Venetoclax acts as an immunometabolic modulator to potentiate adoptive NK cell immunotherapy against leukemia.

Natural killer (NK) cell-based immunotherapy holds promise for cancer treatment; however, its efficacy remains limited, necessitating the development of alternative strategies. Here, we report that venetoclax, an FDA-approved BCL-2 inhibitor, directly activates NK cells, enhancing their cytotoxicity against acute myeloid leukemia (AML) both in vitro and in vivo, likely independent of BCL-2 inhibition. Through comprehensive approaches, including bulk and single-cell RNA sequencing, avidity measurement, and functional assays, we demonstrate that venetoclax increases the avidity of NK cells to AML cells and promotes lytic granule polarization during immunological synapse (IS) formation. Notably, we identify a distinct CD161lowCD218b+ NK cell subpopulation that exhibits remarkable sensitivity to venetoclax treatment. Furthermore, venetoclax promotes mitochondrial respiration and ATP synthesis via the NF-κB pathway, thereby facilitating IS formation in NK cells. Collectively, our findings establish venetoclax as a multifaceted immunometabolic modulator of NK cell function and provide a promising strategy for augmenting NK cell-based cancer immunotherapy.

Towards clinically applicable automated mandibular canal segmentation on CBCT.

OBJECTIVES: To develop a deep learning-based system for precise, robust, and fully automated segmentation of the mandibular canal on cone beam computed tomography (CBCT) images. METHODS: The system was developed on 536 CBCT scans (training set: 376, validation set: 80, testing set: 80) from one center and validated on an external dataset of 89 CBCT scans from 3 centers. Each scan was annotated using a multi-stage annotation method and refined by oral and maxillofacial radiologists. We proposed a three-step strategy for the mandibular canal segmentation: extraction of the region of interest based on 2D U-Net, global segmentation of the mandibular canal, and segmentation refinement based on 3D U-Net. RESULTS: The system consistently achieved accurate mandibular canal segmentation in the internal set (Dice similarity coefficient [DSC], 0.952; intersection over union [IoU], 0.912; average symmetric surface distance [ASSD], 0.046 mm; 95% Hausdorff distance [HD95], 0.325 mm) and the external set (DSC, 0.960; IoU, 0.924; ASSD, 0.040 mm; HD95, 0.288 mm). CONCLUSIONS: These results demonstrated the potential clinical application of this AI system in facilitating clinical workflows related to mandibular canal localization. CLINICAL SIGNIFICANCE: Accurate delineation of the mandibular canal on CBCT images is critical for implant placement, mandibular third molar extraction, and orthognathic surgery. This AI system enables accurate segmentation across different models, which could contribute to more efficient and precise dental automation systems.

Identification and characterization of the karrikins signaling gene SsSMAX1 in Sapium sebiferum.

SUPPRESSOR OF MAX2 LIKE 1 (SMAX1) is a member of the SUPPRESSOR of MAX2 1­LIKE family of genes and is known as a target protein of KARRIKIN INSENSITIVE2 (KAI2)-MORE AXILLARY BRANCHES2 (MAX2), which mediates karrikin signaling in Arabidopsis. SMAX1 plays a significant role in seed germination, hypocotyl elongation, and root hair development in Arabidopsis. SMAX1 has not yet been identified and characterized in woody plants. This study identified and characterized SsSMAX1 in Sapium sebiferum and found that SsSMAX1 was highly expressed in the seed, hypocotyl, and root tips of S. sebiferum. SsSMAX1 was functionally characterized by ectopic expression in Arabidopsis. SsSMAX1 overexpression lines of Arabidopsis showed significantly delayed seed germination and produced seedlings with longer hypocotyl and roots than wild-type and Atsmax1 functional mutants. SsSMAX1 overexpression lines of Arabidopsis also had broader and longer leaves and petioles than wild-type and Atsmax1, suggesting that SsSMAX1 is functionally conserved. This study characterizes the SMAX1 gene in a woody and commercially valuable bioenergy plant, Sapium sebiferum. The results of this study are beneficial to future research on the molecular biology of woody plants.

Utilizing artificial intelligence-based eye tracking technology for screening ADHD symptoms in children.

Objective: To explore the potential of using artificial intelligence (AI)-based eye tracking technology on a tablet for screening Attention-deficit/hyperactivity disorder (ADHD) symptoms in children. Methods: We recruited 112 children diagnosed with ADHD (ADHD group; mean age: 9.40 ± 1.70 years old) and 325 typically developing children (TD group; mean age: 9.45 ± 1.59 years old). We designed a data-driven end-to-end convolutional neural network appearance-based model to predict eye gaze to permit eye-tracking under low resolution and sampling rates. The participants then completed the eye tracking task on a tablet, which consisted of a simple fixation task as well as 14 prosaccade (looking toward target) and 14 antisaccade (looking away from target) trials, measuring attention and inhibition, respectively. Results: Two-way MANOVA analyses demonstrated that diagnosis and age had significant effects on performance on the fixation task [diagnosis: F(2, 432) = 8.231, ***p < 0.001; Wilks' Λ = 0.963; age: F(2, 432) = 3.999, *p < 0.019; Wilks' Λ = 0.982], prosaccade task [age: F(16, 418) = 3.847, ***p < 0.001; Wilks' Λ = 0.872], and antisaccade task [diagnosis: F(16, 418) = 1.738, *p = 0.038; Wilks' Λ = 0.938; age: F(16, 418) = 4.508, ***p < 0.001; Wilks' Λ = 0.853]. Correlational analyses revealed that participants with higher SNAP-IV score were more likely to have shorter fixation duration and more fixation intervals (r = -0.160, 95% CI [0.250, 0.067], ***p < 0.001), poorer scores on adjusted prosaccade accuracy, and poorer scores on antisaccade accuracy (Accuracy: r = -0.105, 95% CI [-0.197, -0.011], *p = 0.029; Adjusted accuracy: r = -0.108, 95% CI [-0.200, -0.015], *p = 0.024). Conclusion: Our AI-based eye tracking technology implemented on a tablet could reliably discriminate eye movements of the TD group and the ADHD group, providing a potential solution for ADHD screening outside of clinical settings.

Alterations in the topological organization of the default-mode network in Tourette syndrome.

BACKGROUND: The exact pathophysiology of TS is still elusive. Previous studies have identified default mode networks (DMN) abnormalities in patients with TS. However, these literatures investigated the neural activity during the tic suppression, not a true resting-state. Therefore, this study aimed to reveal the neural mechanism of Tourette's syndrome (TS) from the perspective of topological organization and functional connectivity within the DMN by electroencephalography (EEG) in resting-state. METHODS: The study was conducted by analyzing the EEG data of TS patients with graph theory approaches. Thirty children with TS and thirty healthy controls (HCs) were recruited, and all subjects underwent resting-state EEG data acquisition. Functional connectivity within the DMN was calculated, and network properties were measured. RESULTS: A significantly lower connectivity in the neural activity of the TS patients in the ß band was found between the bilateral posterior cingulate cortex/retrosplenial cortex (t = -3.02, p < 0.05). Compared to HCs, the TS patients' local topological properties (degree centrality) in the left temporal lobe in the γ band were changed, while the global topological properties (global efficiency and local efficiency) in DMN exhibited no significant differences. It was also demonstrated that the degree centrality of the left temporal lobe in the γ band was positively related to the Yale Global Tic Severity Scale scores (r = 0.369, p = 0.045). CONCLUSIONS: The functional connectivity and topological properties of the DMN of TS patients were disrupted, and abnormal DMN topological property alterations might affect the severity of tic in TS patients. The abnormal topological properties of the DMN in TS patients may be due to abnormal functional connectivity alterations. The findings provide novel insight into the neural mechanism of TS patients.

Impact of non-pharmaceutical interventions during COVID-19 on future influenza trends in Mainland China.

BACKGROUND: Influenza is a common illness for its high rates of morbidity and transmission. The implementation of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic to manage its dissemination could affect the transmission of influenza. METHODS: A retrospective analysis, between 2018 and 2023, was conducted to examine the incidence of influenza virus types A and B among patients in sentinel cities located in North or South China as well as in Wuhan City. For validations, data on the total count of influenza patients from 2018 to 2023 were collected at the Central Hospital of Wuhan, which is not included in the sentinel hospital network. Time series methods were utilized to examine seasonal patterns and to forecast future influenza trends. RESULTS: Northern and southern cities in China had earlier outbreaks during the NPIs period by about 8 weeks compared to the 2018-2019. The implementation of NPIs significantly reduced the influenza-like illness (ILI) rate and infection durations. Influenza B Victoria and H3N2 were the first circulating strains detected after the relaxation of NPIs, followed by H1N1 across mainland China. The SARIMA model predicted synchronized H1N1 outbreak cycles in North and South China, with H3N2 expected to occur in the summer in southern cities and in the winter in northern cities over the next 3 years. The ILI burden is expected to rise in both North and South China over the next 3 years, with higher ILI% levels in southern cities throughout the year, especially in winter, and in northern cities mainly during winter. In Wuhan City and the Central Hospital of Wuhan, influenza levels are projected to peak in the winter of 2024, with 2 smaller peaks expected during the summer of 2023. CONCLUSIONS: In this study, we report the impact of NPIs on future influenza trends in mainland China. We recommend that local governments encourage vaccination during the transition period between summer and winter to mitigate economic losses and mortality associated with influenza.

A single-cell landscape of pre- and post-menopausal high-grade serous ovarian cancer ascites.

High-grade serous ovarian cancer (HGSOC) is a hormone-related cancer with high mortality and poor prognosis. Based on the transcriptome of 57,444 cells in ascites from 10 patients with HGSOC (including 5 pre-menopausal and 5 post-menopausal patients), we identified 14 cell clusters which were further classified into 6 cell types, including T cells, B cells, NK cells, myeloid cells, epithelial cells, and stromal cells. We discovered an increased proportion of epithelial cells and a decreased proportion of T cells in pre-menopausal ascites compared with post-menopausal ascites. GO analysis revealed the pre-menopausal tumor microenvironments (TME) are closely associated with viral infection, while the post-menopausal TME are mostly related to the IL-17 immune pathway. SPP1/CD44-mediated crosstalk between myeloid cells and B cells, NK cells, and stromal cells mainly present in the pre-menopausal group, while SPP1/PTGER4 -mediated crosstalk between myeloid cells and epithelial cells mostly present in the post-menopausal group.

Clinical data analysis of 86 patients with invasive infections caused by Malassezia furfur from a tertiary medical center and 37 studies.

Objective: Malassezia furfur (M. furfur) is a lipophilic, conditionally pathogenic yeast that mainly causes skin infections, but the reports of related invasive infections are increasing. The aim of this study is to provide clinical data to assist physicians in the management of patients with invasive infections caused by M. furfur. Methods: A case of pulmonary infection caused by M. furfur in a hematopoietic stem cell transplant patient for aplastic anemia was reported. In addition, the literature on invasive infection by M. furfur published in PubMed and Web of Science in English until 31 July 2022 was reviewed. Results: Clinical data analysis of 86 patients (from 37 studies and our case) revealed that most of them were preterm (44.2%), followed by adults (31.4%). M. furfur fungemia occurred in 79.1% of the 86 patients, and 45 of them were clearly obtained from catheter blood. Other patients developed catheter-related infections, pneumonia, peripheral thromboembolism, endocarditis, meningitis, peritonitis and disseminated infections. Thirty-eight preterm infants had underlying diseases such as very low birth weight and/or multiple organ hypoplasia. The remaining patients had compromised immunity or severe gastrointestinal diseases. 97.7% of patients underwent invasive procedures and 80.2% received total parenteral nutrition (TPN). Fever, thrombocytopenia and leukocytosis accounted for 55.8%, 38.4% and 24.4% of patients with M. furfur invasive infections, respectively. 69.8% of the patients received antifungal therapy, mainly amphotericin B (AmB) or azoles. Of 84 patients with indwelling catheters, 58.3% underwent the removal of catheters. TPN were discontinued in 30 of 69 patients. The all-cause mortality of 86 patients was 27.9%. Conclusions: M. furfur can cause a variety of invasive infections. These patients mostly occur in premature infants, low immunity and severe gastrointestinal diseases. Indwelling catheters and TPN infusion are major risk factors. AmB, l-AmB and azoles are the most commonly used agents, and simultaneous removal of the catheter and termination of TPN infusion are important for the treatment of M. furfur invasive infections.

[Distribution and Drug Sensitivity Analysis of Pathogenic Bacteria Isolated from Patients in Hematology Department].

OBJECTIVE: To investigate the distribution and drug sensitivity of pathogenic bacteria isolated from patients in hematology department, in order to provide evidence for rational use of antibiotics in clinic. METHODS: The distribution of pathogenic bacteria and drug sensitivity data of patients in the hematology department of The First Affiliated Hospital of Nanjing Medical University from 2015 to 2020 were retrospectively analyzed, and the pathogens isolated from different specimen types were compared. RESULTS: A total of 2 029 strains of pathogenic bacteria were isolated from 1 501 patients in the hematology department from 2015 to 2020, and 62.2% of which were Gram-negative bacilli, mainly Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii. Gram-positive coccus accounted for 18.8%, mainly Coagulase-negative staphylococcus (CoNS) and Staphylococcus aureus. Fungi (17.4%) were mainly candida. The 2 029 strains were mainly isolated from respiratory tract (35.1%), blood (31.8%) and urine (19.2%) specimens. Gram-negative bacilli were the main pathogenic bacteria in different specimen types (>60%). K. pneumoniae, S. maltophilia and A. baumannii were the most common pathogens in respiratory specimens, E. coli, CoNS, K. pneumoniae and P. aeruginosa were common in blood samples, and E. coli and Enterococcus were most common in urine samples. Enterobacteriaceae had the highest susceptibility to amikacin and carbapenems (>90.0%), followed by piperacillin/tazobactam. P. aeruginosa strains had high sensitivity to antibiotics except aztreonam (<50.0%). The susceptibility of A. baumannii to multiple antibiotics was less than 70.0%. The antimicrobial resistance rates of E. coli and K. pneumoniae in respiratory tract specimens were higher than those in blood specimens and urine specimens. CONCLUSION: Gram-negative bacilli are the main pathogenic bacteria isolated from patients in hematology department. The distribution of pathogens is different in different types of specimens, and the sensitivity of each strain to antibiotics is different. The rational use of antibiotics should be based on different parts of infection to prevent the occurrence of drug resistance.

Unique metabolism and protein expression signature in human decidual NK cells.

Human decidual natural killer (dNK) cells are a unique type of tissue-resident NK cells at the maternal-fetal interface. dNK cells are likely to have pivotal roles during pregnancy, including in maternal-fetal immune tolerance, trophoblast invasion, and fetal development. However, detailed insights into these cells are still lacking. In this study, we performed metabolomic and proteomic analyses on human NK cells derived from decidua and peripheral blood. We found that 77 metabolites were significantly changed in dNK cells. Notably, compared to peripheral blood NK (pNK) cells, 29 metabolites involved in glycerophospholipid and glutathione metabolism were significantly decreased in dNK cells. Moreover, we found that 394 proteins were differentially expressed in dNK cells. Pathway analyses and network enrichment analyses identified 110 differentially expressed proteins involved in focal adhesion, cytoskeleton remodeling, oxidoreductase activity, and fatty acid metabolism in dNK cells. The integrated proteomic and metabolomic analyses revealed significant downregulation in glutathione metabolism in dNK cells compared to pNK cells. Our data indicate that human dNK cells have unique metabolism and protein-expression features, likely regulating their function in pregnancy and immunity.

HBV reactivation in patients with chronic or resolved HBV infection following BCMA-targeted CAR-T cell therapy.

B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). Concern of the safety and efficacy of CAR-T cell therapy in patients with chronic or resolved HBV infection is raised. In this study, we retrospectively reviewed 99 patients with r/r MM treated with BCMA-targeted CAR-T cell therapy, of which 7 (7.1%) patients had chronic HBV infection, 43 (43.4%) with resolved HBV infection, and the remaining 49 (49.49%) HBV-uninfected. Patients' characteristics before CAR-T cell administration were comparable in different status of HBV infection. Patients' liver function, cytokine levels, CAR-T cell expansion and cytokine release syndrome (CRS) grade after CAR-T cell therapy did not differ in different HBV serologic status. Furthermore, chronic HBV infection or resolved HBV infection did not affect clinical response, progress-free survival (PFS), or overall survival (OS). Four (4.04%) patients experienced HBV reactivation, 3 (6.98%) with resolved HBV infection, and 1 (14.29%) chronic HBV infection. Of 4 patients with HBV reactivation, 2 cases (50%) of severe hepatitis were noted and reported. Drops of serum IgG and elevation of alanine aminotransferase (ALT), alanine aminotransferase (AST), total bilirubin (TB) were observed in all four patients around the date of HBV reactivation.

Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation.

Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.

Cytokine profiles are associated with prolonged hematologic toxicities after B-cell maturation antigen targeted chimeric antigen receptor-T-cell therapy.

BACKGROUND AIMS: The considerable efficacy of B-cell maturation antigen-targeted chimeric antigen receptor (CAR)-T-cell therapy has been extensively demonstrated in the treatment of relapsed or refractory multiple myeloma. Nevertheless, in clinical practice, prolonged hematologic toxicity (PHT) extends hospital stay and impairs long-term survival. METHODS: This retrospective study reviewed 99 patients with relapsed or refractory multiple myeloma who underwent B-cell maturation antigen CAR-T-cell therapy at our institution between April 2018 and September 2021 (ChiCTR1800017404). RESULTS: Among 93 evaluable patients, the incidence of prolonged hematologic toxicities was high after CAR-T-cell infusion, including 38.71% (36/93) of patients with prolonged neutropenia, 22.58% (21/93) with prolonged anemia and 59.14% (55/93) with prolonged thrombocytopenia. In addition, 9.68% (9/93) of patients experienced prolonged pancytopenia. Our multivariate analyses identified that cytokine profiles were independent risk factors for PHTs, whereas a sufficient baseline hematopoietic function and high CD4/CD8 ratio of CAR-T cells were protective factors for PHTs after CAR-T-cell infusion. Subgroup analyses found that the kinetics of post-CAR-T hematologic parameters were primarily determined by the collective effects of cytokine release syndrome and baseline hematopoietic functions, and showed influential weights for the three lineages. CONCLUSIONS: Our findings improve the understanding of the impact of cytokines on hematopoietic functions, which could contribute to the mechanism investigation and exploration of potential intervention strategies.

Endobronchial removal of the peripherally located foreign body with the ultrathin bronchoscopy and ultrathin cryoprobe guided by a manual navigating method: A case report.

RATIONAL: The bronchoscope is a preferential method used to remove airway foreign bodies, but for those located in the distal lumen of bronchus with long-time retention, how to remove them remains an intractable problem. PATIENT CONCERNS: A 57-year-old male presented with 2-week history of intermittent hemoptysis. Chest CT upon admission revealed a high-density opacity incarcerated in the distal basal segment of the left lower lobe, along with obstructive pneumonia. DIAGNOSES: The patient was diagnosed as foreign body aspiration. INTERVENTIONS: We firstly used a manual navigating method to draw a bronchoscopic map according to the thin-section CT. Then we adopted ultrathin bronchoscope (UTB) to remove the peripherally located foreign body. OUTCOMES: UTB successfully found the foreign body incarcerated in LB10ciiß under the guidance of manual navigation, but it was too tender to be extracted completely by forceps, and it was even pushed further away. Then 1.1 mm ultrathin cryoprobe was used, with an activation time of 4 seconds, the chili was frozen and completely removed. LESSONS: This first combined application of manual navigating method, UTB and ultrathin cryoprobe, successfully extracted foreign bodies lodged in the distal airways and thus avoided thoracic surgery.

Fetuin-A is an immunomodulator and a potential therapeutic option in BMP4-dependent heterotopic ossification and associated bone mass loss.

Heterotopic ossification (HO) is the abnormal formation of bone in extraskeletal sites. However, the mechanisms linking HO pathogenesis with bone mass dysfunction remain unclear. Here, we showed that mice harboring injury-induced and BMP4-dependent HO exhibit bone mass loss similar to that presented by patients with HO. Moreover, we found that injury-induced hyperinflammatory responses at the injury site triggered HO initiation but did not result in bone mass loss at 1 day post-injury (dpi). In contrast, a suppressive immune response promoted HO propagation and bone mass loss by 7 dpi. Correcting immune dysregulation by PD1/PDL1 blockade dramatically alleviated HO propagation and bone mass loss. We further demonstrated that fetuin-A (FetA), which has been frequently detected in HO lesions but rarely observed in HO-adjacent normal bone, acts as an immunomodulator to promote PD1 expression and M2 macrophage polarization, leading to immunosuppression. Intervention with recombinant FetA inhibited hyperinflammation and prevented HO and associated bone mass loss. Collectively, our findings provide new insights into the osteoimmunological interactions that occur during HO formation and suggest that FetA is an immunosuppressor and a potential therapeutic option for the treatment of HO.

CAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies.

Immunotherapy utilizing chimeric antigen receptor T cell (CAR-T) therapy holds promise for hematologic malignancies, however, response rates and associated immune-related adverse effects widely vary among patients. Here we show, by comparing diversity and composition of the gut microbiome during different CAR-T therapeutic phases in the clinical trial ChiCTR1800017404, that the gut flora characteristically differs among patients and according to treatment stages, and might also reflect patient response to therapy in relapsed/refractory multiple myeloma (MM; n = 43), acute lympholastic leukemia (ALL; n = 23) and non-Hodgkin lymphoma (NHL; n = 12). We observe significant temporal differences in diversity and abundance of Bifidobacterium, Prevotella, Sutterella, and Collinsella between MM patients in complete remission (n = 24) and those in partial remission (n = 11). Furthermore, we find that patients with severe cytokine release syndrome present with higher abundance of Bifidobacterium, Leuconostoc, Stenotrophomonas, and Staphylococcus, which is reproducible in an independent cohort of 38 MM patients. This study has important implications for understanding the biological role of the microbiome in CAR-T treatment responsiveness of hematologic malignancy patients, and may guide therapeutic intervention to increase efficacy. The success rate of CAR-T cell therapy is high in blood cancers, yet individual patient characteristics might reduce therapeutic benefit. Here we show that therapeutic response in MM, ALL and NHL, and occurrence of severe cytokine release syndrome in multiple myeloma are associated with specific gut microbiome alterations.

Risk factors associated with radiolucent foreign body inhalation in adults: a 10-year retrospective cohort study.

BACKGROUND: Foreign body aspiration (FBA) is a serious condition with high morbidity and mortality rates. Although chest radiography is generally the first radiologic modality used in diagnosis, a substantial percentage of foreign bodies are radiolucent in adults with diagnosis challenging. METHODS: Retrospective review of adult patients with FBA diagnosed by flexible electronic bronchoscopy from 2012 to 2022 collecting demographics, history, hospital presentation, radiographic, and operative details. Risk factors associated with radiolucent foreign body inhalation in adults were explored using appropriate statistical methods. RESULTS: Between 1 January 2012 and 1 January 2022, 114 adult patients diagnosed with FBA were enrolled. The median age of participants was 65 years (IQR 52-74). Multidetector computed tomography (MDCT) examinations identified 28 cases (25%) showing direct visualization of the foreign body (defined as the radiopaque group) and 86 cases (75%) in the radiolucent group. Multivariable stepwise linear regression analysis showed increased odds of radiolucent foreign body inhalation in adults associated with pneumonic patches in MDCT (OR 6.99; 95% CI 1.80-27.22; P = 0.005) and plants/meat foreign bodies (OR 6.17; 95% CI 1.12-33.96; P = 0.04). A witnessed choking history (OR 0.02; 95% CI 0-0.14; P < 0.001) was a protective factor of radiolucent foreign body inhalation in adults. CONCLUSIONS: Unlike radiopaque FBA, in those presenting with a suspected radiolucent foreign body aspiration, the diagnosis is far more challenging. Risk factors such as lacking a choking history, non-resolving pneumonia (pneumonic patches) in MDCT findings, and plants/meat foreign bodies may help in the early diagnosis of radiolucent foreign body inhalation in adults. Further prospective multicenter studies should be conducted to validate the findings.

Clinical Characteristics and Risk Factors for in-Hospital Mortality in 240 Cases of Infective Endocarditis in a Tertiary Hospital in China: A Retrospective Study.

Purpose: This study aimed (i) to investigate the clinical characteristics and risk factors related to in-hospital mortality in patients with infective endocarditis (IE) and (ii) to compare the differences in three age groups. Methods: A total of 240 IE cases diagnosed using the modified Duke criteria between January 2016 and December 2019 were included and retrospectively studied. Patients were stratified into three age groups: < 50 y, 50-65 y, and > 65 y. Results: The mean age of the patients was 51 ± 14 y, and 154 patients (64.2%) were male. In addition, 136 (56.7%) patients with IE had no previous cardiac disease. Congenital heart disease (CHD, 21.3%) was the most common underlying heart disease, followed by rheumatic heart disease (RHD, 8.8%). Streptococcus was found in 55 (22.9%) patients and was the most common causative pathogen, comprising 52.9% of all positive blood cultures. Echocardiography showed the presence of vegetations in 88.3% of cases and the predominant involvement of the left heart valves. Fever and cardiac murmur were the most frequent presentations, with no significant differences among age groups. Compared with younger patients, elderly patients had a lower operation rate and higher in-hospital mortality. The independent risk factors of in-hospital mortality were age > 65 y, intracranial infection, splenic embolization, cerebral hemorrhage, NYHA class III-IV, and prosthetic valve infection. Conclusion: CHD replaces RHD as the most common underlying heart disease in IE patients. Patients without previous cardiac disease are at increased risk of IE. Streptococcus is still the primary causative pathogen of IE. Elderly patients present with more comorbidities and complications, in addition to a more severe prognosis than younger patients. Age older than 65 y, intracranial infection, splenic embolization, cerebral hemorrhage, NYHA class III-IV, and prosthetic valve infection showed poorer in-hospital outcomes.