bluuebunny/crossref_metadata_2025 huggingface dataset:
Hearing the Voice of a Shadow Child: Healthy Siblings Experience of Cystic Fibrosis and Other Life-Threatening Conditions
Authors: Cox Andrew , Pritchard Colin
Published: August 2020

Cystic fibrosis (CF) is a chronic, life-threatening disease, similar to other chronic life-disrupting pediatric conditions, and this creates physical and psychosocial problems for parents and the healthy sibling/s of the sick child, who often become sibling carers. It is feared that, despite good intentions, professionals fail to hear the authentic voice of those intimately involved, especially these sibling carers, who can feel they became a “shadow child.” This study is a partnership between an academic and a former CF sibling carer, who wrote a “fairy story” for his children about the Uncle they never knew. It is an effort to hear the “voice of shadow children” who can feel left behind and unseen as families and professionals focus upon their ill sibling.
Perspectives on Patient Experience: A National Survey of Hospitalists
Authors: Khateeb Rafina , Keniston Angela , Moore Amber , Hrach Christine , Indovina Kimberly A , Kneeland Patrick , Rudolph Mark , Burden Marisha
Published: August 2020

Despite efforts to improve patient experience (PX), little is known about the perspective of hospitalists regarding PX initiatives and priorities. A survey was distributed to hospitalist groups across the country assessing involvement in PX initiatives and their perceived effectiveness, what PX means to providers, and facilitators/barriers in improving PX. Ninety-nine percent of respondents had encountered some improvement activity around PX. The most prevalent were communication training, group Hospital Consumer Assessment of Healthcare Providers and Systems data, and interdisciplinary bedside rounding. Respondents rated most initiatives a 5 to 6 out of 10 for their effectiveness, with the perception of effectiveness increasing with respondents’ assessment of patient experience priority. Learning about others’ experiences in improving PX and learning about potential collaborations for quality improvement or research in these areas were areas of interest for future work. Qualitative work highlighted potential barriers in improving PX such as workload and staffing constraints, uncontrollable environmental factors, and unrealistic patient expectations. Improving PX is a priority, and there are many initiatives in place with perceived variable success and perceived barriers in improving PX.
Some Biochemical Perturbations May Modify the Understanding of Trypanotolerance in the West African Dwarf Sheep Infected With Trypanosoma brucei brucei and Trypanosoma congolense
Authors: Anyogu Davinson C , Shoyinka Shodeinde VO , Ihedioha John I
Published: August 2020

Trypanosomes are single-celled protozoa that cause severe diseases in both humans and livestock in sub-Saharan African countries. The disease in the West African Dwarf (WAD) sheep is often neglected due to the issue of trypanotolerance. The current study is aimed to evaluate some biochemical changes in this breed that may modify the understanding of trypanotolerance. Fifteen WAD sheep were assigned into 3 groups (A, B, and C). Baseline (day 0) values of the parameters assayed were obtained before groups A and B were infected with Trypanosoma brucei brucei and Trypanosoma congolense, respectively, by intraperitoneal inoculation with 106 trypanosomes per animal. Standard procedures using Quimica Clinica Applicada (Spain) and Randox (UK) test kits were used to evaluate serum levels of AST, ALT, ALP, total protein, albumin, total cholesterol, urea, and creatinine on days 0, 14, 28, 42, 56, and 70 post infection. The infections caused sustained pyrexia, hypoproteinaemia, hypocholesterolaemia, weight loss, hepatitis, and mortalities although parasitaemia was greatly controlled especially in the T congolense infected rams. The findings suggest that the WAD rams are not just passive reservoirs of trypanosomes for human and animal infections, but experience active host-parasite interactions with huge price for resilience, biochemically.
Left Main PCI—Current Evidence, Techniques, and Triumph
Authors: Kuchulakanti Pramod Kumar
Published: August 2020

The left main coronary artery (LMCA) supplies majority of the left ventricular myocardium and atherosclerotic obstruction is associated with significant myocardial jeopardy. Coronary artery bypass surgery (CABG) has been the gold standard for LMCA disease in the past. The LMCA has special characteristics anatomically, poses different challenges with regard to percutaneous coronary intervention (PCI), and is often associated with multivessel disease. However, advancements in technology have established PCI to be a standard, safe, and reasonable alternative to CABG with comparable outcomes. Contemporary PCI of LMCA disease includes proper selection of the patients and correct technique, and is aided by intravascular ultrasound, optical coherence tomography, and physiological assessment with fractional flow reserve. In this review article, we discuss the anatomy, plaque characteristics of LMCA, current evidence from registries and randomized trials comparing with CABG, technical aspects of stent implantation, adjuvant technologies, mechanical circulatory supports, and triumph of PCI.
Strategies for Rhythm Control in Atrial Fibrillation
Authors: Narayanan Kumar
Published: August 2020

Atrial fibrillation (AF), the most common arrhythmia encountered worldwide, is associated with significant morbidity. The three important considerations with regard to AF management are stroke prevention, rate control, and rhythm control, with the latter two overlapping to some extent. While antiarrhythmic drugs have had limited success as a rhythm control strategy, being limited by side effects and proarrhythmia, catheter ablation has emerged as a potentially better alternative. Current ablation techniques afford good success for paroxysmal AF, especially when done in experienced centers; however, further improvements and innovations are required to improve results for more persistent forms of AF. The current review critically summarizes the present strategies employed for rhythm control in AF and briefly outlines some of the newer developments in this field.
Evaluation of Patient Factors Associated With Achieving Goal Hemoglobin A1c in Collaborative Drug Therapy Management Ambulatory Care Clinics by Clinical Pharmacists: A Retrospective Chart Review
Authors: Torkos Stefanos , Burke Jacqueline M. , Zaiken Kathy
Published: August 2020

Background: Literature has shown the positive impact pharmacists have on diabetic outcome measures through collaborative drug therapy management (CDTM). There is minimal literature evaluating characteristics and clinical factors of patients who benefit from CDTM diabetes clinics by pharmacists. Objective: Identify patient characteristics and clinical factors that may be associated with patients who reach goal hemoglobin A1c (HbA1c) of <7% at discharge by pharmacists practicing under CDTM agreements. Methods: This retrospective chart review included patients referred to pharmacist CDTM clinics for type 2 diabetes with an HbA1c goal of <7%. Data were extracted from the electronic medical record at enrollment and discharge. Results: Of the 228 patients included, 84 achieved a goal HbA1c of <7%. Factors predictive of patient success were Asian ethnicity (odds ratio [OR] = 19.32), baseline HbA1c of 7% to 7.9% (OR = 2.34), enrolled in clinic for 5 to 6 months (OR = 2.06), in-person visit every 4 to <8 weeks (OR = 3.06), not on insulin initially or at discharge (OR = 1.79, OR = 2.02), or discharged on a glucagon-like peptide-1 receptor agonist (OR = 1.83). Factors predictive of not reaching goal were Black or African American ethnicity (OR = 0.42), <5 encounters of any type (OR = 0.44), an encounter of any type every 8 weeks or more (OR = 0.08), or discharged on a sodium-glucose cotransporter-2 inhibitor (OR = 0.27). Conclusion: Several clinical and demographic factors were identified that influenced a patient’s ability to reach a goal HbA1c of <7%. The results of this study may be applied to further advance pharmacist-run clinics in optimizing diabetes care for patients.
Implications of Glycopeptide and Lipopeptide Antibiotics on Asthma Exacerbations in a Patient With Hyper-IgE Syndrome and Chronic Severe Asthma: A Case Report
Authors: Reinert Justin P. , Burnham Kevin
Published: August 2020

Objective: To review and consider the immunomodulatory ramifications of glycopeptide and lipopeptide antibiotics in a patient with severe asthma, hyper-immunoglobulin E (IgE) syndrome, and osteonecrosis of the jaw. Case Summary: A 36-year-old male patient with a pertinent past medical history of hyper-IgE syndrome, severe asthma, and osteonecrosis of the jaw attributed to steroid use initially presented to the emergency department, where imaging of the jaw suggested an infectious process. Following months of vancomycin therapy as an outpatient, the patient was switched to daptomycin to facilitate once-daily infusions. Following this change, the patient experienced significantly less asthma exacerbations and fewer admissions to the hospital for asthma-related issues. Discussion: Though daptomycin is associated with eosinophilia, and this patient’s eosinophil counts did increase while on the drug, an inverse relationship developed concerning the number of hospital admissions for asthma exacerbations. A review of the literature indicates that select glycopeptides, such as vancomycin, have pro-inflammatory effects, while other related drugs, such as the lipopeptide daptomycin, may not result in clinical manifestations of an inflammatory process. Tumor necrosis factor-α, interleukin-1β, and interleukin-6 have been implicated in this process. This patient may have been particularly susceptible to the effects of the glycopeptides due to his diagnosis of hyper-IgE syndrome, which has been independently associated with reactive airway diseases. Conclusion: Cytokine migration and activation by select glycopeptide and lipopeptide antibiotics warrant consideration from clinicians when determining the most appropriate treatment regimens. Further research is required to elucidate whether the pro-inflammatory properties of vancomycin warrant a change in first-line therapy to daptomycin in select cases.
How I treat lymphoma in pregnancy
Authors: Dunleavy Kieron , McLintock Claire
Published: August 2020

Lymphomas afflict all age groups of people, with certain types demonstrating a female predilection in adolescents and young adults. A proportion of lymphomas that are diagnosed in this population demographic occur in the setting of pregnancy. Most of these behave aggressively at presentation and require immediate or urgent therapy. Treatment must consider both maternal and fetal health, and management approaches are therefore influenced by gestational age at diagnosis and treatment and timing of delivery. Although there is a paucity of literature on how to treat these patients, limited retrospective reports demonstrate generally good outcomes and highlight the necessity of an experienced multidisciplinary team approach to management.
Delivering HDAC over 3 or 5 days as consolidation in AML impacts health care resource consumption but not outcome
Authors: Dumas Pierre-Yves , Bertoli Sarah , Bérard Emilie , Leguay Thibaut , Tavitian Suzanne , Galtier Jean , Alric Camille , Bidet Audrey , Delabesse Eric , Rieu Jean Baptiste , Vial Jean-Philippe , Vergez François , Lechevalier Nicolas , Luquet Isabelle , Klein Emilie , Sarry Audrey , Rey Héloïse , de Grande Anne-Charlotte , Despas Fabien , Pigneux Arnaud , Récher Christian
Published: August 2020

Postremission treatment is crucial to prevent relapse in acute myeloid leukemia (AML). High-dose cytarabine delivered every 12 hours on days 1, 3, and 5 (HDAC-135) is the standard of care for younger adult patients with AML. Although this standard has been unsuccessfully challenged by other treatment regimens, including multiagent chemotherapy, the timing of HDAC administration has attracted little attention. Here, we retrospectively compared the safety, efficacy, and health care resource consumption associated with HDAC-135 and another standard, condensed HDAC-123 regimen, as consolidation treatment in younger AML patients in first complete response. This study included 221 patients (median age, 46.6 years; range, 18-60 years). HDAC-123 and HDAC-135 were used in 92 and 129 patients, respectively. Both regimens were associated with similar rates of relapse-free survival, cumulative incidence of relapse, nonrelapse mortality, and overall survival, including in core binding factor AML subgroup in which levels of minimal residual disease reduction were similar in both schedules. Hematological recovery times regarding neutrophils and platelets were significantly shorter in patients receiving HDAC-123, with an average difference of 3 to 4 days for each consolidation cycle. The total duration of hospitalization for the whole postremission program was shorter with HDAC-123 (32 days; interquartile ratio [IQR], 22.0,36.5) compared with HDAC-135 (41 days; IQR, 30.5, 50.0) (P < .0001). In conclusion, the condensed HDAC-123 regimen induced faster hematological recovery and therefore significantly reduced the length of hospital stay without affecting treatment response or outcome in younger AML patients.
Epidemiology of brain tumors in the United Arab Emirates: a National Registry Cross-sectional Study
Authors: Khan Sarah , Kambris Mona El Kouatly , AlShamsi Eman T
Published: August 2020

Background

Cancer is the third leading cause of death in the United Arab Emirates (UAE); brain cancer ranks 10th among the cancers, with 2.9% of the primary cancers originating from the nervous system. The epidemiology of brain cancers has not been explored. The unique population dynamics of UAE make it a fertile ground for analyzing the epidemiology of brain cancer. In this study, we aim to look at the frequency patterns and distribution of malignant primary brain tumors in the UAE.

Methods

A cross sectional study was carried out using data obtained from the Tawam Hospital Cancer Registry for the years 1984–2017. The sample size included 756 diagnosed cases of malignant primary brain tumors in the UAE. Using SPSS and Excel software, frequencies, mean ages, histological type frequencies, average annual crude incidence rates and average annual age adjusted incidence rates were analyzed.

Results

The expatriate population had higher percentage of brain tumors (72%) than the locals. The mean age at diagnosis was 33.48 years (± 21.14 years) with a male to female ratio of 1.69. Diffuse astrocytic and oligodendroglial tumors were the most commonly diagnosed tumors overall. Older adults had more cases of lymphoma while embryonal and ependymal tumors were most commonly seen in younger age groups. The overall average annual crude incidence rate for 2013–2016 for all primary brain tumors was 0.56 per 100,000 population.

Conclusion

This is the first cancer registry study in the UAE that describes histological types of primary brain tumors based on the WHO 2016 classification of brain tumors and highlights their incidence rates. Through this study, several patterns of incidence trends for brain tumors in the UAE, according to histological types, sex and age groups have been recognized. Comparative studies would help identify the influence of potential changes in lifestyle, environmental or occupational risk factors on primary brain tumors.
Ipilimumab plus nivolumab and chemoradiotherapy followed by surgery in patients with resectable and borderline resectable T3-4N0–1 non-small cell lung cancer: the INCREASE trial
Authors: Dickhoff Chris , Senan Suresh , Schneiders Famke L. , Veltman Joris , Hashemi Sayed , Daniels Johannes M. A. , Fransen Marieke , Heineman David J. , Radonic Teodora , van de Ven Peter M. , Bartelink Imke H. , Meijboom Lilian J. , Garcia-Vallejo Juan J. , Oprea-Lager Daniela E. , de Gruijl Tanja D. , Bahce Idris
Published: August 2020

Background

The likelihood of a tumor recurrence in patients with T3-4N0–1 non-small cell lung cancer following multimodality treatment remains substantial, mainly due distant metastases. As pathological complete responses (pCR) in resected specimens are seen in only a minority (28–38%) of patients following chemoradiotherapy, we designed the INCREASE trial (EudraCT-Number: 2019–003454-83; Netherlands Trial Register number: NL8435) to assess if pCR rates could be further improved by adding short course immunotherapy to induction chemoradiotherapy. Translational studies will correlate changes in loco-regional and systemic immune status with patterns of recurrence.

Methods/design

This single-arm, prospective phase II trial will enroll 29 patients with either resectable, or borderline resectable, T3-4N0–1 NSCLC. The protocol was approved by the institutional ethics committee. Study enrollment commenced in February 2020.

On day 1 of guideline-recommended concurrent chemoradiotherapy (CRT), ipilimumab (IPI, 1 mg/kg IV) and nivolumab (NIVO, 360 mg flat dose IV) will be administered, followed by nivolumab (360 mg flat dose IV) after 3 weeks. Radiotherapy consists of once-daily doses of 2 Gy to a total of 50 Gy, and chemotherapy will consist of a platinum-doublet. An anatomical pulmonary resection is planned 6 weeks after the last day of radiotherapy. The primary study objective is to establish the safety of adding IPI/NIVO to pre-operative CRT, and its impact on pathological tumor response. Secondary objectives are to assess the impact of adding IPI/NIVO to CRT on disease free and overall survival. Exploratory objectives are to characterize tumor inflammation and the immune contexture in the tumor and tumor-draining lymph nodes (TDLN), and to explore the effects of IPI/NIVO and CRT and surgery on distribution and phenotype of peripheral blood immune subsets.

Discussion

The INCREASE trial will evaluate the safety and local efficacy of a combination of 4 modalities in patients with resectable, T3-4N0–1 NSCLC. Translational research will investigate the mechanisms of action and drug related adverse events.

Trial registration

Netherlands Trial Registration (NTR):NL8435, Registered 03 March 2020.
The characteristics of patients frequently tested and repeatedly infected with Chlamydia trachomatis in Southwest Limburg, the Netherlands
Authors: Wijers Juliën N. A. P. , Dukers-Muijrers Nicole H. T. M. , Hoebe Christian J. P. A. , Wolffs Petra F. G. , van Liere Geneviève A. F. S.
Published: August 2020

Background

Repeat Chlamydia trachomatis (CT) infections are common. To better understand the characteristics of patients frequently infected with CT at our sexually transmitted infection (STI) care services, we assessed the differences between patients repeatedly infected with CT and those who repeatedly tested negative.

Methods

In this cross-sectional analysis of cohort data, we assessed individuals tested for CT at different STI care providers between 2011 and mid-2018 in Southwest Limburg, the Netherlands (n = 17,616). Patients with ≥2 repeat CT infections in the study period were categorized as “patients with repeat CT infections.” Multivariable logistic regression analyses were performed for the binary outcome measure: patients with repeat CT infections versus patients who repeatedly tested negative (reference group). Additional analyses were performed for only the STI clinic population.

Results

Patients aged < 25 years (OR: 1.83; 95%CI:1.38–2.43), co-infected with HIV (OR: 2.07; 95%CI: 1.02–4.22) or co-infected with Neisseria gonorrhoeae (NG) (OR: 5.04; 95%CI: 3.33–7.63) had more repeat CT infections. In additional analyses among exclusively STI clinic visitors, patients with urogenital symptoms (OR: 2.17; 95%CI: 1.41–3.35), and patients notified for STIs (OR: 4.55; 95%CI: 3.17–6.54) had more frequent repeat CT infections.

Conclusions

Patients aged < 25 years and patients coinfected with HIV or NG had more frequent repeat CT infections, accounting for ~ 20% of the diagnosed CT infections. These patients are likely at the highest risk for transmitting and acquiring CT. Therefore, testing and retesting this group remains important to enhance CT control.
Dietary habits and metabolic response improve in obese children whose mothers received an intervention to promote healthy eating: randomized clinical trial
Authors: López-Contreras Iris Nallely , Vilchis-Gil Jenny , Klünder-Klünder Miguel , Villalpando-Carrión Salvador , Flores-Huerta Samuel
Published: August 2020

Background

Lifestyles habits such as eating unhealthy foodscommence at home and are associated with the development of obesity and comorbidities such as insulin resistance, metabolic syndrome, and chronic degenerative diseases, which are the main causes of death in adults. The present study compared changes in dietary habits, behaviors and metabolic profiles of obese children whose mothers attended at the hospital to group sessions, with those who received the usual nutritional consultation.

Methods

Randomized clinical trial, 177 mother/obese child pairs participated, 90 in the intervention group and 87 in the control group. The intervention group attended six group education sessions to promote healthy eating, being this an alternative of change of habits in children with obesity. The control group received the usual nutritional consultation; both groups were followed up for 3 months. Frequency of food consumption, behaviors during feeding in the house and metabolic profile was evaluated. Mixed effect linear regression models were used to evaluate the effect of the intervention on the variables of interest, especially in HOMA-IR.

Results

The intervention group reduced the filling of their dishes (p = 0.009), forcing the children to finish meals (p = 0.003) and food substitution (p <  0.001), moreover increased the consumption of roasted foods (p = 0.046), fruits (p = 0.002) and vegetables (p <  0.001). The children in the control group slightly increased HOMA-IR levels (0.51; 95% CI − 0.48 to 1.50), while the children in the intervention group significantly decreased (− 1.22; 95% CI − 2.28 to − 1.16). The difference in HOMA-IR between the control and intervention group at the end of the follow-up was − 1.67; 95% CI: − 3.11 to − 0.24.

Conclusions

The educational intervention improved some eating habits at home, as well as HOMA-IR levels; why we consider that it can be an extra resource in the management of childhood obesity.

Trial registration

Clinicaltrials.gov,NCT04374292(Date assigned: May 5, 2020). Retrospectively registered.
Indirubin inhibits Wnt/β-catenin signal pathway via promoter demethylation of WIF-1
Authors: Liu Shou Gang , Luo Guang Pu , Qu Yong Bin , Chen Yong Feng
Published: August 2020

Background

Psoriasis is a common inflammatory skin disease. Abnormal proliferation of keratinocytes is one of the psoriatic histopathological features. Indirubin has an essential effect on the proliferation and activation of keratinocytes; however, in psoriasis, the specific mechanism of action of indirubin on keratinocytes is unclear. In the present study, we revealed the effects of indirubin on DNA methyltransferase 1 (DNMT1), wnt inhibitory factor 1 (wif-1), and wnt/β-catenin signal pathway, in the meantime, we explored the effects of indirubin on proliferation, cell cycle and the apoptosis of HaCaT cells.

Methods

The expression of DNMT1, wif-1, Frizzled2, Frizzled5, and β-catenin in HaCaT cells treated with different concentrations of indirubin were detected by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of DNMT1 and wif-1 were observed after treated with different concentrations of indirubin by enzyme-linked immunosorbent assay (ELISA). The wif-1 promoter methylation status was detected by DNA methylation-specific PCR (MSP). The transcriptional activities of wif-1 and β-catenin were discovered by a luciferase reporter gene system. Cell viability was determined by Cell Counting Kit-8 (CCK8) method. The cell cycle was detected by flow cytometry. The apoptotic cells were surveyed by the apoptosis kit. The expression of Inolucrin, Loricrin, Filaggrin, Keratin 17, and transcriptional activation of transglutaminase 1(TGase1) were detected by Western blotting.

Results

Indirubin inhibited the expression of DNMT1 and the methylation of the wif-1 promoter. In the wnt signal pathway, indirubin restored the protein expression of wif-1 and inhibited expression of Frizzled2, Frizzled5, and β-catenin. Besides, indirubin inhibited the proliferation of HaCaT cells, induced apoptosis, and arrest cell cycle. We also reported that indirubin could down-regulate the expression of Involucrin, TGase 1, and keratin 17, but the expression of Filaggrin and Loricrin had no significant effect.

Conclusion

Our research showed that indirubin promoted the demethylation of wif-1 and suppressed the wnt/β-catenin signal pathway, thereby exerted an anti-proliferative effect. This study reveals the anti-proliferation mechanism of indirubin, which may provide an effective option for the treatment of proliferative diseases.
WEARCON: wearable home monitoring in children with asthma reveals a strong association with hospital based assessment of asthma control
Authors: van der Kamp M. R. , Klaver E. C. , Thio B. J. , Driessen J. M. M. , de Jongh F. H. C. , Tabak M. , van der Palen J. , Hermens H. J.
Published: August 2020

Background

Asthma is one of the most common chronic diseases in childhood. Regular follow-up of physiological parameters in the home setting, in relation to asthma symptoms, can provide complementary quantitative insights into the dynamics of the asthma status. Despite considerable interest in asthma home-monitoring in children, there is a paucity of scientific evidence, especially on multi-parameter monitoring approaches. Therefore, the aim of this study is to investigate whether asthma control can be accurately assessed in the home situation by combining parameters from respiratory physiology sensors.

Methods

Sixty asthmatic and thirty non-asthmatic children were enrolled in the observational WEARCON-study. Asthma control was assessed according to GINA guidelines by the paediatrician. All children were also evaluated during a 2-week home-monitoring period with wearable devices; a physical activity tracker, a handheld spirometer, smart inhalers, and an ambulatory electrocardiography device to monitor heart and respiratory rate. Multiple logistic regression analysis was used to determine which diagnostic measures were associated with asthma control.

Results

24 of the 27 uncontrolled asthmatic children and 29 of the 32 controlled asthmatic children could be accurately identified with this model. The final model showed that a larger variation in pre-exercise lung function (OR = 1.34 95%-CI 1.07–1.68), an earlier wake-up-time (OR = 1.05 95%-CI 1.01–1.10), more reliever use (OR = 1.11 95%-CI 1.03–1.19) and a longer respiratory rate recovery time (OR = 1.12 95%-CI 1.05–1.20) were significant contributors to the probability of having uncontrolled asthma.

Conclusions

Home-monitoring of physiological parameters correlates with paediatrician assessed asthma control. The constructed multivariate model identifies 88.9% of all uncontrolled asthmatic children, indicating a high potential for monitoring of asthma control. This may allow healthcare professionals to assess asthma control at home.

Trial registration

Netherlands Trail Register,NL6087. Registered 14 February 2017.
Adjuvant instant preoperative renal artery embolization facilitates the radical nephrectomy and thrombectomy in locally advanced renal cancer with venous thrombus: a retrospective study of 54 cases
Authors: Tang Guangxin , Chen Xiaoxu , Wang Jianwei , He Wei , Niu Zhihong
Published: August 2020

Background

The role of renal artery embolization (RAE) in the therapeutic armamentarium is always controversial. The present study aimed to assess the safety and the surgical outcomes of the instant renal artery embolization (I-RAE) prior to nephrectomy and thrombectomy in patients with locally advanced renal cell carcinoma (RCC) with venous thrombus.

Methods

We performed a retrospective analysis of 54 patients treated with nephrectomy and thrombectomy between January 2012 and January 2019. Twenty-four patients were treated with I-RAE before surgery. Thirty patients received surgery alone (non-RAE group). The patient demographics, operation time, blood loss, transfusion requirements, complications, and other surgical parameters were analyzed between the two groups.

Results

The mean tumor size in the I-RAE group was significantly larger than that in the non-RAE group (11.1 cm versus 7.9 cm;p= .001). The mean estimated blood loss was significantly lower in the I-RAE group compared to that in the non-RAE group (596 ml versus 827 ml;p= .015), and the patients in the non-RAE group were more likely to receive blood transfusion (red blood cell, RBC units, 4 U versus 6 U,p= .025; plasma volume, 200 ml versus 400 ml,p= .01). No differences were found in operative duration, ICU stay, perioperative complications, and length of postoperative hospitalization.

Conclusions

Instant preoperative adjuvant renal artery embolization (I-RAE) is a safe technique. It facilitates nephrectomy and thrombectomy by reducing blood loss, transfusion requirements, and complications of delayed operations, providing urologists with a reliable option for treatment of locally advanced RCC with tumor thrombus.
Zyflamend induces apoptosis in pancreatic cancer cells via modulation of the JNK pathway
Authors: Puckett Dexter L. , Alquraishi Mohammed , Alani Dina , Chahed Samah , Donohoe Dallas , Voy Brynn , Whelan Jay , Bettaieb Ahmed
Published: August 2020

Background

Current pharmacological therapies and treatments targeting pancreatic neuroendocrine tumors (PNETs) have proven ineffective, far too often. Therefore, there is an urgent need for alternative therapeutic approaches. Zyflamend, a combination of anti-inflammatory herbal extracts, that has proven to be effective in various in vitro and in vivo cancer platforms, shows promise. However, its effects on pancreatic cancer, in particular, remain largely unexplored.

Methods

In the current study, we investigated the effects of Zyflamend on the survival of beta-TC-6 pancreatic insulinoma cells (β-TC6) and conducted a detailed analysis of the underlying molecular mechanisms.

Results

Herein, we demonstrate that Zyflamend treatment decreased cell proliferation in a dose-dependent manner, concomitant with increased apoptotic cell death and cell cycle arrest at the G2/M phase. At the molecular level, treatment with Zyflamend led to the induction of ER stress, autophagy, and the activation of c-Jun N-terminal kinase (JNK) pathway. Notably, pharmacological inhibition of JNK abrogated the pro-apoptotic effects of Zyflamend. Furthermore, Zyflamend exacerbated the effects of streptozotocin and adriamycin-induced ER stress, autophagy, and apoptosis.

Conclusion

The current study identifies Zyflamend as a potential novel adjuvant in the treatment of pancreatic cancer via modulation of the JNK pathway.
Role of tyrosine kinases in bladder cancer progression: an overview
Authors: Zangouei Amir Sadra , Barjasteh Amir Hossein , Rahimi Hamid Reza , Mojarrad Majid , Moghbeli Meysam
Published: August 2020

Background

Bladder cancer (BCa) is a frequent urothelial malignancy with a high ratio of morbidity and mortality. Various genetic and environmental factors are involved in BCa progression. Since, majority of BCa cases are diagnosed after macroscopic clinical symptoms, it is required to find efficient markers for the early detection. Receptor tyrosine-kinases (RTKs) and non-receptor tyrosine-kinases (nRTKs) have pivotal roles in various cellular processes such as growth, migration, differentiation, and metabolism through different signaling pathways. Tyrosine-kinase deregulations are observed during tumor progressions via mutations, amplification, and chromosomal abnormalities which introduces these factors as important candidates of anti-cancer therapies.

Main body

For the first time in present review we have summarized all of the reported tyrosine-kinases which have been significantly associated with the clinicopathological features of BCa patients.

Conclusions

This review highlights the importance of tyrosine-kinases as critical markers in early detection and therapeutic purposes among BCa patients and clarifies the molecular biology of tyrosine-kinases during BCa progression and metastasis.
Equity impacts of interventions to increase physical activity among older adults: a quantitative health impact assessment
Authors: Schönbach Johanna-Katharina , Bolte Gabriele , Czwikla Gesa , Manz Kristin , Mensing Monika , Muellmann Saskia , Voelcker-Rehage Claudia , Lhachimi Stefan K.
Published: August 2020

Background

Behavioural interventions may increase social inequalities in health. This study aimed to project the equity impact of physical activity interventions that have differential effectiveness across education groups on the long-term health inequalities by education and gender among older adults in Germany.

Methods

We created six intervention scenarios targeting the elderly population: Scenarios #1–#4 applied realistic intervention effects that varied by education (low, medium high). Under scenario #5, all older adults adapted the physical activity pattern of those with a high education. Under scenario #6, all increased their physical activity level to the recommended 300 min weekly. The number of incident ischemic heart disease, stroke and diabetes cases as well as deaths from all causes under each of these six intervention scenarios was simulated for males and females over a 10-year projection period using the DYNAMO-HIA tool. Results were compared against a reference-scenario with unchanged physical activity.

Results

Under scenarios #1–#4, approximately 3589–5829 incident disease cases and 6248–10,320 deaths could be avoided among males over a 10-year projection period, as well as 4381–7163 disease cases and 6914–12,605 deaths among females. The highest reduction for males would be achieved under scenario #4, under which the intervention is most effective for those with a high education level. Scenario #4 realizes 2.7 and 2.4% of the prevented disease cases and deaths observed under scenario #6, while increasing inequalities between education groups. In females, the highest reduction would be achieved under scenario #3, under which the intervention is most effective amongst those with low levels of education. This scenario realizes 2.7 and 2.9% of the prevented disease cases and deaths under scenario #6, while decreasing inequalities between education groups. Under scenario #5, approximately 31,687 incident disease cases and 59,068 deaths could be prevented among males over a 10-year projection period, as well as 59,173 incident disease cases and 121,689 deaths among females. This translates to 14.4 and 22.2% of the prevented diseases cases among males and females under scenario #6, and 13.7 and 27.7% of the prevented deaths under scenario #6.

Conclusions

This study shows how the overall population health impact varies depending on how the intervention-induced physical activity change differs across education groups. For decision-makers, both the assessment of health impacts overall as well as within a population is relevant as interventions with the greatest population health gain might be accompanied by an unintended increase in health inequalities.
How do short sleepers use extra waking hours? A compositional analysis of 24-h time-use patterns among children and adolescents
Authors: Gába Aleš , Dygrýn Jan , Štefelová Nikola , Rubín Lukáš , Hron Karel , Jakubec Lukáš , Pedišić Željko
Published: August 2020

Background

To examine compositional associations between short sleep duration and sedentary behavior (SB), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) among children and adolescents.

Methods

Multi-day 24-h data on sleep, SB, LPA and MVPA were collected using accelerometers among 343 children (8–13 years old) and 316 adolescents (14–18 years old). Children and adolescents with sleep duration of < 9 and < 8 h, respectively, were classified as short sleepers. Robust compositional regression analysis was used to examine the associations between short sleep duration and the waking-time composition.

Results

Seventy-one percent of children and 75.3% of adolescents were classified as short sleepers. In children, being a short sleeper was associated with higher SB by 95 min/day (p < 0.001) and lower MVPA by 16 min/day (p = 0.002). Specifically, it was associated with a higher amount of time spent in long sedentary bouts (βilr1 = 0.46, 95% confidence interval [CI] = 0.29 to 0.62) and lower amounts of time spent in sporadic SB (βilr1 = − 0.17, 95% CI = –0.24 to − 0.10), sporadic LPA (βilr1 = − 0.09, 95% CI = –0.14 to − 0.04) and sporadic MVPA (βilr1 = − 0.17, 95% CI = –0.25 to − 0.10,p < 0.001 for all), relative to the remaining behaviours. In adolescents, being a short sleeper was associated with a higher amount of time spent in SB by 67 min/day (p = 0.001) and lower LPA by 2 min/day (p = 0.035). Specifically, it was associated with more time spent in sedentary bouts of 1–9 min (βilr1 = 0.08, 95% CI = 0.02 to 0.14,p = 0.007) and 10–29 min (βilr1 = 0.10, 95% CI = 0.02 to 0.18,p = 0.015), relative to the remaining behaviours.

Conclusions

Among children and adolescents, short sleep duration seems to be highly prevalent and associated with less healthy waking time. Public health interventions and strategies to tackle the high prevalence of short sleep duration among children and adolescents are warranted.
Prognostic significance of plasma IL-2 and sIL-2Rα in patients with first-ever ischaemic stroke
Authors: Zhao Haiping , Li Fangfang , Huang Yuyou , Zhang Sijia , Li Lingzhi , Yang Zhenhong , Wang Rongliang , Tao Zhen , Han Ziping , Fan Junfen , Zheng Yangmin , Ma Qingfeng , Luo Yumin
Published: August 2020

Background

An imbalance between circulating neuroprotective and neurotoxic T cell subsets leads to poor prognosis in acute ischaemic stroke (AIS). Preclinical studies have indicated that the soluble form of the interleukin-2 receptor α (sIL-2Rα)-IL-2 complex regulates T cell differentiation. However, the association between sIL-2Rα levels and AIS remains unclear.

Methods

A total of 201 first-ever AIS patients within 24 h after stroke onset and 76 control subjects were recruited. The National Institutes of Health Stroke Scale (NIHSS) score and 3-month functional outcome (modified Rankin Scale [mRS] score) at admission were assessed. Plasma sIL-2Rα and IL-2 levels at admission were measured. Prognostic significance was identified by using univariate and multivariate logistic regression analyses.

Results

Patients with poor functional outcomes at 3 months had significantly higher levels of sIL-2Rα and lower levels of IL-2 than patients with good outcomes. Moreover, sIL-2Rα levels showed a strong positive correlation with NIHSS and mRS scores (p< 0.0001), whereas IL-2 levels were negatively correlated with mRS scores (p< 0.01). Univariate analyses showed that higher sIL-2Rα and IL-2 levels were associated with an increased and reduced risk of unfavourable outcomes, respectively. After adjusting for confounding variables, the sIL-2Rα level remained independently associated with an increased risk of an unfavourable outcome, and adding sIL-2Rα levels to the conventional risk factor model significantly improved risk reclassification (net reclassification improvement 17.56%,p= 0.003; integrated discrimination improvement 5.78%,p =0.0003).

Conclusions

sIL-2Rα levels represent a novel, independent prognostic marker that can improve the currently used risk stratification of AIS patients. Our findings also highlight that elevated plasma sIL-2Rα and IL-2 levels manifested opposite correlations with functional outcome, underlining the importance of IL-2/IL-2R autocrine loops in AIS.
Early leucine programming on protein utilization and mTOR signaling by DNA methylation in zebrafish (Danio rerio)
Authors: Zhu Qiang-Sheng , Wang Jie , He Shan , Liang Xu-Fang , Xie Shuang , Xiao Qian-Qian
Published: August 2020

Background

Early nutritional programming affects a series of metabolism, growth and development in mammals. Fish also exhibit the developmental plasticity by early nutritional programming. However, little is known about the effect of early amino acid programming on growth and metabolism.

Methods

In the present study, zebrafish (Danio rerio) was used as the experimental animal to study whether early leucine stimulation can programmatically affect the mechanistic target of rapamycin (mTOR) signaling pathway, growth and metabolism in the later life, and to undercover the mechanism of epigenetic regulation. Zebrafish larvas at 3 days post hatching (dph) were raised with 1.0% leucine from 3 to 13 dph during the critical developmental stage, then back to normal water for 70 days (83 dph).

Results

The growth performance and crude protein content of zebrafish in the early leucine programming group were increased, and consistent with the activation of the mTOR signaling pathway and the high expression of genes involved in the metabolism of amino acid and glycolipid. Furthermore, we compared the DNA methylation profiles between the control and leucine-stimulated zebrafish, and found that the methylation levels of CG-differentially methylated regions (DMGs) and CHH-DMGs of genes involved in mTOR signaling pathway were different between the two groups. With quantitative PCR analysis, the decreased methylation levels of CG type of Growth factor receptor-bound protein 10 (Grb10), eukaryotic translation initiation factor 4E (eIF4E) andmTORgenes of mTOR signaling pathway in the leucine programming group, might contribute to the enhanced gene expression.

Conclusions

The early leucine programming could improve the protein synthesis and growth, which might be attributed to the methylation of genes in mTOR pathway and the expression of genes involved in protein synthesis and glycolipid metabolism in zebrafish. These results could be beneficial for better understanding of the epigenetic regulatory mechanism of early nutritional programming.
Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells
Authors: Chen Yu-Chen , Chuang Tzu-Yi , Liu Chen-Wei , Liu Chi-Wei , Lee Tzu-Lin , Lai Tsai-Chun , Chen Yuh-Lien
Published: August 2020

Background

Particulate matters (PMs) in ambient air pollution are closely related to the incidence of respiratory diseases and decreased lung function. Our previous report demonstrated that PMs-induced oxidative stress increased the expression of proinflammatory intracellular adhesion molecule-1 (ICAM-1) through the IL-6/AKT/STAT3/NF-κB pathway in A549 cells. However, the role of O-PMs in epithelial-mesenchymal transition (EMT) development and pulmonary fibrosis and the related mechanisms have not been determined. The aim of this study was to investigate the effects of O-PMs on the pathogenesis of EMT and pulmonary fibrosis as well as the expression of ETS-1 and NF-κB p65, in vitro and in vivo.

Results

O-PMs treatment induced EMT development, fibronectin expression, and cell migration. O-PMs affected the expression of the EMT-related transcription factors NF-κB p65 and ETS-1. Interference with NF-κB p65 significantly decreased O-PMs-induced fibronectin expression. In addition, O-PMs affected the expression of fibronectin, E-cadherin, and vimentin through modulating ETS-1 expression. ATN-161, an antagonist of integrin α5β1, decreased the expression of fibronectin and ETS-1 and EMT development. EMT development and the expression of fibronectin and ETS-1 were increased in the lung tissue of mice after exposure to PMs for 7 and 14 days. There was a significant correlation between fibronectin and ETS-1 expression in human pulmonary fibrosis tissue.

Conclusion

O-PMs can induce EMT and fibronectin expression through the activation of transcription factors ETS-1 and NF-κB in A549 cells. PMs can induce EMT development and the expression of fibronectin and ETS-1 in mouse lung tissues. These findings suggest that the ETS-1 pathway could be a novel and alternative mechanism for EMT development and pulmonary fibrosis.
Missed radiation therapy sessions in first three weeks predict distant metastasis and less favorable outcomes in surgically treated patients with oral cavity squamous cell carcinoma
Authors: Chiang Yin-Yin , Chou Yung-Chih , Chang Kai-Ping , Liao Chun-Ta , Wu Yao-Yu , Yap Wing-Keen , Pai Ping-Ching , Chang Joseph Tung-Chieh , Lin Chien-Yu , Fan Kang-Hsing , Huang Bing-Shen , Hung Tsung-Min , Tsang Ngan-Ming
Published: August 2020

Background

We sought to investigate the prognostic impact of missed RT sessions in patients who had undergone surgery for oral cavity squamous cell carcinoma (OCSCC).

Methods

The study sample consisted of 905 patients with surgically treated OCSCC who fulfilled criteria of RT course ≤8 weeks. The study participants were divided into three groups based on the characteristics of missed RT, as follows: 1) early missed RT, 2) late missed RT, and 3) RT as scheduled.

Results

The 5-year overall survival (OS) rates in the early missed RT, late missed RT, and RT as scheduled groups were 53.0, 58.1, and 64.5%, respectively (p = 0.046). In multivariate analysis, early missed RT was independently associated with both OS (hazard ratio (HR) = 1.486; 95% confidence interval (CI): 1.122–1.966;p = 0.006) and the occurrence of distant metastasis (HR = 1.644; 95% CI: 1.047–2.583;p = 0.031).

Conclusion

Early missed RT was independently associated with a higher occurrence of distant metastasis and less favorable OS in patients who had undergone surgery for OCSCC.
Clinical impact of Hypofractionated carbon ion radiotherapy on locally advanced hepatocellular carcinoma
Authors: Shiba Shintaro , Shibuya Kei , Okamoto Masahiko , Okazaki Shohei , Komatsu Shuichiro , Kubota Yoshiki , Nakano Takashi , Ohno Tatsuya
Published: August 2020

Background

Hepatocellular carcinoma (HCC) involving a major branch of the portal or hepatic vein is in a locally advanced stage and remains difficult to cure. This study aimed to evaluate the clinical effects of carbon ion radiotherapy (C-ion RT) in locally advanced HCC (LAHCC).

Methods

The data of 11 consecutive patients with LAHCC who received C-ion RT were analyzed. The C-ion RT doses of 52.8 Gy (relative biological effectiveness [RBE]) and 60.0 Gy (RBE) were delivered in 4 fractions for standard cases, and the 60.0 Gy dose was delivered in 12 fractions for close-to-gastrointestinal-tract cases. Survival and local control probabilities were calculated using the Kaplan-Meier method.

Results

The median follow-up duration after C-ion RT was 36.4 months. The median age at the time of registration for C-ion RT was 76 years. The median tumor size was 53 mm. The numbers of treatment-naive and recurrent HCC patients were 1 and 10, respectively. Direct invasion of the major branch of the portal vein, hepatic vein, or both portal and hepatic veins was observed in three, five, and three patients, respectively. The 3-year overall survival, local control, and progression-free survival rates were 64, 78, and 18%, respectively. No patient developed radiation-induced liver diseases or grade 3 or higher toxicities in the acute and late phases.

Conclusions

C-ion RT showed favorable clinical outcomes with a high rate of local control and minimal toxicities in LAHCC. Our findings suggest that C-ion RT is a promising multidisciplinary treatment option in LAHCC.