bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll‐like receptor‐2 in cardiomyocytes and macrophages mediates isoproterenol‐induced cardiac inflammation and remodeling
Authors: Qian Jinfu , Liang Shiqi , Wang Qinyan , Xu Jiachen , Huang Weijian , Wu Gaojun , Liang Guang
Published: December 2022

Heart failure (HF) is the leading cause of morbidity and mortality worldwide. Activation of the innate immune system initiates an inflammatory response during cardiac remodeling induced by isoproterenol (ISO). Here, we investigated whether Toll‐like receptor‐2 (TLR2) mediates ISO‐induced inflammation, hypertrophy, and fibrosis. TLR2 was found to be increased in the heart tissues of mouse with HF under ISO challenge. Further, cardiomyocytes and macrophages were identified as the main cellular sources of the increased TLR2 levels in the model under ISO stimulation. The effect of TLR2 deficiency on ISO‐induced cardiac remodeling was determined using TLR2 knockout mice and bone marrow transplantation models. In vitro studies involving ISO‐treated cultured cardiomyocytes and macrophages showed that TLR2 knockdown significantly decreased ISO‐induced cell inflammation and remodeling via MAPKs/NF‐κB signaling. Mechanistically, ISO significantly increased the TLR2‐MyD88 interaction in the above cells in a TLR1‐dependent manner. Finally, DAMPs, such as HSP70 and fibronectin 1 (FN1), were found to be released from the cells under ISO stimulation, which further activated TLR1/2‐Myd88 signaling and subsequently activated pro‐inflammatory cytokine expression and cardiac remodeling. In summary, our findings suggest that TLR2 may be a target for the alleviation of chronic adrenergic stimulation‐associated HF. In addition, this paper points out the possibility of TLR2 as a new target for heart failure under ISO stimulation.
Entrustable Professional Activities for the Training of Postgraduate Primary Care Pediatricians
Authors: Villaizán Pérez Carmen , Aparicio Rodrigo María , Kovacs Akos , Barak Shimon , Calamita Patrizia , Dejak Gornik Katja , Jaeger-Roman Elke , Kartousova Beata , Katz Manuel , Rafele Innocenza , Reali Laura , Reingold Stephen , Sauseng Werner , Fehr Folkert
Published: December 2022

Problem

Competency-based training is a model of medical education program that uses an organized framework of competencies to develop entrustable professional activities (EPAs) for each specialty. Implementation of EPAs varies by medical specialty and country. Although national models for primary care pediatrics have been suggested in the past, standardized EPAs have not been established.

Approach

The authors, all members of the curriculum working group of the European Confederation of Primary Care Paediatricians, describe the development and design of a training model based on EPAs specifically for pediatricians in primary care. The objective was to facilitate and disseminate a training model that standardizes and improves training in primary care pediatrics. They aimed to make the model flexible enough so that it can be adapted to different training models and different European health systems.

Outcomes

Between May 2017 and December 2019, the authors developed a framework that includes 7 domains of competencies for the training in pediatric primary care and a set of 11 core EPAs to guide the learning process. They structured each EPA as follows: title, activity profile, domains of competence, competencies within each domain, required knowledge and skills, learning objectives described in terms of outcomes, and a 3-stage rating supervision scale to evaluate the level of performance.

Next Steps

The next step is the progressive implementation of these EPAs into the postgraduate primary care pediatrics training programs of European health systems. To support this implementation, the authors intend to develop training videos to assist in daily teaching of the EPAs. The authors will also develop a pan-European online resident forum designed specifically to facilitate EPA learning by sharing and discussing clinical cases. They plan to launch a pilot study on the use of the EPAs in primary care health centers in 6 European countries.
From surgery to endoscopy: the evolution of the bariatric discipline
Authors: Wei Yongqiu , Li Peng , Zhang Shutian
Published: December 2022

Obesity, with its increasing morbidity and prevalence, is now a worldwide public health problem. Obesity and its related comorbidities impose a heavy burden on societal health and the economy. The practice of bariatric surgery has evolved from its early surgical procedures, many of which are no longer routine operations. With clinical practice, research, and experience, bariatric surgery has gradually become an important last resort for the control of weight and obesity-related metabolic diseases in moderately and severely obese patients. However, there is still room for further improvements in bariatric surgical procedures, especially with regard to long-term issues and complications. Endoscopic weight loss technology has developed rapidly in recent years. The advantages of this technology include minimal invasiveness, an obvious weight loss effect, and few complications, thus filling the gap between medications and lifestyle adjustments and surgical treatment of obesity. Endoscopic weight loss technology may even replace surgical bariatric procedures. This review summarized the current status of bariatric metabolic surgery and newly developed bariatric endoscopic procedures.
Adrenomedullin in paraventricular nucleus attenuates adipose afferent reflex and sympathoexcitation via receptors mediated nitric oxide–gamma-aminobutyric acid A type receptor pathway in rats with obesity-related hypertension
Authors: Wang Fang-Zheng , Qian Pei , Liu Mu-Yue , Ding Lei , Wang Hong-Yu , Wang Qian , Ding Zi-Yang , Jin Fei-Yu , Li Rui-Gang , Zhou Ye-Bo
Published: December 2022

Background:

Hypothalamic paraventricular nucleus (PVN) is an important central site for the control of the adipose afferent reflex (AAR) that increases sympathetic outflow and blood pressure in obesity-related hypertension (OH).

Method:

In this study, we investigated the effects of nitric oxide (NO) and cardiovascular bioactive polypeptide adrenomedullin (ADM) in the PVN on AAR and sympathetic nerve activity (SNA) in OH rats induced by a high-fat diet.

Results:

The results showed that ADM, total neuronal NO synthase (nNOS) and phosphorylated-nNOS protein expression levels in the PVN of the OH rats were down-regulated compared to the control rats. The enhanced AAR in OH rats was attenuated by PVN acute application of NO donor sodium nitroprusside (SNP), but was strengthened by the nNOS inhibitor nNOS-I, guanylyl cyclase inhibitor (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) and gamma-aminobutyric acid A type receptor (GABAA) antagonist Bicuculline. Moreover, PVN ADM microinjection not only decreased basal SNA but also attenuated the enhanced AAR in OH rats, which were effectively inhibited by ADM receptor antagonist ADM22–52, nNOS-I, ODQ or Bicuculline pretreatment. Bilateral PVN acute microinjection of ADM also caused greater increases in NO and cyclic guanosine monophosphate (cGMP) levels, and nNOS phosphorylation. Adeno-associated virus vectors encoding ADM (AAV-ADM) transfection in the PVN of OH rats not only decreased the elevated AAR, basal SNA and blood pressure (BP), but also increased the expression and activation of nNOS. Furthermore, AAV-ADM transfection improved vascular remodeling in OH rats.

Conclusion:

Taken together, our data highlight the roles of ADM in improving sympathetic overactivation, enhanced AAR and hypertension, and its related mechanisms associated with receptors mediated NO–cGMP–GABAA pathway in OH condition.
Hypertension in Turner syndrome: a review of proposed mechanisms, management and new directions
Authors: Jones Lily , Blair Joanne , Hawcutt Daniel B. , Lip Gregory Y.H. , Shantsila Alena
Published: December 2022

Acquired cardiovascular diseases account for much of the increased risk of premature death in patients with Turner syndrome (TS). Hypertension is a major modifiable cardiovascular risk factor. It has a high prevalence in TS developing at an early age and thus leading to prolonged exposure to high blood pressure. The aetiology for hypertension in TS is largely unknown. It is likely multifactorial, and recent hypotheses include altered sympathetic tone, vasculopathy and endocrine factors. In this review article we aim to provide a comprehensive review of data on mechanisms of hypertension in TS and their implication for diagnostics and optimal choice of antihypertensive treatments. Ultimately this knowledge should help prevent hypertension-related complications, and improve quality of life and life expectancy for patients with TS.
Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy
Authors: Dao Kim , Shechtman Svetlana , Diav-Citrin Orna , George Nathan , Richardson Jonathan Luke , Rollason Victoria , Pistelli Alessandra , Eleftheriou Georgios , Berlin Maya , Ekobena Pierre , Rousson Valentin , Addor Marie-Claude , Baud David , Buclin Thierry , Panchaud Alice , Winterfeld Ursula
Published: December 2022

Purpose/Background

Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available.

Methods/Procedures

This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021.

Findings/Results

The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03–1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups.

Implications/Conclusions

This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.
A Structured Rounding Proforma in the Hyper Acute Stroke Unit (HASU): A Quality Improvement Project
Authors: Ludley Alistair , Bahk Anna , Al-Shihabi Ahmed
Published: December 2022

Strokes affect 100,000 patients annually in the United Kingdom. These patients are often complex and require multidisciplinary team input, hence why they are often treated within dedicated and highly specialized “hyper acute stroke units”. However, such specialist care can prove challenging to recently qualified or more junior doctors, who may miss pertinent aspects of the history or examination within the daily patient rounding documentation. Building on evidence-based practice using structured rounds and checklists, this quality improvement aimed to improve adherence of documentation for 20 predetermined key components of a stroke round by introducing a structured daily stroke rounding proforma. Adherence to documentation for the 20 components improved with the introduction of the stroke rounding proforma, with seven components demonstrating statistically significant positive changes in documentation rates, p < .05. Qualitative feedback was collected to aid in the development and acceptability of the proforma. Our study concluded a structured daily stroke rounding proforma can improve adherence to documentation in stroke care. Chiefly, the proforma was of greatest benefit to junior members of the medical team, particularly as an aid memoire.
Transcriptome analysis of the impact of diabetes as a comorbidity on tuberculosis
Authors: Liu Tao , Wang Yaguo , Gui Jing , Fu Yu , Ye Chunli , Hong Xiangya , Chen Ling , Li Yuhua , Zhang Xilin , Hong Wenxu
Published: December 2022

Background:

Diabetes mellitus patients with pulmonary tuberculosis (DMTB) comorbidity has been recognized as a major obstacle towards achieving the World Health Organization goal of reducing the tuberculosis incidence rate by 90% in 2035. Host immune responses affected by diabetes can lead to increased susceptibility, severity and poor treatment outcomes in DMTB patients, and the underlying mechanisms have not yet been fully elucidated. This study aimed to identify key immunological and cellular components that contribute to increased morbidity and mortality in DMTB cases.

Methods:

We performed RNA-Seq of total RNA isolated from peripheral blood mononuclear cells from 3 TB, 3 diabetes mellitus, and 3 DMTB patients and healthy controls, and analyzed differential expression, pathway enrichment and clustering of differentially-expressed genes (DEGs) to identify biological pathways altered specifically in DMTB patients.

Results:

Bioinformatic analysis of DEGs suggested that enhanced inflammatory responses, small GTPases, the protein kinase C signaling pathway, hemostasis and the cell cycle pathway are likely implicated in the pathogenesis of the DMTB comorbidity.

Conclusion:

The DMTB comorbidity is associated with an altered transcriptome and changes in various biological pathways. Our study provides new insights on the pathological mechanism that may aid the development of host-directed therapies for this increasingly prevalent disease in high TB burden countries.
The influence of serum sodium concentration on prognosis in patients with urothelial carcinoma treated by radical cystectomy
Authors: Zhang Yan , Wang Zuojun , Yang Xue , Zhao Qingchun , He Long
Published: December 2022

Serum sodium concentration has been found to be associated with poor survival in many solid tumors. This study investigated the effect of basal serum sodium concentration on prognostic in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). MIBC patients with histologically proven urothelial carcinoma treated by RC were retrospectively reviewed. According to the optimal cutoff value, we divided the patients into 2 groups: high-serum sodium concentration group (≥140 mmol/L, n = 39) and low-serum sodium concentration group (<140 mmol/L, n = 32). Overall survival (OS) was estimated with the Kaplan–Meier method and the significance was examined by the log-rank test. Multivariable Cox regression for OS was performed for lymphatic metastasis, hypertension, diabetes mellitus, and tumor size. A total of 71 MIBC patients (60 males and 11 females) were included who underwent cystectomy between 2014 and 2018. The patients’ ages at the time of operation ranged from 44 to 86 years (mean, 66.66 years). Patients’ serum sodium concentration <140 mmol/L had shorter median OS (1224 days (HR: 2.454 [95% CI, 1.083–5.561; P = .031]). In multivariate analysis, lower serum sodium concentration was significantly associated with worse OS after adjusted (adjusted HR: 2.422 [95% CI, 1.055–5.561; P = .037]). Serum sodium concentration <140 mmol/L was independently associated with a poorer prognosis in patients with MIBC used who underwent RC.
A survey on the impact of IBD in sexual health: Into intimacy
Authors: Pires Francisco , Martins Diana , Ministro Paula
Published: December 2022

Patients with Inflammatory Bowel Disease (IBD) are at increased risk of psychological and physical burden, including sexual dysfunction (SD). This study aimed to assess the prevalence of SD and to identify its predictive factors, in IBD patients. This unicentric cross-sectional case-control survey (ratio 2:1) included patients followed at the day hospital IBD consultation, in the Gastroenterology department of a tertiary referral center, for 2 years. Participants received anonymous questionnaires, concerning basic characteristics and sexual function, and a questionnaire on anxiety and depression, body image, fatigue, and IBD-specific health-related quality of life (QoL). We analyzed data from 120 IBD patients and 60 healthy controls. Forty-two female (56.8%) and 6 male (14.6%) IBD patients, and 6 women (15%) and 2 males (10%) of the control group presented SD. SD was significantly higher in IBD patients with age between 18 and 30 and 51 and 60 than in healthy controls (P < .05) Regarding multivariate analysis, age was a predictive factor for SD in males (P = .014), and anxiety and depression (P = .002) and fatigue (P = .043) in females. SD is a predictor of lower QoL among IBD patients, considering the last 15 (P < .001) and 60 days (P = .001), regarding univariate analysis. SD (P = .007), body image distortion (P < .001), and fatigue (P = .004) were predictors of low QoL (last 15 days, multivariate analysis). SD was more prevalent in IBD patients than in the control group and impacted negatively the QoL of patients. Age was a predictive factor for SD in men while anxiety and depression, and fatigue were predictive of SD in women.
Clinical efficacy of moluodan in the treatment of chronic atrophic gastritis: A protocol for systematic review and meta-analysis
Authors: Yu Yunfeng , Yang Xinyu , Hu Gang , Yin Shuang , Zhang Fei , Wen Yandong , Zhu Ying , Liu Zhenjie
Published: December 2022

Background:

Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer, and also a key period of drug intervention. However, there is still a lack of drugs to maintain the treatment of CAG until the advent of moluodan.

Objective:

This study was conducted to assess the clinical efficacy of moluodan in the treatment of CAG by meta-analysis and trial sequential analysis.

Methods:

China National Knowledge Infrastructure, China Biology Medicine, VIP, Wanfang, Embase, PubMed, the Cochrane Library, and Web of Science databases were searched, all with the time limit from database establishment to July 2022. The published randomized controlled trials of moluodan for CAG were conducted for meta-analysis and trial sequential analysis.

Results:

7 studies with a total sample size of 1143 cases were included. Compared to folic acid/vitamins, moluodan alone significantly increased the effective rate of pathological detection (relative risk [RR] = 1.73, 95% confidence interval [95%CI] = [1.48,2.02], P < .00001), and moluodan in combination with folic acid/vitamins significantly increased the effective rates of pathological detection (RR = 1.37, 95%CI = [1.23,1.52], P < .00001), gastroscopy (RR = 1.37, 95%CI = [1.18,1.60], P < .0001) and symptoms (RR = 1.25, 95%CI = [1.13,1.38], P < .0001). Harbord regression showed no publication bias (P = .22). Quality of evidence evaluation demonstrated moderate quality of evidence for all indicators.

Conclusions:

Moluodan can improve the effective rates of pathological examination, gastroscopy and symptoms in patients with CAG, and play a role in slowing down the disease progression and reducing clinical symptoms. It may be a potential drug for the treatment of CAG and has the value of further exploration.
Analysis of anesthetic effect of dexmedetomidine in femoral shaft fracture surgery
Authors: Chen Yin-Xiao , Lin Jie , Ye Xian-Hua , Zhao Xian-Da , Yan Qun-Xin
Published: December 2022

To investigate the effect of dexmedetomidine (DEX) on hemodynamics and recovery period after femoral shaft fracture surgery. Fifty-two patients, aged 3 to 7 years, who underwent femoral shaft fracture reduction surgery in our hospital in 2019 were randomly divided into the experimental group (n = 26) and the control group (n = 26). Both groups were given routine propofol combined with remifentanil by intravenous anesthesia. The experimental group was continuously pumped with DEX after induction of anesthesia, while the control group was continuously pumped with the same volume of normal saline. The mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia induction (T0), when laryngeal mask was inserted (T1), when skin was cut (T2), when intramedullary needle was inserted (T3), and when laryngeal mask was removed (T4). Extubation time after anesthesia withdrawal was recorded in the 2 groups. According to the Pediatric Anesthesia Emergence Delirium score, the agitation and the incidence of agitation were recorded immediately after extubation (T5), 10 minutes after entering the recovery room (T6) and 30 minutes after entering the recovery room (T7). There was no significant difference in MAP and HR between the 2 groups at T0 and T1 time points (P > .05). The MAP and HR of the experimental group at T2 to T4 were significantly lower than those of the control group (P < .05). The extubation time of the experimental group was longer than that of the control group (P < .05), but the Pediatric Anesthesia Emergence Delirium score and the incidence of agitation in the recovery period of the experimental group were lower than those of the control group (P < .05). In femoral shaft fracture surgery, intravenous anesthesia combined with continuous pumping DEX can effectively stabilize the hemodynamics of patients, and the incidence of postoperative agitation during anesthesia recovery is low.
The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis
Authors: Shi Zuolin , Liu Xiyu , Chen Mengjia , Zhang Na , Guan Hongna , Ye Dongyang
Published: December 2022

Background:

Nivolumab is the human programmed cell death-1 (PD-1)-blocking antibody showing significant effect in many refractory cancers. However, little is known about its risks of hematological toxicities, rare but clinically serious and potentially life-threatening adverse events. We want to explore whether nivolumab can increase the risks of hematological toxicities compared with other immunotherapy or chemotherapy drugs.

Method:

The databases of PubMed, Embase, Web of science, and CNKI were searched. We used the medical subject heading terms “Nivolumab” plus keyword “Nivolumab” to search studies published from August 1990 to October 2021. For the included articles, we calculated the relative risks and the corresponding 95% confidence intervals (CIs) for the risks of anemia, neutropenia, and leukopenia in patients treated with nivolumab versus control drugs.

Results:

Five original articles on the nivolumab trials were identified with 2399 patients enrolled in this meta-analysis. The relative risks of anemia, neutropenia, and leukopenia were 0.343 (95% CI: 0.177–0.663; P = .001), 0.020 (95% CI: 0.008–0.053; P = .000), and 0.054 (95% CI: 0.015–0.191; P = .000), respectively.

Conclusion:

The PD-1 inhibitor-nivolumab did not increase the risk of anemia, neutropenia and leukopenia. It may enhance awareness about lower risks of hematological toxicities when choosing nivolumab as PD-1 inhibitor among clinicians.
H3K9 acetylation modification and TLR9 immune regulation mechanism in patients after anti-HBV treatment
Authors: Zhu Haipeng , Wang Ke , Du Wei , Cao Huanhuan , Zhong Qingyang , Yin Sichun , Zhong Jianbo , Li Fawu
Published: December 2022

To improve the curative effect of anti-hepatitis B virus (HBV) drugs, methods such as thymosin and entecavir combination have become a focus of clinical investigation. The aim of this retrospective experimental study was to explore the potential mechanism of action of thymosin a1 (Ta1) combined with entecavir in the treatment of HBV infection. A total of 28 patients with chronic hepatitis B, 29 patients treated with thymosin a1 and entecavir combination, and 15 healthy individuals were enrolled in this study. RT-qPCR was conducted to evaluate the mRNA levels of TLR9 in peripheral blood mononuclear cells (PBMCs). The serum level of TLR9 protein was analyzed by ELISA. The binding of TLR9 gene to the protein H3K9Ac in PBMCs was assessed by chromatin immunoprecipitation, and serum inflammatory factors were detected by Luminex technology. The expression levels of TLR9 mRNA and serum TLR9 protein in patients with HBV infection were significantly lower than those in subjects in the control group before treatment but increased after treatment with the Ta1 and entecavir combination. Moreover, the acetylation protein H3K9Ac was significantly bound to the promoter region of the TLR9 gene in patients with HBV infection treated with the Ta1 and entecavir combination compared to that in patients with HBV infection without treatment. Furthermore, the expression levels of interleukin 6 (IL-6), interleukin 12 (IL-12), interferon gamma, and necrosis factor alpha in patients with HBV infection after the combination treatment were slightly decreased compared to those in patients with HBV infection without treatment. In conclusion, the histone acetylation modification of TLR9 was significantly improved in patients with HBV infection after treatment with the Ta1 and entecavir combination, which elevated the expression of TLR9 at the mRNA and protein levels and further regulated the expression of IL-6, IL-12, and other cytokines.
Brain natriuretic peptide as a biomarker for predicting contrast-induced nephropathy in patients undergoing coronary angiography/intervention: A systematic review and meta-analysis
Authors: Wu Xuefeng , Yang Xili , Xu Zhaoyan , Li Jianming
Published: December 2022

Background:

Contrast-induced nephropathy (CIN) is associated with adverse events. As there are no effective treatments, the early identification of high-risk patients is required. Individual studies have suggested the utility of brain natriuretic peptide in predicting CIN. Therefore, this meta-analysis aimed to systematically investigate the value of brain natriuretic peptide in predicting CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI).

Methods:

We searched PubMed, Embase, Cochrane Central Register of Controlled Trials Library, and Web of Science from inception date to March 9, 2022. Studies that evaluated the predictive value of brain natriuretic peptide for CIN outcomes in patients after CAG or PCI were included. The quality of the included studies was assessed using the QUADAS-2 tool. Diagnostic accuracy estimates were calculated using a random-effects model. Subgroup and meta-regression analyses were performed to identify the potential sources of heterogeneity.

Results:

Twelve studies with 7789 patients were included in the meta-analysis. The pooled sensitivity and specificity of brain natriuretic peptide for the prediction of CIN were 0.73 (95% CI: 0.67–0.78) and 0.77 (95% CI: 0.71–0.82), respectively. The area under the summary receiver operating characteristic curve was 0.80 (95% CI: 0.77–0.84). Meta-regression analysis indicated that the sources of sensitivity heterogeneity may be the country, mean age, and study population. Additionally, country, study population, study design, and index text contributed to the specificity heterogeneity.

Conclusion:

This study demonstrated that brain natriuretic peptide could function as a novel potential marker for the early detection of CIN in patients undergoing CAG or PCI.
LncRNA LOXL1-AS1 expression in cancer prognosis: A meta-analysis
Authors: Wang Xuhua , Chen Zhaoyuan , Zhou Huaqiang , Liu Wuyang , Luo Jiaquan
Published: December 2022

Background:

Several studies showed that LncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) is overexpressed in a variety of cancers and plays a role as an oncogene in cancer. The present meta-analysis aims to elucidate the relationship between LOXL1-AS1 expression and prognosis and clinicopathological features among cancer patients.

Methods:

PubMed, Web of Science, Cochrane Library, and EMBASE database were comprehensively and systematically searched. Pooled odds ratios (ORs) and hazard ratios with a 95% confidence interval (CI) were employed to assess the relationship between LOXL1-AS1 expression and clinical outcomes and clinicopathological features in cancer patients.

Results:

The present study finally enrolled 8 studies which included 657 cancer patients. The combined results indicated that the overexpression of LOXL1-AS1 was significantly associated with shorter overall survival (pooled hazard ratio = 1.99, 95% CI 1.49–2.65, P < .00001). Meanwhile, regarding clinicopathology of cancer patients, the upregulation of LOXL1-AS1 expression was closely related to lymph node metastasis (yes vs no OR = 4.01, 95% CI: 2.02–7.96, P < .0001) and distant metastasis (yes vs no OR = 3.04, 95% CI: 1.82–5.06, P < .0001), respectively.

Conclusion:

High expression of LOXL1-AS1 in some cancers predicts shorter overall survival, distant metastasis, and lymph node metastasis. LOXL1-AS1 shows great promise as a prognostic biomarker in cancer patients.
Tislelizumab combined with anlotinib in the second-line treatment of malignant pleural mesothelioma
Authors: Zhang Dandan , Liang Jianping , Lv Yanhua , Huang Xikun , Guo Weihong
Published: December 2022

Rationale:

Malignant pleural mesothelioma (MPM) is a malevolent tumor originated from pleura and often leads to poor prognosis. Chemotherapy of pemetrexed and cisplatin combined with antiangiogenic therapy of bevacizumab is recommended as the first-line regimen by guidelines. However, there are few sustainable second-line anti-tumor theraies that bring distinct survival benefit after the occurrence of drug resistance as the reported mPFS (median progression-free survival) scarcely exceeds 6 months. Immune checkpoint inhibitors are extensively investigated in pan-cancer, and dual immunotherapy has been listed in the first-line recommendation of MPM in several guidelines, while MPM patients benefit modestly from immune checkpoint inhibitors combination or monotherapy in second-line practice.

Patient concerns and diagnosis:

We report a 59-year-old male patient who was diagnosed with unresectable MPM in April 2021.

Interventions:

He received firstly pemetrexed combined with platinum and bevacizumab, which barely curbed disease progression; When the first line treatment failed, he was switched to tislelizumab combined with anlotinib.

Outcomes:

Tislelizumab combined with anlotinib significantly relieved his clinical symptoms, and imaging examination further validated the improvement. Until present, the second-line treatment PFS is more than 10 months.

Lessons:

The case firstly demonstrated the efficacy of tislelizumab combined with anlotinib in the second-line management of MPM. Thus, immunotherapy combined with small-molecule multi-target anti-angiogenic medication may be alternative for the second-line schemes of MPM.
Efficacy and safety of radiofrequency ablation and surgery for hepatocellular carcinoma in patients with cirrhosis: A meta-analysis
Authors: Zhang Tong , Hu He , Jia Yushan , Gao Yang , Hao Fene , Wu Jing , Yang Zhenxing , Ren Jialiang , Li Zhihao , Liu Aishi , Wu Hui
Published: December 2022

Background:

The aim of this study was to compare the efficacy and safety of surgical resection (RES) and radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients with cirrhosis and to evaluate short- and long-term clinical outcomes.

Methods:

The EMBASE, Cochrane Central Register of Control Trials and Medline databases were searched for comparative studies of RES and RFA in HCC patients with cirrhosis from inception until 30 April 2021. Overall survival (OS), disease-free survival (DFS), local recurrence rate, complication rate, hospitalization duration and operation time were compared between the 2 groups. Begg’s funnel plot and Egger’s test were performed to assess publication bias.

Results:

A total of 16 studies met our inclusion criteria, including 1 randomized controlled trial. A total of 3760 patients were included, of which 2007 received RES and 1753 received RFA. The results showed that the 3-year OS rate, 5-year OS rate, 1-year DFS rate and 3-year DFS rate in the RFA group compared with the RES treatment group were significantly lower, and the local recurrence rate in the RFA group was significantly higher than that in the RES group. Compared with the RES group, the RFA group had lower postoperative complication rates, shorter operative times, and no significant difference in hospitalization duration. Subgroup analysis of laparoscopic RFA showed that there was no significant difference in 1- and 5-year OS rates and 3-year and 5-year DFS rates between the 2 groups, while the 3-year OS rates and 1-year DFS rates in the RES group were better than those in the laparoscopic RFA group.

Conclusion:

Surgery is widely applied among HCC patients with cirrhosis, providing acceptable short- and long-term results.
A retrospective study of immunotherapy using the cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guérin (BCG-CWS) for cervical cancer
Authors: Shibata Takeo , Takata Emi , Sakamoto Jinichi , Shioya Akihiro , Yamada Sohsuke , Takakura Masahiro , Sasagawa Toshiyuki
Published: December 2022

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) has the potential to promote adaptive immunity. We sought to examine the synergistic effect of BCG-CWS vaccination on cervical cancer patients undergoing standard treatments including surgery, chemotherapy, and/or radiation. We retrospectively analyzed 103 patients (13 cases administered with BCG-CWS vaccine and 90 controls without BCG-CWS) who underwent a standard treatment for cervical cancer from 2005 to 2021. The BCG-CWS group underwent repeated intradermal injections of the BCG-CWS vaccine before or immediately after the standard therapy start from 2011 to 2018. The vaccination was repeated weekly for 1 month, and then every 4 weeks thereafter. The effectiveness of the BCG-CWS vaccination on cervical cancer treatment was evaluated by determining the hazard ratios of overall survival between the BCG-CWS group and the control group with multivariate analysis using the Cox model. Hazard ratios between 2 groups were determined after adjustment by clinical parameters including surgery, chemotherapy, radiation, age, clinical stage, presence of human papillomavirus, and pathology. Long-term follow-up revealed a significantly better prognosis (hazard ratio: 0.2108, P = .008 by the Cox model) for patients with cervical cancer in the BCG-CWS group compared to patients in the control group. Among patients with advanced cancer worse than stage IB2, some completely cleared the disease, whereas the others showed long-term survival with recurrence. BCG-CWS therapy appears to be an effective immune adjuvant therapy for cervical cancer, although randomized control studies are needed to confirm this. We also need to clarify the underlying mechanisms slowing the progression of cervical cancer in those receiving this vaccination. This study sheds light on the potential of immunostimulatory drugs such as BCG-CWS and suggests the important role of immunity for cancer elimination in combination therapy.
Prognostic model for predicting overall and cancer-specific survival among patients with superficial spreading melanoma: A SEER based study
Authors: Ji Qiang , Tang Jun , Li Shulian , Chen Junjie
Published: December 2022

Skin malignant melanoma is one of the most aggressive skin tumors. Superficial spreading melanoma (SSM) is the most common histological type, which can originate from different body skin sites, and some patients can still accumulate regional lymph nodes and even have distant metastasis in some cases. This study used the relevant data from the monitoring, epidemiology and results database of the National Cancer Institute database to study the overall survival (OS) and cancer-specific survival (CSS) of SSM patients and established an SSM nomogram to evaluate the prognosis of patients. A total of 13,922 patients were collected from the monitoring, epidemiology and results database of the National Cancer Institute and randomly divided into a training cohort (8353 cases) and a validation cohort (5569 cases). Univariate and multivariate Cox regression analysis were used to determine prognostic factors, and these factors were used to construct OS and CSS nomograms for patients with SSM. Finally, the discrimination and consistency of the nomogram model were evaluated by the consistency index (C-index), area under the curve (AUC) and calibration curve. Multivariate Cox regression analysis suggested that age, sex, tumor site, the American joint committee on cancer T stage and the first primary melanoma were independent predictors of OS and CSS in patients with SSM and that the American joint committee on cancer N stage was also an independent predictor of CSS in patients with SSM. Based on the above prognostic factors, this study constructed a predictive model. The C-index of the model OS and CSS for this training cohort was 0.805 [95% CI: 0.793–0.817] and 0.896 [95% CI: 0.878–0.913], respectively. The AUC values for 1-, 3-, and 5-year OS were 0.822, 0.820, and 0.821, respectively, and the AUC values for CSS were 0.914, 0.922, and 0.893, respectively. The data indicated that both nomograms showed better predictive accuracy. The calibration curves of the training cohort and the validation cohort were in good agreement. The nomogram has superior predictive performance in predicting 1-, 3-, and 5-year OS and CSS prognosis in patients with SSM and can provide a reference for individualized treatment and clinical counseling of SSM.
Randomized controlled trial of overall functional exercise process in perioperative of percutaneous transforaminal endoscopic discectomy
Authors: Wang Shuang , Yu Hai-Long , Zheng Liang , Ma Jun-Xiong , Wang Hong , Xiang Liang-Bi , Chen Yu
Published: December 2022

Background:

Percutaneous transforaminal endoscopic discectomy (PTED) has become the standard surgery for the patients of lumbar disc herniation with the advantages of less trauma and rapid recovery. But still some patients have poor prognosis after PTED. A major risk factor associated with the poor prognosis may be the unfit function exercise.

Objective:

To discuss the effect of overall functional exercise process for PTED.

Methods:

In January 2019 to June 2020, a single center randomized controlled trial was proceeded. The patients scheduled for PTED were randomly divided into the experimental group, which received overall functional exercise and the control group, which received routine process. The overall process included advance, whole-course exercise and integrating of traditional Chinese medical methods. The general information, visual analog scale (VAS) score and Oswestry Dysfunction Index (ODI) score at each follow-up point perioperative period were compared between the 2 groups.

Results:

There were no significant differences in the general information, the preoperative VAS and ODI. On the 3rd day after operation, the VAS of low back pain and leg pain in the experimental group were lower than the control group. One month after operation, the VAS of low back pain in the experimental group was lower than that in the control group. One to 3 months after operation, the ODI scores of the experimental group were better than that of the control group. There was no significant difference in modified MacNab index between the experimental group and the control group.

Conclusion:

Function exercise is important for the prognosis of minimally invasive lumbar surgery. The overall function exercise process perioperative is helpful to relieve the short-term pain of the patients and significantly improve the prognosis.
Manifestation of an undifferentiated uterine sarcoma in a 51 years old patient and its prognosis: A case report
Authors: Pantelić Miloš , Gvozdenovic Ljiljana , Panjković Milana , Stojić Marko , Stajić Dragan , Petrić Aleksandra , Trajković Sonja Pop , Trenkić Milan , Simić Dušan , Živadinović Lazar , Živadinović Aleksandar
Published: December 2022

Introduction:

Undifferentiated uterine sarcoma is a rare histological subtype of uterine sarcoma. This study aimed to summarize the clinical and pathological presentation of this case.

Case report:

A 51-years-old patient was admitted to the clinic because of severe pain in the lower abdomen, and scanty bleeding from the genitals. Gynecological examination revealed an enlarged uterus. Conventional and Doppler transvaginal sonography detected a tumorously altered uterus with a maximum diameter of 20 cm a tumefaction with unclear borders and a diameter of 10 cm, with hyperechoic and hypoechoic fields within the tumefaction, presenting pathological vascularization and reduced values of the (Pulsatile index  ≤ 1) and (Resistance index  ≤ 0.40). Preoperatively, the chest, abdomen, and pelvis were examined. The patient underwent surgery and total abdominal hysterectomy with bilateral salpingo-oophorectomy, and partial omentectomy, with complete removal of the tumor. A pathohistological diagnosis, of undifferentiated uterine sarcoma, was made by excluding other types of uterine sarcomas. At the control examination after completion of chemotherapy, recurrence was ascertained.

Conclusion:

undifferentiated uterine sarcoma is an aggressive malignant tumor that in most cases shows rapid progression of the disease after complete resection of the tumor, with a poor prognosis.
Variations in cortisol response in patients with known and suspected adrenal insufficiency
Authors: Mahzari Moeber , AlSohaim Abdullah , Al Mulla Abdulrhman , AlAssaf Abdullah , Al Amri Khalid , Hussain Syed D. , Sabico Shaun , Al Daghri Naser M. , Saleh Yousef
Published: December 2022

Adrenal insufficiency (AI) is a relatively rare disease. While the adrenocorticotropic hormone (ACTH) stimulation test remains as one of the commonly used diagnostic test for AI, to date there is no consensus on the cortisol cutoff value post-ACTH stimulation test. This study aimed to investigate and characterize the cortisol response after the standard ACTH stimulation test in a group of Saudi Arabian patients. A single center retrospective study was conducted on Saudi Arabian adult patients who underwent ACTH stimulation test at the endocrinology clinics of King Abdulaziz Medical City in Riyadh, Saudi Arabia between 2015 and 2018. Demographic, clinical and biochemical variables were collected and analyzed. A total of 154 medical records of patients (44 males, 110 females, mean age 44.4 ± 17.0 years) were included in the study. All patients underwent ACTH stimulation test. Fatigue was the most common symptom of participants. Type 1 diabetes was the most frequent comorbidity. Cortisol levels were significantly lower in patients who received corticosteroid replacement therapy, and, within the context of ACTH stimulation tests, were useful in diagnosing AI in patients with vague symptoms and signs. For basal cortisol, the cutoff of ≤258.5 has a sensitivity and specificity of 69.2% and 58.6%, respectively. For 30-minute, the cutoff of ≤386 sensitivity and specificity are 61.5% and 69.0%. For 60-minute, the cutoff of ≤491.5 has a sensitivity and specificity of 61.5% and 65.5%, respectively. Higher cortisol cutoff values have better sensitivity. Patients with AI present with mostly nonspecific symptoms, with type 1 diabetes as the most common comorbidity. The cortisol level cutoffs obtained from Arab patients who underwent ACTH stimulation tests showed wide variability for its utility in AI diagnosis. Further studies to evaluate the optimal cortisol cutoff values for AI diagnosis in this population are needed.
Knowledge, attitude and practices regarding COVID-19 and their associated factors in patients with type 2 diabetes attending Abdullah-Khalil diabetes center, Omdurman: A cross-sectional study
Authors: Ahmed Yousra S. , Mohamed Meirfat I. , Hasabo Elfatih A. , Omer Alaa T. , Abdelgadir Istabraq I. , Bashir Sara N. , EL hag Noha E.
Published: December 2022

Novel corona virus disease 2019 is the major threat for human life nowadays worldwide. This study aims to assess the knowledge, attitude and practices regarding COVID-19 among patients with type 2 diabetes attending Abdullah Khalil diabetes center (Omdurman Teaching Hospital). A facility-based observational descriptive cross-sectional study was carried out between January and February 2021, using non-probability quota sampling technique in Abdullah-Khalil diabetes center via the use of a structured close-ended interview questionnaire. It consisted of 19, 10, and 10 questions pertaining to knowledge, attitude and practices towards COVID-19 respectively. A total of 249 patients with type 2 diabetes were included. Of them, 132 (53.0%) were females and the majority (53.0%) aged between 41 and 60 years old. Concerning their education and marital status, 70 (28.1%) were primary school level and 208 (83.5%) were married. 89.6% of participants reported mass media as main source of information regarding COVID-19. Patients with type 2 diabetes attending Abdullah-Khalil diabetes center have good knowledge, positive attitude and good prevention practices towards COVID-19. Most respondents had good knowledge, positive attitude and good practices as 78.7%, 97.6%, and 69.9%, respectively. Educational level and source of information showed statistically significant association with the knowledge, attitude. However, the practice showed only statistical association with the mass media as a source of information (P = .006).
Modulating factors of fibromyalgia in women during the COVID-19 pandemic: A protocol for systematic review
Authors: Núñez-Recio Iván , García-Iglesias Juan Jesús , Martín-López Cristina , Navarro-Abal Yolanda , Fagundo-Rivera Javier , Climent-Rodríguez José Antonio , Gómez-Salgado Juan
Published: December 2022

Background:

Fibromyalgia is a disease that affects mostly women and is related to stressors. The aim of this study was to assess how the Coronavirus disease 2019 pandemic has affected women with fibromyalgia.

Methods:

A systematic review was conducted in the PubMed, ScienceDirect, and Springer Link databases, following the recommendations of the preferred reporting items for systematic reviews and meta-analyses statement. The methodological quality was assessed using the Joanna Briggs Institute critical appraisal tools for non-randomized studies.

Results:

A total of 6 studies were included. Most results indicated a worsening in the mental health of women with fibromyalgia during the pandemic, and this in turn impacted on physical health.

Conclusion:

The mental health of women with fibromyalgia was more affected during the Coronavirus disease 2019 pandemic period than that of non-fibromyalgia sufferers. This was also reflected in the worsening of symptoms and weakness in performing daily activities.