Anlotinib enhanced CD8+ T cell infiltration via induction of CCL5 improves the efficacy of PD-1/PD-L1 blockade therapy in lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of mortality worldwide and requires effective treatment strategies. Recently, the development of a novel multiple-target tyrosine kinase inhibitor, anlotinib, has drawn increasing attention, especially it shows advantages when combined with PD-1/PD-L1 blockade. However, the mechanism by which anlotinib improves immunotherapy and remodeling of the tumor microenvironment remains unclear. In this study, we found that anlotinib combined with PD-1 blockade significantly inhibited tumor growth and reduced tumor weight in a lung cancer xenograft model compared to any single treatment. Both immunofluorescence and flow cytometry analyses revealed that anlotinib induced a CD8+ T cell dominated tumor microenvironment, which might account for its improved role in immunotherapy. Further investigations showed that CCL5-mediated CD8+ T cell recruitment plays a critical role in anlotinib and PD-1 blockade strategies. The depletion of CD8+ T cells abrogated this process. In conclusion, our findings showed that the combination of anlotinib and PD-1 blockade produced promising effects in the treatment of lung cancer, and that the induction of CCL5-mediced CD8+ T cell recruitment by anlotinib provided a novel mechanism of action.

Quality-of-Life Bronchiectasis Respiratory Symptom Scale Predicts the Risk of Exacerbations in Adults with Bronchiectasis: A Prospective Observational Study.

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.

Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation.

Interleukin-33 (IL-33) is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis. The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation, but the mechanism is still unclear. Here, we found that healthy individuals had higher phosphate-pyridoxal (PLP, an active form of vitamin B6) concentrations in the serum than asthma patients. Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation. In a mouse model of lung inflammation, we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33. A mechanistic study showed that in vivo, pyridoxal (PL) needed to be converted into PLP, which inhibited the type 2 response by regulating IL-33 stability. In mice heterozygous for pyridoxal kinase (PDXK), the conversion of PL to PLP was limited, and IL-33 levels were increased in the lungs, aggravating type 2 inflammation. Furthermore, we found that the mouse double minute 2 homolog (MDM2) protein, an E3 ubiquitin-protein ligase, could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells. PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway. In addition, inhalation of PLP alleviated asthma-related effects in mouse models. In summary, our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response, which might help develop a potential preventive and therapeutic agent for allergy-related diseases.

Updated severity and prognosis score of pulmonary alveolar proteinosis: A multi-center cohort study in China.

Background: The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient. Methods: We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months. Results: The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1-2, 20.3% based on SPSP 1-3, and 20.8% based on SPSPII 1-3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months. Conclusion: The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis. Trial registration: ClinicalTrial.gov, identifier: NCT04516577.

Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

OBJECTIVES: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). METHODS: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). RESULTS: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (ß, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. CONCLUSIONS: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. KEY POINTS: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

Case report: Fibrotic interstitial lung disease as the initial manifestation of hereditary pulmonary alveolar proteinosis caused by CSF2RB mutation.

A 50-year-old male was admitted to the hospital with a 3-year history of dyspnea and cough. Chest high-resolution computed tomography (HRCT) did not show typical features of pulmonary alveolar proteinosis (PAP), but rather atypical features of interstitial lung disease with fibrosis. The diagnosis of PAP was confirmed through transbronchial lung cryobiopsy. Whole exome sequencing identified a rare homozygous frame shift mutation (c.304_305del:p.S102Ffs*5) in exon 3 of the CSF2RB gene in our patient. This case represents a rare occurrence of fibrotic interstitial lung disease in PAP.

HS3ST1 Promotes Non-Small-Cell Lung Cancer Progression by Targeting the SPOP/FADD/NF-κB Pathway.

Heparan sulfate proteoglycan is a key component of cell microenvironment and plays an important role in cell-cell interaction, adhesion, migration, and signal transduction. Heparan sulfate 3-O-sulfotransferase 1 (HS3ST1) is a metabolic-related gene of HS. The present study was aimed at exploring the role of HS3ST1 in the progress of non-small-cell lung cancer (NSCLC). Our results illustrated that HS3ST1 promoted the malignant behaviors of NSCLC cells both in vitro and in vivo. HS3ST1 was found to inhibit spot-type zinc finger protein (SPOP) expression, which might inhibit the NF-κB pathway activation through mediating the degradation of Fas-associated death domain protein (FADD). By analyzing NSCLC patient samples, we also found increased HS3ST1 expression and decreased SPOP expression in tumor tissues in contrast with those in adjoining normal tissues. In conclusion, HS3ST1 promotes NSCLC tumorigenesis by regulating SPOP/FADD/NF-κB pathway.

The diagnostic value of transbronchial lung cryobiopsy combined with rapid on-site evaluation in diffuse lung diseases: a prospective and self-controlled study.

BACKGROUND: The etiology of interstitial lung diseases (ILDs) is varied. Early diagnosis and a specific pathological type could significantly improve the prognosis. Mostly, it is difficult to make the etiology diagnosis of ILD through traditional biopsy methods. It will be of great significance to explore an effective biopsy method. METHODS: The prospective study was designed to evaluate the diagnostic value of transbronchial lung cryobiopsy (TBCB) combined with rapid on-site evaluation (ROSE), compared with conventional transbronchial lung biopsy (TBLB), in a large sample of ILD patients. All patients enrolled will undergo both TBLB and TBCB procedures. The study will observe the differences in the diagnostic efficiency of pathological typing and incidence of operation-related complications between TBCB and TBLB. Besides, it will analyze the relationship between the time of biopsy and the incidence of complications, the relationship between freezing time, size of specimen, and complications. And it will evaluate the consistency of pathological, clinical, and radiology. DISCUSSION: It may be the first time that ROSE technique will be used in the diagnosis of ILD. The results of this study will clarify the value of TBCB in the diagnosis of ILD and confirm its safety and effectiveness, which is expected to significantly improve the efficiency of diagnosis in ILD patients. TRAIL REGISTRATION: The trial was registered on the Chinese Clinical Trial Registry website ( http://www.chictr.org.cn/showproj.aspx?proj=57834 ) (Registration number: ChiCTR2000035492).

Magnetic resonance imaging of focal fibrocartilaginous dysplasia - findings derived from a three-dimensional gradient echo sequence.

BACKGROUND: Focal fibrocartilaginous dysplasia is a rare benign bone lesion of young children that causes deformities in the extremities. However, the pathogenesis and treatments have not been defined and the MR manifestations have been less well described. OBJECTIVE: To describe the MR manifestations of focal fibrocartilaginous dysplasia, especially on the T1-W three-dimensional (3-D) volumetric interpolated breath-hold examination (VIBE) sequence. MATERIALS AND METHODS: In this retrospective study, the authors reviewed the MR and radiographic images, pathology and medical records of 21 cases of focal fibrocartilaginous dysplasia. All cases were evaluated by spin-echo MRI sequence. Among them, 17 cases were evaluated by T1-W 3-D VIBE sequence. RESULTS: The cohort consisted of 13 boys and 8 girls ages 4-75 months. In 14 cases, focal fibrocartilaginous dysplasia was located in the tibia, 3 in the femur and 4 in the ulna. MRI 3-D VIBE sequence findings showed all cases had hypointense fiber band structures in the bone defect areas. The fibrous bands in the lower extremities ended in the epiphysis or epiphyseal plate, and in the upper extremities the epiphysis or carpal bone. Ten cases had hyperintensities that might represent cartilage composition. Four cases had cartilage signals that were continuous with the epiphyseal cartilage. MR spin-echo sequence findings showed that bone marrow edema of the adjacent joint was observed in eight cases, enlargement of the epiphyseal plate in three cases and medial meniscus injury in five cases. CONCLUSION: The 3-D VIBE sequence reveals useful details in focal fibrocartilaginous dysplasia.

The predicting roles of carcinoembryonic antigen and its underlying mechanism in the progression of coronavirus disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has induced a worldwide epidemiological event with a high infectivity and mortality. However, the predicting biomarkers and their potential mechanism in the progression of COVID-19 are not well known. OBJECTIVE: The aim of this study is to identify the candidate predictors of COVID-19 and investigate their underlying mechanism. METHODS: The retrospective study was conducted to identify the potential laboratory indicators with prognostic values of COVID-19 disease. Then, the prognostic nomogram was constructed to predict the overall survival of COVID-19 patients. Additionally, the scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of the most important prognostic indicators in lungs and peripherals, respectively. RESULTS: In total, 304 hospitalized adult COVID-19 patients in Wuhan Jinyintan Hospital were included in the retrospective study. CEA was the only laboratory indicator with significant difference in the univariate (P < 0.001) and multivariate analysis (P = 0.020). The scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of CEA in lungs and peripherals, respectively. The results revealed the potential roles of CEA were significantly distributed in type II pneumocytes of BALF and developing neutrophils of PBMCs, participating in the progression of COVID-19 by regulating the cell-cell communication. CONCLUSION: This study identifies the prognostic roles of CEA in COVID-19 patients and implies the potential roles of CEACAM8-CEACAM6 in the progression of COVID-19 by regulating the cell-cell communication of developing neutrophils and type II pneumocyte.

Comparison of traditional methods and high-throughput genetic sequencing in the detection of pathogens in pulmonary infectious diseases.

BACKGROUND: The major causes of pulmonary infections are various microorganisms. This study aimed to compare the positive rates of pathogenic microorganism DNA/RNA high-throughput genetic sequencing (PMseq), which is an emerging technique, with traditional methods for pulmonary disease detection, and to investigate the differences in different sample types. METHODS: Bronchoalveolar lavage fluid (BALF) and venous blood samples from 104 patients were collected for detection. RESULTS: The positive rates of PMseq in BALF and venous blood were both significantly higher than those of traditional methods in the same sample (P<0.001). For BALF, the detection sensitivities were 96.9% for non-febrile patients and 100% for febrile patients. For venous blood, the detection sensitivities were 50.0% for non-febrile patients and 81.3% for febrile patients. There was no statistical difference in the sensitivity of venous blood samples with or without fever (P=0.075). For patients without fever, the sensitivity of BALF was much higher than venous blood samples (P<0.001). In patients with fever, there were no significant differences between different samples. CONCLUSIONS: This study showed that PMseq has a higher positive rate for the detection of pulmonary diseases. For patients without fever, it is recommended to use BALF instead of venous blood samples because of the higher sensitivity. However, for patients with fever, venous blood samples can be used when bronchoalveolar lavage is inconvenient.

A randomized trial in the investigation of anxiety and depression in patients with coronavirus disease 2019 (COVID-19).

BACKGROUND: In March 2020, the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern. A small proportion of patients infected with COVID-19 go on to develop pneumonia. We speculated that COVID-19 may be likely to result in psychological disorders such as anxiety and depression. In this study, we conducted an investigation of anxiety and depression in patients with COVID-19. METHODS: Sixty-five COVID-19 patients were randomly enrolled into this study. Anxiety and depression among participants were measured through the completion of anonymous Chinese-language Zung self-rating anxiety scale and self-rating depression scale questionnaires. Data were analyzed using independent samples t-tests, Mann-Whitney U-tests, and χ2 tests. RESULTS: The questionnaire results showed that 26.15% and 41.54% of participants suffered from anxiety and depression, respectively, although there was no significantly statistical difference between the proportions of COVID-19 patients with anxiety and depression. Statistically significant differences in employment status, partial pressure of oxygen, and corticosteroid application existed between moderate- and severe COVID-19 patients (P<0.05). In particular, the partial pressure of oxygen was significantly lower in severe COVID-19 patients than in their moderate counter parts (71.31±23.54 vs. 101.06±34.43, U=156, P=0.006). Total lymphocytes was lower in severe group than in moderate group [1.659±0.643 vs. 0.745 (0.645, 0.928), U=109, P=0.000]. Also, a higher proportion of female than male patients had anxiety (χ2=5.388, P=0.02). COVID-19 patients who received antiviral medications also displayed a higher rate of anxiety (χ2=4.481, P=0.034). Total lymphocytes between the non-anxiety and anxiety had statistical difference (U=321, P=0.019). Meanwhile, total lymphocytes between the non-depression and depression also had statistical difference (U=389.5, P=0.01). CONCLUSIONS: Among patients with COVID-19, females and those treated with antiviral medications were more likely to experience anxiety. In addition, our findings reflected the effect of anxiety and depression on immune system.

Associations of serum cryptococcal antigen with different of clinical characteristics: a comprehensive analysis of 378 pulmonary cryptococcosis patients.

BACKGROUND: Pulmonary cryptococcosis (PC) is an infection typically diagnosed in immunocompromised or immunocompetent patients, which can lead to severe disease if not treated appropriately. We aimed to determine the association between clinical manifestations, computed tomography (CT) findings, and host immune status with the serum cryptococcal antigen (CRAG) test results of PC patients. METHODS: The clinical data of 378 PC patients over a 12-year period were retrospectively reviewed at Shanghai Pulmonary Hospital (Shanghai, China). Serum CRAG was detected by a latex agglutination (LA) test using CryptoTrol (Immuno-Mycologics Inc., Norman, OK, USA). Patients were categorized according to their serum LA results, and their clinical characteristics were analyzed: 244 of 378 patients showed positive serum LA results and 134 had negative results. RESULTS: Immunocompromised hosts (ICH) were more likely to present positive LA results. The ICH group had higher titers of LA test than the non-immunocompromised host (NICH) group. Patients with negative LA results often had no symptoms and their CT findings presented a solitary nodule or mass, while LA-positive patients had variable symptoms such as cough, expectoration, fever, etc. A large diversity of CT manifestations were observed in the LA-positive patients, such as multiple nodules, patchy shadows, interstitial infiltrates, and diffuse granular shadows. Patients with a solitary nodule or mass had lower titers than did the patients with other manifestations. The clinical characteristics of LA-positive patients were different from those of LA-negative patients. CONCLUSIONS: Serum CRAG test results were found to be associated with the clinical manifestations, CT findings, and host immune status of PC patients.

Diagnosis and treatment of 471 patients with 2019 novel coronavirus disease (COVID-19).

BACKGROUND: While the 2019 novel coronavirus disease (COVID-19) outbreak has been largely kept under control in China, it remains a global pandemic, and the source, transmission route, and treatments of SARS-COV-2 are still being investigated. Here, we summarized the clinical features, diagnosis, treatment, and prognosis of COVID-19 patients based on our clinical practice. METHODS: The clinical and imaging findings, treatments, and follow-up data of 471 patients with COVID-19 who were discharged from the Wuhan Jinyintan Hospital prior to February 6, 2020, were retrospectively analyzed. RESULTS: Among these patients, there were 2 mild cases, 282 moderate cases, 181 severe cases, and 6 critical cases. There were 250 males and 221 females aged 17 to 90 years. The median age was 54 years in the severe/critical group, which was significantly older than in the mild/moderate group (P<0.05). 44.59% of them had one or more underlying diseases. The most common symptoms were fever, cough, expectoration, and dyspnea. The median body temperature in the severe/critical group was 39°C, which was significantly higher than in the mild/moderate group (P<0.05). The incidences of lymphopenia and CD4+ T lymphocytopenia were 53.5% and 41.86%, respectively. Ground-glass opacity and small patchy shadows were the most common findings on chest computed tomography (CT). Compared with the mild/moderate group, the severe/critical group showed higher proportions of severe lymphocytopenia and CD4+ T lymphocytopenia, along with more ground-glass shadows and large-scale consolidation. After anti-infection, oxygen therapy, and symptomatic support, lymphocytes and CD4+ T lymphocytes were markedly increased, all patients were discharged. The median time of nucleic acid conversion and hospital stay were 9 and 12 days, respectively, which were significantly longer in the severe/critical group than in the mild/moderate group. Of the 390 cases followed, only 19 were hospitalized again due to other diseases. All patients recovered well from COVID-19, with negative nucleic acid test results. CONCLUSIONS: Lymphocytopenia and CD4+ T lymphocytopenia were found to be associated with COVID-19 and thus may be important indicators in evaluating the severity and prognosis. Multidisciplinary management including antiviral treatment, immune regulation, and symptomatic support is effective, and yields a low recurrence rate.

The clinical characteristics and prognosis of ABPA are closely related to the mucus plugs in central bronchiectasis.

INTRODUCTION: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear. OBJECTIVES: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs. METHODS: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated. RESULTS: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse. CONCLUSIONS: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.

The spatial differences in bone mineral density and hip structure between low-energy femoral neck and trochanteric fractures in elderly Chinese using quantitative computed tomography.

The purpose of this study was to investigate the differences in bone mineral density (BMD) and hip structure between femoral neck and trochanteric fractures in elderly Chinese individuals using quantitative computed tomography (QCT). A total of 625 Chinese patients (mean age 75.8 years) who sustained low-energy hip fractures (female: 293 femoral neck, 175 trochanteric; male: 82 femoral neck, 75 trochanteric) were recruited. Each patient underwent a hip QCT scan. The areal BMD (aBMD) of the contralateral normal hip was obtained using a computed tomography X-ray absorptiometry module. Using the bone investigation toolkit (BIT) module, the femoral neck was divided into four quadrants: supero-anterior (SA), infero-anterior (IA), infero-posterior (IP), and supero-posterior (SP). Estimated cortical thickness, cortical BMD, and trabecular BMD were measured in each quadrant. Using the hip structure analysis (HSA) function, several parameters were calculated. Stratified by sex, covariance analyses were applied to compare the femoral neck fractures group with trochanteric fractures group after adjustments for age, height, and weight. In women, trochanteric fractures exhibited lower trabecular BMD and estimated cortical thickness at three quadrants of the femoral neck (IA: P = 0.02, P < 0.01; IP: P < 0.01, P = 0.01; SP: P = 0.01, P < 0.01), and lower aBMD at the trochanter area (P < 0.01); femoral neck fractures exhibited lower cortical BMD and estimated cortical thickness at the SA quadrant (P = 0.04, P = 0.01). Differences in HSA parameters were not statistically significant. Among all parameters, the most valuable ones to discrimination of hip fracture type are estimated cortical thickness of the SA quadrant of femoral neck and the aBMD of the trochanter area. In men, only lower cortical BMD at the SP quadrant and aBMD at the trochanter were found in the trochanteric fractures (P = 0.02, P < 0.01). QCT outcomes indicate that spatial differences are helpful to explore the pathogenesis of different type of hip fractures. In women, trochanteric fractures are related to severer osteoporosis, whereas cortical fragility in the SA region of the femoral neck predominates in cases of femoral neck fractures. In men, trochanteric fractures are related to more bone loss of trochanter.

Clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis.

INTRODUCTION: Lung damage related to tuberculosis is a major contributor to the etiology of bronchiectasis in China. It is unknown whether bronchiectasis severity score systems are applicable in these cases. OBJECTIVES: To evaluate the clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis. METHODS: The study enrolled 596 bronchiectasis patients in Shanghai Pulmonary Hospital between January 2011 and December 2012. The data for calculating FACED and bronchiectasis severity index (BSI) scores along with mortality, readmission, and exacerbation outcomes were collected and analyzed within a follow-up period with a median length of 48 months (interquartile range 43-54 months). RESULTS: The study enrolled 101 post-tuberculosis bronchiectasis patients and 495 non-tuberculosis bronchiectasis patients. Compared with non-post-tuberculosis bronchiectasis, post-tuberculosis bronchiectasis patients experienced less bilateral bronchiectasis (P = .004), a higher frequency of right upper lobe involvement (P < .001) and showed the cylindrical type more often (P < .001). Follow-up data indicated that both scoring systems were able to predict 48(43-54) month mortality in post-tuberculosis patients as assessed by the area under the receiver operator characteristic curve (AUC) (FACED AUC = 0.81, BSI AUC = 0.70), but they did not predict readmission (FACED and BSI = 0.56) or exacerbation (FACED and BSI = 0.52) well. CONCLUSIONS: There are apparent differences on radiologic features between bronchiectasis patients with and without history of pulmonary tuberculosis. Both FACED and BSI can predict mortality in post-tuberculosis bronchiectasis.