Temporal changes in biomarkers in individuals with and without acute mountain sickness following rapid ascent.

BACKGROUND: Field studies have reported conflicting results regarding changes in biomarkers at high altitude. This study measured temporal changes in biomarkers and compared the differences between individuals with and without acute mountain sickness (AMS). MATERIALS AND METHODS: This study included 34 nonacclimatized healthy participants. Ten-milliliters of blood were collected at four time points: 3 days before ascent (T0), on two successive nights at 3150 m (T1 and T2), and 2 days after descent (T3). Participants were transported by bus from 555 m to 3150 m within 3 hours. AMS was diagnosed using the self-reported Lake Louise Scoring (LLS) questionnaire. RESULTS: Compared with T0, significant increases in E-selectin and decreases in vascular endothelial growth factor (VEGF) levels were observed at high altitude. Significantly increased C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and S100 calcium-binding protein B (S100B) levels were observed at T2, and significantly decreased vascular cell adhesion molecule-1 (VCAM-1) levels were observed at T3. Eighteen (53%) participants developed AMS. Changes in E-selectin, CRP, MCP-1, and S100B levels were independent of AMS. Relative to individuals without AMS, those with AMS had significantly higher atrial natriuretic peptide (ANP) and VCAM-1 levels and lower plasminogen activator inhibitor-1 (PAI-1) levels at T1 and higher brain natriuretic peptide and lower VEGF and PAI-1 levels at T3. LLSs were positively correlated with ANP and VCAM-1 levels and negatively correlated with PAI-1 levels measured at T1. CONCLUSIONS: After acute ascent, individuals with and without AMS exhibited different trends in biomarkers associated with endothelial cell activation and natriuretic peptides.

Artificial Intelligence Assisted Computational Tomographic Detection of Lung Nodules for Prognostic Cancer Examination: A Large-Scale Clinical Trial.

Low-dose computed tomography (LDCT) has emerged as a standard method for detecting early-stage lung cancer. However, the tedious computer tomography (CT) slide reading, patient-by-patient check, and lack of standard criteria to determine the vague but possible nodule leads to variable outcomes of CT slide interpretation. To determine the artificial intelligence (AI)-assisted CT examination, AI algorithm-assisted CT screening was embedded in the hospital picture archiving and communication system, and a 200 person-scaled clinical trial was conducted at two medical centers. With AI algorithm-assisted CT screening, the sensitivity of detecting nodules sized 4−5 mm, 6~10 mm, 11~20 mm, and >20 mm increased by 41%, 11.2%, 10.3%, and 18.7%, respectively. Remarkably, the overall sensitivity of detecting varied nodules increased by 20.7% from 67.7% to 88.4%. Furthermore, the sensitivity increased by 18.5% from 72.5% to 91% for detecting ground glass nodules (GGN), which is challenging for radiologists and physicians. The free-response operating characteristic (FROC) AI score was ≥0.4, and the AI algorithm standalone CT screening sensitivity reached >95% with an area under the localization receiver operating characteristic curve (LROC-AUC) of >0.88. Our study demonstrates that AI algorithm-embedded CT screening significantly ameliorates tedious LDCT practices for doctors.

Successful rechallenge of alectinib after remission of severe alectinib-induced interstitial lung disease.

INTRODUCTION: Even though alectinib is a potent second-generation ALK inhibitor with a favorable safety profile, alectinib-induced interstitial lung disease (ILD) could be fatal. There are case reports described successful alectinib rechallenge in mild ILD. However, the feasibility and safety of rechallenge in severe cases remains to be elucidated. CASE REPORT: A 76-year-old female was a case of stage IV lung adenocarcinoma harboring ALK rearrangement. Respiratory failure following severe ILD developed one month after alectinib administration. She received mechanical ventilation in intensive care uint. ILD subsided gradually after methylprednisolone pulse therapy and discontinuation of alectinib.Management and outcome: After the recovery from ILD, the patient attempted a re-escalation of alectinib from a lower dose under close clinical and radiological monitoring. No ILD happened even after 480 days of alectinib rechallenge. DISCUSSION: Given that the ALK inhibitors are the treatment of choice for advanced lung cancer patients with ALK rearrangement. Our report demonstrated the potential feasibility of alectinib re-use in cases of severe druginduced ILD.

Clinical usefulness of bronchoalveolar lavage in patients with interstitial lung diseases: a pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) is a useful tool in the diagnostic work-up of patients with interstitial lung diseases (ILDs). In this prospective study, we investigated the clinical usefulness of BAL in patients with ILD radiographically. METHODS: The enrolled patients were classified into outpatient department (OPD), and inpatients groups who was admitted to general ward (GW) or intensive care unit (ICU) groups based on the time when BAL done. The clinical usefulness of BAL was defined as a new diagnosis established and/or treatment significantly changed. The clinical usefulness of BAL among the three groups of patients and the patients divided by underlying diseases was compared using the χ2 test with or without Fisher's exact test. RESULTS: Among our 184 patients, there were 37 in OPD group, 86 in GW group and 61 in ICU group. The final diagnoses were infectious in 23, non-infectious in 102, mixed etiologies in 19, and non-diagnostic in 40 patients. The diagnostic yields (revised diagnosis after BAL) of BAL among ICU patients, GW patients and OPD patients were 60.6%, 69.7% and 21.6%, respectively (P<0.001), and was 57.1% in total patients. The diagnostic yields of BAL among patients with cancer, organ transplantation and collagen vascular disease were statistically different (P=0.009). CONCLUSIONS: BAL is of use in establishing a diagnosis of ILD and is mandatary especially in the admitted patients with ILD because diagnostic yield was relatively higher in admitted patients than in OPD patients. In addition, BAL should be done more early in the admitted patients with malignancy, stem cell and/or organ transplantation and collagen vascular disease especially when they showed poor response to initial medications.

The usefulness of prophylactic use of acetazolamide in subjects with acute mountain sickness.

BACKGROUND: The mechanisms of acetazolamide (ACZ) in the prophylaxis of acute mountain sickness (AMS) remain unclear. This study evaluated the changes in physiological variables of sleep and heart rate variability (HRV) in subjects with earlier history of AMS who underwent prophylactic treatment of ACZ. METHODS: Nonacclimatized healthy subjects were transported using a bus from 555 m to 3150 m within 3 hours. Polysomnography (PSG) was performed 3 days before ascent (T0), for two consecutive nights at 3150 m (T1 and T2), and 2 days after descent (T3). HRV was measured before sleep and after awakening from T0 to T3. AMS was diagnosed using a self-reported Lake Louise score questionnaire. Subjects found confirmed to have AMS were enrolled in this study. The physiological variables and HRV were compared in AMS subjects without (control group) and with prophylactic ACZ (prophylactic ACZ group). RESULTS: Thirteen AMS subjects were enrolled. The PSG results were analyzed in eight and HRV were analyzed in nine of the 13 subjects. The prophylactic use of ACZ in the subjects with a history of AMS significantly improved sleep efficiency (p = 0.012) and awakening percentages (p = 0.017) at T1, significantly higher levels of arterial oxygen saturation (SaO2) and lower values of partial pressure end-tidal carbon dioxide tension (PETCO2) at four time points. Furthermore, they had a higher rapid eye movement sleep percentage (p = 0.05) at T2. Prophylactic ACZ treatment significantly increased the normalized unit of high frequency at T1 after awakening (p = 0.028). CONCLUSION: Significantly higher quality of sleep, higher SaO2 during sleep, and lower PETCO2 at high altitude were found in the subjects with a history of AMS using prophylactic ACZ before rapid ascent. ACZ may accelerate the acclimatization process for rapid ascents to high altitudes by increasing parasympathetic tone based on HRV analyses.

Clinical Usefulness of HRCT in Assessing the Severity of Pneumocystis jirovecii Pneumonia: A Cross-sectional Study.

The aim of this study was to investigate the clinical relevance of thoracic high-resolution computed tomography (HRCT) in evaluating the severity and outcome of Pneumocystis jirovecii pneumonia (PJP) in non-AIDS immunocompromised patients.We measured mean lung attenuation (MLA) and extent of increased attenuation (EIA) of PJP lesions on thoracic HRCT in 40 non-AIDS immunocompromised patients with PJP diagnosed by demonstration of the pathogens in cytological smears of bronchoalveolar lavage fluid. The MLA and EIA of PJP lesions on thoracic HRCT were used to investigate the severity of PJP. Clinically, the severity of PJP was determined by arterial oxygen tension/fraction of inspired oxygen concentration (PaO2/FiO2) ratio, acute physiology and chronic health evaluation (APACHE) II scores, the need of mechanical ventilation, and death.MLA highly correlated with EIA of PJP lesions (ρ = 0.906, P < 0.001). MLA and EIA of PJP lesions significantly correlated with PaO2/FiO2 (ρ = -0.481 and -0.370, respectively and P = 0.007 and 0.044, respectively). When intensive care unit (ICU) admission and HRCT performed were within 2 days, MLA and EIA of PJP lesions were significantly correlated with APACHE II score (ρ = 0.791 and 0.670, respectively and P = 0.001 and 0.009, respectively). There were significant differences in the values of MLA and EIA of PJP lesions between patients with and without assisted mechanical ventilator (MLA, median and [interquartile range, IQR, 25%, 75%] -516.44 [-572.10, -375.34] vs -649.27 [-715.62, -594.01], P < 0.001 and EIA, median and [IQR 25%, 75%] 0.75 [0.66, 0.82] vs 0.53 [0.45, 0.68], P = 0.003, respectively). The data of MLA and EIA of PJP lesions had limited value in identifying survivors and non-survivors.The MLA and EIA values of PJP lesions measured on thoracic HRCT might be valuable in assessing the severity of PJP in non-AIDS immunocompromised patients, but might have limited value in predicting the mortality of the patients.

The impact of concomitant pulmonary infection on immune dysregulation in Pneumocystis jirovecii pneumonia.

BACKGROUND: Concurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, however, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown. METHODS: We measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-ß1 and IL-1 receptor antagonist (IL-1RA) and inflammatory markers including high mobility group box 1, Krebs von den Lungen-6, receptor for advanced glycation end product, advanced glycation end product, surfactant protein D in bronchoalveolar lavage fluid (BALF) and blood in 47 pure PcP and 18 mixed PJP and other pulmonary infections (mixed PJP) in non-AIDS immunocompromised patients and explored their clinical relevance. The burden of Pneumocystis jirovecii in the lung was determined by counting number of clusters of Pneumocystis jirovecii per slide and the concentration of ß-D-glucan in BALF. PJP severity was determined by arterial oxygen tension/fraction of inspired oxygen concentration ratio, the need of mechanical ventilation and death. RESULTS: Compared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1ß, TNF-α and IL-8 and significantly higher blood levels of IL-8. The BALF ratios of TNF-α/IL-10, IL-8/IL-10, IL-1ß/IL-10, TNF-α/TGF-ß1, IL-8/TGF-ß1, IL-1ß/TGF-ß1 and IL-1ß/IL-1RA were significantly higher in mixed than in pure PJP patients. There was no significant difference in clinical features and outcome between pure and mixed PJP groups, including inflammatory biomarkers and the fungal burden. In pure PJP patients, significantly higher BALF levels of IL-8 and the ratios of IL-8/IL-10, IL-1ß/TGF-ß1, MCP-1/TGF-ß1, MCP-1/IL1RA and IL-8/TGF-ß1 were found in the patients requiring mechanical ventilation and in non-survivors. CONCLUSIONS: In summary, concurrent pulmonary infection might enhance immune dysregulation of PJP in non-AIDS immunocompromised patients, but did not affect the outcome as evidenced by morbidity and mortality. Because of limited number of cases studied, further studies with larger populations are needed to verify these issues.

The importance of pro-inflammatory and anti-inflammatory cytokines in Pneumocystis jirovecii pneumonia.

The role of pro-inflammatory and anti-inflammatory cytokines in Pneumocystis jirovecii pneumonia (PcP) of non-AIDS immunocompromised patients remains unclear. We measured the levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-ß1 in bronchoalveolar lavage fluid (BALF) and blood in 36 non-AIDS immunocompromised patients with PcP diagnosed by BAL and explored their clinical importance. The severity of PcP was determined by arterial oxygen tension/fraction of inspired oxygen concentration (PaO2/FiO2) ratio, the need of mechanical ventilation and the death. Twenty-five subjects without evidence of lung abnormality were included as control group. Compared with control group, PcP patients had significantly higher BALF levels of IL-1ß, TNF-α, IL-6, IL-8 and MCP-1 and significantly higher blood levels of IL-10, TGF-ß1, IL-8, IL-6 and MCP-1. For PcP patients, BALF levels of IL-8, IL-8/IL-10 ratio and IL-8/TGF-ß1 ratio and blood levels of IL-8 and IL-8/IL-10 ratio were significantly higher in the patients with PaO2/FiO2 < 200 mmHg than in those with PaO2/FiO2 > 200 mmHg. Similarly, significantly higher BALF levels of IL-8, IL-8/IL-10 ratio, IL-1ß/IL-10, IL-1ß/TGF-ß1 ratio, MCP-1/TGF-ß1 ratio and IL-8/TGF-ß1 ratio were found in the patients requiring mechanical ventilation and in non-survivors. In summary, an imbalance of pro-inflammatory and anti-inflammatory cytokines in BALF was found in PcP of non-AIDS immunocompromised patients. BALF levels of IL-8, IL-8/IL-10 ratio, IL-1ß/IL-10 ratio, IL-1ß/TGF-ß1 ratio, MCP-1/TGF-ß1 ratio and IL-8/TGF-ß1 ratio may be of value in assessing the severity of PcP and in predicting the outcome of the patients.

Differentiating pyopneumothorax and peripheral lung abscess: chest ultrasonography.

BACKGROUND: Differentiation between pyopneumothorax and lung abscess can be difficult but has important therapeutic consequences. The role of chest ultrasonography in this issue remains undetermined. Sonographic features of hydropneumothorax and/or pyopneumothorax are characteristic and not difficult to recognize. In this study, the authors evaluate the usefulness of a panel of sonographic findings characteristic of hydropneumothorax in distinguishing pyopneumothorax from lung abscess. METHODS: This series included 16 patients with lung abscess and 19 with pyopneumothorax. A diagnosis of lung abscess or pyopneumothorax was based on the following criteria: pus aspiration from the lesion, appropriate clinical setting, thoracic computed tomographic findings, serial follow-up of chest radiograms, and consistent clinical course. The panel of sonographic features suggestive of hydropneumothorax, including the presence of air-fluid level, the curtain sign, loss of gliding sign above the air-fluid level, and the suspended microbubble sign, were recorded and analyzed by a consensus of blinded readers. In addition, sonographic features used to differentiate empyema and lung abscess were also evaluated. RESULTS: The results indicated that the presence of air-fluid level, the curtain sign, loss of gliding sign above the air-fluid level, and the suspended microbubble sign were valuable in distinguishing pyopneumothorax from lung abscess. All four sonographic findings were observed in 17 of 19 patients with pyopneumothorax. In contrast, two or fewer sonographic findings were seen in 16 patients with lung abscess. Our results confirmed that the wall characteristics, shape of the lesion, chest wall angle, and pleural separation were also useful. CONCLUSIONS: The panel of sonographic findings is of considerable value in differentiating pyopneumothorax and lung abscess.

Pleuritis as a presenting manifestation of rheumatoid arthritis: diagnostic clues in pleural fluid cytology.

Pleural effusion is a recognized but relatively uncommon complication of rheumatoid arthritis and has distinctive cytopathologic features. It may occur before, concurrently with, or after the development of joint manifestations of the disease. Clinical diagnosis of rheumatoid pleuritis may be delayed or overlooked in a patient without obvious evidence of arthritis. Failure to recognize the unique cytologic picture of rheumatoid pleuritis caused a 5-month delay in diagnosis of a rheumatoid pleural effusion in an elderly man whose concurrent arthritic symptoms were not given adequate clinical recognition.