Generalized Camera-Based Infant Sleep-Wake Monitoring in NICUs: A Multi-Center Clinical Trial.

The infant sleep-wake behavior is an essential indicator of physiological and neurological system maturity, the circadian transition of which is important for evaluating the recovery of preterm infants from inadequate physiological function and cognitive disorders. Recently, camera-based infant sleep-wake monitoring has been investigated, but the challenges of generalization caused by variance in infants and clinical environments are not addressed for this application. In this paper, we conducted a multi-center clinical trial at four hospitals to improve the generalization of camera-based infant sleep-wake monitoring. Using the face videos of 64 term and 39 preterm infants recorded in NICUs, we proposed a novel sleep-wake classification strategy, called consistent deep representation constraint (CDRC), that forces the convolutional neural network (CNN) to make consistent predictions for the samples from different conditions but with the same label, to address the variances caused by infants and environments. The clinical validation shows that by using CDRC, all CNN backbones obtain over 85% accuracy, sensitivity, and specificity in both the cross-age and cross-environment experiments, improving the ones without CDRC by almost 15% in all metrics. This demonstrates that by improving the consistency of the deep representation of samples with the same state, we can significantly improve the generalization of infant sleep-wake classification.

Transient Neonatal Myasthenia Gravis Born to a Mother with Asymptomatic MG: A Case Report.

Myasthenia gravis (MG) is an autoimmune disease which can impact pregnancy. We describe a transient neonatal myasthenia gravis (TNMG) born to an asymptomatic mother aged 26. The newborn presented cyanosis and generalized muscular weakness quickly after birth. Nasal continuous positive airway pressure (nCPAP) ventilation was performed immediately. On day 3, detailed family history showed that the neonate's 50-year-old maternal grandmother was diagnosed as ocular MG at the age of 40. Ryanodine receptor calcium release channel antibody (RyR-Ab) and acetylcholine receptor antibody (AChR-Ab) tested on day 5 were positive. However, neostigmine tests were negative for the neonate. Intravenous immunoglobulin (IVIG) and oral pyridostigmine were administered. The infant was weaned from the ventilator on day 7. On day 10, the neonate's asymptomatic mother was confirmed to have positive AChR-Ab either. The neonate regained the capability of bottle feeding on day 17 and discharged on day 26. Asymptomatic pregnant women with MG family history can also deliver infants who develop TNMG. Testing AChR antibodies in pregnant women with a family history of MG should be necessary as TNMG was a life-threatening disease. With timely diagnosis and accurate treatment, TNMG can be effectively relieved.

Cigarette excise tax structure and cigarette prices in nine sub-Saharan African countries: evidence from the Global Adult Tobacco Survey.

BACKGROUND: Economic theory predicts that the excise tax structure influences the distribution of cigarette prices. Evidence shows that uniform specific excise tax structures exhibit the least price variability relative to other tax structures. The distribution of cigarette prices under different excise tax structures has never been examined for a group of African countries. OBJECTIVES: To examine the distribution of cigarette prices under different tax structures in nine African countries and to critically evaluate the effectiveness of African regional tax directives in promoting public health. METHODS: Data from the Global Adult Tobacco Survey, conducted in eight African countries during 2012-2018, and data from the 2017 Gambia Tobacco Survey were used to construct survey-derived cigarette prices. The coefficients of variation and skewness of the price distribution were compared in the context of each country's cigarette excise tax structure. RESULTS: The least price variability is found in countries with a uniform specific tax, or a mixed system with a minimum specific floor. Cigarette price variability is largest in countries with uniform ad valorem tax structures. Three of the four countries with ad valorem tax structures are in regional blocs, where the tax directives specify that they should implement an ad valorem structure. CONCLUSIONS: Regional tax directives that require the adoption of uniform specific excise taxes, or high minimum specific floors, could be an efficient way to get multiple African countries to adopt a tax structure that reduces substitution possibilities in response to excise tax increases.

A training program for improving the capacity of infection high-throughput sequencing and diagnosis in China.

BACKGROUND: Infectious diseases are a serious threat to human especially since the COVID-19 outbreak has proved the importance and urgency of their diagnosis and treatment again. Metagenomic next-generation sequencing (mNGS) has been widely used and recognized in clinical and carried out localized testing in hospitals. Increasing the training of mNGS detection technicians can enhance their professional quality and more effectively realize the application value of the hospital platform. METHODS: Based on the initial theoretical understanding and practice of the mNGS platform for localization construction, we have designed a training program to enhance the ability of technicians to detect pathogens by utilizing mNGS, and hence to conduct training practices nationwide. RESULTS: Until August 30, 2022, the page views of online classes have reached 51,500 times and 6 of offline small-scale training courses have been conducted. A total of 67 trainees from 67 hospitals have participated in the training with a qualified rate of 100%. After the training course, the localization platform of 1 participating hospital has been put into use, 2 have added the mNGS localization platform for admission, among which 3 have expressed strong intention of localization. CONCLUSIONS: This study focuses on the training procedures and practical experience of the project which is the first systematic standardized program of mNGS in the world. It solves the training difficulties in the current industry, and effectively promotes the localization construction and application of mNGS in hospitals. It has great development potential in the future and is worth further promotion.

Identification of important modules and biomarkers in tuberculosis based on WGCNA.

Background: Tuberculosis (TB) is a significant public health concern, particularly in China. Long noncoding RNAs (lncRNAs) can provide abundant pathological information regarding etiology and could include candidate biomarkers for diagnosis of TB. However, data regarding lncRNA expression profiles and specific lncRNAs associated with TB are limited. Methods: We performed ceRNA-microarray analysis to determine the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs). Weighted gene co-expression network analysis (WGCNA) was then conducted to identify the critical module and genes associated with TB. Other bioinformatics analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and co-expression networks, were conducted to explore the function of the critical module. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to validate the candidate biomarkers, and receiver operating characteristic analysis was used to assess the diagnostic performance of the candidate biomarkers. Results: Based on 8 TB patients and 9 healthy controls (HCs), a total of 1,372 differentially expressed lncRNAs were identified, including 738 upregulated lncRNAs and 634 downregulated lncRNAs. Among all lncRNAs and mRNAs in the microarray, the top 25% lncRNAs (3729) and top 25% mRNAs (2824), which exhibited higher median expression values, were incorporated into the WGCNA. The analysis generated 16 co-expression modules, among which the blue module was highly correlated with TB. GO and KEGG analyses showed that the blue module was significantly enriched in infection and immunity. Subsequently, considering module membership values (>0.85), gene significance values (>0.90) and fold-change value (>2 or < 0.5) as selection criteria, the top 10 upregulated lncRNAs and top 10 downregulated lncRNAs in the blue module were considered as potential biomarkers. The candidates were then validated in an independent validation sample set (31 TB patients and 32 HCs). The expression levels of 8 candidates differed significantly between TB patients and HCs. The lncRNAs ABHD17B (area under the curve [AUC] = 1.000) and ENST00000607464.1 (AUC = 1.000) were the best lncRNAs in distinguishing TB patients from HCs. Conclusion: This study characterized the lncRNA profiles of TB patients and identified a significant module associated with TB as well as novel potential biomarkers for TB diagnosis.

The incremental value of Mycobacterium tuberculosis trace nucleic acid detection in CT-guided percutaneous biopsy needle rinse solutions for the diagnosis of tuberculosis.

Introduction: Tuberculosis (TB) diagnosis still faces challenges with high proportion of bacteriologic test negative incidences worldwide. We assessed the diagnostic value of digital PCR (dPCR) analysis of ultramicro Mycobacterium tuberculosis (M.tb) nucleic acid in CT-guided percutaneous biopsy needle rinse solution (BNRS) for TB. Methods: BNRS specimens were consecutively collected and total DNA was purified. The concentrations of M.tb-specific IS6110 and IS1081 were quantified using droplet dPCR. The diagnostic performances of BNRS-dPCR and its sensitivity in comparison with conventional tests were analyzed. Results: A total of 106 patients were enrolled, 63 of whom were TB (48 definite and 15 clinically suspected TB) and 43 were non-TB. The sensitivity of BNRS IS6110 OR IS1081-dPCR for total, confirmed and clinically suspected TB was 66.7%, 68.8% and 60.0%, respectively, with a specificity of 97.7%. Its sensitivity was higher than that of conventional etiological tests, including smear microscopy, mycobacterial culture and Xpert using sputum and BALF samples. The positive detection rate in TB patients increased from 39.3% for biopsy AFB test alone to 73.2% when combined with BNRS-dPCR, and from 71.4% for biopsy M.tb molecular detection alone to 85.7% when combined with BNRS-dPCR. Conclusion: Our results preliminarily indicated that BNRS IS6110 OR IS1081-dPCR is a feasible etiological test, which has the potential to be used as a supplementary method to augment the diagnostic yield of biopsy and improve TB diagnosis.

Notch RGB-camera based SpO2 estimation: a clinical trial in a neonatal intensive care unit.

Regular and narrow-band RGB cameras are recently explored for contactless SpO2 monitoring. Regular RGB cameras with cross-band overlap provide a high signal-to-noise-ratio (SNR) in measuring the photoplethysmographic signals but possess high dependency on the spectra of incident light, whereas narrow-band RGB cameras have better spectral independence but lower SNR especially in dim lighting conditions, such as in the neonatal intensive care unit (NICU). This paper proposes a notch RGB camera based SpO2 measurement approach that uses an optical notch filter to attenuate the wavelengths of 580-605 nm of a regular RGB camera to improve the spectral independence while maintaining high SNR in signal measurement. The proposed setup was validated in the lab condition (e.g. dark chamber) against the existing solutions for visible-light based camera-SpO2 measurement and further verified in the NICU on preterm infants. The clinical trial conducted in the NICU with 22 preterm infants shows that the notch RGB camera can achieve a mean absolute error (MAE) less than 4% for SpO2 measurement. This is the first showcase of continuous monitoring of absolute camera-SpO2 values in the NICU.

A Femoral Neck Osteotomy for the Patients with Ankylosing Spondylitis and Thoracolumbar Kyphosis Combined with Hip Flexion Contracture.

OBJECTIVE: The surgical treatment of patients with ankylosing spondylitis and severe thoracolumbar kyphosis combined with hip flexion contracture is very difficult for all the surgeons. The femoral neck osteotomy (FNO) is the first step to break the ice. The evaluation of a new modified FNO method is very important to improve the curative effect. METHODS: Five male patients with nine bone-fused hips who underwent the new femoral neck osteotomy were included from October 2021 to March 2022. The FNO was designed that the saw blade was manipulated from the lateral femoral neck base to the inferior part of the femoral head, keeping Pauwels' angle less than 30° on the coronal plane. On the transverse plane, the angle between the saw blade and the coronal plane was more than 15°. On the sagittal plane, the saw blade cut through the femoral neck. They accepted pedicle subtraction osteotomy (PSO) after FNO according to the patient' recovery. Then, 2 weeks later, the patients underwent total hip arthroplasty (THA). The visual analogue scale (VAS), Harris hip score (HHS) and passive hip flexion-extension range of motion (ROM) were used to evaluate hip function. The data were analyzed by paired t-test. RESULTS: The average operation time and blood loss of FNO, the average interval between FNO and THA were collected. The average angle of the trunk and lower limb (ATL) was 36.33° ± 16.36° pre-FNO, 82.89° ± 13.51° post-FNO and 175.22° ± 3.42° post-THA. The average VAS scores were 0 pre-FNO, 5 ± 1.58 post-FNO and 2.6 ± 0.55 post-THA. The average HHS was 43.56 ± 1.59 preoperatively and 83.89 ± 2.21 postoperatively. The average hip extension ROM was 23.89° ± 12.69° pre-FNO, -22.67° ± 14.18° post-FNO and - 3.33° ± 2.50 post-THA°. The average hip flexion ROM was 23.89° ± 12.69° pre-FNO, 35.56° ± 12.11° post-FNO and 104.44° ± 5.27° post-THA. The differences among them were significant (p < 0.05). Only one hip (11.11%) displaced completely after FNO. CONCLUSION: A new modified FNO was developed, which can provide osteotomy with a certain degree of stability and greater ease for performing PSO and THA.

Transcutaneous auricular vagus nerve stimulation improves working memory in temporal lobe epilepsy: A randomized double-blind study.

AIMS: This study investigated the impact of transcutaneous auricular vagus nerve stimulation (taVNS) on working memory (WM) in refractory temporal lobe epilepsy (rTLE) and the underlying mechanisms. METHODS: In this randomized double-blind study, 28 rTLE patients were subjected to an active or sham taVNS (a/s-taVNS) protocol for 20 weeks (a-taVNS group, n = 19; s-ta VNS group, n = 9). Patients performed visual WM tasks during stimulation and neural oscillations were simultaneously recorded by 19-channel electroencephalography. RESULTS: Compared with the baseline state, reaction time was significantly shorter after 20 weeks of taVNS in the a-taVNS group (p = 0.010), whereas no difference was observed in the s-taVNS group (p > 0.05). The power spectral density (PSD) of the theta frequency band in the Fz channel decreased significantly after a-taVNS during WM-encoding (p = 0.020), maintenance (p = 0.038), and retrieval (p = 0.039) phases, but not in the s-taVNS group (all p > 0.05). CONCLUSION: Neural oscillations during WM were altered by taVNS and WM performance was improved. Alterations in frontal midline theta oscillations may be a marker for the effect of taVNS on cognitive regulation.

Prevalence and Covariates of Electronic Cigarette Use among Students Aged 13-15 Years in the Philippines: 2019 Global Youth Tobacco Survey.

Electronic cigarette use is growing in popularity and accessibility among youth in the Southeast Asia region. We analyzed data on 6670 students, aged 13-15 years, from the Philippines' 2019 Global Youth Tobacco Survey. Prevalence estimates and 95% confidence intervals (CI) were estimated for current use (i.e., past 30 days), ever use, and awareness of e-cigarettes. Chi-square tests compared prevalence differences between groups. Multiple logistic regression models assessed factors associated with e-cigarette use while controlling for sociodemographic characteristics, current use of other tobacco products, and secondhand smoke exposure. Prevalence of current e-cigarette use was 14.1% (95% CI = 12.4%, 15.8%), ever use was 24.6% (95% CI = 22.4%, 26.9%), and awareness was 75.5% (95% CI = 73.0%, 78.0%). Current use of any other tobacco products and exposure to secondhand smoke at home, school, or other public places were positively associated with current and ever use of e-cigarettes. Boys and youth living in Luzon or Mindanao had higher odds of current e-cigarette use compared to girls and youth in Visayas. Findings indicated that one in four Philippine students aged 13-15 years ever used e-cigarettes and one in seven currently use e-cigarettes. This study highlights the importance of implementing evidence-based strategies, including relevant tobacco control policies.

Achieving safe and high-performance gastrointestinal tract spectral CT imaging with small-molecule lanthanide complex.

BACKGROUND: Non-intrusive imaging of gastrointestinal (GI) tract using computed tomography (CT) contrast agents is of the most significant issues in the diagnosis and treatment of GI diseases. Moreover, spectral CT, which can generate monochromatic images to display the X-ray attenuation characteristics of contrast agents, provides a better imaging sensitivity for diagnose inflammatory bowel disease (IBD) than convention CT imaging. METHODS: Herein, a convenient and one-pot synthesis method is provided for the fabrication of small-molecule lanthanide complex Holmium-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (Ho-DOTA) as a biosafe and high-performance spectral CT contrast agent for GI imaging with IBD. In vivo CT imaging was administered with both healthy mice and colitis mice induced by dextran sodium sulfate. RESULTS: We found that Ho-DOTA accumulated in inflammation sites of large intestines and produced high CT contrast compared with healthy mice. Both in vitro and in vivo experimental results also showed that Ho-DOTA provided much more diagnostic sensitivity and accuracy due to the excellent X-ray attenuation characteristics of Ho-DOTA compared with clinical iodinate agent. Furthermore, the proposed contrast media could be timely excreted from the body via the urinary and digestive system, keeping away from the potential side effects due to long-term retention in vivo. CONCLUSION: Accordingly, Ho-DOTA with excellent biocompatibility can be useful as a potential high-performance spectral CT contrast agent for further clinical imaging of gastrointestinal tract and diagnosis of intestinal system diseases.

Reduction quality in lateral view of X-ray and hypoalbuminemia are associated with postoperative mortality in elderly pertrochanteric fracture patients.

Background: Pertrochanteric fracture is one of the most prevalent public health issues across the world for the elderly population. The purpose of this study was to investigate the association between surgical factors and postoperative mortality in patients with intramedullary nail-treated pertrochanteric fractures. Methods: A retrospective cohort study was designed to evaluate the pertrochanteric fracture patients treated with intramedullary nail between January 2016 to February 2021. The surgical factors included the Dorr morphology, Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association (AO/OTA) classification of fractures, the tip-apex distance (TAD), location of the cephalic screw, reduction quality in anterior-posterior (AP) and lateral views, the integrity of the lateral wall, and the design of cephalic screws. Using univariate and multivariate Cox proportional hazard models, the association between these risk factors and postoperative mortality in patients with this type of fractures was evaluated. Results: A total of 169 pertrochanteric fracture patients treated with intramedullary nails were included in our study, with the average age of 82.68±5.93 years. The mortality rates at 3 months, 1 year, and the end of follow-up were 4.14%, 11.24%, and 26.04%, respectively. According to the univariate Cox analysis, age, gender, preoperative levels of hemoglobin (Hb) and albumin (Alb) were associated with a poor overall survival (OS) (P<0.05). After multivariate adjustment, the pre-operative level of Alb (P<0.001) and the reduction in lateral view (P<0.001) were shown to be independent risk factors for poor OS. Conclusions: The preoperative hypoalbuminemia and reduction quality in lateral view were associated with postoperative mortality in our study. Therefore, optimizing both parameters could improve the prognosis in elderly pertrochanteric fracture patients.

The role of Mycobacterium tuberculosis acetyltransferase and protein acetylation modifications in tuberculosis.

Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis (M. tb), which has been a significant burden for a long time. Post-translational modifications (PTMs) are essential for protein function in both eukaryotic and prokaryotic cells. This review focuses on the contribution of protein acetylation to the function of M. tb and its infected macrophages. The acetylation of M. tb proteins plays a critical role in virulence, drug resistance, regulation of metabolism, and host anti-TB immune response. Similarly, the PTMs of host proteins induced by M. tb are crucial for the development, treatment, and prevention of diseases. Host protein acetylation induced by M. tb is significant in regulating host immunity against TB, which substantially affects the disease's development. The review summarizes the functions and mechanisms of M. tb acetyltransferase in virulence and drug resistance. It also discusses the role and mechanism of M. tb in regulating host protein acetylation and immune response regulation. Furthermore, the current scenario of isoniazid usage in M. tb therapy treatment is examined. Overall, this review provides valuable information that can serve as a preliminary basis for studying pathogenic research, developing new drugs, exploring in-depth drug resistance mechanisms, and providing precise treatment for TB.

Changes in Tobacco Product Use Among Students Aged 13 to 15 Years in 34 Countries, Global Youth Tobacco Survey, 2012-2020.

INTRODUCTION: Most adults who currently use tobacco start before age 21. Comprehensive, cost-effective strategies and interventions to prevent initiation and encourage tobacco use cessation among youth are critical aspects of protecting youth from the harms of commercial tobacco. We describe changes in current tobacco product use among youth in 34 sites using data from the Global Youth Tobacco Survey (GYTS). METHODS: GYTS is a nationally representative school-based survey of students aged 13 to 15 years. The analysis included 34 sites that completed 2 survey waves during 2012-2020. Prevalence of current tobacco use was assessed for each country. Marginal effects in multivariable logistic regression models were used to estimate adjusted prevalence difference (aPD) between waves. RESULTS: The adjusted prevalence of current tobacco product use remained unchanged in more than 60% of the included sites. For any tobacco use, significant decreases were reported for Bhutan (aPD = -8.1; 95% CI, -12.9 to -3.4), Micronesia (aPD = -7.2; 95% CI, -9.7 to -4.7), San Marino (aPD = -7.0; 95% CI, -11.2 to -2.7), Togo (aPD = -2.7; 95% CI, -4.6 to -0.7), and Panama (aPD = -2.2; 95% CI, -4.1 to -0.4); significant increases were reported for Moldova, Albania, and Paraguay. Current e-cigarette use increased significantly in 7 of 10 sites. CONCLUSION: Data show that progress toward reducing tobacco use among youth stalled during 2012-2020, while e-cigarette use increased in a few sites with available data.

Reasons to decrease or stop nicotine and tobacco use among adults and association with MPOWER scores in twenty-one middle- and high-income countries, 2019-2020.

INTRODUCTION: This study examined reasons why people planned to reduce or stop tobacco consumption and their relationship with MPOWER scores, adjusting for sociodemographic, cultural, and economic factors. METHODS: Data used were Euromonitor International's Voice of the Consumer: Nicotine Survey 2019-2020, World Bank's country income and WHO's MPOWER policy scores. Analytical sample included 21913 adults of legal smoking age in 21 middle- and high-income countries who used nicotine and tobacco products and planned to reduce or stop their consumption in the next 12 months. Poisson regression models with robust error variance, adjusted for sociodemographic and tobacco use covariables, generated adjusted risk ratios (ARRs) of selecting a certain reason to reduce tobacco consumption dependent on continuous MPOWER scores. RESULTS: Main reasons to reduce or stop tobacco consumption were improving health (85%), saving money (65%), pressure from family (19%), and using another substance instead (4%). Country variation was observed by MPOWER scores. Positive associations were found between some MPOWER scores and reasons to reduce or stop tobacco consumption: enforcing bans on tobacco advertising and using another substance (ARR=1.28; 95% CI: 1.11-1.47); warning about dangers of tobacco and saving money (ARR=1.25; 95% CI: 1.19-1.32); offering help to quit tobacco and using another substance (ARR=1.26; 95% CI: 1.10-1.45) or family pressure (ARR=1.11; 95% CI: 1.04-1.17); anti-tobacco campaigns and using another substance (ARR=1.15; 95% CI: 1.08-1.23); and raising taxes and saving money (ARR=1.11; 95% CI: 1.09-1.13). CONCLUSIONS: MPOWER scores are associated with reported reasons to quit tobacco including to improve health, save money, respond to family pressure or use another substance instead.

Evaluation of the IP-10 mRNA release assay for diagnosis of TB in HIV-infected individuals.

HIV-infected individuals are susceptible to Mycobacterium tuberculosis (M.tb) infection and are at high risk of developing active tuberculosis (TB). Interferon-gamma release assays (IGRAs) are auxiliary tools in the diagnosis of TB. However, the performance of IGRAs in HIV-infected individuals is suboptimal, which limits clinical application. Interferon-inducible protein 10 (IP-10) is an alternative biomarker for identifying M.tb infection due to its high expression after stimulation with M.tb antigens. However, whether IP-10 mRNA constitutes a target for the diagnosis of TB in HIV-infected individuals is unknown. Thus, we prospectively enrolled HIV-infected patients with suspected active TB from five hospitals between May 2021 and May 2022, and performed the IGRA test (QFT-GIT) alongside the IP-10 mRNA release assay on peripheral blood. Of the 216 participants, 152 TB patients and 48 non-TB patients with a conclusive diagnosis were included in the final analysis. The number of indeterminate results of IP-10 mRNA release assay (13/200, 6.5%) was significantly lower than that of the QFT-GIT test (42/200, 21.0%) (P = 0.000026). IP-10 mRNA release assay had a sensitivity of 65.3% (95%CI 55.9% - 73.8%) and a specificity of 74.2% (95%CI 55.4% - 88.1%), respectively; while the QFT-GIT test had a sensitivity of 43.2% (95%CI 34.1% - 52.7%) and a specificity of 87.1% (95%CI 70.2% - 96.4%), respectively. The sensitivity of the IP-10 mRNA release assay was significantly higher than that of QFT-GIT test (P = 0.00062), while no significant difference was detected between the specificities of these two tests (P = 0.198). The IP-10 mRNA release assay showed a lower dependence on CD4+ T cells than that of QFT-GIT test. This was evidenced by the fact that the QFT-GIT test had a higher number of indeterminate results and a lower sensitivity when the CD4+ T cells counts were decreased (P < 0.05), while no significant difference in the number of indeterminate results and sensitivity were observed for the IP-10 mRNA release assay among HIV-infected individuals with varied CD4+T cells counts (P > 0.05). Therefore, our study suggested that M.tb specific IP-10 mRNA is a better biomarker for diagnosis of TB in HIV-infected individuals.

Targeting breast cancer stem cells directly to treat refractory breast cancer.

For patients with refractory breast cancer (BC), integrative immunotherapies are emerging as a critical component of treatment. However, many patients remain unresponsive to treatment or relapse after a period. Different cells and mediators in the tumor microenvironment (TME) play important roles in the progression of BC, and cancer stem cells (CSCs) are deemed the main cause of relapse. Their characteristics depend on their interactions with their microenvironment as well as on the inducing factors and elements in this environment. Strategies to modulate the immune system in the TME of BC that are aimed at reversing the suppressive networks within it and eradicating residual CSCs are, thus, essential for improving the current therapeutic efficacy of BC. This review focuses on the development of immunoresistance in BCs and discusses the strategies that can modulate the immune system and target breast CSCs directly to treat BC including immunotherapy with immune checkpoint blockades.

A Higher Postoperative Barthel Index at Discharge is Associated with a Lower One-Year Mortality After Hip Fracture Surgery for Geriatric Patients: A Retrospective Case‒Control Study.

Purpose: To evaluate the relationship between the postoperative Barthel index assessing activities of daily living at discharge and the one-year mortality after hip fracture surgery. Methods: Patients with hip fracture admitted to Peking University First Hospital from January 2015 to January 2020 were enrolled retrospectively according to the inclusion and exclusion criteria. The Barthel index and other related confounding variables were collected. Logistic regression and Kaplan‒Meier survival curves were constructed to explore the relationship between the postoperative Barthel index at discharge and the one-year mortality of geriatric patients after hip fracture surgery. Results: A total of 444 patients with a mean age of 81.61±6.14 years were included. A significant difference was not observed in the preoperative Barthel index at admission between the deceased group and the surviving group (38.90±15.83 vs 36.96±10.74, p=0.446). However, the difference in the postoperative Barthel index at discharge between these two groups was statistically significant (43.08±14.40 vs 53.18±13.43, P<0.001). The multivariable logistic regression analysis revealed that the postoperative Barthel index at discharge was an independent risk factor for one-year mortality after adjustment for confounding variables (adjusted OR 0.73, 95% CI 0.55-0.98, p˂0.05). The Kaplan‒Meier survival curve showed that patients who had a high Barthel index (≥50) at discharge had a significantly lower mortality in the long term than patients with a low Barthel index (<50) at discharge (P< 0.001). Conclusion: The postoperative Barthel index at discharge was independently associated with the one-year mortality of geriatric patients after hip fracture surgery. A higher postoperative Barthel index at discharge indicated a lower mortality after hip fracture surgery. The Barthel index at discharge has the potential to provide essential prognostic information for early risk stratification and directing future care.

Construction and Validation of a Nomogram for Predicting Acute Kidney Injury After Hip Fracture Surgery.

Background: Acute kidney injury (AKI), characterized by sudden impairment of kidney function, is an uncommon complication following hip fracture surgery that is associated with increased morbidity and mortality. We constructed a nomogram to stratify patients according to risk of AKI after hip fracture surgery to guide clinicians in the implementation of timely interventions. Methods: Patients who received hip fracture surgery from January 2015 to December 2021 were retrospectively identified and divided into a training set (n=448, surgery from January 2015 to December 2019) and a validation set (n=200, surgery from January 2020 to December 2021). Univariate and multivariate logistic regression were used to identify risk factors for AKI after surgery in the training set. A nomogram was constructed based the risk factors for AKI, and was evaluated by receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). Results: The mean age was 82.0±6.22 years-old and the prevalence of post-surgical AKI was 13.3%. Age, American Society of Anesthesiologists (ASA) score, the preexistence of chronic kidney disease (CKD), cemented surgery and the decrease of hemoglobin on the first day after surgery were identified as independent risk factors of AKI after hip fracture surgery, and a predictive nomogram was established based on the multivariable model. The predictive nomogram had good discrimination ability (training set: AUC: 0.784, 95% CI: 0.720-0.848; validation set: AUC: 0.804, 95% CI: 0.704-0.903), and showed good validation ability and clinical usefulness based on a calibration plot and decision curve analysis. Conclusion: A nomogram that incorporated five risk factors including age, ASA score, preexisting CKD, cemented surgery and the decrease of hemoglobin on the first day after surgery had good predictive performance and discrimination. Use of our results for early stratification and intervention has the potential to improve the outcomes of patients receiving hip fracture surgery. Future large, multicenter cohorts are needed to verify the model's performance.

Obese elderly patients with hip fractures may have better survival outcomes after surgery.

BACKGROUND: In recent years, there has been an increasing amount of research on the "obesity paradox". So our primary objective was to explore whether this phenomenon exists in our study, and secondary objective was to determine the effect of body mass index (BMI) on major complications, and the incidence of acute kidney injury (AKI) after hip fracture surgery after controlling for confounding factors. METHODS: We included patients over 70 years old with hip fracture who were admitted to the Department of Orthopedics, Peking University First Hospital between 2015 and 2021. Patients were classified as underweight (UW, < 18.5 kg/m2), normal weight (NW, 18.5-24.9 kg/m2), overweight (OW, 25.0-29.9 kg/m2) and obese (OB, ≥ 30.0 kg/m2). We analyzed demographic characteristics, operation information and postoperative outcomes. Using multivariate regression with normal-weight patients as the reference, we determined the odds of 1-year mortality, major complications, and AKI by BMI category. RESULTS: A total of 644 patients were included. Nine percent of patients died after 1 year, 18% had major postoperative complications, and 12% had AKI. There was a U-shaped relationship between BMI and the rates of major complications or AKI. However, there was a linear decreasing relationship between 1-year mortality and BMI. After controlling for confounding factors, multivariate regression analysis showed that the risk of 1-year mortality after surgery was 2.24 times higher in underweight patients than in normal-weight patients (P < 0.05, OR: 2.24, 95% CI 1.14-4.42). Compared with normal-weight patients, underweight patients had a 2.07 times increased risk of major complications (P < 0.05, OR 2.07, 95% CI 1.21-3.55), and the risk of major complications in obese patients was 2.57 times higher than that in normal-weight patients (P < 0.05, OR 2.57, 95% CI 1.09-6.09). Compared with normal-weight, underweight patients had a 2.18 times increased risk of AKI (P < 0.05, OR 2.18, 95% CI 1.17-4.05). CONCLUSIONS: The 1-year mortality risk of patients with higher BMI was significantly reduced. Besides, compared with normal-weight patients, underweight patients and obese patients have a higher risk of major complications; low-weight and obese patients are at higher risk for AKI.