bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of artificial and natural sweeteners present in packaged non-alcoholic beverages (NABs) sold on the Singapore market
Authors: Tan Rebecca , Chew Sharon , Cleanthous Xenia , Anastasiou Kimberley , Brooker Paige G. , Pham Theresa , Smith Benjamin P. C.
Published: October 2021

Background

New Nutri-Grade labelling, aimed at reducing Singaporeans’ sugar consumption will be implemented for all pre-packaged non-alcoholic beverages (NABs) sold in retail outlets from end 2021 onwards. It is expected such labelling will have a major impact on sugar content of beverages, as well as the replacement of sugar with non-caloric alternatives.

Methods

This study used product label data obtained from in-store surveys to investigate sugar and sweetener composition of NABs present on the Singapore market. Using this data we calculated products prospective Nutri-Grade classification in order to compare the current market composition with relation to sugar and/or sweetener use.

Results

Over half of the NABs on market were sweetened with sugar (59%) and were associated with less healthy Nutri-Grades of ‘C’ and ‘D’. The use of natural sweeteners; Stevia and Monk fruit, remains low (6%).

Conclusion

With continuous efforts by the government in promoting public health nutrition, it is expected that there will be a greater usage of sugar substitutes among NABs in response to the upcoming implementation of Nutri-Grade and ever-fluctuating consumers’ demands. The data collected in this study provide a point estimate (July–September 2020) on market composition and use of both sugar and artificial sweeteners in beverages prior to integration of the mandatory labelling requirements.
Relationship between clinical outcomes and nerve conduction studies before and after surgery in patients with carpal tunnel syndrome
Authors: Ise Masato , Saito Taichi , Katayama Yoshimi , Nakahara Ryuichi , Shimamura Yasunori , Hamada Masanori , Senda Masuo , Ozaki Toshifumi
Published: October 2021

Background

Nerve conduction study (NCS) is the only useful test for objective assessment of carpal tunnel syndrome (CTS). However, the relationship between pre- and postoperative NCS and clinical outcomes was unclear. This study aimed to determine whether pre- and postoperative (6 months) NCS could predict patient-oriented and motor outcomes (6 and 12 months postoperatively) in patients with CTS.

Method

Of the 85 patients with CTS, 107 hands were analyzed from March 2011 to March 2020. All patients underwent open carpal tunnel release and were examined using the disabilities of the arm, shoulder and hand (DASH) questionnaire and grip strength (GS) preoperatively and 6 and 12 months postoperatively. Moreover, NCS was examined preoperatively and 6 months postoperatively. Distal motor latency (DML) and sensory conduction velocity (SCV) were the parameters used for NCS. The correlation coefficient between NCS and DASH or GS was calculated. A receiver operating characteristic curve was utilized to determine the NCS threshold value to predict DASH and GS improvement.

Results

The average scores of GS preoperatively and 6 and 12 months postoperatively were 21.3, 22.3, and 22.8, respectively. On the other hand, the average scores of DASH preoperatively and 6 and 12 months postoperatively were 28.8, 18.3, and 12.2, respectively. The average NCS scores (DML and SCV) preoperatively/6 months postoperatively were 7.3/5.4 and 27.8/36.7, respectively. Preoperative NCS did not correlate with DASH and GS. Postoperative SCV correlated with the change in grip strength (6–12 months, r = 0.67; 0–12 months, r = 0.60) and DASH (0–12 months, r = 0.77). Moreover, postoperative DML correlated with the change in DASH (6–12 months, r = − 0.33; 0–12 months, r = − 0.59). The prediction for the improvement of GS/DASH achieved a sensitivity of 50.0%/66.7% and a specificity of 100%/100%, at an SCV cutoff score of 38.5/45.0 or above. The prediction for improvement of GS/DASH achieved a sensitivity of 83.3%/66.7% and a specificity of 100%/66.7% at a DML cutoff score of 4.4/4.4 or below.

Conclusion

NCS at 6 months postoperatively can be used to predict the improvement of clinical outcome after 6 months postoperatively in patients with CTS.
How nurses support family caregivers in the complex context of end-of-life home care: a qualitative study
Authors: Becqué Yvonne N. , Rietjens Judith A. C. , van der Heide Agnes , Witkamp Erica
Published: October 2021

Background

Family caregivers are crucial in providing end-of-life care at home. Without their care, it would be difficult for many patients to die at home. In addition to providing care, family caregivers also need support for themselves. Nurses could play an important role in supporting family caregivers, but little is known about if and how they do so. The aim of this study is to explore how nurses currently approach and support family caregivers in end-of-life home care and which factors influence their support of family caregivers.

Methods

Data were collected using semi-structured interviews with 14 nurses from nine home care organisations in the Netherlands, in 2018. Interviews were audio-taped, transcribed verbatim and analysed using a thematic analysis approach.

Results

We identified two underlying nursing perspectives on supporting family caregivers: an instrumental perspective (seeing family caregivers mostly as collaborative partners in care) and a relational perspective (seeing family caregivers as both providing and needing support). All the interviewed nurses stated that they pay attention to family caregivers’ needs. The activities mentioned most often were: identification of support needs, practical education, support in decision-making about the patient’s treatment, emotional support, and organising respite care, such as night care, to relieve the family caregiver. The provision of support is usually based on intuition and experience, rather than on a systematic approach. Besides, nurses reported different factors at the individual, organisational and societal levels that influenced their support of family caregivers, such as their knowledge and experience, the way in which care is organised, and laws and regulations.

Conclusions

Nurses tend to address family caregivers’ needs, but such care was affected by various factors at different levels. There is a risk that nursing support does not meet family caregivers’ needs. A more reflective approach is needed and evidence-based needs assessment tools may help nurses to systematically assess family caregivers’ needs and to provide appropriate support.
Career choice regret during COVID-19 among healthcare students and professionals in mainland China: a cross-sectional study
Authors: Yang Guoyi , Wang Ling , Wang Jia , Geng Zixian , Liu Huixin , Xu Tao
Published: October 2021

Background

The COVID-19 epidemic affected the career choice of healthcare professionals and students. Career choice regret of healthcare professionals and students during COVID-19 outbreak and its affected factors are largely unexplored.

Methods

Convenience sample of nurses, doctors, and medical students were recruited from hospitals and universities nationwide. The data collected including demographic information, professional value before and after the COVID-19 outbreak, the Connor-Davidson Resilience Scale, and career choice regret level by an online questionnaire. Multinominal logistic regression was employed to explore the factors associated with career choice regret.

Results

In total, 9322 participants of convenience sampling were enrolled in, including 5786 nurses, 1664 doctors, and 1872 medical students. 6.7% participants had career choice regret. Multinominal logistic regression analysis showed, compared to participants with no regret, that as levels of psychological resilience increased, the odds of experiencing career choice regret decreased (OR = 0.95, 95% CI 0.94–0.96), while participants with lower professional value evaluation after the COVID-19 outbreak had higher probability to experience career choice regret (OR = 1.55,95% CI 1.50–1.61). Medical students were more likely to regret than nurses (OR = 1.65,95% CI 1.20–2.28), participants whose career/major choice was not their personal ideal had higher risk of experience career choice regret (OR = 1.59,95% CI 1.29–1.96), while participants who were very afraid of the coronavirus had higher risk to experience career choice regret then participants with no fear at all (OR = 2.00,95% CI 1.24–3.21).

As for the medical students, results indicated that medical students major in nursing and undergraduates had higher risk to experience career choice regret compared to medical students major in clinical medicine and postgraduate (Master or PhD), with an odds ratios of 2.65(95% CI 1.56–4.49) and 6.85 (95% CI 2.48–18.91)respectively.

Conclusions

A minority of healthcare professionals and medical students regretted their career choices during the COVID-19 outbreak. Enhance personal psychological resilience and professional value would helpful to reduce career choice regret among healthcare professionals and students during pandemic.
Impact of COVID-19 and mitigation plans on essential health services: institutional experience of a hospital in Ethiopia
Authors: Dandena Firaol , Teklewold Berhanetsehay , Anteneh Dagmawi
Published: October 2021

Background

Health systems around the world are being challenged by an on-going COVID-19 pandemic. The COVID-19 pandemic and associated response can have a significant downstream effect on access to routine health care services, and indirectly cause morbidity and mortality from causes other than the disease itself, especially in resource-poor countries such as Ethiopia. This study aimed to explore the impact of the pandemic on these services and measures taken to combat the effect.

Methods

The study was conducted at St. Paul’s hospital millennium medical college (SPHMMC) from December 15, 2020 to January 15, 2021 using a comparative cross-sectional study design. We collected data on the number of clients getting different essential health care services from May to October 2019 (Pre COVID) and the same period in 2020 (during a COVID-19 pandemic) from the patient registry book. The analysis was done with SPSS version 24 software.

Result

Overall, the essential services of SPHMMC were affected by the COVID-19 pandemic. The most affected service is inpatient admission, which showed a 73.3% (2044 to 682) reduction from the pre-COVID period and the least affected is maternal service, which only decreased by 13% (3671 to 3177). During the 6 months after the COVID-19 pandemic, there was a progressive increment in the number of clients getting essential health services.

Conclusion and recommendation

The establishment of a triple setup for fighting against COVID-19, which encompasses non-COVID services, an isolation center and a COVID-19 treatment center, played a vital role in preserving essential health services.
Visit-to-visit fasting blood glucose variability and lifetime risk of cardiovascular disease: a prospective study
Authors: Bi Jianing , Song Lulu , Wang Lulin , Wu Mingyang , Chen Shouhua , Wang Youjie , Wu Shouling , Tian Yaohua
Published: October 2021

Aims

Previous studies suggested an adverse association between higher fasting blood glucose (FBG) variability and cardiovascular disease (CVD). Lifetime risk provides an absolute risk assessment during the remainder of an individual’s life. However, the association between FBG variability and the lifetime risk of CVD is uncertain.

Objective

We aimed to investigate the effect of the visit-to-visit FBG variability on the lifetime risk of CVD.

Methods

This study included participants from the Kailuan Study who did not have CVD at index ages 35, 45, and 55 years. The FBG variability was defined as the coefficient of variation (CV) of three FBG values that were measured during the examination periods of 2006–2007, 2008–2009, and 2010–2011. We used a modified Kaplan-Merrier method to estimate lifetime risk of CVD according to tertiles of FBG variability.

Results

At index age 35 years, the study sample comprised 46,018 participants. During a median follow-up of 7.0 years, 1889 participants developed CVD events. For index age 35 years, participants with high FBG variability had higher lifetime risk of CVD (32.5%; 95% confidence interval [CI]: 28.9–36.1%), compared with intermediate (28.3%; 95% CI: 25.5 –31.1%) and low (26.3%; 95% CI: 23.0–29.5%) FBG variability. We found that higher FBG variability was associated with increased lifetime risk of CVD in men but not women. Similar patterns were observed at index ages 45 and 55 years.

Conclusions

Higher FBG variability was associated with increased lifetime risk of CVD at each index age. Focusing on the FBG variability may provide an insight to the clinical utility for reducing the lifetime risk of CVD.
Comparison of ticagrelor with clopidogrel on quality of life in patients with acute coronary syndrome
Authors: Moon Hyeyeon , Jo Yoon-Sung , Kim Soo-Jin , Jo Sua , Park Kyungil
Published: October 2021

Background

Ticagrelor has a Class I recommendation for use following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). However, ticagrelor needs to be taken twice a day, as compared to clopidogrel. Its adverse effects, such as dyspnea or bleeding, are known to be more common than with clopidogrel. Dyspnea may tend to be uncomfortable and limit activity. Major bleeding often leads to hospitalization or transfusions, and frequent minor bleeding, which might not result in patients seeking medical care, can make ACS patients feel unhealthy. Thus, these characteristics may affect the health-related quality of life (HQOL).

Methods

In the PLEIO (comParison of ticagreLor and clopidogrEl on mIcrocirculation in patients with acute cOronary syndrome) trial, we randomized 120 participants to receive ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for at least 12 months. We carried out an HQOL assessment with the Short Form 36 Health Survey (SF-36) questionnaire on the day of discharge following PCI, as well as six months later.

Results

At discharge, the HQOL measures were similar in the ticagrelor and clopidogrel groups, both having a physical component summary (PCS) and a mental component summary (MCS) score. A six-month HQOL follow-up assessment showed that there were no differences between the two study groups in either the PCS or the MCS scores. In both groups, the PCS scores significantly increased over six months of treatment (both p < 0.01). However, the MCS score did not differ significantly. A baseline MCS score is an independent predictor of better physical and mental health status at six months.

Conclusions

Ticagrelor, as compared to clopidogrel, did not significantly reduce the HQOL during the six months following PCI in patients with ACS.

Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02618733.
Extracellular vesicles: mediators of intercellular communication in tissue injury and disease
Authors: Berumen Sánchez Greg , Bunn Kaitlyn E. , Pua Heather H. , Rafat Marjan
Published: October 2021

Intercellular communication is a critical process that ensures cooperation between distinct cell types and maintains homeostasis. EVs, which were initially described as cellular debris and devoid of biological function, are now recognized as key components in cell–cell communication. EVs are known to carry multiple factors derived from their cell of origin, including cytokines and chemokines, active enzymes, metabolites, nucleic acids, and surface molecules, that can alter the behavior of recipient cells. Since the cargo of EVs reflects their parental cells, EVs from damaged and dysfunctional tissue environments offer an abundance of information toward elucidating the molecular mechanisms of various diseases and pathological conditions. In this review, we discuss the most recent findings regarding the role of EVs in the progression of cancer, metabolic disorders, and inflammatory lung diseases given the high prevalence of these conditions worldwide and the important role that intercellular communication between immune, parenchymal, and stromal cells plays in the development of these pathological states. We also consider the clinical applications of EVs, including the possibilities for their use as novel therapeutics.
miR-3065-3p promotes stemness and metastasis by targeting CRLF1 in colorectal cancer
Authors: Li Yifan , Xun Jing , Wang Botao , Ma Yuan , Zhang Lanqiu , Yang Lei , Gao Ruifang , Guan Jun , Liu Tianyu , Gao Hejun , Wang Ximo , Zhang Qi
Published: October 2021

Background

Colorectal cancer is one of the most common malignancy in the world. It has been reported that cancer stem cells (CSCs) serve as the primary drivers of tumorigenesis and tumor progression. There is an urgent need to explore novel molecules that regulate CSCs or their signatures. Increasing evidence has shown that miRNAs are involved in tumorigenesis and progression. Here, we aim to explore the regulatory effect and mechanism of miR-3065-3p on the stemness of colorectal cancer.

Methods

The expression of miR-3065-3p in colorectal cancer and the association of miR-3065-3p expression with prognosis of patients with colorectal cancer were analyzed using TCGA dataset or clinical cases. Gain or loss of function in different models, including colorectal cancer cell lines and orthotopic xenograft or liver metastatic mouse model, were used to investigate the effects of miR-3065-3p on colorectal cancer stemness and metastasis in vitro and in vivo. Cancer stemness was analyzed by detecting the ability of migration and invasion, NANOG, OCT4, and SOX2 expression, ALDH activity and sphere formation. In addition, the interaction of miR-3065-3p and cytokine receptor-like factor 1 (CRLF1) was analyzed theoretically and identified by the luciferase reporter assay. Moreover, the correlation between CRLF1 expression and miR-3065-3p was analyzed in colorectal cancer tissues. Finally, the effect of CRLF1 on the stemness and metastasis of colorectal cancer in vitro and in vivo was assessed.

Results

In this report, we found that miR-3065-3p was overexpressed in colorectal cancer and that its high expression was associated with poor prognosis of patients with colorectal cancer. miR-3065-3p promotes the stemness and metastasis of colorectal cancer. Furthermore, CRLF1 was the downstream target of miR-3065-3p and inhibited the stemness of colorectal cancer. In addition, CRLF1 expression was negatively correlated with miR-3065-3p in colorectal cancer tissues. And, CRLF1 mediated the effects of miR-3065-3p on promoting stemness of colorectal cancer cells.

Conclusion

Our data suggest that miR-3065-3p promoted the stemness and metastasis of colorectal cancer by targeting CRLF1. miR-3065-3p might serve as a promising prognostic marker as well as a therapeutic target for colorectal cancer.
Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa
Authors: Chimukangara Benjamin , Lessells Richard J. , Singh Lavanya , Grigalionyte Indra , Yende-Zuma Nonhlanhla , Adams Rochelle , Dawood Halima , Dlamini Linda , Buthelezi Sibonisile , Chetty Sheldon , Diallo Karidia , Duffus Wayne A. , Mogashoa Mary , Hagen Melissa B. , Giandhari Jennifer , de Oliveira Tulio , Moodley Pravi , Padayatchi Nesri , Naidoo Kogieleum
Published: October 2021

Background

Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa.

Methods

We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG.

Results

From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7–96.4) had ADR. The proportion with ADR was similar for participants on first-line ART (65/70, 92.9%, 95% CI 84.1–97.6) and those on second-line ART (40/44, 90.9%, 95% CI 78.3–97.5), and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs).

Conclusions

Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens.
Analysis of the management of the tenth Ebola virus disease outbreak in the Democratic Republic of Congo: developing a multidisciplinary response model to strengthen the healthcare system during disease outbreaks
Authors: Vivalya Bives Mutume , Ayodeji Okesina Akeem , Bafwa Yves Tibamwenda , Muyisa Louis Kasereka , Piripiri Astride Lina , Mbeva Jean-Bosco Kahindo
Published: October 2021

The declaration of any public health emergency in the Democratic Republic of Congo (DRC) is usually followed by the provision of technical and organizational support from international organizations, which build a parallel and short-time healthcare emergency response centered on preventing the extension of health emergencies across the countries and over the world. Previous Ebola virus disease (EVD) outbreaks have highlighted the need to reinforce the healthcare sector in different countries.

Based on the difficulty to implement the International Health Regulations (2005) to the local level of affected countries including the DRC, this paper proposes a multidisciplinary model based on the health zones through the strengthening of preparedness and response structures to public health emergencies vis-à-vis the existing weak health systems existing in DRC. A commitment to integrating the emergency response in the existing health system should work to reduce the tension that exists between local recruitment and its impact on the quality of daily healthcare in the region affected by EVD outbreak on one hand, and the involvement of international recruitment and its impact on the trust of the population on the emergency response on the other. This paper highlights the provision of a local healthcare workforce skilled to treat infectious diseases, the compulsory implementation of training programs focused on the emergency response in countries commonly affected by EVD outbreaks including the DRC. These innovations should reduce the burden of health problems prior to and in the aftermath of any public health emergency in DRC hence increasing the wellbeing of the community, especially the vulnerable people as well as the availability of trained healthcare providers able to early recognize and treat EVD.
Influence of light intensity distribution characteristics of light source on measurement results of canopy reflectance spectrometers
Authors: Yu Hongfeng , Ding Yongqian , Xu Huanliang , Wu Xueni , Dou Xianglin
Published: October 2021

Background

The characteristics of light source have an important influence on the measurement performance of canopy reflectance spectrometer. The size of the effective irradiation area and the uniformity of the light intensity distribution in the irradiation area determine the ability of the spectrometer to express the group characteristics of the measured objects.

Methods

In this paper, an evaluation method was proposed to theoretically analyze the influence of the light intensity distribution characteristics of the light source irradiation area on the measurement results. The light intensity distribution feature vector and the reflectance feature vector of the measured object were constructed to design reflectance difference coefficient, which could effectively evaluate the measurement performance of the canopy reflectance spectrometer. By using self-design light intensity distribution test system and GreenSeeker RT100, the evaluation method was applied to evaluate the measurement results.

Results

The evaluation results showed that the vegetation indices based on the arithmetic average reflectance of the measured object could be obtained theoretically only when the light intensity distribution of the light source detected by the spectrometer was uniform, which could fully express the group characteristics of the object. When the light intensity distribution of the active light source was not uniform, the measure value was difficult to fully express the group characteristics of the object. And the measured object reflectance was merely the weighted average value based on the light intensity distribution characteristics.

Conclusions

According to the research results of this paper, sunlight is the most ideal detection light source. If the passive light source spectrometer can improve the measurement method to adapt to the change of sunlight intensity, its measurement performance will be better than any active-light spectrometer.
Accuracy of the WSES classification system for pelvic ring disruptions: an international validation study
Authors: Wang Szu-Han , Fu Chih-Yuan , Bajani Francesco , Bokhari Marissa , Mis Justin , Poulakidas Stathis , Bokhari Faran
Published: October 2021

Background

In 2017, a novel classification for pelvic injuries was established by the World Society of Emergency Surgery (WSES). We validated its effectiveness using nationwide real-world data. The roles of associated vascular injury and open fracture in this system were also evaluated.

Methods

Patients with pelvic fractures in the National Trauma Data Bank 2015 dataset were retrospectively studied. First, the mortality rates were compared by WSES classification. Second, independent predictors of mortality were evaluated using a multivariate logistic regression model. Patients with and without associated vascular injuries and the same hemodynamic and pelvic ring stability statuses were compared. Patients with associated vascular injuries were compared to the proportion of nonsurvivors and survivors with unstable pelvic ring injuries. Third, the outcomes were compared between patients with open pelvic fracture and closed pelvic fracture in the mild, moderate and severe WSES classes.

Results

During the 12-month study period, 44,163 blunt pelvic fracture patients were included. The mortality rates were 1.8%, 3.8% and 10.6% for the mild, moderate and severe WSES classes, respectively (p < 0.001). MLR analysis showed that unstable pelvic ring injury did not significantly affect mortality (p = 0.549), whereas open pelvic fracture and associated vascular injury were independent predictors of mortality (odds of mortality: open pelvic fracture 1.630, p < 0.001; associated vascular injury 1.602, p < 0.001). Patients with associated vascular injuries showed that there was no significant difference in the proportion of patients with unstable pelvic ring injuries between survivors and nonsurvivors (37.2% vs. 32.7%, p = 0.323). In all three classes, patients with open pelvic fractures had significantly higher mortality rates and infection rates than patients with closed fractures (mortality rates: minor 3.5% vs. 1.8%, p = 0.009, moderate 11.2% vs. 3.3%, p < 0.001, severe 23.8% vs. 9.8%, p < 0.001; infection rates: minor 3.3% vs. 0.7%, p < 0.001, moderate 6.7% vs. 2.1%, p < 0.001, severe 7.9% vs. 2.8%, p < 0.001).

Conclusions

Based on this nationwide study, the WSES guideline provides an accurate and reproducible classification of pelvic fractures. It is recommended that open/closed fractures and associated vascular injuries be evaluated as supplements of the WSES classification.
Cementless total hip arthroplasty for three different degrees of hip involved secondary to ankylosing spondylitis: an analysis of 195 hips
Authors: Mou Ping , Li Hua , Chen An-Jing , Ji Zheng , Dai Xin-Yi , Zhou Zong-Ke
Published: October 2021

Background

Hip involved secondary to ankylosis spondylitis (AS) had a huge influence on hip function. Cementless total hip arthroplasty (THA) can improve hip function. However, no previous study compared the outcomes of THA for AS patients with three different degrees of hip involvement.

Methods

The 195 hips were retrospectively analyzed and divided into non-ankylosed group (group A, 94 hips), fibrous ankylosed group (group B, 49 hips), and bony ankylosed group (group C, 52 hips). postoperative range of motion (ROM), harris hip scores (HHS), the short-form 12 health survey (SF-12), length of stay (LOS), cost, radiological assessments, and complications were compared.

Results

The follow-up time was (79.4 ± 29.5) months for group A, (80.6 ± 28.9) months for group B, and (79.1 ± 28.9) months for group C (P = 0.966). Group A had the best postoperative hip ROM (P < 0.001), while group A and B can realize better HHS than group C (P < 0.001). The three groups had similar SF-12 postoperatively. For group A, LOS and cost for unilateral procedure were the least than that for group B and C (P = 0.003 and P = 0.001). Similar radiological assessments were achieved for three groups. 1 hip in group A encountered delay union of wound. 1 hip in group C encountered delay union of wound and dislocation and another patient encountered femoral fracture intraoperatively. 12 hips (12.8%) in group A, 6 hips (12.2%) in group B, and 6 hips (11.5%) in group C encountered asymptomatic heterotopic ossification (P = 0.977).

Conclusion

For AS patients with hip involvement, THA can improve hip ROM and function. THA for the non-ankylosed hip can realize the better hip function and postoperative ROM than ankylosed hip.
Greater presence of receptors for relaxin in the ligamentum teres of female infants who undergo open reduction for developmental dysplasia of the hip
Authors: Ayanoğlu Semih , Çabuk Haluk , Kuşku Çabuk Fatmagül , Beng Kubilay , Yildirim Timur , Uyar Bozkurt Süheyla
Published: October 2021

Background

While many factors involved in the etiology of developmental dysplasia of the hip (DDH), one of which is the hormone relaxin. Relaxin concentrations in patients with DDH may lead to pathodynamic changes during hip development by altering the physiological nature of the ligament, as well as by long-term exposure to relaxin during pregnancy. Our objective in this study was to determine the number of relaxin receptors in the ligamentum teres and their role in causing DDH.

Methods

We identified 26 infants between birth and 3 years of age who had undergone open reduction for DDH between 2010 and 2012. 12 hips of 12 miss abortus fetus between 20 to 35 weeks of gestation were used as control group. Specimens obtained from two groups were stained with Relaxin-2 antibody, and the amount of staining for relaxin receptors was determined using an ordinal H score.

Results

The mean (SD) H scores of infants with DDH were significantly higher than those of controls: 215 (59) versus 52 (48); P = 0.00; 95% CI. Statistically significant difference between the two groups in terms of gender was not found.

Conclusion

As a result, increased number of relaxin receptors in the ligamentum teres could be a risk factor for DDH.

Level of evidence

Level 2, Prospective comparative study.
Video-assisted thoracic surgery sleeve resection and bronchoplasty using 3D imaging system: its safety and efficacy
Authors: Seong Yong Won , Jeon Jae Hyun , Jang Hyo-Jun , Cho Sukki , Jheon Sanghoon , Kim Kwhanmien
Published: October 2021

Background

Video-assisted thoracic surgery sleeve resection with bronchial anastomosis or bronchoplasty is a technically demanding procedure. Three-dimensional endoscopic surgery has been reported to be helpful in decreasing operation time and improving spatial perception with less surgical errors, but there have been rare reports about relatively difficult thoracoscopic procedures utilizing 3D thoracoscope. We performed this study to evaluate early clinical outcomes of thoracoscopic sleeve resection and bronchoplasty utilizing 3D thoracoscope.

Methods

Data from a total of 36 patients who underwent thoracoscopic sleeve lobectomy or bronchoplasty at our institution from December 2015 to October 2017 were retrospectively reviewed. Three-port approach with one utility incision was used with a 10 mm, 30° three-dimensional thoracoscope. Twenty-three patients (81%) were male, and mean age was 65.9 ± 9.4 years. Fourteen patients (38.9%) underwent sleeve resection with bronchial anastomosis, 22 (61.1%) underwent wedge or simple bronchoplasty, and one patient received concomitant PA procedure. Bronchial anastomosis sites were not covered with viable tissue flaps.

Results

There was no (0%) suture needle injury from spatial misperception during bronchoplasty or sleeve anastomosis. There was no (0%) operative mortality. The pathologic report revealed squamous cell carcinoma (63.9%), adenocarcinoma (19.4%), carcinoid (6.9%), adenosquamous carcinoma (3.4%), and sarcomatoid carcinoma (2.8%). One (2.8%) late mortality was due to systemic recurrence of sarcomatoid carcinoma. There was no (0.0%) anastomotic failure. The mean number of dissected lymph nodes were 27.4 ± 13.2, and mean operation time was 216.8 ± 60.0 min. Median postoperative 24-h drain amount was 315 mL. Median chest tube days and hospital days were 4 and 6, respectively. Two patients (5.6%) had complications greater than Clavien-Dindo grade II—one case of ARDS, and the other case of a delayed bronchopleural fistula.

Conclusions

Thoracoscopic sleeve resection and bronchoplasty utilizing HD 3D thoracoscope is a safe and effective procedure with excellent early clinical outcomes. Further investigation for long-term outcomes will be needed.
Risk factors for lymph node metastasis and surgical scope in patients with cN0 non-small cell lung cancer: a single-center study in China
Authors: Jianlong Bu , Pinyi Zhang , Xiaohong Wu , Su Zhao , Sainan Pang , Jinfeng Ning , Shidong Xu
Published: October 2021

Background

It is difficult to determine the lymph node metastasis of patients with clinically negative lymph nodes (cN0) non-small cell lung cancer (NSCLC) before surgery. The purpose of this study is to investigate risk factors of lymph node metastasis in cN0 NSCLC, thereby to identify the surgical indications for lymph node dissection in cN0 NSCLC.

Methods

We conducted a retrospective study of patients with tumor size ≤ 30 mm who underwent radical resection of NSCLC. Binary logistic regression analysis was applied to predict risk factors for lymph node metastasis, and subject operating characteristics (ROC) curve was used to evaluate the independent risk factors.

Results

Overall, 44 patients (6.8%) with cN0 NSCLC had lymph node metastasis. Factors of tumor consolidation diameter (p < 0.001) and preoperative serum carcinoembryonic antigen (CEA) level (p = 0.017) are independent risk factors lymph node metastasis in cN0 NSCLC. The ROC curve showed that the cut-off value of consolidation diameter was 16.5 mm, and the area under the curve (AUC) was 0.825 (p < 0.001, 95% CI 0.780–0.870); the cut-off value of serum CEA level was 1.765 μg/L, and the AUC was 0.661 (p < 0.001, 95% CI: 0.568–0.754). Moreover, 8 of 461 patients with tumor parenchyma ≤ 16.5 mm had lymph node metastasis, and 36 of 189 patients with tumor parenchyma > 16.5 mm had lymph node metastasis.

Conclusion

Tumor consolidation diameter and preoperative serum CEA are independent factors to predict cN0 NSCLC with tumor size ≤ 30 mm. For patients with tumor parenchyma > 16.5 mm, the probability of lymph node metastasis is higher and lymph node dissection is recommended. For patients with tumor parenchyma ≤ 16.5 mm, the probability of lymph node metastasis is lower and lymph node sampling is feasible.
Comprehensive molecular characterization of lung tumors implicates AKT and MYC signaling in adenocarcinoma to squamous cell transdifferentiation
Authors: Quintanal-Villalonga Alvaro , Taniguchi Hirokazu , Zhan Yingqian A. , Hasan Maysun M. , Chavan Shweta S. , Meng Fanli , Uddin Fathema , Allaj Viola , Manoj Parvathy , Shah Nisargbhai S. , Chan Joseph M. , Ciampricotti Metamia , Chow Andrew , Offin Michael , Ray-Kirton Jordana , Egger Jacklynn D. , Bhanot Umesh K. , Linkov Irina , Asher Marina , Roehrl Michael H. , Ventura Katia , Qiu Juan , de Stanchina Elisa , Chang Jason C. , Rekhtman Natasha , Houck-Loomis Brian , Koche Richard P. , Yu Helena A. , Sen Triparna , Rudin Charles M.
Published: October 2021

Background

Lineage plasticity, the ability to transdifferentiate among distinct phenotypic identities, facilitates therapeutic resistance in cancer. In lung adenocarcinomas (LUADs), this phenomenon includes small cell and squamous cell (LUSC) histologic transformation in the context of acquired resistance to targeted inhibition of driver mutations. LUAD-to-LUSC transdifferentiation, occurring in up to 9% ofEGFR-mutant patients relapsed on osimertinib, is associated with notably poor prognosis. We hypothesized that multi-parameter profiling of the components of mixed histology (LUAD/LUSC) tumors could provide insight into factors licensing lineage plasticity between these histologies.

Methods

We performed genomic, epigenomics, transcriptomics and protein analyses of microdissected LUAD and LUSC components from mixed histology tumors, pre-/post-transformation tumors and reference non-transformed LUAD and LUSC samples. We validated our findings through genetic manipulation of preclinical models in vitro and in vivo and performed patient-derived xenograft (PDX) treatments to validate potential therapeutic targets in a LUAD PDX model acquiring LUSC features after osimertinib treatment.

Results

Our data suggest that LUSC transdifferentiation is primarily driven by transcriptional reprogramming rather than mutational events. We observed consistent relative upregulation of PI3K/AKT, MYC and PRC2 pathway genes. Concurrent activation of PI3K/AKT and MYC induced squamous features inEGFR-mutant LUAD preclinical models. Pharmacologic inhibition of EZH1/2 in combination with osimertinib prevented relapse with squamous-features in an EGFR-mutant patient-derived xenograft model, and inhibition of EZH1/2 or PI3K/AKT signaling re-sensitized resistant squamous-like tumors to osimertinib.

Conclusions

Our findings provide the first comprehensive molecular characterization of LUSC transdifferentiation, suggesting putative drivers and potential therapeutic targets to constrain or prevent lineage plasticity.
Replication catastrophe is responsible for intrinsic PAR glycohydrolase inhibitor-sensitivity in patient-derived ovarian cancer models
Authors: Coulson-Gilmer Camilla , Morgan Robert D. , Nelson Louisa , Barnes Bethany M. , Tighe Anthony , Wardenaar René , Spierings Diana C. J. , Schlecht Helene , Burghel George J. , Foijer Floris , Desai Sudha , McGrail Joanne C. , Taylor Stephen S.
Published: October 2021

Background

Patients with ovarian cancer often present at advanced stage and, following initial treatment success, develop recurrent drug-resistant disease. PARP inhibitors (PARPi) are yielding unprecedented survival benefits for women with BRCA-deficient disease. However, options remain limited for disease that is platinum-resistant and/or has inherent or acquired PARPi-resistance. PARG, the PAR glycohydrolase that counterbalances PARP activity, is an emerging target with potential to selectively kill tumour cells harbouring oncogene-induced DNA replication and metabolic vulnerabilities. Clinical development of PARG inhibitors (PARGi) will however require predictive biomarkers, in turn requiring an understanding of their mode of action. Furthermore, differential sensitivity to PARPi is key for expanding treatment options available for patients.

Methods

A panel of 10 ovarian cancer cell lines and a living biobank of patient-derived ovarian cancer models (OCMs) were screened for PARGi-sensitivity using short- and long-term growth assays. PARGi-sensitivity was characterized using established markers for DNA replication stress, namely replication fibre asymmetry, RPA foci, KAP1 and Chk1 phosphorylation, and pan-nuclear γH2AX, indicating DNA replication catastrophe. Finally, gene expression in sensitive and resistant cells was also examined using NanoString or RNAseq.

Results

PARGi sensitivity was identified in both ovarian cancer cell lines and patient-derived OCMs, with sensitivity accompanied by markers of persistent replication stress, and a pre-mitotic cell cycle block. Moreover, DNA replication genes are down-regulated in PARGi-sensitive cell lines consistent with an inherent DNA replication vulnerability. However, DNA replication gene expression did not predict PARGi-sensitivity in OCMs. The subset of patient-derived OCMs that are sensitive to single-agent PARG inhibition, includes models that are PARPi- and/or platinum-resistant, indicating that PARG inhibitors may represent an alternative treatment strategy for women with otherwise limited therapeutic options.

Conclusions

We discover that a subset of ovarian cancers are intrinsically sensitive to pharmacological PARG blockade, including drug-resistant disease, underpinned by a common mechanism of replication catastrophe. We explore the use of a transcript-based biomarker, and provide insight into the design of future clinical trials of PARGi in patients with ovarian cancer. However, our results highlight the complexity of developing a predictive biomarker for PARGi sensitivity.
M6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a notch signaling activation dependent way
Authors: Li Kai , Peng Zi-Yang , Gao Shan , Wang Qing-Shi , Wang Rui , Li Xiang , Xiao Guo-Dong , Zhang Jing , Ren Hong , Tang Shou-Ching , Sun Xin
Published: October 2021

Background

The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects. Methods: Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections.

Results

We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed TUSC7, both of which contributed to the resistant features. Functionally, the sponge type of TUSC7 regulation of miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells’ renewal in Erlotinib resistant PC9 cells (PC9ER) and Erlotinib resistant HCC827 cells (HCC827ER) cells. The Notch signaling functions manipulated the cMYC and DICER inner cytoplasm, and the absence of either cMYC or DICER1 lead to TUSC7 and miR-146a decreasing respectively, formed the closed circle to maintain the balance.

Conclusion

PC9ER and HCC827ER cells harbored much more stem-like cells, and the resistance could be reversed by Notch signaling inactivation. The intrinsic miR-146 and TUSC7 levels are monitored by m6A effectors, the alternation of either miR-146 or TUSC7 expression could lead to the circling loop to sustain the new homeostasis. Further in clinics, the combined delivery of TKIs and Notch specific inhibitory non-coding RNAs will pave the way for yielding the susceptibility to targeted therapy in lung cancer.
Confidence interval of risk difference by different statistical methods and its impact on the study conclusion in antibiotic non-inferiority trials
Authors: Bai Anthony D. , Komorowski Adam S. , Lo Carson K. L. , Tandon Pranav , Li Xena X. , Mokashi Vaibhav , Cvetkovic Anna , Findlater Aidan , Liang Laurel , Tomlinson George , Loeb Mark , Mertz Dominik ,   the McMaster Infectious Diseases Fellow Research Group
Published: October 2021

Background

Numerous statistical methods can be used to calculate the confidence interval (CI) of risk differences. There is consensus in previous literature that the Wald method should be discouraged. We compared five statistical methods for estimating the CI of risk difference in terms of CI width and study conclusion in antibiotic non-inferiority trials.

Methods

In a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, reported risk differences for the primary outcome, and described the number of successes and/or failures as well as patients in each arm. For each study, we re-calculated the risk difference CI using the Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and skewness-corrected asymptotic score (SCAS) methods. The CIs by different statistical methods were compared in terms of CI width and conclusion on non-inferiority. A wider CI was considered to be more conservative.

Results

The analysis included 224 comparisons from 213 studies. The statistical method used to calculate CI was not reported in 134 (59.8%) cases. The median (interquartile range IQR) for CI width by Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and SCAS methods was 13.0% (10.8%, 17.4%), 13.3% (10.9%, 18.5%), 13.6% (11.1%, 18.9%), 13.6% (11.1% and 19.0%), and 13.4% (11.1%, 18.9%), respectively. In 216 comparisons that reported a non-inferiority margin, the conclusion on non-inferiority was the same across the five statistical methods in 211 (97.7%) cases. The differences in CI width were more in trials with a sample size of 100 or less in each group and treatment success rate above 90%. Of the 18 trials in this subgroup with a specified non-inferiority margin, non-inferiority was shown in 17 (94.4%), 16 (88.9%), 14 (77.8%), 14 (77.8%), and 15 (83.3%) cases based on CI by Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and SCAS methods, respectively.

Conclusions

The statistical method used to calculate CI was not reported in the majority of antibiotic non-inferiority trials. Different statistical methods for CI resulted in different conclusions on non-inferiority in 2.3% cases. The differences in CI widths were highest in trials with a sample size of 100 or less in each group and a treatment success rate above 90%.

Trial registration

PROSPEROCRD42020165040. April 28, 2020.