Non-POEMS osteosclerotic multiple myeloma: Clinical characteristics and differential diagnosis.

Osteosclerosis in multiple myeloma (MM) is typically associated with rare POEMS syndrome, characterized by polyneuropathy (P), organomegaly (O), endocrinopathy (E), M-protein (M), and skin changes (S). However, osteosclerosis in multiple myeloma (MM) without POEMS syndrome, defined as non-POEMS Osteosclerotic MM, is exceedingly rare. We report a 70-year-old man with rib pain, remarkably high bone mineral density and diffuse osteosclerosis. The diagnosis of non-POEMS osteosclerotic MM was confirmed by biopsy and aspiration of bone marrow through surgery. A literature review spanning from 1990 identified 12 cases of similar non-POEMS osteosclerotic MM, including 5 males and 7 females with a mean age of 59.7 ± 10.6 years. The non-POEMS osteosclerotic MM can be divided into two subtypes, the osteosclerotic lesion subtype and the diffuse osteosclerosis subtype. Absence of polyneuropathy and organomegaly are the main factors that differentiate non-POEMS osteosclerotic MM from POEMS. A hyperactive osteoblastic process might be the etiology of diffuse osteosclerosis. Further research is needed to understand its etiology and pathophysiology.

Quantitative analyzes of the variability in airways via four-dimensional dynamic ventilation CT in patients with chronic obstructive pulmonary disease: correlation with spirometry data and severity of airflow limitation.

Background: In chronic obstructive pulmonary disease (COPD) patients, the diagnosis and assessment of disease severity are mainly based on spirometry, which may lead to misjudgments due to poor patient compliance. Thoracic four-dimensional dynamic ventilation computed tomography (4D-CT) provides more airway data approximating true physiological function than conventional CT. We aimed to determine dynamic changes in airways to elucidate the pathological mechanism underlying COPD and predict the severity of airflow limitation in patients. Methods: Forty-two COPD patients underwent 4D-CT and spirometry. The minimum lumen diameter changed with the breathing cycle in 4th-generation airways and was continuously measured in the apical (RB1), lateral (RB4) and posterior basal segments (RB10) of the right lung. The minimum lumen diameter in the peak inspiration and peak expiration as well as the peak expiratory/peak inspiratory ratio (E/I ratio), and dynamic coefficient of variance (CV) were calculated. Results: Correlations of FEV1% with the CV of minimum lumen diameter in RB1 (ρ=-0.473, P=0.002) and in RB10 (ρ=-0.480, P=0.005) were observed, suggesting that the dynamic variability in 4th-generation airways was associated with airflow limitation in COPD patients. The CV of the minimum lumen diameter in RB1 significantly differed between the GOLD I + II and GOLD III + IV groups {8.59 [interquartile range (IQR), 6.63-14.86] vs. 14.64 (10.65-25.88), respectively; P=0.016}, suggesting that the dynamic CV in RB1 increased significantly in the GOLD III + IV group, which had worse pulmonary ventilation function. Based on the receiver operating characteristic (ROC) curve analysis, CV-RB1 predicted FEV1% <50% with an optimal cut-off of 9.43% [sensitivity 85.7%, specificity 57.1%, area under the curve (AUC) 0.717]. Conclusions: 4D-CT might be an available method to help diagnose and evaluate the severity of COPD.

Exogenous Ang-(1-7) inhibits autophagy via HIF-1α/THBS1/BECN1 axis to alleviate chronic intermittent hypoxia-enhanced airway remodelling of asthma.

Obstructive sleep apnoea (OSA)-induced chronic intermittent hypoxia (CIH) has been considered a risk factor for severe asthma. Airway remodelling, which could be modulated by autophagy, plays a key role in severe asthma. However, the extent of autophagy's involvement in CIH-potentiated airway remodelling remains largely unexplored. Furthermore, we had found that angiotensin-(1-7) [Ang-(1-7)] has therapeutic effects on airway remodelling in asthma, but the underlying mechanism is either unclear. This study aimed to explore how CIH aggravates asthma and mechanism of protective effects of Ang-(1-7) on airway remodelling, with a focus on autophagy. We observed that CIH promoted epithelial-to-mesenchymal transition (EMT), indicated by elevated EMT and fibrotic markers such as Snail and Collagen IV, both in vitro and in vivo. CIH intensified cell autophagy, evident from increased LC3B expression and reduced p62 levels. Ang-(1-7) reversed the CIH-enhanced expression of Snail, Collagen IV, and LC3B. To explore how CIH enhanced autophagy in cellular and animal model of asthma, overexpression of hypoxia-inducible factor 1-alpha (HIF-1α) and Thrombospondin 1 (THBS1) were identified in CIH-exposure mice lung compared with normal mice lung tissues from the GEO database. Finally, through chromatin immunoprecipitation and immunoprecipitation assays, we verified that Ang-(1-7) inhibits CIH-induced binding of HIF-1α to the promoter of THBS1, and also disrupts the protein-protein interaction between THBS1 and the autophagy-associated protein Beclin 1 (BECN1), ultimately leading to autophagy inhibition. Our findings suggest that exogenous Ang-(1-7) can inhibit autophagy via HIF-1α/THBS1/BECN1 axis, thereby alleviating CIH-enhanced airway remodelling in asthma. These findings imply the potential therapeutic effect of Ang-(1-7) in asthma with OSA.

Short Sleep Duration is Associated with Prolonged Virus Shedding in SARS-CoV-2 Omicron-Infected Patients.

Purpose: Sleep disturbance has been implicated in poor prognosis of coronavirus disease 2019 (COVID-19), but less is known about the influence of short sleep duration on COVID-19 outcomes. We aim to investigate whether short sleep duration is associated with prolonged virus shedding duration in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-infected patients. Patients and Methods: A total of 270 patients with a laboratory confirmed COVID-19 diagnosis during SARS-CoV-2 Omicron-predominant period were recruited. Self-reported sleep duration of the patients was collected. The two-way analysis of variance (ANOVA) was used to determine the interactions between sleep duration and variables, and multivariate logistic regression analysis was used to analyze the effect of independent variables on longer virus shedding duration. Results: The two-way ANOVA revealed a significant sleep duration × snoring interaction effect for virus shedding duration, and a sleep duration × sex interaction effect for virus shedding duration. Multivariate logistic regression model illustrated that patients sleeping <6 h were at greater risk of prolonged virus shedding duration compared to those sleeping ≥6 hours (OR = 1.80, 95% CI = 1.01-3.26), independent of age, sex, co-existing diseases, vaccination condition, and antiviral treatment. Conclusion: Short sleep duration (<6 h) was associated with increased virus shedding in SARS-CoV-2 Omicron-infected patients.

Diagnosis of obstructive sleep apnea using a bio-radar contact-free system compared with an established HST device in older adults.

GOAL AND AIMS: To compare a bio-radar contact-free monitoring device in diagnosing obstructive sleep apnea (OSA) in older people with an established home sleep apnea testing system (HST). FOCUS METHOD/TECHNOLOGY: A bio-radar contact-free monitoring device (OrbSense+). REFERENCE METHOD/TECHNOLOGY: An established HST, Alice NightOne. SAMPLE: Fifty-three out of 63 recruited subjects were included in the final analysis. Seventy-two percent were male (age 72 ± 9 years; body mass index 31.05 ± 5.56 kg/m2). DESIGN: An observational, prospective study. CORE ANALYTICS: Intraclass correlation coefficient (ICC), Bland-Altman analysis, and receiver operating characteristic analysis. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: None. CORE OUTCOMES: Both 45 (84.91%) were diagnosed with OSA by Alice NightOne (average respiratory event index = 21.23 events/h) and by OrbSense+ (average respiratory event index = 25.98 events/h). Respiratory event index and oxygen desaturation index obtained by Alice NightOne and OrbSense+ were highly correlated, with ICC of 0.93 and 0.88, respectively. The Bland-Altman plot comparing the means showed good agreement between the 2 diagnostic techniques. With more than 5 respiratory events per hour as the standard for OSA diagnosis, OrbSense+ had a sensitivity of 100% and a specificity of 100% in diagnosis of OSA (P < .0001). With more than 15 respiratory events per hour as the standard for OSA diagnosis, OrbSense+ was found to have a sensitivity of 100% and a specificity of 86.96% in diagnosis of OSA (P < .0001). IMPORTANT ADDITIONAL OUTCOMES: None. CORE CONCLUSION: The bio-radar sleep monitoring device is a reasonably accurate home sleep apnea test for use in older patients.

Hedgehog signaling modulates cigarette-induced COPD development.

Hedgehog (Hh) signaling is involved in early embryogenesis and maintains quiescence in the adult lungs. The interruption of Hh signaling may lead to the development of chronic obstructive pulmonary disease (COPD). The current study aimed to assess whether the Hh pathway affects cigarette-induced emphysema and airway inflammation by regulating inflammatory cytokines. C57BL/6J mice were randomized into control, cigarette smoke (CS) or CS + cyclopamine (CSC) groups. Control mice were exposed to normal room air, CS mice were exposed to tobacco smoke and CSC mice were exposed to CS and received cyclopamine treatment. Histopathological examination of lung tissues was performed, and the expression of sonic hedgehog (HH), glioma-associated oncogene homolog 1 (Gli1), hedgehog-interacting protein (HIP) and several inflammatory mediators (intracellular adhesion molecule-1, IL-6, IL-8 and TNF-α) were compared using reverse transcription-quantitative PCR and western blotting. The emphysema of lung tissues by histopathological examination demonstrated partial amelioration in the CSC group compared with that in the CS group. Additionally, expression levels of SHH, Gli1 and inflammatory mediators were significantly higher in the CS group compared with the control group but were significantly decreased in the CSC group. The expression of HIP was decreased in the CS group, but significantly increased in the CSC group. Hh signaling may serve an important role in cigarette-induced emphysema and airway inflammation by regulating inflammatory cytokines in animal models. Therefore, diminishing the activation of the Hh signal may serve as a novel therapeutic strategy for patients suffering from smoking-related COPD.

Absolute Neutrophil Count in the Peripheral Blood Predicts Prognosis in Lung Cancer Patients Treated with Anlotinib.

PURPOSE: Anlotinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis and cell proliferation. It is widely used as a third-line therapy for lung cancer. However, reliable prognostic biomarkers for predicting the efficacy of anlotinib are lacking. We conducted a retrospective study to investigate the prognostic value of serological inflammatory biomarkers in anlotinib treatment. PATIENTS AND METHODS: Patients with advanced lung cancer treated with anlotinib monotherapy were enrolled. Cox regression was conducted to analyze the significant factors related to progression-free survival (PFS) and overall survival (OS). The objective response rate (ORR) was compared based on the median cut-off value of the significant inflammation index. Meanwhile, we created survival curves to compare the two groups and performed receiver operating characteristic curve analysis to assess the predictive ability of the inflammation index. RESULTS: Among a total of 71 patients, the median PFS was 5.5 months and the median OS was 9.5 months. The ORR and disease control rate were 16.9% and 84.5%, respectively. According to univariate and multivariate analyses, absolute neutrophil count (ANC) was the only indicator associated with both PFS (hazard ratio [HR] =1.095, 95% confidence interval [CI] 1.030-1.163, P=0.003) and OS (HR=1.057, 95% CI 1.003-1.113, P=0.037). In the group with ANC ≥4.58, the ORR was relatively lower (8.1% vs 26.5%, P=0.057), but not statistically significant; PFS and OS were relatively shorter (median PFS 5.0 [95% CI 4.4-9.6] vs 7.0 months [95% CI 4.4-5.7], P=0.024 and median OS 7.3 [95% CI 4.7-10.0] vs 17.6 months [95% CI 12.3-22.9], P < 0.001). ANC had a relatively high discriminatory ability to predict 10-month survival, with an area under the curve of 0.729, sensitivity of 82.5%, and specificity of 67.7%. CONCLUSION: Elevated pre-treatment ANC was associated with a poor prognosis. Patients with lower peripheral blood levels of ANC might benefit from anlotinib.

Neutrophil-to-Lymphocyte Ratio Predicts Clinical Outcome of Severe Acute Exacerbation of COPD in Frequent Exacerbators.

PURPOSE: Frequent exacerbators are a specific phenotype of chronic obstructive pulmonary disease (COPD), whose clinical characteristics and prognostic biomarkers during severe acute exacerbation (AECOPD) have not yet been fully elucidated. The aim of this study was to investigate the clinical features of severe AECOPD in frequent exacerbators and explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for outcome in this phenotype during severe exacerbation. PATIENTS AND METHODS: A total of 604 patients with severe AECOPD were retrospectively included in the study. Subjects were defined as frequent exacerbators if they experienced two or more exacerbations in the past year. Clinical characteristics and worse outcome (ICU admission, or invasive ventilation, or in-hospital mortality) during severe AECOPD were compared between frequent exacerbators and non-frequent ones. Furthermore, the relationship between NLR and worse outcome in frequent exacerbators was analyzed using logistic regression and receiver operating characteristic (ROC). RESULTS: Among 604 patients with severe AECOPD, 282 (46.69%) were frequent exacerbators and 322 (53.31%) were non-frequent exacerbators. Compared with the non-frequent ones, frequent exacerbators presented higher levels of NLR (5.93 [IQR, 3.40-9.28] vs 4.41 [IQR, 2.74-6.80]; p<0.001), and more worse outcome incidence (58 [20.57%] vs 38 [11.80%]; p=0.003). Moreover, among the frequent exacerbators, NLR levels in the patients with worse outcome were much higher than in those without worse outcome (11.09 [IQR, 7.74-16.49] vs 5.28 [IQR, 2.93-7.93]; p<0.001). Increased NLR was significantly associated with a higher risk of worse outcome in frequent exacerbators (OR, 1.43; 95% CI, 1.28-1.64; p<0.001). Furthermore, ROC analysis revealed that a cut-off value of 10.23, NLR could predict worse outcome of severe AECOPD in frequent exacerbators (sensitivity 62.1%, specificity 92.0%, AUC 0.833). CONCLUSION: Frequent exacerbators exhibited an increased level of NLR and a higher proportion of worse outcome during severe AECOPD. NLR is expected to be a promising predictive biomarker for the prognosis of severe AECOPD in frequent exacerbators.

The Role of Aldosterone in OSA and OSA-Related Hypertension.

Obstructive sleep apnea (OSA) is regarded as an independent risk factor for hypertension. The possible mechanism includes oxidative stress, endothelial injury, sympathetic excitement, renin-angiotensin-aldosterone system activation, etc. Clinical studies have found that there is a high coexistence of OSA and primary aldosteronism in patients with hypertension and that elevated aldosterone levels are independently associated with OSA severity in resistant hypertension. The underlying mechanism is that aldosterone excess can exacerbate OSA through increasing overnight fluid shift and affecting the mass and function of upper airway muscles during the sleep period. Thus, a bidirectional influence between OSA and aldosterone exists and contributes to hypertension in OSA patients, especially resistant hypertension.