bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction in number to treat versus number needed to treat
Authors: Zhang Chenyang , Yin Guosheng
Published: March 2021

Background

We propose a new measure of treatment effect based on the expected reduction in the number of patients to treat (RNT) which is defined as the difference of the reciprocals of clinical measures of interest between two arms. Compared with the conventional number needed to treat (NNT), RNT shows superiority with both binary and time-to-event endpoints in randomized controlled trials (RCTs).

Methods

Five real RCTs, two with binary endpoints and three with survival endpoints, are used to illustrate the concept of RNT and compare the performances between RNT and NNT. For survival endpoints, we propose two versions of RNT: one is based on the survival rate and the other is based on the restricted mean survival time (RMST). Hypothetical scenarios are also constructed to explore the advantages and disadvantages of RNT and NNT.

Results

Because there is no baseline for computation of NNT, it fails to differentiate treatment effect in the absolute scale. In contrast, RNT conveys more information than NNT due to its reversed order of differencing and inverting. For survival endpoints, two versions of RNT calculated as the difference of the reciprocals of survival rates and RMSTs are complementary to each other. The RMST-based RNT can capture the entire follow-up profile and thus is clinically more intuitive and meaningful, as it inherits the time-to-event characteristics for survival endpoints instead of using truncated binary endpoints at a specific time point.

Conclusions

The RNT can serve as an alternative measure for quantifying treatment effect in RCTs, which complements NNT to help patients and clinicians better understand the magnitude of treatment benefit.
Endoscopic resections for superficial esophageal squamous cell epithelial neoplasia: focus on histological discrepancies between biopsy and resected specimens
Authors: Yang Lang , Jin Hua , Xie Xiao-li , Cao Yang-tian , Liu Zhen-hua , Li Na , Jin Peng , He Yu-qi , Sheng Jian-qiu
Published: March 2021

Background

Endoscopic resection has been used for high-grade intraepithelial neoplasia (HGIN) and superficial esophageal squamous cell carcinoma (ESCC) with limited risk of lymph node metastasis. However, some of these lesions cannot be accurately diagnosed based on forceps biopsy prior to treatment. In this study we aimed to investigate how to solve this histological discrepancy and avoid over- and under-treatment.

Methods

The medical records of patients with superficial esophageal squamous cell neoplasia who underwent endoscopic resection at our hospital from January 2012 to December 2019 were reviewed retrospectively. The histological discrepancy between the biopsy and resected specimens was calculated and its association with clinicopathological parameters was analyzed.

Results

A total of 137 lesions from 129 patients were included. The discrepancy rate between forceps biopsy and resected specimens was 45.3% (62/137). Histological discrepancy was associated with the histological category of the biopsy (p < 0.001). In addition, 17 of the 30 (56.7%) biopsies that was diagnosed as indefinite/negative for neoplasia or low-grade intraepithelial neoplasia were upgraded to HGIN or ESCC after resection. The upgrade was due to lesion size ≥ 10 mm (p = 0.002) and type B intrapapillary capillary loops (p < 0.001). Moreover, 34 of the 83 biopsies that were diagnosed with HGIN were upgraded to ESCC after resection, which was related to lesion size (p = 0.001), location (p = 0.018), and pink color sign (p = 0.002).

Conclusions

Histological discrepancy between forceps biopsy and resected specimens is common in clinical practice. Recognizing the risk factors for each histological category of biopsy may reduce these discrepancies and improve clinical management.
Clinical characteristics of acute pancreatitis in children: a single-center experience in Western China
Authors: Zhong Rui , Tan Shali , Peng Yan , Xu Huan , Jiang Xin , Yan Yongfeng , Lv Muhan , Liu Li , Tang Xiaowei
Published: March 2021

Background

The diagnosis of pediatric pancreatitis has been increasing over the last 20 years. We aimed to compare the clinical characteristics for pediatric acute pancreatitis (AP) with adult AP, and investigate the risk factor for acute recurrent pancreatitis (ARP) in children.

Method

From June 2013 to June 2019, a total of 130 pediatric patients with AP at the inpatient database were enrolled. Univariate analysis and multivariate Cox regression analysis were performed to identify the risk factors for ARP in children.

Result

Major etiologic factors in 130 patients were biliary (31.5%), idiopathic (28.5%). The etiology of pancreatitis in children was markedly different from that in adults (p < 0.001). Compared with the adult patients, the pediatric patients had significantly lower severity (p = 0.018) and occurrence rate of pancreatic necrosis (p = 0.041), SIRS (p = 0.021), acute peripancreatic fluid collection (p = 0.014). Univariate and Multivariate Cox regression analysis showed that female (p = 0.020; OR 3.821; 95% CI 1.231–11.861), hypertriglyceridemia (p = 0.045; OR 3.111; 95% CI 1.024–9.447), pancreatic necrosis (p = 0.023; OR 5.768; 95% CI 1.278–26.034) were the independent risk factors of ARP. Hypertriglyceridemia AP had the highest risk of recurrence compared to other etiology (p = 0.035).

Conclusion

Biliary and idiopathic disease were the major etiologies of AP in children. Children have simpler conditions than adults. Female, hypertriglyceridemia, and pancreatic necrosis were associated with the onset of ARP.
Cardio-metabolic and socio-demographic risk factors associated with dependency in basic and instrumental activities of daily living among older Iranian adults: Bushehr elderly health program
Authors: Khalagi Kazem , Ansarifar Akram , Fahimfar Noushin , Sanjari Mahnaz , Gharibzdeh Safoora , Sharifi Farshad , Shafiee Gita , Heshmat Ramin , Nabipour Iraj , Larijani Bagher , Ostovar Afshin
Published: March 2021

Background

Iran’s population is aging. Disability is a major public health problem for older adults, not only in Iran but all over the world. The purpose of this study was to investigate the relationship between cardio-metabolic and socio-demographic risk factors and disability in people 60 years and older in Iran.

Methods

The baseline (cross-sectional) data of 2426 samples from the Bushehr Elderly Health (BEH) program was included in the analysis. The participants were selected through multi-stage random sampling in Bushehr, southern Iran. Socio-demographic characteristics, as well as the history of diabetes and other chronic diseases, and smoking were measured using standardized questionnaires. Anthropometric measurements and laboratory tests were performed under standard conditions. Dependency was determined by the questionnaires of basic activities of daily living (BADL) and instrumental activities of daily living (IADL) using Barthel and Lawton scales respectively. Multiple logistic regression was used in the analysis.

Results

Mean (Standard Deviation) of the participants’ age was 69.3 (6.4) years (range: 60 and 96 years), and 48.1% of the participants were men. After adjusting for potential confounders, being older, being female (OR (95%CI): 2.3 (1.9–2.9)), having a lower education level, a history of diabetes mellitus (OR: 1.4 (1.2–1.7)) and past smoking (OR: 1.3 (1.0–1.6)), and no physical activity (OR: 1.5 (1.2–1.9)) were significantly associated with dependency in IADL. Also, being older and female (OR: 2.4 (1.9–3.0)), having a lower education level, no physical activity (OR: 2.2 (1.6–2.9)) and daily intake of calories (OR: 0.99 (0.99–0.99)) were associated with dependency in BADL.

Conclusion

Dependency in older adults can be prevented by increasing community literacy, improving physical activity, preventing and controlling diabetes mellitus, avoiding smoking, and reducing daily calorie intake.
Prescription practice and clinical utility of chest radiographs in a pediatric intensive care unit: a prospective observational study
Authors: Gupta Rajeev , Nallasamy Karthi , Williams Vijai , Saxena Akshay Kumar , Jayashree Muralidharan
Published: March 2021

Background

Chest radiograph (CXR) prescribing pattern and practice vary widely among pediatric intensive care units (PICU). ‘On demand’ approach is increasingly recommended as against daily ‘routine’ CXRs; however, the real-world practice is largely unknown.

Methods

This was a prospective observational study performed in children younger than 12 years admitted to PICU of a tertiary care teaching hospital in India. Data were collected on all consecutive CXRs performed between December 2016 and April 2017. The primary outcome was to assess the factors that were associated with higher chest radiograph prescriptions in PICU. Secondary outcomes were to study the indications, association with mechanical ventilation, image quality and avoidable radiation exposure.

Results

Of 303 children admitted during the study period, 159 underwent a total of 524 CXRs in PICU. Median (IQR) age of the study cohort was 2 (0.6–5) years. More than two thirds [n = 115, 72.3%] were mechanically ventilated. Most CXRs (n = 449, 85.7%) were performed on mechanically ventilated patients, amounting to a median (IQR) of 3 (2–5) radiographs per ventilated patient. With increasing duration of ventilation, the number of CXRs proportionately increased in the first two weeks of mechanical ventilation. In non-ventilated children, about two thirds (68%) underwent only one CXR. Majority of the prescriptions were on demand (n = 461, 88%). Most common indications were peri-procedure prescriptions (37%) followed by evaluation for respiratory disease status (24%). About 40% CXRs resulted in interventions; adjustment in ventilator settings (13.5%) was the most frequent intervention. In 26% (n = 138) of radiographs, image quality required improvement. One or more additional body part exposure other than chest and upper abdomen were noted 336 (64%) images. Children with > 3 CXR had higher PRISM III score, more often mechanically ventilated, had higher number of indwelling devices [mean (SD) 2.6 (1.2) vs. 1.7 (1.0)] and stayed longer in PICU [median (IQR) 11(7.5–18.5) vs. 6 (3–9)].

Conclusion

On demand prescription was the prevalent practice in our PICU. Most non-ventilated children underwent only one CXR while duration of PICU stay and the number of devices determined the number of CXRs in mechanically ventilated children. Quality improvement strategies should concentrate on the process of acquisition of images and limiting the radiation exposure to unwanted body parts.
Evidence from 2016 Ethiopian demographic and health survey data: association between post health education maternal knowledge and neonatal danger signs
Authors: Kassaw Mesfin Wudu , Abebe Ayele Mamo , Abate Biruk Beletew , Masresha Seteamlak Adane , Kassie Ayelign Mengesha , Adisu Molalign Aligaz
Published: March 2021

Background

Globally, 4 million infants die in their first 4weeks of life every year; above 8 million infants died before their first year of birthday, and nearly 10 million children died before their 5th birthday. Majority of the deaths were occurred at home because of not receiving health care. In Ethiopia, 120,000 infants died during their first 4 weeks of life. The aim of this study was to assess maternal knowledge about neonatal danger signs and its associations after they had been thought by health professionals in Ethiopia.

Methods

This study used the 2016 Ethiopian Demographic and Health Survey data (EDHS) as a data source. The 2016 EDHS data were collected using a two stage sampling method. All the regions were stratified into urban and rural areas. The study sample taken from the 2016 EDHS data and used in this further analysis was 325. A logistic regression model was used to assess the associations with post health education maternal knowledge on neonatal danger signs.

Results

In this study, mothers who had poor knowledge about neonatal danger signs (NDS) were 69.8 % (227) (95 %CI (64.8, 74.8 %). In the final logistic model, wanted no more child ((AOR = 4.15), (95 %CI = 1.12, 15.41)), female child ((AOR = 0.58), (95 %CI = 0.34, 0.98)), primary level maternal education ((AOR = 0.42), (95 %CI = 0.19, 0.92)), secondary level maternal education ((AOR = 0.37), (95 %CI = 0.16, 0.91)), and average size of child ((AOR = 2.64), (95 %CI = 1.26, 5.53)), and small size child ((AOR = 4.53), (95 %CI = 1.52, 13.51)) associated with post health education maternal knowledge about NDS.

Conclusion

The mothers’ knowledge about NDS is poor even they were gave a birth in health facilities. Wanting of additional child, child sex, maternal education and size of child were associated with NDS knowledge. This indicates that the mode of health education provided for mother might not be appropriate and needs protocol changes.
Explaining the impact of mHealth on maternal and child health care in low- and middle-income countries: a realist synthesis
Authors: Kabongo Eveline M. , Mukumbang Ferdinand C. , Delobelle Peter , Nicol Edward
Published: March 2021

Background

Despite the growing global application of mobile health (mHealth) technology in maternal and child health, contextual factors, and mechanisms by which interventional outcomes are generated, have not been subjected to a systematic examination. In this study, we sought to uncover context, mechanisms, and outcome elements of various mHealth interventions based on implementation and evaluation studies to formulate theories or models explicating how mHealth interventions work (or not) both for health care providers and for pregnant women and mothers.

Method

We undertook a realist synthesis. An electronic search of five online databases (PubMed/Medline, Google Scholar, Scopus, Academic Search Premier and Health Systems Evidence) was performed. Using appropriate Boolean phrases terms and selection procedures, 32 articles were identified. A theory-driven approach, narrative synthesis, was applied to synthesize the data. Thematic content analysis was used to delineate elements of the intervention, including its context, actors, mechanisms, and outcomes. Abduction and retroduction were applied using a realist evaluation heuristic tool to formulate generative theories.

Results

We formulated two configurational models illustrating how and why mHealth impacts implementation and uptake of maternal and child health care. Implementation-related mechanisms include buy-in from health care providers, perceived support of health care providers’ motivation and perceived ease of use and usefulness. These mechanisms are influenced by adaptive health system conditions including organization, resource availability, policy implementation dynamics, experience with technology, network infrastructure and connectivity. For pregnant women and mothers, mechanisms that trigger mHealth use and consequently uptake of maternal and child health care include perceived satisfaction, motivation and positive psychological support. Information overload was identified as a potential negative mechanism impacting the uptake of maternal and child health care. These mechanisms are influenced by health system conditions, socio-cultural characteristics, socio-economic and demographics characteristics, network infrastructure and connectivity and awareness.

Conclusion

Models developed in this study provide a detailed understanding of implementation and uptake of mHealth interventions and how and why they impact maternal and child health care in low- and middle-income countries. These models provide a foundation for the ‘white box’ of theory-driven evaluation of mHealth interventions and can improve rollout and implementation where required.
Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans: a case-control study
Authors: Choi Chang Kyun , Yang Jungho , Kweon Sun-Seog , Cho Sang-Hee , Kim Hye-Yeon , Myung Eun , Shin Min-Ho
Published: March 2021

Background

Alcohol consumption is a major risk factor for esophageal cancer; however, a high incidence of esophageal cancer is observed particularly among Eastern Asians, although they consume relatively less alcohol, presumably due to the high frequency of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms. Nevertheless, the association between ALDH2 polymorphisms and esophageal cancer remains under debate. In the present study, we evaluated the association between ALDH2 rs671 polymorphisms and the risk of esophageal cancer in the South Korean population.

Methods

This study included 783 hospital based-cases and 8732 population-based controls. Information on smoking history and alcohol consumption was obtained from the medical records or interview questionnaires. Age-adjusted logistic regression analysis was performed to assess the association between ALDH2 rs671 polymorphisms and esophageal cancer.

Results

Odds ratios (ORs) for esophageal cancer in men with GA and AA genotypes were 2.75 (95% confidence interval [CI]: 2.34–3.23) and 0.08 (95% CI: 0.00–0.35), respectively; whereas, in women, these ratios were 2.99 (95% CI: 1.43–6.34) and 6.18 (95% CI: 1.40–19.62), respectively, taking subjects with the ALDH2 GG genotype as a reference. In men, the association between ALDH2 polymorphisms and esophageal cancer was modified by alcohol consumption.

Conclusion

In Eastern Asians, ALDH2 rs671 polymorphisms are associated with esophageal cancer, which may be linked to acetaldehyde accumulation.
The evolution of an active solitary idiopathic choroiditis (focal scleral nodule): a case report of the natural course and a review of the literature
Authors: Feng Yilin , Conrady Christopher D. , Demirci Hakan
Published: March 2021

Background

To describe the clinical course of an active solitary idiopathic choroiditis (focal scleral nodule) that nearly resolved over six weeks without intervention.

Case presentation

An 18-year-old man presented to the emergency department with headaches and new onset central scotoma in the right eye. Visual acuity was 20/20 in both eyes. Fundus examination revealed an amelanotic choroidal lesion with associated shallow subretinal fluid. It measured 6.1 × 6.3 × 1.4mm on A- and B-scan. Evaluation for systemic inflammatory and infectious diseases was negative. A week later, the lesion remained stable, and a month later, there was improvement of the lesion with a decrease in size on OCT and exam and resolution of the subretinal fluid suggesting that the lesion had become inactive.

Conclusions

Solitary idiopathic choroiditis (Focal scleral nodule) is a rare condition characterized by inflammatory granulomatous reaction. This case report sheds light on the unknown natural course of a solitary idiopathic choroiditis (focal scleral nodule).
Recurrence rate with inferior conjunctival autograft transplantation compared with superior conjunctival autograft transplantation in pterygium surgery: a meta-analysis
Authors: Li Wenwei , Lou Yaoyong , Wang Bin
Published: March 2021

Background

Conjunctival autograft transplantation from superior conjunctiva is often chosen to lower the postoperative recurrence rate for pterygium treatment. However, inferior conjunctival autograft (ICA) might be taken as an alternative surgery method, especially under certain conditions. Consequently, we designed this research to estimate and contrast the result of inferior conjunctival autograft and superior conjunctival autograft (SCA) on the postoperative recurrence rate.

Methods

We searched through network database (PubMed, Embase and Cochrane Central Register of Controlled Trials) to choose suitable randomized controlled trials (RCTs). Based on Cochrane review methods, we evaluated eligibility and risk of bias of included studies. The primary measures included postoperative recurrence rate. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were assessed. RevMan 5.3 software was utilized to conduct statistical analysis.

Results

Four RCTs composed of a total of 438 eyes were included in this meta-analysis, with 234 eyes in the inferior conjunctival autograft group and 204 eyes in the superior conjunctival autograft group. Statistical meta-analysis revealed that the postoperative recurrence rate was similar between the two groups (RR = 0.77, 95% CI: 0.36 to 1.62,P = 0.49). Only two RCTs applied the postoperative pain scale and one of them did not provided adequate numbers.

Conclusions

Our meta-analysis indicated that inferior autograft transplantation and superior autograft transplantation had a similar effect on postoperative recurrence rate. The inferior autograft group might have a less postoperative pain. Subsequent RCTs which have more patients participated and more outcomes are needed to confirm our conclusions in years to come.
Low muscle mass affect hip fracture treatment outcomes in older individuals: a single-institution case-control study
Authors: Iida Hiroki , Seki Taisuke , Sakai Yoshihito , Watanabe Tsuyoshi , Wakao Norimitsu , Matsui Hiroki , Imagama Shiro
Published: March 2021

Background

Although sarcopenia has been known as a risk factor for hip fracture, only a few reports have described the impact of muscle mass on hip fracture treatment outcomes. The current study aimed to investigate the impact of muscle mass on hip fracture treatment outcomes.

Methods

This case–control study involved 337 patients (67 males and 270 females) with hip fracture aged ≥65 years (mean age: 84.1 ± 7.1 years) who underwent orthopedic surgery from January 2013 to June 2019. The mean follow-up period was 17.1 (1–60) months. Upon admission, all patients were assessed for low muscle mass according to the Asian Working Group for Sarcopenia criteria (male, SMI < 7.00 kg/m2; female, SMI < 5.40 kg/m2) using dual-energy X-ray absorptiometry. Treatment outcomes (stays at acute care institutions, hospital mortality, the Barthel index at discharge, and home discharge rates, and one-year mortality) were compared between patients with and without low muscle mass by Student’s t-test, Mann-Whitney U test and the Pearson Chi-Square test. A multivariate logistic regression model was used to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for factors related to low muscle mass. Kaplan–Meier survival curves on one-year mortality of hip fracture patients for those with and without low muscle mass were prepared, and log-rank tests were performed. Furthermore, we determined whether low muscle mass was a risk factor for one-year mortality in hip fracture patients using a Cox proportional hazards model.

Results

The prevalence of low muscle mass in patients with hip fracture was 231(68.5%). Those with low muscle mass had a lower Barthel index (P < 0.0001), hospital discharge rate (P = 0.035) and higher one-year mortality (P = 0.010). Cox proportional hazards regression analysis adjusted for age and sex found that low muscle mass was a risk factor for one-year mortality (hazard ratio, 3.182, 95% confidence interval, 1.097–9.226, P = 0.033).

Conclusions

Patients with hip fracture who had low muscle mass had a lower Barthel index, lower home discharge rate, and higher one-year mortality. Moreover, low muscle mass was identified as a risk factor for one-year mortality among those with hip fracture. The aforementioned findings may help clinicians better manage those with hip fracture.
Discrete choice experiment for eliciting preference for health services for patients with ALS and their informal caregivers
Authors: Tobin Katy , Maguire Sinead , Corr Bernie , Normand Charles , Hardiman Orla , Galvin Miriam
Published: March 2021

Background

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative condition with a mean life expectancy of 3 years from first symptom. Understanding the factors that are important to both patients and their caregivers has the potential to enhance service delivery and engagement, and improve efficiency. The Discrete Choice Experiment (DCE) is a stated preferences method which asks service users to make trade-offs for various attributes of health services. This method is used to quantify preferences and shows the relative importance of the attributes in the experiment, to the service user.

Methods

A DCE with nine choice sets was developed to measure the preferences for health services of ALS patients and their caregivers and the relative importance of various aspects of care, such as timing of care, availability of services, and decision making. The DCE was presented to patients with ALS, and their caregivers, recruited from a national multidisciplinary clinic. A random effects probit model was applied to estimate the impact of each attribute on a participant’s choice.

Results

Patients demonstrated the strongest preferences about timing of receiving information about ALS. A strong preference was also placed on seeing the hospice care team later rather than early on in the illness. Patients also indicated their willingness to consider the use of communication devices. Grouping by stage of disease, patients who were in earlier stages of disease showed a strong preference for receipt of extensive information about ALS at the time of diagnosis. Caregivers showed a strong preference for engagement with healthcare professionals, an attribute that was not prioritised by patients.

Conclusions

The DCE method can be useful in uncovering priorities of patients and caregivers with ALS. Patients and caregivers have different priorities relating to health services and the provision of care in ALS, and patient preferences differ based on the stage and duration of their illness. Multidisciplinary teams must calibrate the delivery of care in the context of the differing expectations, needs and priorities of the patient/caregiver dyad.
Distance to primary care facilities and healthcare utilization for preschool children in rural northwestern Burkina Faso: results from a surveillance cohort
Authors:   for the Étude CHAT Study Group, Oldenburg Catherine E. , Sié Ali , Ouattara Mamadou , Bountogo Mamadou , Boudo Valentin , Kouanda Idrissa , Lebas Elodie , Brogdon Jessica M. , Lin Ying , Nyatigo Fanice , Arnold Benjamin F. , Lietman Thomas M.
Published: March 2021

Background

Delays in care-seeking for childhood illness may lead to more severe outcomes. We evaluated whether community distance from a primary healthcare facility was associated with decreased healthcare utilization in a rural district of northwestern Burkina Faso.

Methods

We conducted passive surveillance of all government-run primary healthcare facilities in Nouna District, Burkina Faso from March 1 through May 31, 2020. All healthcare visits for children under 5 years of age were recorded on a standardized form for sick children. We recorded the age, sex, and community of residence of the child as well as any diagnoses and treatments administered. We calculated healthcare utilization per 100 child-months by linking the aggregate number of visits at the community level to the community’s population of children under 5 months per a census that was conducted from August 2019 through February 2020. We calculated the distance between each community and its corresponding healthcare facility and assessed the relationship between distance and the rate of healthcare utilization.

Results

In 226 study communities, 12,676 primary healthcare visits were recorded over the three-month period. The median distance between the community and primary healthcare facility was 5.0 km (IQR 2.6 to 6.9 km), and median number of healthcare visits per 100 child-months at the community level was 6.7 (IQR 3.7 to 12.3). The rate of primary healthcare visits declined with increasing distance from clinic (Spearman’s rho − 0.42, 95% CI − 0.54 to − 0.31, P < 0.0001). This relationship was similar for cause-specific clinic visits (including pneumonia, malaria, and diarrhea) and for antibiotic prescriptions.

Conclusions

We documented a distance decay effect between community distance from a primary healthcare facility and the rate of healthcare visits for children under 5. Decreasing distance-related barriers, for example by increasing the number of facilities or targeting outreach to more distant communities, may improve healthcare utilization for young children in similar settings.
Vegetable intake and the risk of bladder cancer in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study
Authors: Yu Evan Yi-Wen , Wesselius Anke , Mehrkanoon Siamak , Goosens Mieke , Brinkman Maree , van den Brandt Piet , Grant Eric J. , White Emily , Weiderpass Elisabete , Le Calvez-Kelm Florence , Gunter Marc J. , Huybrechts Inge , Riboli Elio , Tjonneland Anne , Masala Giovanna , Giles Graham G. , Milne Roger L. , Zeegers Maurice P.
Published: March 2021

Background

Although a potential inverse association between vegetable intake and bladder cancer risk has been reported, epidemiological evidence is inconsistent. This research aimed to elucidate the association between vegetable intake and bladder cancer risk by conducting a pooled analysis of data from prospective cohort studies.

Methods

Vegetable intake in relation to bladder cancer risk was examined by pooling individual-level data from 13 cohort studies, comprising 3203 cases among a total of 555,685 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox proportional hazards regression models stratified by cohort for intakes of total vegetable, vegetable subtypes (i.e. non-starchy, starchy, green leafy and cruciferous vegetables) and individual vegetable types. In addition, a diet diversity score was used to assess the association of the varied types of vegetable intake on bladder cancer risk.

Results

The association between vegetable intake and bladder cancer risk differed by sex (P-interaction = 0.011) and smoking status (P-interaction = 0.038); therefore, analyses were stratified by sex and smoking status. With adjustment of age, sex, smoking, energy intake, ethnicity and other potential dietary factors, we found that higher intake of total and non-starchy vegetables were inversely associated with the risk of bladder cancer among women (comparing the highest with lowest intake tertile: HR = 0.79, 95% CI = 0.64–0.98, P = 0.037 for trend, HR per 1 SD increment = 0.89, 95% CI = 0.81–0.99; HR = 0.78, 95% CI = 0.63–0.97, P = 0.034 for trend, HR per 1 SD increment = 0.88, 95% CI = 0.79–0.98, respectively). However, no evidence of association was observed among men, and the intake of vegetable was not found to be associated with bladder cancer when stratified by smoking status. Moreover, we found no evidence of association for diet diversity with bladder cancer risk.

Conclusion

Higher intakes of total and non-starchy vegetable are associated with reduced risk of bladder cancer for women. Further studies are needed to clarify whether these results reflect causal processes and potential underlying mechanisms.
The importance of CDC27 in cancer: molecular pathology and clinical aspects
Authors: Kazemi-Sefat Golnaz Ensieh , Keramatipour Mohammad , Talebi Saeed , Kavousi Kaveh , Sajed Roya , Kazemi-Sefat Nazanin Atieh , Mousavizadeh Kazem
Published: March 2021

Background

CDC27 is one of the core components of Anaphase Promoting complex/cyclosome. The main role of this protein is defined at cellular division to control cell cycle transitions. Here we review the molecular aspects that may affect CDC27 regulation from cell cycle and mitosis to cancer pathogenesis and prognosis.

Main text

It has been suggested that CDC27 may play either like a tumor suppressor gene or oncogene in different neoplasms. Divergent variations inCDC27DNA sequence and alterations in transcription ofCDC27have been detected in different solid tumors and hematological malignancies. ElevatedCDC27expression level may increase cell proliferation, invasiveness and metastasis in some malignancies. It has been proposed thatCDC27upregulation may increase stemness in cancer stem cells. On the other hand, downregulation ofCDC27may increase the cancer cell survival, decrease radiosensitivity and increase chemoresistancy. In addition,CDC27downregulation may stimulate efferocytosis and improve tumor microenvironment.

Conclusion

CDC27 dysregulation, either increased or decreased activity, may aggravate neoplasms. CDC27 may be suggested as a prognostic biomarker in different malignancies.
Evaluation of exosome derivatives as bio-informational reprogramming therapy for cancer
Authors: Gonzalez Michael J. , Kweh Mercedes F. , Biava Pier Mario , Olalde Jose , Toro Alondra P. , Goldschmidt-Clermont Pascal J. , White Ian A.
Published: March 2021

Exosomes are nanoparticle sized (100 ± 50 nm) extracellular vesicles (ECVs) that play important roles in cell-to-cell communication. They do this by utilizing their natural ability to shuttle signaling molecules across the cellular microenvironment and promote paracrine signaling. Currently, exosomes are being explored for their potential as therapeutic agents for various degenerative diseases including cancer. The rationale behind their therapeutic ability is that they can transfer signaling biomolecules, and subsequently induce metabolic and physiological changes in diseased cells and tissues. In addition, exosomes can be used as a drug delivery system and may be very effective at reducing toxicity and increasing bioavailability of therapeutic molecules and drugs. Although exosomes were first believed to be a waste product of the cell, current research has demonstrated that these particles can serve as modulators of the immune system, act as cancer biomarkers, cause re-differentiation of cancer cells, and induce apoptosis in diseased cells. Extensive research has been performed specifically using amniotic fluid-derived extracellular vesicles, named “cytosomes”. While the use of cytosomes in clinical application is still in the early stages, researchers have shown great potential for these EVs in regenerative medicine as immune modulators, in controlling microbial infection and by inducing tissue repair through the activation of endogenous, tissue-specific stem cells. This review emphasizes the capabilities of specific subsets of extracellular vesicles that can potentially be used for cancer therapy, principally as a source of bi-informational reprogramming for malignant cells.
Radiotherapy of oligometastatic prostate cancer: a systematic review
Authors: Rogowski Paul , Roach Mack , Schmidt-Hegemann Nina-Sophie , Trapp Christian , von Bestenbostel Rieke , Shi Run , Buchner Alexander , Stief Christian , Belka Claus , Li Minglun
Published: March 2021

Background

Due to improved imaging sensitivity, the term “oligometastatic” prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients.

Methods

A systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence.

Findings

Evidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called “synchronous” versus “metachronous” oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of68Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing.

Conclusions

To our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.
Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma
Authors: Le Large T. Y. S. , Bijlsma M. F. , El Hassouni B. , Mantini G. , Lagerweij T. , Henneman A. A. , Funel N. , Kok B. , Pham T. V. , de Haas R. , Morelli L. , Knol J. C. , Piersma S. R. , Kazemier G. , van Laarhoven H. W. M. , Giovannetti E. , Jimenez C. R.
Published: March 2021

Background

Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC.

Methods

Mass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines was used to evaluate active kinases. Pathway analysis and inferred kinase activity analysis was performed to identify novel targets. Subsequently, we investigated targeting of focal adhesion kinase (FAK) in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Tyrosine phosphoproteomics upon treatment was performed to evaluate signaling. An orthotopic model of PDAC was used to evaluate the combination of defactinib with nab-paclitaxel.

Results

PDAC cell lines portrayed high activity of multiple receptor tyrosine kinases to various degree. The non-receptor kinase, FAK, was identified in all cell lines by our phosphotyrosine proteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo.

Conclusions

Our study shows high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel against this devastating disease.
The impact of Pegylated liposomal doxorubicin in recurrent ovarian cancer: an updated meta-analysis of randomized clinical trials
Authors: Li Xin-Ru , Zhu Yi , Zhang Guo-Nan , Huang Jian-Ming , Pei Li-Xia
Published: March 2021

Background

Previous meta-analysis studies suggested that pegylated liposomal doxorubicin (PLD) may improve the survival rate of patients with recurrent ovarian cancer. The aim of the present meta-analysis, then, was to further update the role of PLD in the treatment of recurrent ovarian cancer.

Methods

We performed a literature search using the electronic databases Medicine, EMBASE, Web of Science, and the Cochrane Library to 27 July 2020. We only restricted the randomized clinical trials. Study-specific hazard ratios and 95% confidence interval (HR/95% CI) and risk ratios and 95% confidence interval (RR/95% CI) were pooled using a random-effects model.

Results

Ten studies (12 trials) were included after screening 940 articles. We categorized the eligible studies into two groups: the doublet regimens (four trials, 1767 patients) showed that PLD plus carbo provided superior progression-free survival (PFS) (HR, 0.85; 95% CI, 0.74–0.97) and similar overall survival (OS) (HR, 1.00; 95% CI, 0.88–1.14) compared to paclitaxel (PAC) plus carboplatin (carbo). PLD plus carbo was associated with significantly more anemia and thrombocytopenia, and other side effects were well tolerated. The monotherapy regimens (eight trials, 1980 patients) showed that PLD possessed a similar PFS (HR, 1.02; 95% CI, 0.90–1.16) and OS (HR, 0.88; 95% CI, 0.77–1.01) relative to other monotherapies. PLD alone was also more associated with mucositis/stomatitis and hand-foot syndrome, while other side effects were well tolerated.

Conclusions

In platinum-sensitive recurrent ovarian cancer, PLD plus carbo was more effective than PAC plus carbo, while in platinum-resistant or -refractory recurrent ovarian cancer, PLD exhibited similar survival to other monotherapies. Regarding side effects, PLD plus carbo and mono chemotherapy were both well tolerated.
Definition and prevalence of familial short stature
Authors: Grigoletto Veronica , Occhipinti Alessandro Agostino , Pellegrin Maria Chiara , Sirchia Fabio , Barbi Egidio , Tornese Gianluca
Published: March 2021

Objective

To verify the prevalence of novel definitions of familial short stature on a cross-sectional cohort of children referred for short stature when their height and that of both parents were measured.

Methods

We consecutively enrolled 65 individuals referred for short stature when both parents were present. We defined “target height-related short stature” (TH-SS) when child’s height is ≤ − 2 SDS and included in the range of target height; suspected “autosomal dominant short stature” (AD-SS) when child height and at least one parent height are ≤ − 2 SDS; “constitutional familial short stature” (C-FSS) when a child with TH-SS does not have any parents with height ≤ − 2 SDS.

Results

Of 65 children referred for SS, 48 individuals had a height ≤ − 2 SDS. Based on the parents’ measured heights, 24 children had TH-SS, 16 subjects AD-SS, and 12 individuals C-FSS. If we had considered only the parents’ reported height, 3 of 24 children with TH-SS, 9 of 16 with AD-SS, and 10 of 12 with C-FSS would have been lost.

Conclusion

We suggest novel definitions to adequately detect and approach the cases of FSS since C-FSS (25%) might not need any specific investigation, while on the contrary, AD-SS (33%) should undergo genetic evaluation. Moreover, this study underlines that adequate measurement and consideration of children’s and parents’ heights (individually and together) are crucial in the clinical evaluation of every child with short stature.
Stable DNMT3L overexpression in SH-SY5Y neurons recreates a facet of the genome-wide Down syndrome DNA methylation signature
Authors: Laufer Benjamin I. , Gomez J. Antonio , Jianu Julia M. , LaSalle Janine M.
Published: March 2021

Background

Down syndrome (DS) is characterized by a genome-wide profile of differential DNA methylation that is skewed towards hypermethylation in most tissues, including brain, and includes pan-tissue differential methylation. The molecular mechanisms involve the overexpression of genes related to DNA methylation on chromosome 21. Here, we stably overexpressed the chromosome 21 geneDNA methyltransferase 3L(DNMT3L) in the human SH-SY5Y neuroblastoma cell line and assayed DNA methylation at over 26 million CpGs by whole genome bisulfite sequencing (WGBS) at three different developmental phases (undifferentiated, differentiating, and differentiated).

Results

DNMT3Loverexpression resulted in global CpG and CpG island hypermethylation as well as thousands of differentially methylated regions (DMRs). TheDNMT3LDMRs were skewed towards hypermethylation and mapped to genes involved in neurodevelopment, cellular signaling, and gene regulation. ConsensusDNMT3LDMRs showed that cell lines clustered by genotype and then differentiation phase, demonstrating sets of common genes affected across neuronal differentiation. The hypermethylatedDNMT3LDMRs from all pairwise comparisons were enriched for regions of bivalent chromatin marked by H3K4me3 as well as differentially methylated sites from previous DS studies of diverse tissues. In contrast, the hypomethylatedDNMT3LDMRs from all pairwise comparisons displayed a tissue-specific profile enriched for regions of heterochromatin marked by H3K9me3 during embryonic development.

Conclusions

Taken together, these results support a mechanism whereby regions of bivalent chromatin that lose H3K4me3 during neuronal differentiation are targeted by excess DNMT3L and become hypermethylated. Overall, these findings demonstrate thatDNMT3Loverexpression during neurodevelopment recreates a facet of the genome-wide DS DNA methylation signature by targeting known genes and gene clusters that display pan-tissue differential methylation in DS.
A systematic review of the cost-effectiveness of ultrasound in emergency care settings
Authors: Lentz Brian , Fong Tiffany , Rhyne Randall , Risko Nicholas
Published: March 2021

Background

The use of ultrasound (US) in emergency departments (ED) has become widespread. This includes both traditional US scans performed by radiology departments as well as point-of-care US (POCUS) performed by bedside clinicians. There has been significant interest in better understanding the appropriate use of imaging and where opportunities to enhance cost-effectiveness may exist. The purpose of this systematic review is to identify published evidence surrounding the cost-effectiveness of US in the ED and to grade the quality of that evidence.

Methods

We performed a systematic review of the literature following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Studies were considered for inclusion if they were: (1) economic evaluations, (2) studied the clinical use of ultrasound, and (3) took place in an emergency care setting. Included studies were critically appraised using the Consolidated Health Economic Evaluation Reporting Standards checklist.

Results

We identified 631 potentially relevant articles. Of these, 35 studies met all inclusion criteria and were eligible for data abstraction. In general, studies were supportive of the use of US. In particular, 11 studies formed a strong consensus that US enhanced cost-effectiveness in the investigation of pediatric appendicitis and 6 studies supported enhancements in the evaluation of abdominal trauma. Across the studies, weaknesses in methodology and reporting were common, such as lack of sensitivity analyses and inconsistent reporting of incremental cost-effectiveness ratios.

Conclusions

The body of existing evidence, though limited, generally demonstrates that the inclusion of US in emergency care settings allows for more cost-effective care. The most definitive evidence for improvements in cost-effectiveness surround the evaluation of pediatric appendicitis, followed by the evaluation of abdominal trauma. POCUS outside of trauma has had mixed results.