bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in initiating ART among HIV-Infected patients in China-risk factors and management
Authors: Yang Honghong , Liu Qian , Wu Yushan , He Kun , Zeng Qin , Liu Min
Published: January 2024

Background

China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory.

Methods

We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student’s t-test or rank sum test. Counting data were compared using the chi-square test or Fisher’s exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant.

Results

A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS.

Conclusion

Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).
The co-infection of pulmonary hydatid cyst, lophomoniasis and tuberculosis in a patient with resistant respiratory symptoms; a case report study
Authors: Jalayeri Mohammad Hadi Tajik , Sharifi far Rahmat Allah , Lashkarbolouk Narges , Mazandarani Mahdi
Published: January 2024

Background

Lophomonas blattarum is a rare protozoan that causes opportunistic infections, and the co-infection of lophomonas with tuberculosis and human hydatidosis is a serious public problem in the co-endemic areas of developing countries.

Case report

We presented a 58-year-old female with fever, losing weight, and cough with whitish-yellow sputum that started one month ago. Increasing inflammatory markers and hypereosinophilia in laboratory tests, and a cavity with thick, regular walls and undulating air-fluid levels measuring 43 × 30, evident in the upper segment of the right lower lobe (RLL), along with consolidation and the ground glass opacity of the upper segment and posterior basal of the RLL is apparent in CT scan were reported. Then, a bronchoscopy was requested, and the BAL specimen reported a negative fungal and bacterial infection in the samples. Several live and oval flagellated lophomonas protozoa, hydatid cyst protoscoleces (the larval forms of the parasites), and M. tuberculosis were observed in microscopic evaluation. The patient was treated with metronidazole, oral albendazole, and a combination of TB regimen.

Conclusion

Physicians should always consider the possibility of co-infections of lophomonas with tuberculosis and human hydatidosis and investigate patients with risk factors such as immunodeficiency conditions or treated with immunosuppressive medications.
Association between serum carotenoids and bacterial vaginosis infection among American women
Authors: Tan Ming-Zhi , Feng Yu-Xue , Hong De-Yao , Guo Xu-Guang
Published: January 2024

Background

Bacterial vaginosis (BV) is a widely occurring vaginal inflammation in women of childbearing age caused by dysbiosis of the vaginal flora. Few studies have investigated the effect of serum carotenoids on the development and pathogenesis of BV. This study thus aimed to explore the correlation between serum carotenoids and BV in American women.

Method

The analysis included 1252 participants with BV from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2004. Multiple logistic regression was conducted to explore the correlation between BV and serum carotenoids, while smooth curve fitting was utilized to examine potential nonlinear correlations. Furthermore, stratified subgroup analyses and sensitivity analyses were conducted. ORs reflected the correlation between BV and serum carotenoids.

Result

Results of multiple logistic regression indicated that total serum carotenoids and BV had an inverse correlation. In the fully adjusted model II, the quartile with the highest levels of α-carotene and β-cryptoxanthin had a substantially lower incidence of BV. Smooth curve fitting revealed a significant negative linear correlation between serum carotenoids and the incidence of BV. The negative correlation between serum carotenoids and BV was relatively stable in stratified analyses. Moreover, in sensitivity analyses, the association between serum carotenoids and BV persisted, and β-carotene became significantly negatively correlated with BV.

Conclusion

This study found an inverse correlation between serum carotenoids and the prevalence of BV.
Prevalence of acquired and transmitted HIV drug resistance in Iran: a systematic review and meta-analysis
Authors: Mirzaei Hossein , Eybpoosh Sana , Mehrabi Fatemeh , Shojaei Mohammad Reza , Mirzazadeh Ali , Khezri Mehrdad , Nasiri Naser , Sharifi Hamid
Published: January 2024

Background

There is no systematic review on the prevalence of HIV drug resistance (HIVDR) in Iran. We aimed to estimate the prevalence of HIVDR among people living with HIV (PLHIV) in Iran. We assessed HIVDR prevalence in antiretroviral therapy (ART) naïve PLHIV (i.e., those without a history of ART) and PLHIV receiving ART.

Method

We systematically searched Scopus, PubMed, Web of Science, Embase, Iranian databases (Iranian Medical Research Information System, Magiran, and Scientific Information Database), the references of studies, and Google Scholar until March 2023. A random-effects model was used to calculate a point estimate and 95% confidence interval (95% CI) for the prevalence of HIVDR in PLHIV.

Results

Among 461 potential publications, 22 studies were included in the meta-analysis. The pooled prevalence of acquired HIVDR in PLHIV receiving ART was 34% (95% CI: 19, 50) for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), 27% (95% CI: 15, 41) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 9% (95% CI: 3, 18) for protease inhibitors (PIs). The pooled prevalence of acquired HIVDR in treatment failure PLHIV was 50% (95% CI: 31, 69) for NRTIs, 49% (95% CI: 29, 69) for NNRTIs, 11% (95% CI: 2, 24) for PIs, and 1% (95% CI: 0, 4) for integrase inhibitors (INIs). The pooled prevalence of transmitted HIVDR in ART-naïve people was 3% (95% CI; 1, 6) for NRTIs, 5% (95% CI: 2, 9) for NNRTIs, and 0 for PIs and INIs.

Conclusion

The prevalence of HIVDR was relatively high in both ART-naïve PLHIV and those receiving ART. Without universal pretreatment HIVDR testing and more frequent routine HIV viral load testing among PLHIV who are on ART, the HIVDR prevalence might increase in PLHIV in Iran.
Clinical evolution and mortality of critically ill patients with SARS-CoV-2 pneumonia treated with remdesivir in an adult intensive care unit of Paraguay
Authors: Figueredo Jessica , Lopez Lorena Fontclara , Leguizamon Belinda Figueredo , Samudio Margarita , Pederzani Marcelo , Apelt Federico Fretes , Añazco Patricia , Caballero Ricardo , Bianco Hugo
Published: January 2024

Background

The health crisis due to Covid-19 led to the search for therapeutics that could improve the evolution of the disease. Remdesivir, an antiviral that interferes with viral replication, was one of the first to be used for the treatment of this pathology.

Objective

To determine clinical course and mortality of patients with severe SARS-CoV‐2 pneumonia treated with remdesivir, in comparison of those who didn’t receive the medication.

Patients and methods

Retrospective cohort study, with medical records review of COVID-19 patients, between August 2020 and August 2021. The subjects were divided into two groups, those who received remdesivir before or after admission to intensive care and those who didn’t. The primary outcome variable was mortality in intensive care.

Results

Of 214 subjects included, 109 (50,9%) received remdesivir. The median of days for the drug administration was 8 (2-20), IQR: 3. The bivariate analysis prove that the use of remdesivir was related with lower risk of develop Acute Respiratory Distress Syndrome (ARDS) (p = 0,019; OR: 0,521) and lower requirement of mechanical ventilation (p = 0,006; OR:0,450). Additionally, patients treated with remdesivir develop less kidney injury (p = 0,009; OR: 0,441). There was a total of 82 deaths, 29 (26,6%) in the remdesivir group and 53 (50,5%) in the control group [p < 0,001; OR: 0,356 (0,201-0,630)]. All the risk factors associated with mortality in the bivariate analysis were entered into the multivariate analysis by logistic regression, the use of remdesivir remained associated as an independent protective factor to mortality (p = 0.034; OR: 0.429).

Conclusion

Critically ill patients with SARS-CoV-2 pneumonia treated with remdesivir had a lower risk of death and need for mechanical ventilation and develop less ARDS as compared to the control group. No differences were found in the presentation of adverse effects.
A stronger antibody response in increased disease severity of SARS-CoV-2
Authors: de Oliveira Marta Iglis , Aciole Melayne Rocha , Neves Patrícia Areias Feitosa , Silva Vitor Palmares Oliveira e , Silva Marcelo Palmares Oliveira e , de Lorena Virginia Maria Barros , de Araújo Paulo Sérgio Ramos
Published: January 2024

Background

An assessment of the factors that interfere with serum levels and the persistence of anti-SARs-CoV-2 IgG antibodies is essential in order to estimate the risk of reinfection and to plan vaccination. We analyzed the impact of the severity of coronavirus disease 2019 (COVID-19) and the clinical and biological factors regarding the persistence of SARs-CoV-2 anti-spike protein (IgG-S) antibodies at 12 months.

Methods

This was an observational, longitudinal study with individuals who had recovered from COVID-19 between August 2020 and June 2021. Peripheral blood samples were collected from volunteers who were hospitalized (SERIOUS COVID-19) and those who required no hospitalization (COVID-19 LIGHT). Samples were grouped according to days after symptom onset: up to 90, between 91 and 180, ≥ 180 days after symptom onset. A semiquantitative test for IgG anti-spike protein S1(IgG-S1) was used.

Results

We analyzed 238 individuals who had recovered from COVID-19, of whom 87 had been hospitalized and 151 had not. They provided 148 and 220 samples, respectively. Among those hospitalized, males (65.5%), volunteers aged over 60 years (41.1%), comorbidities such as arterial hypertension (67.8%) and diabetes mellitus (37.9%) were most frequent. We observed higher median serum IgG-S1 titers among those who had recovered from COVID-19 and had been hospitalized, at all collection time intervals (p < 0.001). We observed a weak correlation of increasing age with humoral IgG-S1 response (Spearman correlation = 0.298). There was a greater probability of IgG-S1 antibody persistence over time among samples from hospitalized individuals compared to samples from non-hospitalized participants (p = 0.001).

Conclusion

This study has revealed higher titers and a higher probability of the persistence of IgG-S1 in severe cases after SARs-CoV-2 primary infection in unvaccinated recovered patients. Thus, in this study, the severe clinical presentation of COVID-19 was the main factor influencing serum levels and the persistence of IgG-S1 antibodies in COVID-19.
Multiple cytokine analysis based on QuantiFERON-TB gold plus in different tuberculosis infection status: an exploratory study
Authors: Zhang Lifan , Yang Zhengrong , Wu Fengying , Ge Qiping , Zhang Yueqiu , Li Dongyu , Gao Mengqiu , Liu Xiaoqing
Published: January 2024

Background

More efficient and convenient diagnostic method is a desperate need to reduce the burden of tuberculosis (TB). This study explores the multiple cytokines secretion based on QuantiFERON-TB Gold Plus (QFT-Plus), and screens for optimal cytokines with diagnostic potential to differentiate TB infection status.

Methods

Twenty active tuberculosis (ATB) patients, fifteen patients with latent TB infection (LTBI), ten patients with previous TB and ten healthy controls (HC) were enrolled. Whole blood samples were collected and stimulated by QFT-Plus TB1 and TB2 antigens. The levels of IFN-γ, TNF-α, IL-2, IL-6, IL-5, IL-10, IP-10, IL-1Ra, CXCL-1 and MCP-1 in supernatant were measured by Luminex bead-based multiplex assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different TB infection status.

Results

After stimulation with QFT-Plus TB1 and TB2 antigens, the levels of all cytokines, except IL-5 in TB2 tube, in ATB group were significantly higher than that in HC group. The levels of IL-1Ra concurrently showed the equally highest AUC for distinguishing TB infection from HC, followed by the levels of IP-10 in both TB1 tube and TB2 tube. Moreover, IP-10 levels displayed the largest AUC for distinguishing ATB patients from non-ATB patients. Meanwhile, the levels of IP-10 also demonstrated the largest AUC in both TB1 tube and TB2 tube for distinguishing ATB patients from LTBI.

Conclusions

In addition to conventional detection of IFN-γ, measuring IP-10 and IL-1Ra based on QFT-Plus may have the more tremendous potential to discriminate different TB infection status.
First report of Acinetobacter pittii acute community-acquired pneumonia in an immunocompetent patient in France following a heat wave
Authors: Souhail Bérénice , Danjean Maxime , Mercier-Darty Mélanie , Amaddeo Giuliana , Sessa Anna , Fihman Vincent , Galy Adrien , Woerther Paul Louis , Lepeule Raphaël
Published: January 2024

Background

In recent years, Acinetobacter baumannii-calcoaceticus complex (ABC) infections have attracted attention, mainly because of the impact of carbapenem-resistant isolates in hospital-acquired infections. However, acute community-acquired ABC infections are not uncommon in warm and humid countries, where they are responsible for community-acquired infections with specific clinical features. To date, such infection has not been reported in France.

Case presentation

We report the case of a 55-year-old non-immunocompromised patient living in France with no known risk factors for community-acquired ABC infections who presented pneumonia with bloodstream infection due to wild-type A. pittii. The outcome was favorable after 7 days of antibiotic treatment with cefepime. We confirmed bacterial identification with whole-genome sequencing, and we examined the A. pitii core-genome phylogeny for genomic clusters.

Conclusions

This situation is uncommon in Europe and occurred after a heat wave in France with temperatures above 38 °C. Herein, we discuss the possibility that this pneumonia may be emerging in the current context of global warming.
Analysis of influencing factors on long COVID in COVID-19 patients infected with omicron variant three months after discharge: a cross-sectional study
Authors: Shang Hang , Chang Tianying , Yang Wei , Shi Li , Hu Shaodan , Tian Lin , Ren Jixiang , Wang Tan , Wang Jian , Guo Jiajuan , Cui Yingzi
Published: January 2024

Background

The purpose of this study is to analyze the influencing factors associated with Long-COVID in patients infected with Omicron variant of COVID-19 in Changchun City, Jilin Province, China three months after discharge in March 2022.

Methods

In this study, we conducted a telephone follow-up based on the real-world data collected from the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun Tongyuan Shelter Hospital and Changchun Infectious Disease Hospital during the COVID-19 epidemic in Changchun in March 2022. We used the Global COVID-19 Clinical Platform Case Report Form for Post COVID condition as a follow-up questionnaire to collect the general information, past medical history, clinical symptoms, COVID-19 vaccine inoculation doses, and other relevant information to analyze the symptom characteristics of COVID-19 patients three months after discharge from the hospital and related factors affecting Long COVID.

Results

A total of 1,806 patients with COVID-19 were included in this study, 977 males and 829 females, with a mean age of 38.5 [30.0, 49.4] years, and the number of female patients suffering from Long COVID (50.87%) was greater than male patients (p = 0.023). The binary logistic regression analysis of factors influencing Long COVID showed that smoking history (OR (95%CI) = 0.551(0.425–0.714), p < 0.001, taking never smoking as a reference), allergy history (OR (95%CI) = 1.618 (1.086–2.413), p-value 0.018, taking no allergy as a reference), first symptoms (OR (95%CI) = 0.636 (0.501–0.807), p < 0.001, with no first symptoms as reference) and COVID-19 vaccine inoculation doses (OR (95%CI) = 1.517 (1.190–1.933), p-value 0.001, with ≤ 2 doses of COVID-19 vaccine inoculation doses as reference) constituted its influencing factors. The first symptoms of patients on admission mainly included fever (512 cases, 71.81%), cough (279 cases, 39.13%) and dry or itchy throat (211 cases, 29.59%). The most common symptoms of Long COVID were persistent fatigue (68 cases), amnesia (61 cases), insomnia (50 cases) and excessive sweating (50 cases).

Conclusion

The first symptoms on admission were predominantly fever, cough and dry or itchy throat. The most common symptoms of Long COVID were persistent fatigue, amnesia, insomnia and excessive sweating, and female patients were at a higher risk of Long COVID.
A predicted-loss based active learning approach for robust cancer pathology image analysis in the workplace
Authors: Kim Mujin , Quiñones Robles Willmer Rafell , Ko Young Sin , Wong Bryan , Lee Sol , Yi Mun Yong
Published: January 2024

Background

Convolutional neural network-based image processing research is actively being conducted for pathology image analysis. As a convolutional neural network model requires a large amount of image data for training, active learning (AL) has been developed to produce efficient learning with a small amount of training data. However, existing studies have not specifically considered the characteristics of pathological data collected from the workplace. For various reasons, noisy patches can be selected instead of clean patches during AL, thereby reducing its efficiency. This study proposes an effective AL method for cancer pathology that works robustly on noisy datasets.

Methods

Our proposed method to develop a robust AL approach for noisy histopathology datasets consists of the following three steps: 1) training a loss prediction module, 2) collecting predicted loss values, and 3) sampling data for labeling. This proposed method calculates the amount of information in unlabeled data as predicted loss values and removes noisy data based on predicted loss values to reduce the rate at which noisy data are selected from the unlabeled dataset. We identified a suitable threshold for optimizing the efficiency of AL through sensitivity analysis.

Results

We compared the results obtained with the identified threshold with those of existing representative AL methods. In the final iteration, the proposed method achieved a performance of 91.7% on the noisy dataset and 92.4% on the clean dataset, resulting in a performance reduction of less than 1%. Concomitantly, the noise selection ratio averaged only 2.93% on each iteration.

Conclusions

The proposed AL method showed robust performance on datasets containing noisy data by avoiding data selection in predictive loss intervals where noisy data are likely to be distributed. The proposed method contributes to medical image analysis by screening data and producing a robust and effective classification model tailored for cancer pathology image processing in the workplace.
Aneurysmal subarachnoid hemorrhage complicating spinal subarachnoid hematoma causing acute cauda equina syndrome: a case report
Authors: Ni Heng , Zheng Yu , Lu Shanshan , Jia Zhenyu , Shi Haibin , Liu Sheng , Zhao Linbo
Published: January 2024

Background

Spinal subarachnoid hematoma (SSH) is a known but rare entity that can cause cauda equina compression. The occurrence of SSH associated with aneurysmal subarachnoid hemorrhage has rarely been described in the literature.

Case presentation

A 56-year-old woman presented with subarachnoid hemorrhage secondary to a ruptured middle cerebral artery aneurysm and was managed with coiling embolization without stent assistance. There was no history of either lumbar puncture or the use of anticoagulants. The patient developed severe lumbago radiating to bilateral legs nine days after the procedure. Subsequent magnetic resonance imaging demonstrated a SSH extending from L5 to S2 and wrapping around the cauda equina. The patient was treated with intravenous methylprednisolone (250 mg/day) for four consecutive days, followed by a taper of oral prednisolone (20 mg/day) until complete recovery. Magnetic resonance imaging at one month follow-up revealed complete resolution of the SSH.

Conclusions

Here, we report a case of acute cauda equina syndrome caused by a SSH after aneurysmal subarachnoid hemorrhage, which will facilitate timely intervention of patients with this disorder.
Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance
Authors: Cook Aaron M. , Hall Kaylee , Kolpek Jimmi Hatton , Morbitzer Kathryn A. , Jordan J. Dedrick , Rhoney Denise H.
Published: January 2024

Background

The purpose of this study was to examine the impact of ARC on levetiracetam concentrations during the first week following acute TBI. The hypothesis was levetiracetam concentrations are significantly lower in TBI patients with augmented renal clearance (ARC) compared to those with normal renal clearance.

Methods

This is a prospective cohort pharmacokinetic study of adults with moderate to severe TBI treated with levetiracetam during the first week after injury. Serial blood collections were performed daily for analysis of levetiracetam, cystatin C, and 12-hr creatinine clearance (CrCl) determinations. Patients were divided into two cohorts: with (CrCl ≥130 ml/min/1.73 m2) and without ARC.

Results

Twenty-two patients with moderate to severe TBI were included. The population consisted primarily of young male patients with severe TBI (mean age 40 years old, 68% male, median admission GCS 4). Each received levetiracetam 1000 mg IV every 12 h for the study period. ARC was present in 77.3% of patients, with significantly lower levetiracetam concentrations in ARC patients and below the conservative therapeutic range (< 6mcg/mL) for all study days. In patients without ARC, the serum concentrations were also below the expected range on all but two study days (Days 4 and 5). Four of the 22 (18.2%) patients exhibited seizure activity during the study period (two of these patients exhibited ARC). Cystatin C concentrations were significantly lower in patients with ARC, though the mean for all patients was within the typical normal range.

Conclusions

ARC has a high prevalence in patients with moderate to severe TBI. Levetiracetam concentrations after standard dosing were low in all TBI patients, but significantly lower in patients with ARC. This study highlights the need to consider personalized drug dosing in TBI patients irrespective of the presence of ARC.

Clinical trial registration

This study was registered at cliicaltrials.gov (NCT02437838) Registered on 08/05/2015, https://clinicaltrials.gov/ct2/show/NCT02437838.
White matter hyperintensity burden and collateral circulation in acute ischemic stroke with large artery occlusion
Authors: Chen Wang , Wang Meihong , Yang Lei , Wang Xianjun , Jin Qianxiu , Zhao Zhenyu , Hu Wenli
Published: January 2024

Objective

This study aimed to investigate the association between white matter hyperintensity (WMH) burden and pial collaterals in acute strokes caused by intracranial large artery occlusion treated with mechanical thrombectomy in the anterior circulation, focusing on stroke subtypes.

Methods

Consecutive patients undergoing mechanical thrombectomy between December 2019 and June 2022 were retrospectively screened. The Fazekas scale assessed WMH burden. Pial collaterals were categorized as either poor (0–2) or good (3–4) based on the Higashida score. A multivariable analysis was used to determine the relationship between WMH burden and pial collaterals. Subgroup analyses delved into associations stratified by stroke subtypes, namely cardioembolism (CE), tandem lesions (TLs), and intracranial atherosclerosis (ICAS).

Results

Of the 573 patients included, 274 (47.8%) demonstrated poor pial collaterals. Multivariable regression indicated a strong association between extensive WMH burden (Fazekas score of 3–6) and poor collaterals [adjusted OR 3.04, 95% CI 1.70–5.46, P < 0.001]. Additional independent predictors of poor collaterals encompassed ICAS-related occlusion (aOR 0.26, 95% CI 0.09–0.76, P = 0.014), female sex (aOR 0.63, 95% CI 0.41–0.96, P = 0.031), and baseline Alberta Stroke Program Early Computed Tomography scores (aOR 0.80, 95% CI 0.74–0.88, P < 0.001). Notably, an interaction between extensive WMH burden and stroke subtypes was observed in predicting poor collaterals (P = 0.001), being pronounced for CE (adjusted OR 2.30, 95% CI 1.21–4.37) and TLs (adjusted OR 5.09, 95% CI 2.32–11.16), but was absent in ICAS (adjusted OR 1.24, 95% CI 0.65–2.36).

Conclusions

Among patients treated with mechanical thrombectomy for anterior circulation large artery occlusion, extensive WMH burden correlates with poor pial collaterals in embolic occlusion cases (CE and TLs), but not in ICAS-related occlusion.
Factors intervening in the childbirth experience: a mixed-methods study
Authors: de Oliveira Paes Luciana Braz , Fabbro Márcia Regina Cangiani , de Oliveira Toso Beatriz Rosana Gonçalves , de Castro Bussadori Jamile Claro , Ruiz Mariana Torreglosa , Salim Natália Rejane , Wernet Monika , Silveira Aline Oliveira , de Abreu D Agostini Flávia Corrêa Porto
Published: January 2024

Objective

To analyze the childbirth experience focusing on the intervening factors and on the delivery method.

Method

A sequential and explanatory mixed-methods study guided by the World Health Organization document for positive childbirth experiences. The participants were puerperal women in a maternity teaching hospital from inland São Paulo (Brazil). The first quantitative stage involved descriptive analysis with Poisson regression of 265 answers to the “Termômetro da Iniciativa Hospital Amigo da Mulher e da Criança” (“Women- and Baby-Friendly Hospital Initiative Thermometer”) questionnaire. The second stage, qualitative, thematically analyzed the interviews conducted with 44 puerperal women who took part in the first stage. Data integration was by connection.

The results and discussion

The analysis by connection showed that among the factors that restricted the positive experience, C-section was predominant (61.9%), understood as an option due to fear of pain, the treatment modality and previous traumas. Restrictions referring to the presence of a companion (99.6%), not having privacy (83%), disrespectful situations (69.5%), too many touches (56.9%) and the absence of skin-to-skin contact (55%), among others, potentiated fear, loneliness, concern, shame, the perception of disrespect and insecurity with the assistance provided. The promoting factors were as follows: choosing the companion (95.4%) for collaborating in the safety perception, not having infections (83.9%), having continuous team monitoring (82.2%) and pain relief methods (78.9%), which were valued by the women.

Conclusion

The intervening factors that promoted positive experiences were related to clinical and protocol-related issues and to service availability. The restrictive factors were associated with excess interventions, deprivation of rights and of choice, absence of privacy and restriction referring to the presence of a companion. Women with a normal postpartum period felt more insecure and disrespected when compared to those subjected to C-sections, whose choices were considered, although they had lower prevalence of skin-to-skin contact. There is an urgent need to apprehend women's experiences and turn them into actions that guarantee their lives in a safe and respectful way.
Correlation between TCF7L2 and CAPN10 gene polymorphisms and gestational diabetes mellitus in different geographical regions: a meta-analysis
Authors: He Jingjing , Zhang Meng , Ren Jianhua , Jiang Xiaolian
Published: January 2024

Background

The association between TCF7L2 and CAPN10 gene polymorphisms and gestational diabetes mellitus (GDM) has been explored in diverse populations across different geographical regions. Yet, most of these studies have been confined to a limited number of loci, resulting in inconsistent findings. In this study, we conducted a comprehensive review of published literature to identify studies examining the relationship between TCF7L2 and CAPN10 gene polymorphisms and the incidence of GDM in various populations. We specifically focused on five loci that were extensively reported in a large number of publications and performed a meta-analysis.

Methods

We prioritized the selection of SNPs with well-documented correlations established in existing literature on GDM. We searched eight Chinese and English databases: Cochrane, Elton B. Stephens. Company (EBSCO), Embase, Scopus, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database and retrieved all relevant articles published between the inception of the database and July 2022. The Newcastle Ottawa Scale (NOS) was used to evaluate the selected articles, and the odds ratio (OR) was used as the combined effect size index to determine the association between genotypes, alleles, and GDM using different genetic models. Heterogeneity between the studies was quantified and the I2 value calculated. Due to large heterogeneities between different ethnic groups, subgroup analysis was used to explore the correlation between genetic polymorphisms and the incidence of GDM in the different populations. The stability of the results was assessed using sensitivity analysis. Begg’s and Egger’s tests were used to assess publication bias.

Results

A total of 39 articles reporting data on 8,795 cases and 16,290 controls were included in the analysis. The frequency of the rs7901695 genotype was statistically significant between cases and controls in the European population (OR = 0.72, 95% CI: 0.65–0.86) and the American population (OR = 0.61, 95% CI: 0.48–0.77). The frequencies of rs12255372, rs7901695, rs290487, and rs2975760 alleles were also considerably different between the cases and controls in the populations analyzed.

Conclusions

rs7903146, rs12255372, rs7901695, rs290487, and rs2975760 were associated with the incidence of GDM in different populations.
Dose-response associations of maternal prenatal noise exposure duration with antepartum depression status
Authors: Hu Jiajin , Liu Borui , Cui Hong , Liu Yilin , Wan Ningyu , Li Lin , Zheng Lu , Wang Xiaochuan , Yang Zhe , Ma Yanan , Liu Caixia , Qiao Chong , Wen Deliang
Published: January 2024

Background

Antepartum depression has been reported to be associated with the intensity of maternal prenatal noise exposure; however, the association between noise exposure duration and the development of antepartum depression has not been established. This study aimed to determine the total and trimester-specific association of prenatal noise exposure duration with the development of antepartum depression.

Methods

From May 2018 to June 2021, we recruited 2,166 pregnant women from Shengjing Hospital, northeast China. We used a standardized questionnaire to assess women’s prenatal noise exposure and used the Edinburgh Postnatal Depression Scale to assess pregnant women’s antepartum depression during the 1st -, 2nd -, and 3rd - trimesters. We calculated a cumulative noise exposure score ranging from 0 to 3, with a higher score reflecting higher frequency and longer duration of noise exposure during pregnancy.

Results

Women who were exposed to noise for ≥ 15 min per day had an increased risk of antepartum depression compared with women who were not exposed to noise during pregnancy [odds ratio (OR) = 1.83, 95%CI:1.18, 2.83]. Noise exposure in a specific trimester was associated with higher risk of depression in the same trimester and subsequent trimesters. We observed increases in antepartum depression risk with increasing cumulative noise exposure scores (P for trend < 0.05 for all). Pregnant women with the highest scores had the highest risk of antepartum depression during the first (OR = 1.30, 95%CI:1.02, 1.65), second (OR = 1.75, 95%CI:1.23, 2.50) trimesters. Women with a cumulative noise exposure score of 2 had the highest risk of antepartum depression during the third trimester (OR = 1.79, 95%CI:1.14, 2.80), as well as during the whole pregnancy (OR = 1.94, 95%CI:1.14, 3.30).

Conclusions

Maternal prenatal noise exposure duration was positively associated with antepartum depression risk in a dose-response manner. It is necessary to develop strategies by which pregnant women can avoid excessive exposure to noise to prevent antepartum depression.
Evaluation of extravascular lung water and cardiac function in normal vaginal delivery by intrapartum bedside ultrasound
Authors: Zhang Shi-jie , He Shao-zheng , Wu Jing-jing , Chen Yong-jian , Lyu Guo-rong
Published: January 2024

Background

Healthy parturients may experience pulmonary edema and disturbed cardiac function during labor. We aimed to evaluate the extravascular lung water (EVLW), intravascular volume, and cardiac function of normal parturients during spontaneous vaginal delivery by bedside ultrasound. And to explore the correlation between EVLW and intravascular volume, cardiac function.

Methods

This was a prospective observational study including 30 singleton-term pregnant women undergoing spontaneous vaginal delivery. Bedside ultrasound was performed at the early labor, the end of the second stage of labor, 2 and 24 h postpartum, and 120 scanning results were recorded. EVLW was evaluated by the echo comet score (ECS) obtained by the 28-rib interspaces technique. Inferior vena cava collapsibility index (IVC-CI), left ventricle ejection fraction, right ventricle fractional area change, left and right ventricular E/A ratio, and left and right ventricular index of myocardial performance (LIMP and RIMP) were measured. Measurements among different time points were compared, and the correlations between ECS and other measurements were analyzed.

Results

During the spontaneous vaginal delivery of healthy pregnant women, 2 had a mild EVLW increase at the early labor, 8 at the end of the second stage of labor, 13 at 2 h postpartum, and 4 at 24 h postpartum (P < 0.001). From the early labor to 24 h postpartum, ECS first increased and then decreased, reaching its peak at 2 h postpartum (P < 0.001). IVC-CI first decreased and then increased, reaching its minimum at the end of the second stage of labor (P < 0.001). RIMP exceeded the cut-off value of 0.43 at the end of the second stage of labor. ECS was weakly correlated with IVC-CI (r=-0.373, P < 0.001), LIMP (r = 0.298, P = 0.022) and RIMP (r = 0.211, P = 0.021).

Conclusions

During spontaneous vaginal delivery, the most vital period of perinatal care is between the end of the second stage of labor and 2 h postpartum, because the risk of pulmonary edema is higher and the right ventricle function may decline. IVC-CI can be used to evaluate maternal intravascular volume. The increase in EVLW may be related to the increase in intravascular volume and the decrease in ventricular function.
Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening
Authors: Wan Rui , Yao Peng , Wang Yuxiu , Zhang Lele , Guo Wei , Du Meiying , Wang Yu , Shi Wenbiao , Li Weili
Published: January 2024

Background

Preeclampsia is a life-threatening disease of pregnancy that lacks effective pharmaceuticals which can target its pathogenesis. Since preeclampsia involves complex pathological processes, including autophagy, this study aims to explore autophagy-related mechanisms of preeclampsia and to screen potential drugs.

Methods

Firstly, the datasets GSE75010, GSE24129, GSE66273, and autophagic genes lists were downloaded from public databases. Then, a weighted gene co-expression network analysis (WGCNA) was applied to filter autophagic-related hub genes of preeclampsia. The differential expression levels of the hub genes were validated with datasets GSE24129 and GSE66273. Next, the GO and KEGG enrichment, protein-protein interacting (PPI) network, as well as the downstream pathways was analyzed via the starBase, STRING and Cytoscape to determine the functions and regulatory network of the hub genes. Additionally, the immune microenvironment of preeclampsia was investigated by the CIBERSORTX database. Finally, three herb ingredients, berberine, baicalein, and luteolin were screened by molecular docking in comparison to pravastatin, metformin, and aspirin, to predict potential drugs for treating preeclampsia.

Results

A total of 54 autophagy-related genes were filtered by WGCNA. After filtering with |GS| > 0.5 and |MM| > 0.8, three hub genes, namely PKM, LEP, and HK2, were identified and validated. Among these genes, PKM and LEP were overexpressed in women older than 35 years old ( p<0.05; p<0.05); the expression of PKM, LEP, and HK2 differed remarkably in women with different BMI (all p<0.05); PKM overexpressed in women with hypertension (p<0.05). The regulatory network of hub genes demonstrated that they were mainly enriched in metabolic pathways, including the AMPK signaling pathway, glucagon signaling pathway, adipocytokine signaling pathway, and central carbon metabolism. Then, immune microenvironment analysis turned out that M2 macrophages were reduced in preeclampsia women (p<0.0001) and were negatively correlated with the expression of PKM (r=-0.2, p<0.05), LEP (r=-0.4, p<0.0001), and HK2 (r=-0.3, p<0.001). Lastly, molecular docking showed baicalein and luteolin could bind intimately to hub genes.

Conclusion

PKM, LEP, and HK2 could be promising biomarkers for preeclampsia, which might regulate the pathogenesis of preeclampsia via metabolism pathways and immune microenvironment. Baicalein and luteolin could be potential therapeutics for preeclampsia.
Regorafenib monotherapy or combined with an immune-checkpoint inhibitor as later-line treatment for metastatic colorectal cancer: a multicenter, real-world retrospective study in China
Authors: Qu Wang , Liu Zimin , Chen Xiaobing , Liu Bo , Zhao YunBo , Yan Hao , Qu Xiujuan , Li Shengmian , Zang Aimin , Sun Yongkun , Zhu Liangjun , Zhou Aiping
Published: January 2024

Objective

To evaluate the efficacy and safety of regorafenib monotherapy or in combination with immune-checkpoint inhibitor while treating Chinese patients with metastatic colorectal cancer (mCRC): a real-world study.

Methods

The data of patients with metastatic colorectal cancer who received regorafenib-containing regimen as the third or later line treatment at ten Chinese hospitals from Aug 2017 to Jun 2020 were retrospectively analyzed, including dosing details, survival data as well as adverse events. Survival analysis was further performed for patients administrated with regorafenib monotherapy and combined with an immune-checkpoint inhibitor based on Kaplan-Meier and Cox regression methods. The primary endpoint was overall survival.

Results

A total of 537 patients were included with a median age of 61, among whom 376 received regorafenib monotherapy and 245 received regorafenib combined with immune-checkpoint inhibitors. The clinicopathological characteristics of the two groups at baseline were mainly balanced. No significant difference in progression-free survival (PFS) was observed in patients receiving regorafenib monotherapy or combination therapy (3.8 vs. 5.5 months, p = 0.170). In contrast, patients receiving combination therapy had a more prolonged overall survival (OS) than those receiving regorafenib monotherapy (13.5 vs. 10.0 months, p = 0.001). The treatment regimen and regorafenib dosage were significant prognostic factors in the multivariate analysis. Significant benefits in PFS and OS were achieved in KRAS mutant and anti-angiogenesis treatment-naïve subgroups receiving combination therapy compared to monotherapy. No apparent increase was recorded in treatment-related adverse events in patients receiving combination therapy.

Conclusion

Regorafenib plus an immune-checkpoint inhibitor has already been a widely adopted strategy in the later-line treatment for mCRC in the real world. The combination therapy yielded a significantly prolonged overall survival than regorafenib alone, with a manageable safety profile in Chinese patients, and warrants further investigation.

Trial registration

ClinicalTrials.gov Identifier: NCT04835324. Registered 6th April 2021.
The value of oral selective estrogen receptor degraders in patients with HR-positive, HER2-negative advanced breast cancer after progression on ≥ 1 line of endocrine therapy: systematic review and meta-analysis
Authors: Huang Xiewei , Yu Yushuai , Luo Shiping , Fu Wenfen , Zhang Jie , Song Chuangui
Published: January 2024

Background

Currently, the value of oral selective estrogen receptor degraders (SERDs) for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (aBC) after progression on ≥ 1 line of endocrine therapy (ET) remains controversial. We conducted a meta-analysis to evaluate progression-free survival (PFS) and safety benefits in several clinical trials.

Materials and methods

Cochrane Library, Embase, PubMed, and conference proceedings (SABCS, ASCO, ESMO, and ESMO Breast) were searched systematically and comprehensively. Random effects models or fixed effects models were used to assess pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for treatment with oral SERDs versus standard of care.

Results

A total of four studies involving 1,290 patients were included in our analysis. The hazard ratio (HR) of PFS showed that the oral SERD regimen was better than standard of care in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET (HR: 0.75, 95% CI: 0.62-0.91, p = 0.004). In patients with ESR1 mutations, the oral SERD regimen provided better PFS than standard of care (HR: 0.58, 95% CI: 0.47-0.71, p < 0.00001). Regarding patients with disease progression following previous use of CDK4/6 inhibitors, PFS benefit was observed in oral SERD-treatment arms compared to standard of care (HR: 0.75, 95% CI: 0.64-0.87, p = 0.0002).

Conclusions

The oral SERD regimen provides a significant PFS benefit compared to standard-of-care ET in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET. In particular, we recommend oral SERDs as a preferred choice for those patients with ESR1m, and it could be a potential replacement for fulvestrant. The oral SERD regimen is also beneficial after progression on CDK4/6 inhibitors combined with endocrine therapy.
Screening of novel tumor-associated antigens for lung adenocarcinoma mRNA vaccine development based on pyroptosis phenotype genes
Authors: Zhou Fang , Wang Meng , Wang Zheng , Li Wei , Lu Xike
Published: January 2024

This study aimed to identify new pyroptosis-associated tumor antigens for use in mRNA vaccines and the screening of sensitive LUAD populations suitable for vaccination. The association between tumor immune infiltrating cell abundance and potential tumor antigens was investigated and visualized using the analysis modules of gene expression, clinical outcomes, and somatic copy number variation. In addition, the pyroptosis-related genes (PRGs) were clustered, the relative pyroptosis subtypes (PSs) and gene modules were identified, and the prognostic value of the PSs was examined. The expression of key PRGs in two lung adenocarcinoma cell lines was verified by RT-qPCR. Four tumor pyroptosis-associated antigens, CARD8, NAIP, NLRP1, and NLRP3, were screened as potential candidates for LUAD mRNA vaccine development. In the construction of consensus clusters for PRGs, two PSs, PS1 and PS2, were classified, in which patients with PS1 LUAD had a better prognosis. In contrast, patients with PS2 LUAD may have better responsiveness to mRNA vaccine treatment. The key PRGs can be regarded as biomarkers to predict the LUAD prognosis and identify patients suitable for mRNA vaccines. The RT-qPCR results showed that the expression levels of CSMD3, LRP1B, MUC16 and TTN were significantly increased in the two lung adenocarcinoma cell lines, while the expression levels of CARD8, TP53 and ZFHX4 were significantly reduced. The antigens CARD8, NAIP, NLRP1, and NLRP3, which are associated with tumor pyroptosis, could be candidate molecules for LUAD mRNA vaccine development. Patients with PS2 LUAD may be suitable candidates for mRNA vaccine treatment.