bluuebunny/crossref_metadata_2025 huggingface dataset:
Microvascular decompression in trigeminal neuralgia - a prospective study of 115 patients
Authors: Andersen Anne Sofie Schott , Heinskou Tone Bruvik , Rochat Per , Springborg Jacob Bertram , Noory Navid , Smilkov Emil Andonov , Bendtsen Lars , Maarbjerg Stine
Published: November 2022

Background

Trigeminal neuralgia is a severe facial pain disorder. Microvascular decompression is first choice surgical treatment of patients with classical TN. There exist few prospective studies with an independent evaluation of efficacy and complications after MVD.

Objectives

We aimed to assess outcome and complications after microvascular decompression from our center.

Methods

We prospectively recorded clinical characteristics, outcome, and complications from consecutive patients with either classical or idiopathic (only patients with a neurovascular contact) trigeminal neuralgia undergoing microvascular decompression. Neurovascular contact was evaluated by 3.0 Tesla MRI. Patients were assessed before and 3, 6, 12, and 24 months after surgery by independent assessors.

Results

Of 115 included patients, 86% had a clinically significant outcome (i.e., BNI I – BNI IIIb). There was a significant association between an excellent surgical outcome and the male sex (OR 4.9 (CI 1.9–12.8), p = 0.001) and neurovascular contact with morphological changes (OR 2.5 (CI 1.1–6.0), p = 0.036). Significantly more women (12/62 = 19%) than men (2/53 = 4%) had a failed outcome, p = 0.019. The most frequent major complications were permanent hearing impairment (10%), permanent severe hypoesthesia (7%), permanent ataxia (7%), and stroke (6%). Most patients (94%) recommend surgery to others.

Conclusion

Microvascular decompression is an effective treatment for classical and idiopathic (only patients with a neurovascular contact) trigeminal neuralgia with a high chance of a long-lasting effect. The chance of an excellent outcome was highest in men and in patients with classical trigeminal neuralgia. Complications are relatively frequent warranting thorough patient evaluation and information preoperatively.

Trial registration

Clinical.trials.gov registration no. NCT04445766.
Analysis and Interpretation of metagenomics data: an approach
Authors: Navgire Gauri S. , Goel Neha , Sawhney Gifty , Sharma Mohit , Kaushik Prashant , Mohanta Yugal Kishore , Mohanta Tapan Kumar , Al-Harrasi Ahmed
Published: November 2022

Advances in next-generation sequencing technologies have accelerated the momentum of metagenomic studies, which is increasing yearly. The metagenomics field is one of the versatile applications in microbiology, where any interaction in the environment involving microorganisms can be the topic of study. Due to this versatility, the number of applications of this omics technology reached its horizons. Agriculture is a crucial sector involving crop plants and microorganisms interacting together. Hence, studying these interactions through the lenses of metagenomics would completely disclose a new meaning to crop health and development. The rhizosphere is an essential reservoir of the microbial community for agricultural soil. Hence, we focus on the R&D of metagenomic studies on the rhizosphere of crops such as rice, wheat, legumes, chickpea, and sorghum. These recent developments are impossible without the continuous advancement seen in the next-generation sequencing platforms; thus, a brief introduction and analysis of the available sequencing platforms are presented here to have a clear picture of the workflow. Concluding the topic is the discussion about different pipelines applied to analyze data produced by sequencing techniques and have a significant role in interpreting the outcome of a particular experiment. A plethora of different software and tools are incorporated in the automated pipelines or individually available to perform manual metagenomic analysis. Here we describe 8–10 advanced, efficient pipelines used for analysis that explain their respective workflows to simplify the whole analysis process.
Multi-omics to predict changes during cold pressor test
Authors: Kogelman Lisette J. A. , Ernst Madeleine , Falkenberg Katrine , Mazzoni Gianluca , Courraud Julie , Lundgren Li Peng , Laursen Susan Svane , Cohen Arieh , Olesen Jes , Hansen Thomas Folkmann
Published: November 2022

Background

The cold pressor test (CPT) is a widely used pain provocation test to investigate both pain tolerance and cardiovascular responses. We hypothesize, that performing multi-omic analyses during CPT gives the opportunity to home in on molecular mechanisms involved. Twenty-two females were phenotypically assessed before and after a CPT, and blood samples were taken. RNA-Sequencing, steroid profiling and untargeted metabolomics were performed. Each ‘omic level was analyzed separately at both single-feature and systems-level (principal component [PCA] and partial least squares [PLS] regression analysis) and all ‘omic levels were combined using an integrative multi-omics approach, all using the paired-sample design.

Results

We showed that PCA was not able to discriminate time points, while PLS did significantly distinguish time points using metabolomics and/or transcriptomic data, but not using conventional physiological measures. Transcriptomic and metabolomic data revealed at feature-, systems- and integrative- level biologically relevant processes involved during CPT, e.g. lipid metabolism and stress response.

Conclusion

Multi-omics strategies have a great potential in pain research, both at feature- and systems- level. Therefore, they should be exploited in intervention studies, such as pain provocation tests, to gain knowledge on the biological mechanisms involved in complex traits.
Evaluation of inorganic phosphate solubilizing efficiency and multiple plant growth promoting properties of endophytic bacteria isolated from root nodules Erythrina brucei
Authors: Berza Belay , Sekar Jegan , Vaiyapuri Prabavathy , Pagano Marcela C. , Assefa Fassil
Published: November 2022

Background

In soils, phosphorous (P) mostly exists in fixed/insoluble form and unavailable for plants use in soil solution, hence it is in scarcity. P is fixed in the form of aluminium, iron and manganese phosphates in acidic soils and calcium phosphate in alkaline soils. Phosphate solubilizing bacteria, the ecological engineers play a pivotal role in the mobilization of fixed forms of P by using different mechanisms. The objectives of this study were to evaluate inorganic phosphate solubilizing efficiency and other multiple plant growth promoting traits of Erythrina brucei root nodule endophytic bacteria and to investigate effects of the selected endophytic bacteria on the growth of wheat plant under phosphorous deficient sand culture at greenhouse conditions.

Results

Among a total of 304 passenger endophytic bacteria, 119 (39%) exhibited tricalcium phosphate (TCP) solubilization; however, none of them were formed clear halos on solid medium supplemented with aluminum phosphate (Al-P) or iron phosphate (Fe–P). Among 119 isolates, 40% exhibited IAA production. The selected nine potential isolates also exhibited potentials of IAA, HCN, NH3 and/or hydrolytic enzymes production. All the selected isolates were potential solubilizers of the three inorganic phosphates (Al-P, Fe–P and TCP) included in liquid medium. The highest values of solubilized TCP were recorded by isolates AU4 and RG6 (A. soli), 108.96 mg L−1 and 107.48 mg L−1, respectively at sampling day3 and 120.36 mg L−1 and 112.82 mg L−1, respectively at day 6. The highest values of solubilized Al-P and Fe–P were recorded by isolate RG6, 102.14 mg L−1 and 96.07 mg L−1, respectively at sampling days 3 and 6, respectively. The highest IAA, 313.61 µg mL−1 was recorded by isolate DM17 (Bacillus thuringiensis). Inoculation of wheat with AU4, RG6 and RG5 (Acinetobacter soli) increased shoot length by 11, 17.4 and 14.6%, respectively compared to the negative control. Similarly, 76.9, 69.2 and 53.8% increment in shoot dry weight is recorded by inoculation with RG6, AU4 and RG5, respectively. These nine potential endophytic isolates are identified to Gluconobacter cerinus (4), Acinetobacter soli (3), Achromobacter xylosoxidans (1) and Bacillus thuringiensis (1).

Conclusion

AU4, RG6 and RG5 can be potential bio-inoculants candidates as low cost agricultural inputs in acidic and/or alkaline soils for sustainable crop production.
CXCL1/CXCR2 is involved in white matter injury in neonatal rats via the gut–brain axis
Authors: Yang Can , Feng Zhiyuan , Deng Hong , Dai Lu , He Ling , Yin Linlin , Zhao Jing
Published: November 2022

Background

This study aimed to investigate whether CXCL1/CXCR2 mediates intestinal injury or white matter injury by delivering inflammatory mediators through the gut–brain regulation axis.

Methods

Neonatal SD rats, regardless of sex, were administered 3% dextran sulfate sodium via intragastric administration at different time points to construct necrotizing enterocolitis (NEC) models. Meanwhile, hypoxia and ischemia were induced in 3 day-old SD rats to construct hypoxic–ischemic brain injury (HIBI) and NEC + HIBI models, without gender discrimination. Hematoxylin–eosin staining was used to observe pathological changes in neonatal rat intestinal and brain tissues. Western blotting detected CXCL1 and CXCR2 expression in NEC, HIBI, and NEC + HIBI rat intestinal and brain tissues.

Results

Compared with normal rats, pathological damage to periventricular white matter was observed in the NEC group. In addition to the increased mortality, the histopathological scores also indicated significant increases in brain and intestinal tissue damage in both HIBI and NEC + HIBI rats. Western blotting results suggested that CXCL1 and CXCR2 expression levels were upregulated to varying degrees in the intestinal and brain tissues of NEC, HIBI, and NEC + HIBI neonatal rats compared to that in the normal group. Compared with the HIBI group, the expression of CXCL1 and CXCR2 continued to increase in NEC + HIBI rats at different time points.

Conclusions

CXCL1/CXCR2 may be involved in white matter injury in neonatal rats by delivering intestinal inflammatory mediators through the gut–brain axis.
Role of CD8+ T cell exhaustion in the progression and prognosis of acute respiratory distress syndrome induced by sepsis: a prospective observational study
Authors: Yan Lei , Chen Yumei , Han Yi , Tong Chaoyang
Published: November 2022

Background

CD8+T cells are important for protective immunity against intracellular pathogens. Excessive amounts of antigen and/or inflammatory signals often lead to the gradual deterioration of CD8+T cell function, a state called “exhaustion”. However, the association between CD8+T cell exhaustion and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how CD8+T cells and inhibitory receptors were related to the clinical prognosis of ARDS.

Methods

A prospective observational study in an emergency department enrolled patients who were diagnosed with sepsis-associated ARDS according to the sepsis-3 criteria and Berlin definition. Peripheral blood samples were collected within 24 h post recruitment. CD8+T cell count, proliferation ratio, cytokine secretion, and the expression of coinhibitory receptors were assayed.

Results

Sixty-two patients with ARDS met the inclusion criteria. CD8+T cell counts and proliferation rates were dramatically decreased in non-surviving ARDS patients. Increasing programmed cell death 1 (PD-1) expression on the CD8+T cell surface was seen in patients with worse organ function, while an increasing level of T cell immunoglobulin mucin-3 (Tim-3) was associated with a longer duration of the shock. Kaplan–Meier analysis showed that low CD8+T cell percentages and increased inhibitory molecule expression were significantly associated with a worse survival rate.

Conclusions

CD8+T cells and coinhibitory receptors are promising independent prognostic markers of sepsis-induced ARDS, and increased CD8+T cell exhaustion is significantly correlated with poor prognosis.
The role of socio-demographic and health factors during COVID-19 in remote access to GP care in low-income neighbourhoods: a cross-sectional survey of GP patients
Authors: Sana S. , Kollmann J. , Magnée T. , Merkelbach I. , Denktaş S. , Kocken P. L.
Published: November 2022

Objectives

Remote consultations were common in general practice during the COVID-19 pandemic. This approach may have affected access to GP care for people with low socio-economic status: this group has a high prevalence of chronic conditions and a higher mortality rate due to COVID-19. This study explores the association of sociodemographic and health factors with the decision to contact a GP practice, and care utilisation, among patients in low-income neighbourhoods in the Netherlands.

Design

Cross-sectional survey study.

Setting

General practice in low-income neighbourhoods in the Netherlands.

Participants

Patients from low-income neighbourhoods were selected from fourteen general practices on the basis of ethnic background, chronic disease or health literacy. Participants were stratified according to categories of these background characteristics to obtain equal numbers per category. A total of 213 surveys were retained for analysis.

Main outcome measures

Need for GP contact, decision to contact a GP practice, and GP service utilisation.

Results

Forty-five percent (N = 88) of the participants experienced health problems for which they wished to consult their GP at the start of the outbreak of COVID-19. A majority of them (81%) had contact with a GP service. The need to contact the GP was significantly associated with financial difficulties (OR 2.20 CI (1.10 to 4.39)). An interaction effect was found of health literacy with concerns about COVID-19 with in respondents with low health literacy a significant association between concerns about COVID-19 and a need for a GP appointment (OR 5.33 CI (2.09 to 13.59)) and absence of a significant association in the higher health literacy group (OR 1.14 CI (0.51 to 2.56)) . Moreover, 56% (N = 74) of the participants received remote care at least one time during the first wave of COVID-19. Female participants used remote care more often (OR 3.22 CI (1.57 to 6.59)) and participants aged 50 and over used remote care less often (OR 0.46 CI (0.21 to 0.97)).

Conclusion

Many patients in low-income neighbourhoods were able to consult a GP, often remotely. However from the equity perspective, access to GP care should be safeguarded for patients with health problems, financial difficulties and low health literacy because of their greater need to consult a GP during times of crisis.
Can the organization of health resource integration be analyzed in terms of the current state of unmet demand for health services? take the health needs of the elderly in a place in zhejiang province, china, as an example
Authors: Gao Li , Wang Bing , Yang Xiaohong , Pan Yongliang , Feng Wenming , Pei Xuedan , Fan Yanfang , Liu Bing
Published: November 2022

Background

The aging of the population has made the health problems of the elderly increasingly prominent, and their health needs are increasing. Existing studies on health resource integration approaches are mostly incomplete in assessing the health service capacity from the perspective of the health service provider.

Objective

The unmet health needs of the elderly were sampled and analyzed from the perspective of health service demanders. To explore how to build an integrated medical organization structure to better meet the health needs of the elderly.

Methods

A whole-group sampling method was used to conduct a questionnaire survey of 1527 older adults in N district of H city, Zhejiang province, China, to cross-sectionally analyze their current status of unmet health needs.

Results

The survey and analysis found that the needs of the elderly in this community to obtain disease-related knowledge, rational exercise, a healthy diet, and access to health information were not met. There were more patients with chronic diseases, and the top three chronic disease prevalence rates were hypertension (40.2%), dyslipidemia (8.4), and diabetes (7%). Chronic disease co-morbidities accounted for 13.3%.

Conclusion

The relatively independently set up health service system at the present stage in China can no longer fully meet the health needs of the elderly, and the health service providers should provide integrated and continuous health services to meet the needs of whole-cycle health management. Therefore, we believe that effectively integrating various health service providers in the region and building an integrated health service organization with general practitioners as the core may be a solution to the current situation of unmet health needs of the elderly.
A comparison of NAFLD and MAFLD diagnostic criteria in contemporary urban healthy adults in China: a cross-sectional study
Authors: Liu Qiling , Zhao Gang , Li Qian , Wu Weiyun , Zhang Yan , Bian Hua
Published: November 2022

Background

A recently proposed diagnostic criteria of metabolic dysfunction-associated fatty liver disease (MAFLD) is more available for various clinical situations than nonalcoholic fatty liver disease (NAFLD), but understanding about differences between NAFLD and MAFLD in clinical practice remains limited in the general adult urban population in China.

Methods

A total of 795 subjects were recruited from Wu Song Branch of Zhongshan Hospital who participated in the general health assessment. Examination results was obtained through analysis of blood samples and abdominal ultrasonography. Participants were divided into four subgroups according to whether they had NAFLD or MAFLD (NAFLD- MAFLD-, NAFLD + MAFLD-, NAFLD- MAFLD + and NAFLD + MAFLD+).

Results

Among the urban healthy adults investigated, 345 people (43.4%) were diagnosed with NAFLD and 356 people (44.8%) with MAFLD. No significant differences in the prevalence, age, fasting blood glucose, glycosylated hemoglobin, liver enzyme examination, percentage of overweight, hypertension or dyslipidaemia were found between NAFLD and MAFLD patients. Patients with MAFLD had worse metabolic disorders than NAFLD + MAFLD- patients. The NAFLD fibrosis score (NFS) of the NAFLD- MAFLD + group was higher than that of the NAFLD + MAFLD- group. Higher proportion of patients in the NAFLD- MAFLD + group have NFS ≥-1.455.

Conclusion

MAFLD criteria have similar prevalence and patient characteristics compared with previous NAFLD but help to identify a group of patients with high risks of metabolic disorders and liver fibrosis who have been missed with NAFLD, and has superior utility.
Challenges faced by community connectors: lessons learned from a Taiwan public health initiative
Authors: Ni Lee-Fen , Lo Shu-Ying , Chia Shu-Li , Wu Chao-Chun , Chung Fen-Fang , Wang Yu-Hsin , Hsiao Ping-Ru , Lin Chia-Ling , Xiao Xaviera , Lin Chiu-Tzu , Chao Li-Fen
Published: November 2022

Background

Effective solutions that meet the diverse community health needs of older adult populations are of critical importance. To address these needs, a nationwide community connector team—tasked with providing referral support to older adult populations and completing an asset mapping resource inventory initiative centered around the needs of older adult populations—was developed in Taiwan. The purpose of this qualitative study was to explore community connectors’ experiences and challenges.

Methods

Community connectors (n = 26) across four diverse sites participated in focus group interviews in July 2020. Interviews explored the challenges community connectors encountered in their roles; the strategies used to address these challenges; the asset mapping process; and on how they conceptualized their roles. Qualitative content analysis was applied.

Results

Three themes were uncovered: developing community ties, cross-organization interactions and professional conflicts. The findings show that community connectors face hurdles in uncovering community resources and that they experience considerable professional instability. The findings also shed light on the day-to-day approaches used to navigate on-the-job challenges and the steps taken to develop community partnerships.

Conclusions

The experiences of community connectors provide important insights and can serve to illuminate the development of similar initiatives that seek to use community connectors for community health related purposes.
Incidence of falls and fall-related injuries and their predictive factors in frail older persons with cancer: a multicenter study
Authors: Kenis Cindy , Decoster Lore , Flamaing Johan , Debruyne Philip R. , De Groof Inge , Focan Christian , Cornélis Frank , Verschaeve Vincent , Bachmann Christian , Bron Dominique , Van den Bulck Heidi , Schrijvers Dirk , Langenaeken Christine , Specenier Pol , Jerusalem Guy , Praet Jean-Philippe , De Cock Jessie , Lobelle Jean-Pierre , Wildiers Hans , Milisen Koen
Published: November 2022

Background

Falls and fall-related injuries are a major public health problem. Data on falls in older persons with cancer is limited and robust data on falls within those with a frailty profile are missing. The aim of this study is to investigate the incidence and predictive factors for falls and fall-related injuries in frail older persons with cancer.

Methods

This study is a secondary data analysis from data previously collected in a large prospective multicenter observational cohort study in older persons with cancer in 22 Belgian hospitals (November 2012–February 2015). Patients ≥70 years with a malignant tumor and a frailty profile based on an abnormal G8 score were included upon treatment decision and evaluated with a Geriatric Assessment (GA). At follow-up, data on falls and fall-related injuries were documented.

Results

At baseline 2141 (37.2%) of 5759 included patients reported at least one fall in the past 12 months, 1427 patients (66.7%) sustained an injury. Fall-related data of 3681 patients were available at follow-up and at least one fall was reported by 769 patients (20.9%) at follow-up, of whom 289 (37.6%) fell more than once and a fall-related injury was reported by 484 patients (62.9%). Fear of falling was reported in 47.4% of the patients at baseline and in 55.6% of the patients at follow-up. In multivariable analysis, sex and falls history in the past 12 months were predictive factors for both falls and fall-related injuries at follow-up. Other predictive factors for falls, were risk for depression, cognitive impairment, dependency in activities of daily living, fear of falling, and use of professional home care.

Conclusion

Given the high number of falls and fall-related injuries and high prevalence of fear of falling, multifactorial falls risk assessment and management programs should be integrated in the care of frail older persons with cancer. Further studies with long-term follow-up, subsequent impact on cancer treatment and interventions for fall prevention, and integration of other important topics like medication and circumstances of a fall, are warranted.

Trial registration

B322201215495.
Clinical muscle mass-related biomarkers that predict mortality in older patients with community-acquired pneumonia
Authors: Huang Sha , Guo Yan , Chen Lanlan , Wang Yan , Chen Xiaoyan
Published: November 2022

Objective

Community-acquired pneumonia (CAP) is associated with elevated morbidity and mortality, and it usually occurs in older adults. Our goal here was to assess the efficacies of muscle mass-related biomarkers, such as, aspartate transaminase/alanine transaminase (AST/ALT) and creatinine/cystatin C*100 (Cr/CysC*100), in predicting 1-, 2-, and 3-year mortalities of older CAP patients.

Methods

Design: Retrospective cohort study. Setting and Participants: A teaching hospital in western China. Hospitalized CAP patients, aged≥60 years. We separated patients into a high or low muscle mass group, according to the median AST/ALT and Cr/CysC*100, respectively. We acquired data from medical records and local government mortality databases, as well as telephonic interviews. We analyzed the association between low muscle mass (AST/ALT and Cr/CysC*100) and all-cause mortality at 1, 2, and 3 years in older patients with CAP.

Results

We enrolled 606 patients (58.58% male; median age: 81 years) for analysis. The 1-, 2-, and 3-year mortality in older patients with CAP in the low muscle mass group (AST/ALT) was higher than in the high muscle mass group (AST/ALT) (1-year: 51.16% vs. 36.96%, p < 0.001; 2-year: 54.46% vs. 41.25%, p = 0.001; 3-year: 54.79% vs. 42.9%, p = 0.003). Upon adjustment of potential confounding factors, we revealed, using cox regression analysis, that the low muscle mass group (AST/ALT) experienced enhanced mortality risk at the 1-, 2-, and 3-year follow-ups, compared to the high muscle mass group (AST/ALT) (1-year: hazard ratios (HR) = 1.46, 95% confidence interval (CI): 1.13–1.88; 2-year: HR = 1.39, 95% CI: 1.09–1.77; 3-year: HR = 1.35, 95% CI: 1.06–1.72). The 1-, 2-, and 3-year mortality of older CAP patients in the low muscle mass group (Cr/CysC*100) was also higher than the high muscle mass group (Cr/CysC*100) (1-year: 56.29% vs. 31.91%, p < 0.001; 2-year: 60.26% vs. 35.53%, p < 0.001; 3-year: 61.26% vs. 36.51%, p < 0.001). Compared to the high muscle mass group (Cr/CysC*100), the low muscle mass group (Cr/CysC*100) experienced enhanced mortality risk at the 1-, 2-, and 3-year follow ups (1-year: HR = 1.9, 95% CI: 1.46–2.48; 2-year: HR = 1.85, 95% CI: 1.44–2.39; 3-year: HR = 1.85, 95% CI: 1.44–2.37).

Conclusions

Low muscle mass (AST/ALT and Cr/CysC*100) were associated with enhanced 1-, 2-, and 3-year mortality risk in older patients with CAP.
Influences on intentions for obstetric practice among family physicians and residents in Canada: an explorative qualitative inquiry
Authors: Marshall Emily Gard , Horrey Kathleen , Moritz Lauren R. , Buote Richard , Grudniewicz Agnes , Goldsmith Laurie J. , Randall Ellen , Jones Lori , Lavergne M Ruth
Published: November 2022

Background

Many family medicine residency graduates indicate a desire to provide obstetric care, but a low proportion of family physicians (FPs) provide obstetric care within their practice. This suggests personal preference alone may not account for the low proportion of FPs who ultimately provide full obstetric care. If decisionmakers plan to augment the number of FPs providing obstetric care, barriers to the provision of such care must first be identified. Within this paper, we explore the perspectives of both family practice residents and early-career FPs on the factors that shaped their decision to provide obstetric care.

Methods

In this qualitative study, we analyzed a subset of interview data from three Canadian provinces: British Columbia, Ontario, and Nova Scotia (n = 18 family practice residents; n = 39 early-career FPs). We used thematic analysis to analyze data relevant to obstetric care practice, applying the socio-ecological model and comparing themes across participant types, gender, and province.

Results

Participants described influences affecting their decision about providing obstetric care. Key influencing factors aligned with the levels of the socio-ecological model of public policy (i.e., liability), community (i.e., community needs), organizational (e.g., obstetric care trade-offs, working in teams, sufficient exposure in training), interpersonal practice preferences (i.e., impact on family life, negative interactions with other healthcare professionals), and individual factors (i.e., defining comprehensive care as “everything but obstetrics”). Many participants were interested in providing obstetric care within their practice but did not provide such care. Participants’ decision-making around providing or not providing obstetric care included considerations of personal preferences and outside influences.

Conclusions

Individual-level factors alone do not account for the decrease in the type and amount of obstetric care offered by FPs. Instead, FPs’ choice to provide or not provide obstetric care is influenced by factors at higher levels of the socio-ecological model. Policymakers who want to encourage obstetric practice by FPs should implement interventions at the public policy, community, organizational, interpersonal, and individual levels.
Prenatal diagnosis and mRNA profiles of fetal tetralogy of Fallot
Authors: Gou Zhongshan , Zhou Yan , Jia Hongjing , Yang Zhong , Zhang Qian , Yan Xinxin
Published: November 2022

Tetralogy of fallot (TOF) in the fetus is a typical congential heart disease that occurs during the early embryonic period, being characterized by the abnormal development of conus arteriosus. The early diagnosis and prevention of fetal TOF is very important and there is a great need for exploring the pathogenesis of it in clinic. In this study, there were three cases being detected with TOF by fetal echocardiogram and confirmed by autopsy. We characterize the difference of expression of lncRNAs and mRNAs through sequencing analysis of 3 pairs of myocardial tissues of fetal TOF and those of age-matched controls. Compared with normal group, there were 94 differentially expressed lncRNAs and 83 mRNA transcripts in TOF (P < 0.05). Correlation analysis between lncRNA and mRNA further showed that differentially expressed lncRNA can be linked to mRNAs, suggesting the potential regulator role of lncRNA in mRNA expression. Our data serve as a fundamental resource for understanding the disease etiology of TOF.
Comparative safety of infliximab and adalimumab on pregnancy outcomes of women with inflammatory bowel diseases: a systematic review & meta-analysis
Authors: Wang Han , Hu Yue , Chen Fang , Shen Mengdie
Published: November 2022

Background

Inflammatory bowel disease (IBD) is a condition that affects most of the digestive tract. There is no report of fertility reduction in medically managed IBD women compared with the general population. On the other hand, active IBD can lead to significantly decreased fertility. Over the previous 2 decades, anti-tumor necrosis factor (anti-TNF) has been an effective treatment for managing patients with IBD, increasing the use of infliximab and adalimumab in clinical practice. However, it is unclear which biologics are better for pregnant women with IBD.

Aim

We conducted a systematic review and meta-analysis for the risk of adverse pregnancy outcomes following treatment with infliximab and adalimumab in women with IBD.

Methods

Bibliographic databases were retrieved from their inception to July 2022. The results were adverse pregnancy outcomes, including congenital malformations and spontaneous abortion.

Results

A total of 8 studies included 527 pregnant women with IBD. Of these, 343 received infliximab, and 184 received adalimumab therapy. Compared to adalimumab, adverse pregnancy outcomes were not increased in infliximab therapy including congenital malformations and spontaneous abortion.

Conclusion

Infliximab and adalimumab therapy did not show the difference of risk in adverse pregnancy outcomes in women with IBD.

Systematic review registration

http://www.crd.york.ac.uk/PROSPERO, identifier: CRD 42,021,277,869.
Differential in vitro effects of targeted therapeutics in primary human liver cancer: importance for combined liver cancer
Authors: Malik Ihtzaz Ahmed , Rajput Mansi , Werner Rieke , Fey Dorothea , Salehzadeh Niloofar , von Arnim Christine A. F. , Wilting Jörg
Published: November 2022

The incidence of primary liver tumors, hepatocellular carcinoma (HCC), intrahepatic cholangiocellular carcinoma (ICC), and combined HCC/ICC (cHCC/CC) is increasing. For ICC, targeted therapy exists only for a small subpopulation of patients, while for HCC, Sorafenib and Lenvatinib are in use. Diagnosis of cHCC/CC is a great challenge and its incidence is underestimated, bearing the risk of unintended non-treatment of ICC. Here, we investigated effects of targeted inhibitors on human ICC cell lines (HUH28, RBE, SSP25), in comparison to extrahepatic (E)CC lines (EGI1, CCC5, TFK1), and HCC/hepatoblastoma cell lines (HEP3B, HUH7, HEPG2). Cells were challenged with: AKT inhibitor MK-2206; multikinase inhibitors Sorafenib, Lenvatinib and Dasatinib; PI3-kinase inhibitors BKM-120, Wortmannin, LY294002, and CAL-101; and mTOR inhibitor Rapamycin. Dosage of the substances was based on the large number of published data of recent years. Proliferation was analyzed daily for four days. All cell lines were highly responsive to MK-2206. Thereby, MK-2206 reduced expression of phospho(p)-AKT in all ICC, ECC, and HCC lines, which mostly corresponded to reduction of p-mTOR, whereas p-ERK1/2 was upregulated in many cases. Lenvatinib showed inhibitory effects on the two HCC cell lines, but not on HEPG2, ICCs and ECCs. Sorafenib inhibited proliferation of all cells, except the ECC line CCC5. However, at reduced dosage, we observed increased cell numbers in some ICC experiments. Dasatinib was highly effective especially in ICC cell lines. Inhibitory effects were observed with all four PI3-kinase inhibitors. However, cell type-specific differences were also evident here. Rapamycin was most effective in the two HCC cell lines. Our studies show that the nine inhibitors differentially target ICC, ECC, and HCC/hepatoblastoma lines. Caution should be taken with Lenvatinib and Sorafenib administration in patients with cHCC/CC as the drugs may have no effects on, or might even stimulate, ICC.
Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA
Authors: Oh Tae Jeong , Lim Eunkyung , Bang Bo-Ram , Lee Justin Junguek , Na Yong Gil , Shin Ju Hyun , Lim Jae Sung , Song Ki Hak , An Sungwhan
Published: November 2022

Background

Early detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa. Certain specific aberrant methylations could serve as useful biomarkers. The aim of this study was to identify methylation biomarkers for early detection of BCa.

Methods

CpG methylation microarray analysis was conducted on primary tumors with varying stages (T1—T4) and paired nontumor tissues from nine BCa patients. Bisulfite-pyrosequencing was performed to confirm the methylation status of candidate genes in tissues and urine sediments (n = 51). Among them, PENK was selected as a potential candidate and validated using an independent set of 169 urine sediments (55 BCa, 25 benign urologic diseases, 8 other urologic cancers, and 81 healthy controls) with a quantitative methylation-specific real time PCR (mePENK-qMSP). All statistical analyses were performed using MedCalc software version 9.3.2.0.

Results

CpG methylation microarray analysis and stepwise validation by bisulfite-pyrosequencing for tissues and urine sediments supported aberrant methylation sites of the PENK gene as potential biomarkers for early detection of BCa. Clinical validation of the mePENK-qMSP test using urine sediment-DNA showed a sensitivity of 86.5% (95% CI: 71.2 – 95.5%), a specificity of 92.5% (95% CI: 85.7 – 96.7%), and an area under ROC of 0.920 (95% CI: 0.863 – 0.959) in detecting Ta high-grade and advanced tumor stages (T1-T4) of BCa patients. Sensitivities for Ta low-grade, Ta high-grade, T1 and T2-T4 were 55.6, 83.3, 88.5, and 100%, respectively. Methylation status of PENK was not correlated with sex, age or stage, while it was associated with the tumor grade of BCa.

Conclusions

In this study, we analyzed the comprehensive patterns of DNA methylation identified that PENK methylation possesses a high potential as a biomarker for urine-based early detection of BCa. Validation of PENK methylation confirms that it could significantly improve the noninvasive detection of BCa.
Comparison of clinicopathological features and prognostic significance between synchronous multiple primary and solitary esophageal squamous cell carcinomas
Authors: Yang Yueyang , Tang Peng , Ma Mingquan , Zhang Hongdian , Wang Haitong , Zhu Kai , Xiao Wanyi , Gong Lei , Yu Zhentao
Published: November 2022

Background

Synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) refers to more than one primary esophageal carcinoma detected in a solitary patient at the time of initial presentation. The purpose of this study was to evaluate the clinicopathological features, appropriate surgical approaches and long-term survival in patients with S-MPESCC by comparing with those with solitary esophageal squamous cell carcinoma (SESCC).

Methods

In total, 567 patients with esophageal squamous cell carcinoma surgically resected in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened for retrospective analysis (50 in the S-MPESCC group and 516 in the SESCC group).

Results

No significant difference was observed in terms of other characteristics except total alcohol consumption (P = 0.029). S-MPESCC had higher lymph node rate than SESCC (62.0% and 44.1%, respectively; P = 0.015) especially in upper mediastinal (32.0% and 18.6%, respectively; P = 0.023) and abdominal (38.0% and 22.8%, respectively; P = 0.017) regions. The survival was not different between the two groups, and the 5-year survival rates of S-MPESCC and SESCC were 46.2% and 50.8%, respectively (P = 0.507). But for patients with pT3-4 cancers, the survival in S-MPESCC was worse than that in SESCC (P = 0.033). In the multivariate analysis, pT stage of primary cancer was an important independent predictor of prognosis in patients with S-MPESCC (hazard ratio [HR], 3.968; 95% confidence interval [CI], 1.031 to 15.268; P = 0.045).

Conclusions

S-MPESCC was significantly different from SESCC in terms of clinicopathological characteristics include alcohol intake and pattern of lymphatic metastasis. Furthermore, S-MPESCC showed worse long-term survival than SESCC with increasing depth of primary cancer infiltration.
Impact of fibrinogen levels and modified Glasgow prognostic score on survival of stage III/N2 non-small cell lung cancer patients treated with neoadjuvant therapy and radical resection
Authors: Sinn Katharina , Mosleh Berta , Grusch Michael , Klepetko Walter , Hoetzenecker Konrad , Klikovits Thomas , Gompelmann Daniela , Hoda Mir Alireza
Published: November 2022

Purpose

The prognostic value of pretreatment and preoperative fibrinogen plasma levels and the modified Glasgow prognostic score (mGPS) in stage III/N2 non-small cell lung cancer (NSCLC) patients who receive neoadjuvant treatment followed by radical surgery is yet unclear.

Methods

Fibrinogen levels and mGPS of 84 patients with initial stage III/N2 NSCLC, who received neoadjuvant therapy followed by complete surgical resection from 2002 to 2014 were retrospectively analyzed and correlated with clinical parameters and overall survival (OS). Data were analyzed using log-rank and Cox regression analysis adjusted for clinical and pathological factors.

Results

Median serum fibrinogen level after neoadjuvant treatment was 439 mg/dL (IQR 158 mg/dL). Elevated fibrinogen levels (> 400 mg/dL) after neoadjuvant treatment were significantly associated with poorer OS (28.2 months vs. 60.9 months, HR 0.562, p = 0.048). Importantly, a decrease in fibrinogen levels after neoadjuvant treatment (n = 34) was found to be an independent predictor for favorable OS in multivariate analysis (HR 0.994, p = 0.025). Out of 80 patients, 55, 19 and 6 patients had a mGPS of 0, 1 and 2, respectively. Moreover, elevated mGPS after neoadjuvant treatment (mGPS 1–2) showed a non-significant trend for poorer OS compared to mGPS 0 (28.2 vs. 46.5 months, HR 0.587, p = 0.066).

Conclusion

Elevated fibrinogen levels after neoadjuvant therapy prior to surgery in stage III/N2 NSCLC patients are associated with significant disadvantage for OS. A decrease in fibrinogen levels after neoadjuvant therapy was found to be a predictor for superior OS in this retrospective patient cohort.
Dentate line invasion as a predictive factor of poor distant relapse-free survival in locally advanced lower rectal cancer with anal sphincter involvement
Authors: Song Maxiaowei , Wang Hongzhi , Wang Lin , Li Shuai , Zhang Yangzi , Geng Jianhao , Zhu Xianggao , Li Yongheng , Cai Yong , Wang Weihu
Published: November 2022

Background

While an important surgical landmark of the dentate line has been established for locally advanced lower rectal cancer (LALRC), the prognostic significance of dentate line invasion (DLI) has not been well defined. This study aimed to explore the impact of DLI on prognosis in LALRC patients with anal sphincter involvement after neoadjuvant chemoradiotherapy followed by surgery.

Methods

We analyzed 210 LALRC patients and classified them into DLI group (n = 45) or non-DLI group (n = 165). The exact role of DLI in survival and failure patterns was assessed before and after propensity-score matching(PSM). Finally, 50 patients were matched.

Results

Before matching, patients in the DLI group had poorer 5-year distant relapse-free survival (DRFS) (P < 0.001), disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P = 0.022) than those in the non-DLI group, with the exception of local recurrence-free survival (LRFS) (P = 0.114). After PSM, the 5-year DRFS, DFS, OS, and LRFS were 51.7% vs. 79.8%(P = 0.026), 51.7% vs. 79.8%(P = 0.029), 71.6% vs. 85.4%(P = 0.126), and 85.7% vs. 92.0%(P = 0.253), respectively, between the two groups. DLI was also an independent prognostic factor for poor DRFS with (Hazard ratio [HR] 3.843, P = 0.020) or without matching (HR 2.567, P = 0.001). The DLI group exhibited a higher rate of distant metastasis before (44.4% vs. 19.4%, P < 0.001) and after matching (48.0% vs. 20.0%, P = 0.037) and similar rates of locoregional recurrence before (13.3% vs.7.9%, P = 0.729) and after matching (16.0% vs.12.0%, P = 1.000).

Conclusions

DLI may portend worse DRFS and distant metastasis in LALRC patients with anal sphincter involvement, and this may be an important variable to guide clinicians.
Impact of posttransplant cyclophosphamide on the outcome of patients undergoing unrelated single-unit umbilical cord blood transplantation for pediatric acute leukemia
Authors: Li Xin-Yu , Zhan Li-Ping , Liu Dian-Dian , Han Xia-Wei , Chen Han , Wu Zheng-Zhou , Wang Yin , Que Li-Ping , Wu Xiao-Jun , Liu Su , Wang Kai-Mei , Huang Shao-Liang , Fang Jian-Pei , Huang Ke , Xu Hong-Gui
Published: November 2022

Background

Umbilical cord blood transplantation (UCBT) from unrelated donors is one of the successful treatments for acute leukemia in childhood. The most frequent side effect of UCBT is peri-engraftment syndrome (PES), which is directly associated with the greater prevalence of acute and chronic graft-versus-host-disease (aGvHD and cGvHD). In haploidentical stem cell transplantation, posttransplant cyclophosphamide (PTCY) has been demonstrated to be an effective method against GvHD. However, the effects of PTCY as a GvHD prophylactic in UCBT had not been investigated. This study aimed to evaluate the effects of PTCY on the outcomes of UCBT for pediatric acute leukemia.

Methods

This retrospective study included 52 children with acute leukemia who underwent unrelated single-unit UCBT after myeloablative conditioning regimens. The results from the PTCY and non-PTCY groups were compared.

Results

The incidence of transplantation-related mortality in non-PTCY and PTCY were 5% and 10% (p = 0.525), respectively. The incidence of relapse in non-PTCY and PTCY were 5% and 23% (p = 0.095), respectively. Second complete remission status (CR2) was an independent risk factor for relapse-free survival (hazard ratio = 9.782, p = 0.001). The odds ratio for sepsis or bacteremia incidence was significantly greater in the PTCY group (9.524, p = 0.017). PTCY group had increased rates of cytomegalovirus activity and fungal infection. The incidence of PES, aGvHD, cGvHD, and hemorrhagic cystitis in the PTCY group was lower than that in the non-PTCY group, although it was not significantly different. Additionally, higher doses of PTCY (29 mg/kg and 40 mg/kg) were associated with lower incidences of aGvHD and severe GvHD (65% and 29%, respectively) than lower doses (93% and 57%, respectively). Engraftment time and graft failure incidence were similar across groups.

Conclusion

The results support the safety and efficiency of PTCY as part of PES controlling and GvHD prophylaxis in single-unit UCBT for children with acute leukemia. A PTCY dosage of 29 mg/kg to 40 mg/kg appears to be more effective in GvHD prophylaxis for UCBT patients.
The possible pathogenesis of macular caldera in patients with North Carolina macular dystrophy
Authors: Zhu Zhe , Zou He , Li Chuanyu , Tong Bainan , Zhang Chenchen , Xiao Jun
Published: November 2022

Background

This study provides a detailed description of a Chinese family with North Carolina macular dystrophy (NCMD) and explores its possible pathogenesis.

Methods

Five individuals from a three-generation family underwent general ophthalmic examination, multi-imaging examinations and visual electrophysiology examinations when possible. Genetic characterization was carried out by target region sequencing and high-throughput sequencing in affected patients.

Results

Despite severe fundus changes, patients had relatively good visual acuity. Genetic analysis showed that affected patients had PRDM13 gene duplication and heterozygous mutations of the ABCA4 gene. Optical coherence tomography (OCT) showed an abnormal retinal pigment epithelium (RPE) layer in patients with grade 2 lesions, while the neurosensory retina was relatively normal. In grade 3 patients, RPE and choroid atrophy were greater than that of the neurosensory retina, showing concentric atrophy.

Conclusions

RPE and choroidal atrophy were found to play an important role in the development of macular caldera.
Optical coherence tomography findings in three patients with Werner syndrome
Authors: Nagai Tatsuya , Yokouchi Hirotaka , Miura Gen , Koshizaka Masaya , Maezawa Yoshiro , Oshitari Toshiyuki , Yokote Koutaro , Baba Takayuki
Published: November 2022

Background

Werner syndrome is a rare, autosomal recessive disorder characterised by premature aging. It is a typical hereditary progeroid syndrome that can be difficult to diagnose owing to its rarity and the similarity of some of its symptoms, such as juvenile cataracts, to other common ophthalmologic conditions. Early onset of bilateral cataracts is currently used as the ophthalmological feature for Werner syndrome; however, ophthalmologists often find performing a detailed examination of the medical history and genetic testing for Werner syndrome at the time of an ophthalmologic consultation challenging. If a unique ocular finding was observed on ocular examinations in cases of juvenile bilateral cataracts, we could consider Werner syndrome as a differential diagnosis. 

Case presentation

We documented the cases of three patients with Werner syndrome in whom thinning of the retina in the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were observed using optical coherence tomography (OCT). Visual field tests revealed the loss of visual field mainly owing to glaucoma.

The thinnig of the choroidal thickness (CT) in three patients was also observed using enhanced depth imaging (EDI)-OCT.

Conclusions

Three patients have thinning of the RNFL, GCC, and choroidal thickness and the loss of visual field. These findings suggest the need for including Werner syndrome in the differential diagnosis when patients presenting with juvenile cataracts of unknown cause also show abnormal retinal and choroidal thinning in the OCT images.