bluuebunny/crossref_metadata_2025 huggingface dataset:
Potentials of truffles in nutritional and medicinal applications: a review
Authors: Lee Heayyean , Nam Kyungmin , Zahra Zahra , Farooqi Muhammad Qudrat Ullah
Published: June 2020

Truffles, the symbiotic hypogeous edible fungi, have been worldwide regarded as a great delicacy because of their unique flavor and high nutritional value. By identifying their bioactive components such as phenolics, terpenoids, polysaccharides, anandamide, fatty acids, and ergosterols, researchers have paid attention to their biological activities including antitumor, antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. In addition, numerous factors have been investigating that can affect the quality and productivity of truffles to overcome their difficulty in culturing and preserving. To provide the information for their potential applications in medicine as well as in functional food, this review summarizes the relevant literature about the biochemical composition, aromatic and nutritional benefits, and biological properties of truffles. Besides, various factors affecting their productivity and quality as well as the preservation methods are also highlighted.
Resection of pancreatic and splenic metastases from alveolar soft part sarcoma: a case report
Authors: Arakawa Satoshi , Asano Yukio , Kawabe Norihiko , Nagata Hidetoshi , Kondo Yuka , Furuta Shinpei , Shimura Masahiro , Hayashi Chihiro , Ochi Takayuki , Kamio Kenshiro , Kawai Toki , Yasuoka Hironobu , Higashiguchi Takahiko , Ishihara Shin , Ito Masahiro , Imaeda Yoshihiro , Horiguchi Akihiko
Published: June 2020

Background

We present a case of pancreatic and splenic metastases following alveolar soft part sarcoma (ASPS), which was successfully treated by surgery.

Case presentation

A 41-year-old male was referred to our hospital in 2012. Computed tomography (CT) showed the presence of a pancreatic tumor. In 2002, the patient had undergone surgical resection of an ASPS of the anal region. In 2009, during follow-up, CT revealed lung metastases, which prompted surgical resection of the lung, followed by resection of the head skin in 2011. Abdominal ultrasonography (US) revealed the presence of isodense masses sized 34 mm in the pancreatic head and 60 mm within the spleen. The contrast-enhanced US revealed a solitary lesion with enhancement. Contrast-enhanced CT revealed solitary lesions with enhancement within the pancreatic head, spleen, and liver. The patient underwent metastasectomies from the pancreas, spleen, and liver. The patient was discharged on postoperative day 22 without recurrence for 18 months after metastasectomy. Twelve years after primary resection and 2 years after metastasectomy, the patient died as a consequence of multiple metastases.

Conclusions

We have presented a rare case of pancreatic and spleen metastases from ASPS. Resection by radical metastasectomy was successful without morbidity. Thus, for improved survival of patients with multiple metastases from ASPS, metastasectomy may be indicated. If multiple metastases are resectable, surgical approaches may be the preferred treatment.
Reducing instruments in a vitrectomy surgical tray: cost savings and results from a major academic hospital
Authors: Grodsky Jacob D. , Theophanous Christos N. , Schechet Sidney A. , Veldman Peter B. , Hariprasad Seenu M.
Published: June 2020

Background

Unused or rarely used instruments in standard surgical trays can unnecessarily increase costs. Prior studies have demonstrated the practicality and cost savings of reduced instrument tray sizes in various subspecialties. This study describes results and estimated cost savings from a reduced instrument tray used for vitrectomy surgery at a large, tertiary academic medical center.

Methods

Common usage patterns of vitrectomy instruments by one retina surgeon were reviewed and a reduced instrument vitrectomy tray was created and implemented in successive vitrectomy surgeries. Need for opening the previously utilized larger tray was recorded. Estimated cost savings of the new trays were calculated based upon per instrument sterilization, processing, and instrument replacement costs.

Results

New vitrectomy trays including just 7 instruments (89% reduction compared to original trays) were created and implemented in 189 successive cases. The original tray was never opened. Estimated cost savings from saved sterilization and processing resources is approximately $9588 per year. Assuming 5- and 10-year lifespan per instrument, annual cost avoidance is projected at $7886 and $15,772, respectively. Other indirect benefits relevant to healthcare quality were also noted.

Conclusion

A reduced instrument tray can be successfully implemented for vitrectomy surgery and can result in significant indirect benefits as well as direct cost savings from reduced sterilization costs. Our study highlights the substantial impact made by evaluating the usage pattern and making appropriate instrument tray changes for just one retina surgeon. Applying these same methods to other surgeons and specialties can have significant implications on healthcare costs and quality.
A retrospective descriptive study of cranioplasty failure rates and contributing factors in novel 3D printed calcium phosphate implants compared to traditional materials
Authors: Koller Michael , Rafter Daniel , Shok Gillian , Murphy Sean , Kiaei Sheena , Samadani Uzma
Published: June 2020

Background

Failure rates with cranioplasty procedures have driven efforts to improve graft material and reduce reoperation. One promising allograft source is a 3D-printed titanium mesh with calcium phosphate filler. This study evaluated failure rates and pertinent characteristics of these novel 3D-grafts compared to traditional materials.

Methods

Sixty patients were retrospectively identified who underwent a cranioplasty between January 2015–December 2017. Specific data points related to graft failure were collected for all surgical admissions, from the primary injury to their most recent. These included, but were not limited to, initial physical exam findings, vitals, comorbid conditions, surgery length, estimated blood loss, incision type, and need for revision. Failure rates of 3D-printed allografts were compared to traditional grafts.

Results

A total of 60 subjects were identified who underwent 71 unique cranioplasty procedures (3D = 13, Synthetic = 12, Autologous = 46). There were 14 total failures, demonstrating a 19.7% overall failure rate. Specifically, 15.4% (n = 2) of 3D, 19.6% (n = 9) of autologous, and 25.0% (n = 3) of synthetic grafts required revision. Patients receiving 3D-grafts had the shortest overall mean surgery times (200.8 ± 54.3 min) and lowest infection rates (7.7%) compared to autologous (210.5 ± 47.9 min | 25.0%) and synthetic models (217.6 ± 77.3 min | 8.7%), though significance was unable to be determined. Tobacco use and trap-door incisions were associated with increased failure rates relative to straight or curved incisions in autologous grafts. Cranioplasties performed less than 3 months after craniectomy appeared to fail more often than those performed at least three months after craniectomy, for the synthetic group.

Conclusion

We concluded that 3D-printed cranioplasty grafts may lead to lower failure rates and shorter surgery times compared to traditional cranioplasty materials in our limited population. 3D-implants hold promise for cranial reconstruction after TBI.
Intraventricular neurocysticercosis presenting as Bruns’ syndrome: An uncommon presentation
Authors: Arshad Faheem , Rao Shilpa , Kenchaiah Raghavendra , Prasad Chandrajit , Shashidhar Abhinith
Published: June 2020

Background

Though parenchymal neurocysticercosis is common and a major contributor to burden of seizures in most parts of the world, intraventricular neurocysticercosis (IVNCC) comprises 10–20% of cases and poses a diagnostic challenge to the clinician.

Case presentation

We report an adult female presenting with intermittent occipital headache, used to be worse in lying down position, and aggravated with head movements, and there was mild relief in the sitting position. Her physical examination was unremarkable, and laboratory tests were within normal limits. Her multimodal neuroimaging showed cystic lesion in the fourth ventricle suggestive of neurocysticercosis. Patient underwent neuroendoscopic removal of the cyst, and the final diagnosis was confirmed on histopathology. Post removal of cyst patient had complete resolution of her symptoms.

Discussion

Intraventricular neurocysticercosis can present as acute hydrocephalus which may clinically manifest as Bruns’ syndrome in which sudden attacks of headache vertigo and nausea or vomiting are precipitated by abrupt head movements which was observed in our patient. Multimodal neuroimaging supported by histopathology helped in confirmation of the diagnosis, thus averting an inadvertent use of unnecessary medications in such patients. Furthermore, neuroendoscopy has evolved as minimally invasive technique for extirpation of fourth ventricular cysts.
Risk factors for early and late recurrent ischemic strokes
Authors: Elnady Hassan Mohammed , Mohammed Gharib Fawi , Elhewag Hazem Kamal , Mohamed Mohamed Khodery , Borai Ahmed
Published: June 2020

Background

Nationally, information regarding risk factors for early and late recurrence of ischemic stroke is limited.

Objectives

The aim of this study was to identify the risk factors for early and late recurrent ischemic stroke.

Patients and methods

We prospectively compared data from 58 patients with early (within 1 year after the index stroke) recurrent ischemic stroke with 64 patients with late (1 year or more after the index stroke) recurrent ischemic stroke. Patients in the study were admitted to the Department of Neurology and Psychological Medicine, Sohag University Hospital, in the period between April 2017 and August 2017. The etiology of recurrent stroke was determined according to the TOAST classification. The presence of vascular risk factors was registered and compared in both groups.

Results

Systolic blood pressure was significantly higher among those with late recurrence compared to those with early recurrence (p = 0.026). Patients with early recurrent ischemic stroke were more likely to be aphasic (p = 0.047). Regarding the TOAST classification, small vessel disease and undetermined etiology were significantly higher among patients with late recurrence, while cardioembolism and large artery atherosclerosis were significantly higher among those with early recurrence (p = 0.008).

Conclusion

Patients with large artery atherosclerosis and cardioembolism are at increased risk of early recurrence and warrant special efforts for secondary prevention.
New stroke prognostic factors
Authors: Elsheikh Wafeek M. , Alahmar Ibrahim E. , Salem Gelan Mahmoud , Matar Eman S.
Published: June 2020

Background

Understanding ischemic stroke pathogenesis helps in prevention, prognosis, and treatment. Stroke is greatly related to inflammation and thrombo-genesis as inflammatory cells (as neutrophils-lymphocytes) and thrombo-genic agents as von Willebrand factor antigen (VWF: Ag) and epicardial fat.

Objectives of the study

Evaluation of epicardial fat thickness (EFT), neutrophil/lymphocytic ratio (NLR), and (VWF: Ag) levels as predisposing and prognostic factors of ischemic stroke.

Patients and methods

Sixty acute ischemic stroke patients were subjected to clinical assessment (Oxford stroke sheet), National Institute Health Stroke Scale: NIHSS), Modified Rankin Scale (MRS), NLR and VWF: Ag levels, transthoracic echo, duplex on carotid and vertebro-basilar arteries, and brain computed tomography (CT). Thirty-five healthy controls matched for age and sex were subjected to the same steps except NIHSS and MRS.

Results

EFT, NLR, and VWF among patients were significantly higher than control group. NLR ≥ 2 and VWF: Ag were significant risk factors among stroke patients with VWF: Ag had the higher risk than NLR ≥ 2. NLR was a high valid prognostic marker in predicting stroke outcome (MRS) with (optimal cutoff value 2.05) for prediction of primary unfavorable outcome. There was no statistical significance between (MRS) and EFT or VWF: Ag level.

Conclusion

EFT represents inexpensive and readily available clinical marker that may be useful in estimating risk of ischemic stroke. NLR is non-expensive easy marker for predicting stroke severity and primary unfavorable outcome. High VWF level increases ischemic stroke risk.
Zinc-oxide and nano ZnO oxide effects on growth, some biochemical aspects, yield quantity, and quality of flax (Linum uitatissimum L.) in absence and presence of compost under sandy soil
Authors: Sadak Mervat Shamoon , Bakry Bakry Ahmed
Published: June 2020

Background

Nanofertilizers have been provided a new efficient alternative to normal regular fertilizers. Nano-particles can help in increasing reactive points of these nanoparticles, which increases the absorption of these fertilizers in plants.

Materials and methods

Thus, a field experiment was conducted in sandy soil during two winter seasons of 2016/2017 and 2017/2018 at experimental station of National conditions, El-Behira Governorate-Egypt. The objective of this study was the effect of ZnO as normal chelated micronutrient and ZnO as nanoparticle foliar application at rates of 0, 20, 40, and 60 mg/L, with two rates of compost (0.0 and 3.00 ton/fed) on growth parameters, photosynthetic pigments, yield, and chemical analysis of flax (Linum usitatissimum L cv., Sakha-2) plants.

Results

The obtained results showed that adding of compost to the sandy soil by 3.0 ton/fed, increased markedly growth parameters (shoot and root length (cm), fresh and dry weights (g), photosynthetic pigments (chlorophyll a, chlorophyll b, carotenoids, and total pigments (μg/g fresh wt)), free amino acids and proline (mg/100 g dry wt), total carbohydrate percentage, yield quantity and quality (technical shoot, fruiting zone lengths and plant height (cm), No. of fruiting branches/plant and No. of capsules/plant, weight of straw (g), weight of 1000 seeds (g), biological yield (kg/fed), seed yield (kg/fed), and straw yield (kg/fed)), oil percentage, and oil yield (kg/fed) compared to control treatments (without compost). Also, the obtained data clarified that applied foliar treatment with normal ZnO with rates 40 mg/L significantly increased the yield and all parameters of flax plant during studied growing seasons. The interaction between compost addition and different concentrations of either ZnO or nano ZnO revealed that different concentrations increased different studied parameters without or with the addition of compost to sandy soil as compared with untreated plants.

Conclusion

Treatment of flax plant with ZnO and nano ZnO improved the studied growth parameters, biochemical aspects, and consequent yield in the absence and presence of compost.
Clinical and neurophysiological correlation in axonal and demyelinating polyneuropathy
Authors: Hewedi Kamel Mahmoud Ali , Monzer Mahmoud Abdelmoety , Sobh Khaled Mohammad , Aboelmakarem Mohammad Abdelhady M. , Mohammady Amir Abdelghaffar , Hasan Mahmoud Mohamad , Abdulsalam Mohammad Fathi , Helal Suzette Ibrahim Ibrahim Ibrahim
Published: June 2020

Background

The neurophysiological examination provides valuable pathophysiological information for the diagnosis, prognosis, and therapy of patients with polyneuropathy (Fuglsang- Fredriksen A., Pugdahl K. Clin Neurophysilogy 122:440–455, 2011). Nerve conduction study (NCS) is the most objective and reliable measure of peripheral nerve function and is considered the gold standard for the diagnosis of most neuropathies.

Aim of the study

To evaluate the clinical usefulness of nerve conduction study (NCS) in the differentiation between axonal and demyelinating polyneuropathies.

Methods

In the present study, 125 patients with polyneuropathy were studied ranging age from 9 to 79 years. Thirty-six patients were classified as axonal polyneuropathy, 23 patients as demyelinating, and 9 as mixed, while 57 patients were classified as neuropathic. Nerve conduction study (NCS) and electromyography (EMG) were performed using Nihon Kochden electromyography machine with surface recording and stimulating electrodes.

Results

There is statistically significant linear correlation between reduction in sensory nerve action potential (SNAP) amplitude and decrease in sensory conduction velocity (SCV) of median and ulnar nerves. Also, there is statistically significant inverse correlation between reduction in compound motor action potential (CMAP) amplitude and increase in distal motor latency (DML). There is statistically significant linear correlation between reduction in compound motor action potential (CMAP) amplitude and decrease in motor conduction velocity (MCV). There is statistically significant linear correlation between reduction in compound motor action potential (CMAP) amplitude and decreased grade of power in both axonal and demyelinating polyneuropathy; statistically significant linear correlation was found between decrease in conduction velocity and decrease in grade of power.

Conclusion

The present study demonstrates significant correlation between amplitude reduction and conduction slowing in demyelinating as well as axonal polyneuropathy.
Effect of garlic extract, ascorbic acid and nicotinamide on growth, some biochemical aspects, yield and its components of three faba bean (Vicia faba L.) cultivars under sandy soil conditions
Authors: Mohamed Magda H. , Badr Elham A. , Sadak Mervat Sh. , Khedr Howida H.
Published: June 2020

Background

Garlic extract is a highly nutritive value extract; it contains large number of important enzymes and more than 200 biochemical compounds such as antioxidants and vitamins. Ascorbic acid and nicotinamide are considered as antioxidants and also known as growth-regulating compounds that influence different physiological and biochemical processes in plants.

Methodology

A field experiment was conducted in sandy soil during two successive seasons of 2015/2016 and 2016/2017 at Research and Production Station, National Research Centre, El-Nubaria Province, El-Behera Governorate, Egypt. The objective of this investigation was to study the effect of foliar application of garlic extract (5%), ascorbic acid (200 ppm) and nicotinamide (50 ppm) compared with tap water on growth, some biochemical aspects, yield, yield components and some chemical components of three faba bean cultivars (Vicia fabaL, cv., Nubaria-1, Nubaria-2 and Giza-843).

Results

The obtained results showed that Nubaria-1 was superior to Nubaria-2 and Giza-843 in all growth and yield criteria in the growing seasons except plant height was superior in Nubaria-2. Foliar treatment of garlic extract had the superiority effect in all characters of growth and yield and its components, and consequently increased significantly all yield criteria of Nubaria-1 cultivar. Data clearly showed that the effect of different treatments caused marked increases in photosynthetic pigments, indole acetic acid, phenolics, carbohydrate constituents, free amino acids and proline contents of Nubaria 1 cultivar which was sprayed by garlic extract at 5% followed by nicotinamide and ascorbic acid, respectively.

Conclusions

In general, the current research suggested that garlic extract at 5% as a foliar application increased the quantity of faba bean cultivars grown under sandy soil conditions. Therefore, garlic extract at the rate of 5% and Nubaria1 encourage the farmers to use of garlic extract to give promising seed yield under reclaimed sandy soil.
Clinical and genetic relationships between the QTc interval and risk of a stroke among atrial fibrillation patients undergoing catheter ablation
Authors: Hong Myunghee , Chun Kyeong-Hyeon , Hwang Inseok , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: June 2020

Background and objectives

A prolonged QTc interval is associated with an increased risk of a stroke or atrial fibrillation (AF). However, its direct causal relationship with AF associated a stroke has not been proven yet. To examine whether QTc interval is causally linked with risk of stroke in AF patients, we used the Mendelian randomization analysis.

Subjects and methods

Among 2742 patients (73.6% male; 58.2 ± 11.0 years old; 69.5% with paroxysmal AF) who underwent AF catheter ablation, we analyzed 1766 patients who had preablation sinus rhythm electrocardiograms off antiarrhythmic drugs after excluding amiodarone users. Among them, 1213 subjects had genome-wide association study dataset analyzable for the Mendelian randomization. We explored the mechanistic relationships between QTc interval (ms) and the risk of a stroke by analyzing the Mendelian randomization (1213 subjects) after reviewing 35 genetic polymorphisms associated with the QTc in 31 European descent studies.

Results

Among the patients in the higher quartile with a higher QTc, CHA2DS2-VASc score (p < 0.001), and age (p < 0.001), the proportions of a prior stroke (p < 0.001), females, heart failure, and persistent AF were significantly higher than in those in the lower quartile. The QTc was independently associated with the CHA2DS2-VASc score (β, 4.63E−5; 95% confidence interval, 3.57E−6–8.90E−5; p = 0.034) and ischemic strokes (odds ratio, 1.01; 95% confidence interval, 1.00–1.01; p = 0.027). However, there was no direct causal relationship between the QTc and CHA2DS2-VASc score or a prior stroke in either the one-sample or two-sample Mendelian randomizations.

Conclusion

The QTc was independently associated with the CHA2DS2-VASc score and strokes among the patients with AF who underwent catheter ablation, despite no genetically direct causal relationship.
Pulmonary ct manifestations of COVID-19: changes within 2 weeks duration from presentation
Authors: Sultan Omar Muayad , Al-Tameemi Haider , Alghazali Dhia Mahdey , Abed Mohammed , Ghniem Muthana Naser Abu , Hawiji Dhaffer Abdullah , Alwateefee Enas Abdulhussain , Shubbar Hayder Dhajir Abbas , Tauah Amal Hussein , Ibraheem Nisreen Mohammed , Abdulwahab Ahmed D. , Abedtwfeq Raad Hefdhi
Published: June 2020

Background

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chest computed tomography (CT) plays an essential role in the evaluation of COVID-19. This retrospective study aims to determine and compare the pulmonary changes in Iraqi patients with COVID-19 disease across the first two weeks after onset of symptoms using computerized tomography (CT) scan.

Ninety-six patients with COVID-19 disease were enrolled in this study. Patients were divided into two groups according to the duration of symptoms (the first group has been scanned within the first week of presentation while the second group has been scanned in the second week).

Results

The CT findings in the first and second group were as follows: ground glass opacity (GGO) were 94.3% vs. 88.5%, consolidation were 25.7% vs. 34.6%, broncho vascular thickening were 18.6% vs. 7.7%, crazy paving appearance were 15.7% vs. 3.8%, tree-in-bud appearance were 4.3% vs. 10.7%, pulmonary nodules were 5.1% vs. 7.7%, and bronchiectasis were 5.5% vs. 7.7%. Pleural effusion and cavitation were seen only in the first group (2.9% and 1.4% respectively).

The distribution of CT changes across the two groups were as follows: bilateral changes were 85.7% vs. 100%; central distribution were 11.4% vs. 11.5%; peripheral distribution were 64.3% vs. 42.3%, and diffuse (central and peripheral) distribution were 24.3% vs. 46.2% while multilobar distribution were 70% vs. 80.8%.

Conclusion

The type, extent, and distributions of pulmonary manifestations associated with COVID-19 infection are significantly different between the two groups who have been scanned in different stages of the disease.
Growth spillover: a spatial dynamic panel data and spatial cross section data approaches in selected Asian countries
Authors: Amidi Sahar , Fagheh Majidi Ali , Javaheri Bakhtiar
Published: June 2020

One of the most fundamental issues worldwide is the economic interdependence of countries which affects their economic growth. Some new growth theorists such as Mankiw et al., Islam, Ertur and Koch, Lee, Yu and Yu Ho et al. consider geographical proximity and trade as spatial variables. This study aims to investigate the spatial effects of geographical distance on economic growth using the spatial dynamic panel data model and the spatial cross section data model for the period 1992–2016 in selected Asian countries. The findings demonstrate that the effect of spatial spillover or spatial dependency is one of the main causes of economic growth spillovers. In the spatial dynamic panel data model, log of gross domestic product (GDP), gross fixed capital formation and growth rate of labor force had negative, positive and negative impacts on economic growth, respectively. In the spatial cross-sectional data models including human capital, log of GDP, gross fixed capital formation and growth rate of labor force had negative impacts on economic growth, while in a model without human capital log of GDP, gross fixed capital formation and growth rate of labor force, respectively, had positive and negative effects on economic growth.
Perspective of Oncology Patients During COVID-19 Pandemic: A Prospective Observational Study From India
Authors: Ghosh Joydeep , Ganguly Sandip , Mondal Debapriya , Pandey Prashant , Dabkara Deepak , Biswas Bivas
Published: June 2020

PURPOSE

The coronavirus disease 2019 (COVID-19) pandemic has imposed a unique challenge to oncology patients and their treatment. There is no study related to the patients’ preference for systemic therapy during this pandemic. We have conducted a prospective study to analyze that aspect.

METHODS

All consecutive patients who visited during the lockdown period from April 1-10, 2020, for systemic chemotherapy were included in the study for a questionnaire-based survey to evaluate the willingness to continue chemotherapy during this pandemic and factors influencing the decisions.

RESULTS

A total of 302 patients were included (median age, 56 years; range, 21-77 years). Most common sites of cancer were breast (n = 114), lung (n = 44), ovary (n = 34), and colon (n = 20). Home address was within the city for 125 patients (42%), outside the city for 138 (46%), and outside the state for 37 (12%). Treatment was curative in 150 patients and palliative in 152. Educational status was primary and above for 231 patients and no formal schooling for 71. A total of 203 patients wanted to continue chemotherapy, 40 wanted to defer, and 56 wanted the physician to decide. Knowledge about COVID-19 strongly correlated with intent of treatment ( P = .01), disease status ( P = .02), knowledge about immunosuppression ( P < .001), home location ( P = .02), and education status ( P = .003). The worry about catching SARS-CoV-2 was high in those with controlled disease ( P = .06) and knowledge about immunosuppression ( P = .02). Worry about disease progression was more with palliative intent ( P < .001).

CONCLUSION

This study shows that oncology patients in our country are more worried about disease progression than the SARS-CoV-2 and wish to continue chemotherapy during this pandemic. The treatment guidelines in the COVID-19 scenario should incorporate patients’ perspectives.
Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer
Authors: Vuky Jacqueline , Balar Arjun V. , Castellano Daniel , O’Donnell Peter H. , Grivas Petros , Bellmunt Joaquim , Powles Thomas , Bajorin Dean , Hahn Noah M. , Savage Mary J. , Fang Xiao , Godwin James Luke , Frenkl Tara L. , Homet Moreno Blanca , de Wit Ronald , Plimack Elizabeth R.
Published: June 2020

PURPOSE

The phase II single-arm KEYNOTE-052 study evaluated the efficacy and safety of first-line pembrolizumab for patients with locally advanced or metastatic cisplatin-ineligible urothelial carcinoma (UC).

PATIENTS AND METHODS

Three hundred seventy patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months. Positive tumor programmed death ligand 1 (PD-L1) expression was defined as combined positive score (CPS) ≥ 10. Response was assessed by independent central review every 9 weeks per RECIST v1.1. The primary end point was objective response rate (ORR).

RESULTS

At data cutoff (September 26, 2018), the minimum follow-up was 2 years since the last patient enrolled. ORR was 28.6% (95% CI, 24.1% to 33.5%); 33 patients (8.9%) and 73 patients (19.7%) achieved complete and partial response, respectively. The median duration of response was 30.1 months (95% CI, 18.1 months to not reached [NR]); responses lasted ≥ 12 and ≥ 24 months in 67% and 52% of patients, respectively. Forty patients with complete or partial response completed 2 years of study treatment, and 32 had ongoing response at completion. Median overall survival (OS) was 11.3 months (95% CI, 9.7 to 13.1 months), and 12- and 24-month OS rates were 46.9% and 31.2%, respectively. In patients with CPS ≥ 10, ORR was 47.3% (95% CI, 37.7% to 57.0%) and median OS was 18.5 months (95% CI, 12.2 to 28.5 months). In patients with lymph node–only disease, ORR was 49.0% (95% CI, 34.8% to 63.4%), and median OS was 27.0 months (12.4 months to NR). There were no new safety signals.

CONCLUSION

First-line pembrolizumab confers meaningful and durable clinical response in cisplatin-ineligible patients with advanced UC and is associated with prolonged OS, particularly with PD-L1 CPS ≥ 10 and lymph node–only disease.
Evaluation of a Virtual Learning Collaborative to Integrate Palliative Care Into Routine Oncology Practice
Authors: Kamal Arif H. , Bossley Heidi , Blum Ronald , Berman Amy J. , von Gunten Charles , Von Roenn Jamie
Published: June 2020

PURPOSE:

The integration of palliative care into usual oncology care is a best practice, but implementation can be challenging.

METHODS:

We convened a virtual learning collaborative (VLC) of oncology practices with a focus on integrating palliative care. The entire program was virtual, with teams meeting via online Webinar and conference call and accessing content via an online portal. Because of the need to pause and retool after the first 5 months, the VLC evolved into 2 phases, with feedback after the first phase informing the second. We primarily evaluated the reaction of participants and project team members after the completion of the VLC using 2 quantitative surveys (after each phase) and semistructured interviews with participants.

RESULTS:

A total of 24 oncology practices entered the VLC. Evaluation after each of 2 phases was conducted. For the first evaluation, 67% of respondents agreed a quality improvement coach was helpful to complete the program; 61% agreed a palliative care expert was helpful. The most common reasons for withdrawal involved organizational and VLC factors. Organizational factors included: time constraints, personnel changes (turnover), loss of the champion, and lack of team engagement. Twenty-two active participants and 8 former participants completed the second survey. Of those, 79% agreed the experience with the VLC was valuable, and 74% agreed the virtual delivery mode was useful. We identified 3 themes to drive future improvements related to structure, engagement, and content.

CONCLUSION:

VLCs are a potential mechanism to disseminate information and facilitate learning in oncology. Further study of program characteristics that promote acceptance of VLCs are needed.
Determinants of Bone Material Strength and Cortical Porosity in Patients with Type 2 Diabetes Mellitus
Authors: Samakkarnthai Parinya , Sfeir Jad G , Atkinson Elizabeth J , Achenbach Sara J , Wennberg Paul W , Dyck Peter J , Tweed Amanda J , Volkman Tammie L , Amin Shreyasee , Farr Joshua N , Vella Adrian , Drake Matthew T , Khosla Sundeep
Published: June 2020

Context

Reduced bone material strength index (BMSi) and increased cortical porosity (CtPo) have emerged as potentially contributing to fracture risk in type 2 diabetes mellitus (T2DM) patients.

Objective

To determine whether BMSi or CtPo are related to other diabetic complications.

Design

Cross-sectional observational study.

Setting

Subjects recruited from a random sample of southeast Minnesota residents.

Participants

A total of 171 T2DM patients (mean age, 68.8 years) and 108 age-matched nondiabetic controls (mean age, 67.3 years).

Main Measures

Bone material strength index was measured using microindentation, skin advanced glycation end-products (AGEs) measured using autofluorescence, high-resolution peripheral quantitative computed tomography at the distal radius and tibia, assessment of diabetic microvascular complications including urine microalbuminuria, retinopathy, neuropathy, and vascular disease (ankle brachial index and transcutaneous oxygen tension [TcPO2]). All analyses were adjusted for age, sex, and body mass index.

Results

Skin AGEs were negatively correlated with the BMSi in both T2DM (r = -0.30, P < 0.001) and control (r = -0.23, P = 0.020) subjects. In relating diabetic complications to CtPo, we found that T2DM patients with clinically significant peripheral vascular disease (TcPO2 ≤ 40 mm Hg) had higher (+21.0%, P = 0.031) CtPo at the distal tibia as compared to controls; in these subjects, CtPo was negatively correlated with TcPO2 at both the distal tibia (r = -0.39, P = 0.041) and radius (r = -0.41, P = 0.029).

Conclusions

Our findings demonstrate that bone material properties are related to AGE accumulation regardless of diabetes status, while CtPo in T2DM patients is linked to TcPO2, a measure of microvascular blood flow.
Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
Authors: Nüske Elisabeth , Marini Guendalina , Richter Doris , Leng Weihua , Bogdanova Aliona , Franzmann Titus M. , Pigino Gaia , Alberti Simon
Published: June 2020

Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis are still unknown. Here, we report that the essential translation initiation factor eIF2B forms filaments in starved budding yeast cells. We demonstrate that filamentation is triggered by starvation-induced acidification of the cytosol, which is caused by an influx of protons from the extracellular environment. We show that filament assembly by eIF2B is necessary for rapid and efficient downregulation of translation. Importantly, this mechanism does not require the kinase Gcn2. Furthermore, analysis of site-specific variants of eIF2B suggests that eIF2B assembly results in enzymatically inactive filaments that promote stress survival and fast recovery of cells from starvation. We propose that translation regulation through filament formation is an efficient mechanism that allows yeast cells to adapt to fluctuating environments.
Vascular Protection by Exercise in Obesity: Inflammasome-associated Mechanisms
Authors: LEE JONGHAE , HONG JUNYOUNG , UMETANI MICHIHISA , LAVOY EMILY C. , KIM JONG-HEE , PARK YOONJUNG
Published: June 2020

Purpose

The nodlike receptor family pyrin domain containing 3 (NLRP3) inflammasome is a critical player in vascular pathology as it regulates caspase-1-mediated interleukin (IL)-1β processing. Physical activity ameliorates obesity-induced inflammation and vascular dysfunction, but the mechanisms responsible for these positive changes are incompletely understood. Here, the protective effect of physical activity on the inflammasome-associated vascular dysfunction in obesity and its putative mechanisms were investigated.

Methods

Mice were fed a control low-fat diet (LFD) or a high-fat diet (HFD; 45% of calories from fat) and provided with running wheel access (LF-RUN or HF-RUN) or denied wheel access for our sedentary condition (LF-SED or HF-SED). The NLRP3 inflammasome-associated pathway, including NLRP3, caspase-1, and IL-1β, in mice aorta was examined by RT-qPCR and FLICA and DAB staining. The protein expression of zonula occluden-1 (ZO-1), ZO-2, adiponectin (APN), and adiponectin receptor 1 (AdipoR1) in aortic endothelial cells was determined by immunofluorescence double staining. Intracellular reactive oxidative stress and nitric oxide (NO) production were monitored with fluorescence probes, dihydroethidium, and diaminofluorecein.

Results

HFD increased caspase-1 and IL-1β at mRNA and protein levels in endothelial cells of the aorta, and this was attenuated by voluntary running. HFD decreased ZO-1 and ZO-2 expression and reduced APN and AdipoR1 signaling; these were restored by running. The elevated intracellular superoxide (O2
.-) production observed in HF-SED was ameliorated in HF-RUN. Finally, HF-RUN improved NO production in the aorta compared with HF-SED.

Conclusions

Our findings suggest that voluntary running ameliorates mechanisms associated with vascular dysfunction by suppressing NLRP3 inflammasome, improving NO production, and reducing oxidative stress. Such benefits of physical activity may be, at least in part, associated with APN–AdipoR1 signaling and tight junction protein expression.
Elevated Perceived Exertion in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Meta-analysis
Authors: BARHORST ELLEN E. , ANDRAE WILLIAM E. , RAYNE TESSA J. , FALVO MICHAEL J. , COOK DANE B. , LINDHEIMER JACOB B.
Published: June 2020

Purpose

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating illnesses primarily characterized by chronic symptoms of fatigue and musculoskeletal pain, respectively. Some investigators have observed an elevated sense of effort in these patient groups; however, this effect has not been substantiated via quantitative review. As such, we conducted a meta-analysis of RPE responses to aerobic exercise in ME/CFS and FM compared with healthy adults.

Methods

Case–control studies involving adults with ME/CFS or FM that measured RPE and heart rate responses to acute aerobic exercise were included. Data sources included PubMed, Scopus/Embase, CINAHL, CENTRAL, and Google Scholar. Risk of bias was assessed by evaluating each study’s description of participant characteristics, matching procedures, and administration of RPE scales. Hedges’ d effect sizes for RPE were calculated and aggregated using random-effects models, and potential moderators were explored with meta-regression analysis.

Results

Forty-one effects were extracted from 37 studies involving 1016 patients and 686 healthy controls. We observed a large (Hedges’ d = 0.85, 95% confidence interval = 0.62–1.08) effect indicating higher RPE in patients than controls. The mean effect size was significantly moderated (P < 0.001, R
2 = 0.38) by whether RPE data were analyzed at a peak or submaximal intensity (b = 0.60, z = 4.6, P < 0.001) and the type of patient group that was studied (b = 0.25, z = 2.08, P = 0.04).

Conclusions

People with ME/CFS and FM perceive aerobic exercise as more effortful than healthy adults, but the exact causes are unclear. The large magnitude of this effect merits further exploration of underlying mechanisms that could provide insight into the pathophysiology of ME/CFS and FM or the broader debate about the nature of central and/or peripheral signals that influence RPE.
Development of Concise Physical Performance Test Batteries in Young Athletes
Authors: LENTZ TREVOR A. , MAGILL JOHN , MYERS HEATHER , PIETROSIMONE LAURA S. , REINKE EMILY K. , MESSER MICHAEL , RIBOH JONATHAN C.
Published: June 2020

Purpose

This study aimed 1) to define the principal components of physical function assessed by 10 common lower extremity physical performance tests and 2) to derive a reduced-item set of physical performance tests that efficiently and accurately measures raw performance and limb symmetry on each underlying component in pediatric and adolescent athletes.

Methods

This study included healthy, uninjured volunteers (n = 100) between the ages 6 and 18 yr (mean age = 11.7 ± 3.6 yr; 52 females). Subjects performed the stork balance, stork balance on BOSU® Balance Trainer, single leg squat (SLS), SLS on BOSU, clockwise and counterclockwise quadrant single leg hop (SLH), forward SLH, timed SLH, triple crossover SLH, and lower quarter Y-Balance Test™. Item reduction was performed using principal components analysis (PCA). We developed separate principal components analysis for average raw performance and side-to-side limb symmetry, with secondary analyses to evaluate consistency of results by age and sex.

Results

We identified two components for average raw performance (accounting for 65.2% of the variance in total test battery) with a reduced-item set composed of five tests, and four components for limb symmetry (accounting for 62.9% of the variance in total test battery) with a reduced-item set of seven tests. The most parsimonious test suitable for screening both average raw performance and limb symmetry would consist of five tests (stork balance on BOSU, SLS on BOSU, forward SLH, timed SLH, and lower quarter Y-Balance Test™). Age- and sex-specific test batteries may be warranted.

Conclusion

Comprehensive screening for lower extremity average raw performance and limb symmetry is possible with short physical performance test batteries.
Validation and Cardiorespiratory Response of the 1-Min Sit-to-Stand Test in Interstitial Lung Disease
Authors: TREMBLAY LABRECQUE PIERRE-FRANÇOIS , HARVEY Jany , NADREAU ÉRIC , MALTAIS FRANÇOIS , DION GENEVIÈVE , SAEY DIDIER
Published: June 2020

Purpose

To assess the 1-min sit-to-stand test (1STS) test–retest reliability and construct validity and its associated cardiorespiratory response in comparison to the 6-min walk test (6MWT) and symptom-limited cycling cardiopulmonary exercise test (CPET) in people with interstitial lung disease (ILD).

Methods

Fifteen participants with ILD performed two 1STS tests, a 6MWT and a CPET. The three tests were administered on three separate visits, and cardiorespiratory parameters were continuously recorded during the tests.

Results

The number of repetitions during both 1STS tests was 22 ± 4 and 22 ± 4 (mean difference of 0.53 ± 2.00 repetitions,P= 0.32) with an intraclass correlation of 0.937 (95% confidence interval, 0.811–0.979]) and a minimal detectable change of 2.9 repetitions. The number of 1STS repetitions was highly correlated with the 6MWT distance (r= 0.823,P< 0.001) and with the peak cycling power output expressed in % predicted values (r= 0.706,P< 0.003). Oxygen consumption (V˙O2) peak during the 1STS reached 83% and 78% of V˙O2peak during 6MWT and CPET, respectively. Peak 1STS HR, minute ventilation (V˙E,), V˙O2values, as well as nadir SpO2were achieved during the recovery phase of the test, whereas peak 6MWT and CPET HR,V˙E, V˙O2and nadir SpO2always occurred at the end of the test. The three tests elicited a similar fall in SpO2ranging between 8% and 12%. Symptom scores after the 1STS were similar to those seen at the end of the 6MWT but lower than those of CPET.

Conclusions

The 1STS showed excellent test–retest reliability in patients with ILD in whom it elicited a substantial, but submaximal cardiorespiratory response. Our data also support the construct validity of the 1STS to assess functional exercise capacity in patients with ILD and to detect exercise-induced O2desaturation.
Modeling the Recovery of W′ in the Moderate to Heavy Exercise Intensity Domain
Authors: SREEDHARA VIJAY SARTHY M. , ASHTIANI FARAZ , MOCKO GREGORY M. , VAHIDI ARDALAN , HUTCHISON RANDOLPH E.
Published: June 2020

Purpose

This study (i) investigates the effect of recovery power (Prec) and duration (t
rec) on the recovery of the curvature constant (W′) of the power–duration relationship, (ii) compares the experimentally measured W′ balance to that predicted (W′
bal) by two models (SK2 and BAR), and (iii) presents a case of real-time performance optimization using the critical power (CP) concept.

Methods

Seven competitive amateur cyclists performed a ramp test to determine their V˙O2peak and gas exchange threshold, two to four 3-min all-out tests to determine CP and W′, and nine intermittent cycling tests to investigate W′ recovery. The intermittent cycling tests involved a 2-min constant work-rate interval above CP, followed by a constant work-rate recovery interval below CP (Prec and t
rec were varied), followed by a 3-min all-out interval.

Results

There was a significant two-way interaction between Prec and t
rec on W′ recovery, P = 0.004 (η
2 = 0.52). Simple main effects were present only with respect to Prec at each t
rec. The actual W′ balance at the end of the recovery interval was less than the W′
bal predicted by both SK2 (P = 0.035) and BAR (P = 0.015) models. The optimal strategy derived from the subject-specific recovery model reduced the race time by 55 s as compared with the self-strategy.

Conclusions

This study has shown that in a recovery interval, Prec has a greater influence than t
rec on W′ recovery. The overprediction of W′
bal from SK2 and BAR suggests the need for individualized recovery parameters or models for sub-CP exercise. Finally, the optimal strategy results provide encouraging signs for real-time, model-based performance optimization.
Development of a Cadence-based Metabolic Equation for Walking
Authors: MOORE CHRISTOPHER C. , AGUIAR ELROY J. , DUCHARME SCOTT W. , TUDOR-LOCKE CATRINE
Published: June 2020

Purpose

This study aimed to develop cadence-based metabolic equations (CME) for predicting the intensity of level walking and evaluate these CME against the widely adopted American College of Sports Medicine (ACSM) Metabolic Equation, which predicts walking intensity from speed and grade.

Methods

Two hundred and thirty-five adults (21–84 yr of age) completed 5-min level treadmill walking bouts between 0.22 and 2.24 m·s−1, increasing by 0.22 m·s−1 for each bout. Cadence (in steps per minute) was derived by dividing directly observed steps by bout duration. Intensity (oxygen uptake; in milliliters per kilogram per minute) was measured using indirect calorimetry. A simple CME was developed by fitting a least-squares regression to the cadence–intensity relationship, and a full CME was developed through best subsets regression with candidate predictors of age, sex, height, leg length, body mass, body mass index (BMI), and percent body fat. Predictive accuracy of each CME and the ACSM metabolic equation was evaluated at normal (0.89–1.56 m·s−1) and all (0.22–2.24 m·s−1) walking speeds through k-fold cross-validation and converted to METs (1 MET = 3.5 mL·kg−1·min−1).

Results

On average, the simple CME predicted intensity within ~1.8 mL·kg−1·min−1 (~0.5 METs) at normal walking speeds and with negligible (<0.01 METs) bias. Including age, leg length, and BMI in the full CME marginally improved predictive accuracy (≤0.36 mL·kg−1·min−1 [≤0.1 METs]), but may account for larger (up to 2.5 mL·kg−1·min−1 [0.72 MET]) deviations in the cadence–intensity relationships of outliers in age, stature, and/or BMI. Both CME demonstrated 23%–35% greater accuracy and 2.2–2.8 mL·kg−1·min−1 (0.6–0.8 METs) lower bias than the ACSM metabolic equation’s speed-based predictions.

Conclusions

Although the ACSM metabolic equation incorporates a grade component and is convenient for treadmill-based applications, the CME developed herein enables accurate quantification of walking intensity using a metric that is accessible during overground walking, as is common in free-living contexts.