bluuebunny/crossref_metadata_2025 huggingface dataset:
One-week multidisciplinary post-graduate palliative care training: an outcome-based program evaluation
Authors: Paal Piret , Brandstötter Cornelia , Bükki Johannes , Elsner Frank , Ersteniuk Anna , Jentschke Elisabeth , Stähli Andreas , Slugotska Iryna
Published: August 2020

Background

A multi-professional, post-graduate, one-week palliative care training program was piloted in November 2019 at the University of Ivano-Frankivsk, Ukraine. A formal evaluation of this program was performed.

Methods

This is a comparative, retrospective outcome-based evaluation of an educational intervention. Participants completed evaluation forms at the end of the course (post-intervention = T1), covering demographics, comparative retrospective self-assessment (40 items, 6-point Likert scale), organizational aspects, and general feedback (free text). At T1, the responses represent actual self-assessment, pre-interventional (T0) scores were generated by retrospective self-assessment. The Retrospective Performance Gain (RPG) was calculated on group level for the comparative self-assessment, demographic and organizational variables were analyzed by descriptive statistics, and free text answers were processed by qualitative methodology (content analysis).

Results

Fifty-three of 56 attendants from all professions relevant to palliative care completed the evaluation forms (response 94,6%), with mean age 39y (22–64) and mean working experience 13,6y (1–44). Overall ratings of the program were very positive. Comparative retrospective self-assessment demonstrated a marked RPG from T0 to T1 on all items. Free text comments emphasized the need for regular nation-wide educational programs and for further education in bereavement care; inter-professional practice; communication; palliative care philosophy; professional self-care; specific nursing skills; dementia care; and advocacy, while the general contribution of the program to palliative care development in Ukraine was acknowledged.

Conclusions

Systematic evaluation of a post-graduate international training program in palliative care may provide a mutual learning experience and map country-specific barriers and facilitators that have to be addressed when setting up palliative care services.
Insulin: too much of a good thing is bad
Authors: Kolb Hubert , Kempf Kerstin , Röhling Martin , Martin Stephan
Published: August 2020

Background

Insulin shares a limited physiological concentration range with other endocrine hormones. Not only too low, but also too high systemic insulin levels are detrimental for body functions.

Main body

The physiological function and clinical relevance of insulin are usually seen in association with its role in maintaining glucose homeostasis. However, insulin is an anabolic hormone which stimulates a large number of cellular responses. Not only too low, but also excess insulin concentrations are detrimental to the physiological balance. Although the glucoregulatory activity of insulin is mitigated during hyperinsulinemia by dampening the efficiency of insulin signaling (“insulin resistance”), this is not the case for most other hormonal actions of insulin, including the promotion of protein synthesis, de novo lipogenesis, and cell proliferation; the inhibition of lipolysis, of autophagy-dependent cellular turnover, and of nuclear factor E2-related factor-2 (Nrf2)-dependent antioxidative; and other defense mechanisms. Hence, there is no general insulin resistance but selective impairment of insulin signaling which causes less glucose uptake from the blood and reduced activation of endothelial NO synthase (eNOS). Because of the largely unrestricted insulin signaling, hyperinsulinemia increases the risk of obesity, type 2 diabetes, and cardiovascular disease and decreases health span and life expectancy. In epidemiological studies, high-dose insulin therapy is associated with an increased risk of cardiovascular disease. Randomized controlled trials of insulin treatment did not observe any effect on disease risk, but these trials only studied low insulin doses up to 40 IU/day. Proof for a causal link between elevated insulin levels and cardiovascular disease risk comes from Mendelian randomization studies comparing individuals with genetically controlled low or high insulin production.

Conclusions

The detrimental actions of prolonged high insulin concentrations, seen also in cell culture, argue in favor of a lifestyle that limits circadian insulin levels. The health risks associated with hyperinsulinemia may have implications for treatment regimens used in type 2 diabetes.
Compassionate drug (mis)use during pandemics: lessons for COVID-19 from 2009
Authors: Rojek Amanda M. , Martin Genevieve E. , Horby Peter W.
Published: August 2020

Background

New emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics.

Methods

We searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease.

Results

Thirty-three thousand eight hundred sixty-nine treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. Five hundred ninety-two patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results was available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended.

Conclusion

Patients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.
Laryngopharyngeal reflux in chronic obstructive pulmonary disease - a multi-centre study
Authors: Sanchez Julia , Schumann Desiree M. , Karakioulaki Meropi , Papakonstantinou Eleni , Rassouli Frank , Frasnelli Matthias , Brutsche Martin , Tamm Michael , Stolz Daiana
Published: August 2020

Reflux of gastric content has been associated with recurrent exacerbations of chronic obstructive pulmonary disease (COPD). We aimed to assess the prevalence of laryngopharyngeal reflux (LPR) in COPD and if LPR is a contributing factor to clinically relevant outcomes in COPD. We evaluated a total of 193 COPD patients (GOLD I-IV) with a 24-h laryngo-pharyngeal pΗ-monitor. LPR was observed in 65.8% of COPD patients and it was not significantly associated with clinically relevant outcomes of COPD. Treatment with PPI significantly decreased the upright RYAN score (p = 0.047) without improving lung function. Furthermore, the presence or severity of LPR cannot be diagnosed based solely on symptoms and questionnaires.
Effect of niacin monotherapy on high density lipoprotein composition and function
Authors: Gordon Scott M. , Amar Marcelo J. , Jeiran Kianoush , Stagliano Michael , Staller Emma , Playford Martin P. , Mehta Nehal N. , Vaisar Tomas , Remaley Alan T.
Published: August 2020

Background

Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL’s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function.

Methods

A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement.

Results

In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q < 0.01; LDL-C − 20%, q < 0.01; and triglyceride − 15%, q = 0.1). HDL proteomics revealed significant effects of niacin on 5 proteins: serum amyloid A (SAA), angiotensinogen (AGT), apolipoprotein A-II (APOA2), clusterin (CLUS), and apolipoprotein L1 (APOL1). SAA was the most prominently affected protein, increasing 3-fold in response to niacin (q = 0.008). Cholesterol efflux capacity was not significantly affected by niacin compared to baseline, however, stopping niacin resulted in a 9% increase in efflux (q < 0.05). Niacin did not impact HDL’s ability to influence endothelial function.

Conclusion

Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.
Magnitude of rise in proneurotensin is related to amount of triglyceride appearance in blood after standardized oral intake of both saturated and unsaturated fat
Authors: Fawad Ayesha , Fernandez Celine , Bergmann Andreas , Struck Joachim , Nilsson Peter M. , Bennet Louise , Orho-Melander Marju , Melander Olle
Published: August 2020

Background

In rodents, neurotensin contributes to high fat diet induced obesity by facilitation of intestinal fat absorption. The effect of oral lipid load on plasma proneurotensin and relationship with plasma triglycerides in humans is unknown.

Aim

To investigate the acute effects of an oral lipid load on proneurotensin and plasma triglycerides and their interrelationships in healthy individuals.

Setting/ methods

Twenty-two healthy subjects were given 150 mL of full milk cream (54 g fat) and 59 mL of pure olive oil (54 g fat) in the fasted state at two different occasions separated by at least 1 week in random order. Venous blood was drawn at fasted before 0 h (h) and at 1 h, 2 h and 4 h after ingestion. Post-ingested values of proneurotensin and plasma triglycerides were compared with fasting levels and post ingestion Area Under the Curve (AUC) of proneurotensin was correlated with that of plasma triglycerides.

Results

An immediate rise of plasma proneurotensin and plasma triglycerides were observed after ingestion of cream with maximum increase at 2 h for proneurotensin [mean (95% confidence interval)] of 22 (12–31) pmol/L (P < 0.001) and at 3 h for triglycerides of 0.60 (0.43–0.78) mmol/L (P < 0.001). Similarly, plasma proneurotensin and plasma triglycerides increased after ingestion of olive oil with maximum increase of proneurotensin at 3 h of 62 (46–78) pmol/L (P < 0.001) and plasma triglycerides at 3 h of 0.32 (0.18–0.45) mmol/L (P < 0.001). The post lipid load AUC for proneurotensin correlated significantly with the AUC for plasma triglycerides both after cream (r = 0.49, P = 0.021) and olive oil (r = 0.55, P = 0.008), respectively.

Conclusion

Proneurotensin increases after an oral lipid load of both cream and olive oil and the rise of post-ingestion plasma triglycerides is significantly related to the rise of post-ingestion proneurotensin.
Atherogenic L5 LDL induces cardiomyocyte apoptosis and inhibits KATP channels through CaMKII activation
Authors: Ma Yanzhuo , Cheng Nancy , Sun Junping , Lu Jonathan Xuhai , Abbasi Shahrzad , Wu Geru , Lee An-Sheng , Sawamura Tatsuya , Cheng Jie , Chen Chu-Huang , Xi Yutao
Published: August 2020

Background

Cardiac Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation plays a critical role in cardiomyocyte (CM) apoptosis and arrhythmia. Functional ATP-sensitive potassium (KATP) channels are essential for cardiac protection during ischemia. In cultured CMs, L5 low-density lipoprotein (LDL) induces apoptosis and QTc prolongation. L5 is a highly electronegative and atherogenic aberrant form of LDL, and its levels are significantly higher in patients with cardiovascular-related diseases. Here, the role of L5 in cardiac injury was studied by evaluating the effects of L5 on CaMKII activity and KATP channel physiology in CMs.

Methods

Cultured neonatal rat CMs (NRCMs) were treated with a moderate concentration (ie, 7.5 μg/mL) of L5 or L1 (the least electronegative LDL subfraction). NRCMs were examined for apoptosis and viability, CaMKII activity, and the expression of phosphorylated CaMKIIδ and NOX2/gp91phox. The function of KATP and action potentials (APs) was analyzed by using the patch-clamp technique.

Results

In NRCMs, L5 but not L1 significantly induced cell apoptosis and reduced cell viability. Furthermore, L5 decreased Kir6.2 expression by more than 50%. Patch-clamp analysis showed that L5 reduced the KATP current (IKATP) density induced by pinacidil, a KATP opener. The partial recovery of the inward potassium current during pinacidil washout was susceptible to subsequent inhibition by the IKATP blocker glibenclamide. Suppression of IKATP by L5 significantly prolonged the AP duration. L5 also significantly increased the activity of CaMKII, the phosphorylation of CaMKIIδ, and the expression of NOX2/gp91phox. L5-induced apoptosis was prevented by the addition of the CaMKII inhibitor KN93 and the reactive oxygen species scavenger Mn (III)TBAP.

Conclusions

L5 but not L1 induces CM damage through the activation of the CaMKII pathway and increases arrhythmogenicity in CMs by modulating the AP duration. These results help to explain the harmful effects of L5 in cardiovascular-related disease.
Treatment plan quality during online adaptive re-planning
Authors: van Timmeren Janita E. , Chamberlain Madalyne , Krayenbuehl Jérôme , Wilke Lotte , Ehrbar Stefanie , Bogowicz Marta , Hartley Callum , Zamburlini Mariangela , Andratschke Nicolaus , Garcia Schüler Helena , Pavic Matea , Balermpas Panagiotis , Ryu Chaehee , Guckenberger Matthias , Tanadini-Lang Stephanie
Published: August 2020

Background

Online adaptive radiotherapy is intended to prevent plan degradation caused by inter-fractional tumor volume and shape changes, but time limitations make online re-planning challenging. The aim of this study was to compare the quality of online-adapted plans to their respective reference treatment plans.

Methods

Fifty-two patients treated on a ViewRay MRIdian Linac were included in this retrospective study. In total 238 online-adapted plans were analyzed, which were optimized with either changing of the segment weights (n = 85) or full re-optimization (n = 153). Five different treatment sites were evaluated: prostate, abdomen, liver, lung and pelvis. Dosimetric parameters of gross tumor volume (GTV), planning target volume (PTV), 2 cm ring around the PTV and organs at risk (OARs) were considered. The Wilcoxon signed-rank test was used to assess differences between online-adapted and reference treatment plans, p < 0.05 was considered significant.

Results

The average duration of the online adaptation, consisting of contour editing, plan optimization and quality assurance (QA), was 24 ± 6 min. The GTV was slightly larger (average ± SD: 1.9% ± 9.0%) in the adapted plans than in the reference plans (p < 0.001). GTV-D95% exhibited no significant changes when considering all plans, but GTV-D2% increased by 0.40% ± 1.5% on average (p < 0.001). There was a very small yet significant decrease in GTV-coverage for the abdomen plans. The ring Dmean increased on average by 1.0% ± 3.6% considering all plans (p < 0.001). There was a significant reduction of the dose to the rectum of 4.7% ± 16% on average (p < 0.001) for prostate plans.

Conclusions

Dosimetric quality of online-adapted plans was comparable to reference treatment plans and OAR dose was either comparable or decreased, depending on treatment site. However, dose spillage was slightly increased.
Neoadjuvant metformin added to conventional chemotherapy synergizes anti-proliferative effects in ovarian cancer
Authors: Wen Kuo-Chang , Sung Pi-Lin , Wu Alexander T. H. , Chou Ping-Chieh , Lin Jun-Hung , Huang Chi-Ying F. , Yeung Sai-Ching J. , Lee Mong-Hong
Published: August 2020

Background

Ovarian cancer is the leading cause of cancer-related death among women. Complete cytoreductive surgery followed by platinum-taxene chemotherapy has been the gold standard for a long time. Various compounds have been assessed in an attempt to combine them with conventional chemotherapy to improve survival rates or even overcome chemoresistance. Many studies have shown that an antidiabetic drug, metformin, has cytotoxic activity in different cancer models. However, the synergism of metformin as a neoadjuvant formula plus chemotherapy in clinical trials and basic studies remains unclear for ovarian cancer.

Methods

We applied two clinical databases to survey metformin use and ovarian cancer survival rate. The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy.

Results

We found that ovarian cancer patients treated with metformin had significantly longer overall survival than patients treated without metformin. The protein profile induced by low- concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway. In combination with chemotherapy, the neoadjuvant metformin protocol showed beneficial synergistic effects in vitro and in vivo.

Conclusions

This study shows that neoadjuvant metformin at clinically relevant dosages is efficacious in treating ovarian cancer, and the results can be used to guide clinical trials.
Hand hygiene improvement or antibiotic restriction to control the household transmission of extended-spectrum β-lactamase-producing Escherichia coli: a mathematical modelling study
Authors: Kardaś-Słoma Lidia , Yazdanpanah Yazdan , Perozziello Anne , Zahar Jean-Ralph , Lescure François-Xavier , Cousien Anthony , Lucet Jean-Christophe
Published: August 2020

Background

The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking.

Methods

We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon.

Results

The probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0–5.6) or 6.6% (6.3–6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9–62.0) to 68.8% (68.3–69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33–62%. Antibiotic restriction by 50% reduced the transmission by 2–6%.

Conclusions

The transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.
Antimicrobial drug use in the first decade of life influences saliva microbiota diversity and composition
Authors: Raju Sajan C. , Viljakainen Heli , Figueiredo Rejane A. O. , Neuvonen Pertti J. , Eriksson Johan G. , Weiderpass Elisabete , Rounge Trine B.
Published: August 2020

Background

The human microbiota contributes to health and well-being. Antimicrobials (AM) have an immediate effect on microbial diversity and composition in the gut, but next to nothing is known about their long-term contribution to saliva microbiota. Our objectives were to investigate the long-term impact of AM use on saliva microbiota diversity and composition in preadolescents. We compared the lifetime effects by gender and AMs. We used data from 808 randomly selected children in the Finnish Health In Teens (Fin-HIT) cohort with register-based data on AM purchases from the Social Insurance Institution of Finland. Saliva microbiota was assessed with 16S rRNA (V3-V4) sequencing. The sequences were aligned to the SILVA ribosomal RNA database and classified and counted using the mothur pipeline. Associations between AM use and alpha-diversity (Shannon index) were identified with linear regression, while associations between beta-diversity (Bray-Curtis dissimilarity) and low, medium or high AM use were identified with PERMANOVA.

Results

Of the children, 53.6% were girls and their mean age was 11.7 (0.4) years. On average, the children had 7.4 (ranging from 0 to 41) AM prescriptions during their lifespan. The four most commonly used AMs were amoxicillin (n= 2622, 43.7%), azithromycin (n= 1495, 24.9%), amoxicillin-clavulanate (n= 1123, 18.7%) and phenoxymethylpenicillin (n= 408, 6.8%). A linear inverse association was observed between the use of azithromycin and Shannon index (b− 0.015,pvalue = 0.002) in all children, the effect was driven by girls (b− 0.032,pvalue = 0.001), while not present in boys. Dissimilarities were marked between high, medium and low users of all AMs combined, in azithromycin users specifically, and in boys with amoxicillin use. Amoxicillin and amoxicillin-clavulanate use was associated with the largest decrease in abundance ofRikenellaceae. AM use in general and phenoxymethylpenicillin specifically were associated with a decrease ofPaludibacterand pathways related to amino acid degradations differed in proportion between high and low AM users.

Conclusions

A systematic approach utilising reliable registry data on lifetime use of AMs demonstrated long-term effects on saliva microbiota diversity and composition. These effects are gender- and AM-dependent. We found that frequent lifelong use of AMs shifts bacterial profiles years later, which might have unforeseen health impacts in the future. Our findings emphasise a concern for high azithromycin use, which substantially decreases bacterial diversity and affects composition as well. Further studies are needed to determine the clinical implications of our findings.
Relationship between dexamethasone added to periarticular anesthetic infiltration and postoperative nausea and vomiting following total knee arthroplasty under general anesthesia: a retrospective observational study
Authors: Yano Toshiyuki , Imaizumi Takashi , Matsu-ura Hidemi , Takahashi Tomoki
Published: August 2020

Background

Periarticular anesthetic infiltration (PAI) with a corticosteroid is a modality for pain control following total knee arthroplasty (TKA). Systemic corticosteroids are an established antiemetic for the prophylaxis of postoperative nausea and vomiting (PONV). The purpose of this retrospective observational study was to elucidate the relationship between dexamethasone added to PAI and PONV in patients who underwent TKA.

Methods

Data from 435 patients who received PAI using ropivacaine with or without dexamethasone were reviewed. The primary outcome was the incidence of PONV within 24 h following TKA. The incidence of deep incisional and organ/space surgical site infection (SSI) within the first year was also assessed.

Results

The overall incidence of PONV was 23.2%. A multivariate logistic regression analysis showed that dexamethasone added to PAI was independently associated with a reduced incidence of PONV (adjusted odds ratio, 0.23; 95% confidence interval, 0.12–0.44,P< 0.001). The incidence of PONV and rescue analgesic requirements within 24 h were lower in patients who received PAI with dexamethasone than in those who received PAI alone (19.5% vs 49.1%,P< 0.001, 7.9% vs 29.1%,P< 0.001, respectively). SSI developed in one out of the 55 patients who received PAI alone, but in none of those who received PAI with dexamethasone.

Conclusions

Dexamethasone added to PAI for postoperative pain management was independently associated with a lower risk of PONV within 24 h of TKA.
Role of multi-detector CT venography in evaluation of pelvic congestion syndrome
Authors: Awad Ahmad Sayed , Taha Mohammed Medhat Mohammed , Manaf Mohammed Hamam Abd , Gad Mostafa Mahmoud Mohamad , Mashhour Shady Nabil
Published: August 2020

Background

Pelvic congestion syndrome (PCS) is a problematic cause of chronic pelvic pain in women. It is thought to result from venous insufficiency of either ovarian or pelvic veins. Patients also present a variety of symptoms including dysuria and dyspareunia as well as vulva and buttock varicosities. The aim of this study is to evaluate the efficacy of multi-detector CT (MDCT) in diagnosis of PCS. Two hundred patients were included in our study and underwent CT venography of the abdomen and pelvis.

Results

We performed a prospective comparative study conducted on 200 patients. Thirty patients (15%) were diagnosed as PCS. There were congestion of the ovarian venous plexus and uterine venous engorgement in all patients. Filling of the veins across the midline was noted in 10 patients and filling of the vulval and thigh varicosities was noted in 3 patients. Ten patients had right ovarian vein dilatation; 12 patients had left ovarian vein dilatation; while 8 patients had bilateral ovarian vein dilatation. The right ovarian vein mean diameter (± SD) = 7.1 ± 0.8 mm; while the left ovarian vein mean diameter (± SD) = 7.6 ± 1 mm. Left ovarian venous reflux was found in 6 cases while no pathological reflux depicted on right side.

Conclusions

CT venography is considered as one of the initial investigations for the diagnosis of PCS in female patients with chronic pelvic pain making the further assessment by ovarian venography is for interventional management of diagnosed cases.
Students’ Understanding of the Dynamic Nature of Genetics: Characterizing Undergraduates’ Explanations for Interaction between Genetics and Environment
Authors: Haskel-Ittah Michal , Duncan Ravit Golan , Yarden Anat
Published: August 2020

This research investigates how students reason about the phenomenon of phenotypic plasticity. An analysis of student interviews reviled two types of mechanistic explanations, one of which seems to be less intuitive but is critical for reasoning about core biological ideas such as homeostasis and development.
Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma
Authors: McBride Sean , Sherman Eric , Tsai C. Jillian , Baxi Shrujal , Aghalar Jahan , Eng Juliana , Zhi Wanqing Iris , McFarland Daniel , Michel Loren Scott , Young Robert , Lefkowitz Robert , Spielsinger Daniel , Zhang Zhigang , Flynn Jessica , Dunn Lara , Ho Alan , Riaz Nadeem , Pfister David , Lee Nancy
Published: August 2020

PURPOSE

The objective response rate (ORR) for single-agent anti–programmed death receptor 1 (anti–PD-1) therapy is modest in patients with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). We aimed to test whether radiotherapy may act synergistically with anti–PD-1 therapy to improve response through the abscopal effect.

PATIENTS AND METHODS

We conducted a single-center, randomized, phase II trial of nivolumab (anti–PD-1 therapy) versus nivolumab plus stereotactic body radiotherapy (SBRT) in patients with metastatic HNSCC. Patients had at least two metastatic lesions: one that could be safely irradiated and one measurable by RECIST version 1.1. Patients were randomly assigned (1:1), stratified by human papillomavirus status, to nivolumab (3 mg/kg intravenously every 2 weeks) or nivolumab (same dose) plus SBRT (9 Gy × 3) to 1 lesion. The primary end point was ORR in nonirradiated lesions, which was assessed by RECIST in patients with at least one available set of on-treatment images; safety was assessed in a per-protocol population.

RESULTS

Between March 11, 2016, and June 22, 2018, 62 patients were randomly assigned to nivolumab (n = 30) or nivolumab plus SBRT (n = 32). There was no statistically significant ORR difference between arms (34.5% [95% CI, 19.9% to 52.7%] v 29.0% [95% CI, 16.1% to 46.6%]; P = .86). There was no significant difference in overall survival ( P = .75), progression-free survival ( P = .79), or response duration ( P = .26). Grade 3-5 toxicities were similar (13.3% v 9.7%; P = .70).

CONCLUSION

We found no improvement in response and no evidence of an abscopal effect with the addition of SBRT to nivolumab in unselected patients with metastatic HNSCC.
Implementing Quality Colon Cancer Survivorship Care: A Practical Proposal for a Path Forward
Authors: Kline Ronald M. , Temple Larissa K. F. , Nekhlyudov Larissa
Published: August 2020

There are currently close to 17 million survivors of cancer in the United States. This number is expected to grow as both an aging population and improved treatment increase the number of survivors. Consequently, the importance of quality survivorship care has been recognized, but implementing, measuring, and paying for this care in a highly fragmented health care system, across a broad spectrum of diseases, is difficult. Quality measurement tied to payment is one approach that has commonly been used to improve the quality of care in the US health care system, but the complexity of applying quality measurement metrics across the spectrum of cancer survivorship care had led to stalemate. In this article, we draw on prior work to develop a quality cancer survivorship framework and propose a practical path forward with a focus on the provision of colon cancer survivorship care within integrated health care delivery networks. With this narrowly defined approach, we hope that we can promote a practical solution that can be extended to other diseases and payment systems over time.
Changes in Intravenous Immunoglobulin Usage for Hypogammaglobulinemia After Implementation of a Stewardship Program
Authors: Derman Benjamin A. , Schlei Zachary , Parsad Sandeep , Mullane Kathleen , Knoebel Randall W.
Published: August 2020

PURPOSE:

Intravenous immunoglobulin (IVIG) is used to replenish immunoglobulins in hypogammaglobulinemia (HG) caused by hematologic malignancies (HM) or their treatment (autologous stem-cell transplantation [ASCT] and chimeric antigen receptor T-cell therapy [CAR-T]), in an effort to reduce the risk of infections. However, there is limited evidence to support this use, and IVIG supplies are limited and shortages are common.

METHODS:

An IVIG stewardship program (ISP) was implemented with the following requirements for IVIG administration: immunoglobulin G (IgG) level < 400 mg/dL (corrected for paraprotein) for post-ASCT and post–CAR-T patients, or IgG < 400 mg/dL with a history of a bacterial infection within the preceding 3 months for those with HM. Comparisons of the amount of IVIG administered, the incidence of infections, and the use of antimicrobials were performed between the 3 months before ISP and the 3 months after ISP.

RESULTS:

IVIG administered for HG decreased from 4,902 g in 86 patients before ISP to 1,777 g in 55 patients after ISP, a cost savings of $44,700. Adherence to ISP guidelines was 80%. Compared with before ISP, patients who stopped receiving IVIG after ISP had lower nadir IgG, fewer infections/patient-months, less antimicrobial usage, and a lower hospitalization rate for infection; no deaths occurred. Compared with before ISP, patients receiving IVIG after ISP had lower predose IgG and fewer infections/patient-months; the antibiotic usage, hospitalization rate for infection, and deaths from infection remained stable.

CONCLUSION:

To our knowledge, this is the first ISP to lead to a dramatic decrease in IVIG usage with high adherence, primarily by selecting out patients at low risk of infection after IVIG discontinuation. Such an ISP is replicable and warrants adoption.
Quantitative and Functional Analysis of PD-1+ NK Cells in Patients With Autoimmune Thyroid Disease
Authors: Ortega-Rodríguez Alma Cesleste , Martínez-Hernández Rebeca , Monsiváis-Urenda Adriana , Serrano-Somavilla Ana , Sánchez-Gutiérrez Raquel , González-Amaro Roberto , Marazuela Mónica
Published: August 2020

Context

Natural killer (NK) cells have an important role in innate immunity and in the regulation of immune response. The role of NK cells expressing the programmed cell death protein-1 (PD-1) regulatory receptor has not been explored in patients with autoimmune thyroid disease (AITD).

Purpose

To analyze the levels and function of PD-1+ NK cells in samples from AITD patients.

Design

Cases and controls, observational study.

Setting

Hospital Universitario la Princesa, Spain.

Patients

Forty patients with AITD, 16 with Hashimoto thyroiditis (HT), 24 with Graves’ disease (GD), and 15 healthy controls.

Intervention

Multiparametric flow cytometry analysis of peripheral blood NK cells. In vitro assays of cytotoxic activity of NK cells, and synthesis of cytokines.

Main outcome measures

Levels and function of PD-1+ NK cells in blood samples from AITD patients and controls.

Results

Increased levels of NK cells and the CD56dimPD-1+ subset were observed in GD patients. In HT, an enhanced expression of the regulatory receptors NKG2A and NKG2C by CD56brightPD-1+ NK cells was detected. AITD patients showed an increased synthesis of IL-10 by CD56brightPD-1– NK cells, whereas CD56dimPD-1+ cells from GD patients exhibited an enhanced production of interferon-γ. PD-1+ NK cells from patients with GD and HT showed an increased cytotoxic activity. Significant associations were observed in patients with GD or HT between the levels of PD-1+ NK cells and clinical laboratory parameters.

Conclusions

The different abnormalities in NK cell subset levels, in the expression of PD-1 and its function in AITD patients’ further support the complex role of these cells in this pathogenesis.
Whole-Body Vibration Stimulates Microvascular Blood Flow in Skeletal Muscle
Authors: BETIK ANDREW C. , PARKER LEWAN , KAUR GUNVEEN , WADLEY GLENN D. , KESKE MICHELLE A.
Published: August 2020

Purpose

Whole-body vibration (WBV) therapy has been reported to potentially act as an exercise mimetic by improving muscle function and exercise capacity in a variety of healthy and clinical populations. Considering the important role that microvascular blood flow plays in muscle metabolism and exercise capacity, we investigated the muscle microvascular responses of acute WBV to knee extension exercise (KEX) in healthy individuals.

Methods

Eleven healthy adults (age: 33 ± 2 yr; body mass index: 23.6 ± 1.1 kg·m−2) underwent 3 min of WBV, or 3 min of KEX at 25% of one-repetition maximum, in a randomized order separated by a minimum of 72 h. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh muscle microvascular blood flow was measured via contrast-enhanced ultrasound at baseline and throughout the 3-min postintervention recovery period.

Results

Both WBV and KEX significantly increased peak microvascular blood flow (WBV, 5.6-fold; KEX, 21-fold; both P < 0.05) during the 3-min recovery period. Despite a similar increase in femoral arterial blood flow (~4-fold; both P < 0.05 vs baseline) and whole-body oxygen consumption measured by indirect calorimetry (WBV, 48%; KEX, 60%; both P < 0.05 vs baseline) in both conditions, microvascular blood flow was stimulated to a greater extent after KEX.

Conclusion

A single 3-min session of WBV in healthy individuals is sufficient to significantly enhance muscle microvascular blood flow. Despite KEX providing a more potent stimulus, WBV may be an effective method for improving microvascular blood flow in populations reported to exhibit microvascular dysfunction such as patients with type 2 diabetes.
Interaction of Exercise Intensity and Simulated Burn Injury Size on Thermoregulation
Authors: BELVAL LUKE N. , CRAMER MATTHEW N. , MORALEZ GILBERT , HUANG MU , CIMINO FRANK A. , WATSO JOSEPH C. , CRANDALL CRAIG G.
Published: August 2020

The U.S. Department of Defense’s Medical Standards for Appointment, Enlistment, or Induction into the Military Services excludes personnel with burn injuries covering 18% or more of their body surface area (BSA). However, this requirement does not consider the metabolic heat loads associated with physical activities of different intensities that may influence a burn survivor’s ability to perform his/her duties.

Purpose

This study aimed to test the hypothesis that the elevation in internal body temperature during exercise in a hot environment is influenced by the combination of exercise intensity and BSA burned.

Methods

Ten healthy participants (8 males, 2 females; 32 ± 9 yr; 75.3 ± 11.7 kg) completed eight exercise trials on a cycle ergometer, each with different combinations of metabolic heat productions (low, 4 W·kg−1; moderate, 6 W·kg−1) and simulated BSA burn in a hot environmental chamber (39.9°C ± 0.3°C, 20.1% ± 1.5% RH). Burns were simulated by covering 0%, 20%, 40%, or 60% of participants’ BSA with a highly absorbent, vapor-impermeable material. Gastrointestinal temperature (T
GI) was recorded, with the primary analysis being the increase in T
GI after 60 min of exercise.

Results

We identified an interaction effect for the increase in T
GI (P < 0.01), suggesting T
GI was influenced by both intensity and simulated burn BSA. Regardless of the percentage BSA burn simulated, the increase in T
GI was similar across low-intensity trials (0.70°C ± 0.26°C, P > 0.11 for all). However, during moderate-intensity exercise, the increase in T
GI was greater for the 60% (1.78°C ± 0.38°C, P < 0.01) and 40% BSA coverage trials (1.33°C ± 0.44°C, P = 0.04), relative to 0% (0.82°C ± 0.36°C). There were no differences in T
GI responses between 0% and 20% trials.

Conclusion

These data suggest that exercise intensity influences the relationship between burn injury size and thermoregulatory responses in a hot environment.
Sharp recanalization of peripheral arterial chronic total occlusions
Authors: Kim Kyungmin , Moore Christian , Alfahad Aws
Published: August 2020

Peripheral arterial chronic total occlusions (CTOs) usually have calcified caps at either ends. When attempting endovascular recanalization, these calcified CTO caps may prevent the interventionist in crossing the lesion with conventional catheter and guidewire techniques. Using specialized CTO devices or re-entry devices can help crossing the CTO, but such devices are usually expensive, not always readily available and require specialist training prior to usage.

“Sharp recanalization” is an alternative method of crossing the CTOs. If it is not possible to cross the CTO with conventional catheter and guidewire technique, one can take out the floppy end of the guidewire and use the stiff or the “sharp” end of the guidewire to break the hard CTO cap. Once the CTO cap is broken, the stiff end is replaced by the floppy end of the guidewire again to proceed with balloon angioplasty and/or stenting.

In order to safely use the sharp recanalization technique while minimizing the risk of perforation, sharp recanalization should only be attempted once conventional methods have failed. The interventionist should plan sharp recanalization with the vascular path in mind and decide in advance how far s/he will proceed. It can be helpful to set a time limit together with the intervention team, past which the sharp recanalization attempt will be abandoned. Using straight catheters can help directing the stiff guidewire tip to the center of the vascular lumen and reduce the risk of sub intimal dissection or arterial wall perforation.
Radiomic signatures derived from multiparametric MRI for the pretreatment prediction of response to neoadjuvant chemotherapy in breast cancer
Authors: Bian Tiantian , Wu Zengjie , Lin Qing , Wang Haibo , Ge Yaqiong , Duan Shaofeng , Fu Guangming , Cui Chunxiao , Su Xiaohui
Published: August 2020

Objectives:

To investigate the ability of radiomic signatures based on MRI to evaluate the response and efficiency of neoadjuvant chemotherapy (NAC) for treating breast cancers.

Methods:

152 patients were included in this study at our institution between March 2017 and September 2019. All patients with breast cancer underwent a preoperative breast MRI and the Miller–Payne grading system was applied to evaluate response to NAC. Quantitative parameters were compared between patients with sensitive and insensitive responses to NAC and between those with pathological complete responses (pCR) and non-pCR. Four radiomic signatures were built based on T2W imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging and their combination, and radiomics scores (Rad-score) were calculated. The combination of the clinical factors and Rad-scores created a nomogram model. Multivariate logistic regression was performed to assess the association between MRI features and independent clinical risk factors.

Results:

20 features and 18 features were selected to build the radiomic signature for evaluating sensitivity and the possibility of pCR, respectively. The combined radiomic signature and nomogram model showed a similar discrimination in the training (AUC 0.91, 0.92, 95% confidence interval [CI], 0.85–0.96, 0.86–0.98) and validation (AUC 0.93, 0.91, 95% CI, 0.86–1.00, 0.82–1.00) sets. The clinical factor model exhibited reduced performance (AUC 0.74, 0.64, 95% CI, 0.64–0.84, 0.46–0.82) in terms of NAC sensitivity and pCR.

Conclusions:

The combined radiomic signature and nomogram model exhibited potential predictive power for predicting effective NAC treatment which can aid in the prognosis and guidance of treatment regimens.

Advances in knowledge:

Identifying a means of assessing the efficacy of NAC before surgery can guide follow-up treatment and avoid chemotherapy-induced toxicity.
Patient-based low dose cone beam CT acquisition settings for prostate image-guided radiotherapy treatments on a Varian TrueBeam linear accelerator
Authors: Piliero Maria Antonietta , Casiraghi Margherita , Bosetti Davide Giovanni , Cima Simona , Deantonio Letizia , Leva Stefano , Martucci Francesco , Tettamanti Marino , Pupillo Francesco , Bellesi Luca , Richetti Antonella , Presilla Stefano
Published: August 2020

Objective:

To evaluate the performance of low dose cone beam CT (CBCT) acquisition protocols for image-guided radiotherapy of prostate cancer.

Methods:

CBCT images of patients undergoing prostate cancer radiotherapy were acquired with the settings currently used in our department and two low dose settings at 50% and 63% lower exposure. Four experienced radiation oncologists and two radiation therapy technologists graded the images on five image quality characteristics. The scores were analysed through Visual Grading Regression, using the acquisition settings and the patient size as covariates.

Results:

The low dose acquisition settings have no impact on the image quality for patients with body profile length at hip level below 100 cm.

Conclusions:

A reduction of about 60% of the dose is feasible for patients with size below 100 cm. The visibility of low contrast features can be compromised if using the low dose acquisition settings for patients with hip size above 100 cm.

Advances in knowledge:

Low dose CBCT acquisition protocols for the pelvis, based on subjective evaluation of patient images.
Validation of self-reported physical activity by accelerometry among primary school children in Kilimanjaro, Tanzania: a pilot study
Authors: Mosha Mary Vincent , Kasagama Elizabeth , Ayieko Philip , Todd Jim , Msuya Sia E. , Grosskurth Heiner , Filteau Suzanne
Published: August 2020

Background: Self-reports are commonly used to assess physical activity in children.  Existing self-reports for physical activity have not been validated for use among primary school children in Kilimanjaro, Tanzania. In order to understand if primary school children can accurately report their physical activity, we examined the validity of self-reported physical activity against accelerometer measured physical activity.

Methods: A community based cross-sectional study was conducted from May to July, 2018 among four primary schools in Moshi municipal and Moshi rural districts, Kilimanjaro, Tanzania.  A total of 51 primary school children aged 9–11 years were enrolled using a simple random sampling technique. A self-reported questionnaire was used to collect physical activity related variables. In addition, children wore accelerometers for seven consecutive days to capture physical activity movements. Spearman’s rank test and Bland Altman plots were used for assessing validity and agreement between self-reports and accelerometer moderate to vigorous physical activity (MVPA).

Results: The mean age of the study participants was 10 (SD=0.8) years. Majority of the study participants were female 32 (63%). A moderate, positive correlation was found between self-reports and accelerometer MVPA (rho=0.36, p=0.009). Accelerometer had higher MVPA compared to self-reports. Children who reported walking to school had higher MVPA for both accelerometer and self- reports compared to children who use other means of transport to school, e.g. school buses (p < 0.001).

Conclusions: This study found the moderate positive correlation between self-reports and accelerometers. Self-reports are prone to errors due to recall bias, and this interferes their validity.  More research is needed to develop better self-reported measures with specific activities which can easily be recalled by children. Also, researchers have to be aware of self-reports validity limitation.
Protocol for a controlled, randomized, blind, clinical trial to assess the effects of transcranial direct current stimulation associated with balance training using games in the postural balance of elderly people
Authors: Kunitake Andre Issao , Corrêa João Carlos Ferrari , Nascimento Klaine Silva , Oliveira Bianca Barioni Cardoso de , Muniz Natalia Maciel , Silva Soraia Micaela , Corrêa Fernanda Ishida
Published: August 2020

Aims: This study aims to evaluate the additional effect of transcranial direct current stimulation (tDCS) on training postural balance with the use of video games in aged.

Methods: This is a blinded, randomized, controlled clinical trial protocol, with elderly people of both genders. Participants will be randomized into three training groups: Group 1 (videogame balance training), group 2 (videogame balance training associated with active tDCS), group 3 (videogame balance training associated with sham tDCS). The training will be carried out twice a week for four weeks, totaling eight sessions, and will be performed with the Nintendo Wii videogame console, using games that stimulate the postural balance associated with tDCS, with anode applied over the left dorsolateral prefrontal cortex and cathode on the contralateral supraorbital region at 2 mA for 20 minutes. The postural balance will be assessed using the Mini Test of the Balance Assessment System and posturography. Evaluations will be carried out before and after eight training sessions and 30 days after the end of treatment.

Discussion: Some studies show favorable results from the use of video games in improving postural balance in the elderly; however, their effect does not remain long-term. TDCS associated with other therapies can potentiate and prolong the effects of these therapies owing to its ability to stimulate neurotrophins important for neurogenesis, facilitating tasks that require attention, and helping to consolidate learning and memory. The effect of the two associated techniques on balance have not yet been tested in this population.

Registration: Brazilian Registry of Clinical Trials ID U1111-1213-4266; registered on 15 October, 2018.