negative predictive value (96.2%, 95% CI 89.6–98.7% vs 93.3%, 95% CI 84.4–97.3%). Efficiency of Wells score + LUS outperformed the conventional strategy based on Wells score + d-dimer (56.7%, 95% CI 48.5–65% vs 42.5%, 95% CI 34.3–51.2%, p = 0.02). Conclusions In a population of patients suspected of PE, LUS showed better sensitivity for the diagnosis of PE when applied to the subgroup with pleuritic chest pain. In these patients, a diagnostic strategy based on Wells score and LUS performed better to exclude PE than the conventional strategy combining Wells score and d-dimer.
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