bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcutaneous Mepolizumab Injection: An Adjunctive Treatment for Recalcitrant Allergic Fungal Rhinosinusitis Patients With Asthma
Authors: Karp John , Dhillon India , Panchmatia Rikesh , Javer Amin
Published: August 2020

Background

Allergic Fungal Rhinosinusitis (AFRS) is a non-invasive fungal disease that results from chronic allergic inflammation of the sinonasal mucosa. Failure to respond to mainstay medical therapies and sinus surgery leaves AFRS patients with limited alternatives and a decreased quality of life. Mepolizumab is a known IL-5 antagonist for patients with severe eosinophilic asthma.

Objective

To identify the efficacy of mepolizumab on improving Modified Lund-Kennedy (MLK) endoscopic scores in recalcitrant AFRS patients with asthma.

Methods

Retrospective chart review of 27 recalcitrant AFRS patients with asthma receiving a monthly mepolizumab injection between January 2017 and July 2019. Patients were evaluated endoscopically at baseline and at each follow-up visit every 6–8 weeks until their third visit. Secondary outcomes included SNOT-22 scores, serum eosinophil counts and the rate of prednisone rescues required in patients receiving mepolizumab compared to a retrospective control arm.

Results

Total median MLK scores improved significantly for all patients over three follow-up visits (6[4,7], 4[2,6], 5[2,6], 3.5[2.25,5]; p = 0.04). Amongst patients with a baseline polyposis score of 1 or more, combined MLK edema and polyposis sub-scores significantly improved (6[5.25,6], 3.5[2.25,5,75], 4[2.75,5.25], 4[3,4]; p = 0.02) versus patients with no polyposis (4[3,4], 3[1,4], 4[2,4], 3[0,4]; p = 0.90). Total SNOT-22 scores (56 vs 43; p = 0.04) and eosinophil counts (0.40 × 109/L vs 0.00 × 109/L; p < 0.01) decreased significantly when comparing baseline to last follow up. There was no significant difference in rate of prednisone rescues per 1000 person-days when comparing control to Mepolizumab population (1.19 vs 1.23; p = 1).

Conclusion

Mepolizumab injections administered once monthly as an adjunctive treatment for recalcitrant AFRS patients with asthma appear to significantly reduce endoscopic signs of inflammation, patient-reported symptomatology and serum eosinophil levels. Patients with evidence of more severe endoscopic inflammation appear to benefit the most. Adjunctive treatment with mepolizumab does not reduce the need for prednisone rescues.
Anti-N-methyl-D-aspartate receptor encephalitis in a young female with subclinical hypothyroidism associated with anti-thyroid peroxidase and anti-thyroglobulin antibodies: A case report
Authors: Khoodoruth Mohamed Adil Shah , Chut-kai Khoodoruth Widaad Nuzhah , Alshawwaf Mahmoud Khalil Mahmoud
Published: August 2020

Anti- N-methyl-D-aspartate receptor encephalitis is a life-threatening medical emergency that can be clinically misperceived as Hashimoto’s encephalopathy. We present a case of anti- N-methyl-D-aspartate receptor encephalitis in an otherwise healthy young female with subclinical hypothyroidism without an associated ovarian teratoma. She was first misdiagnosed as Hashimoto’s encephalopathy due to delirium and behavioral changes, seizures, psychosis, and increased amount of thyroid peroxidase and thyroglobulin antibodies in serum. Final diagnosis was established by third week following presentation with the detection of anti- N-methyl-D-aspartate receptor antibodies in her cerebrospinal fluid. After treatment with intravenous immunoglobulin, methylprednisolone, and amisulpride, she recovered significantly with minimal sequelae at 3-week follow-up.
Content moderation, AI, and the question of scale
Authors: Gillespie Tarleton
Published: August 2020

AI seems like the perfect response to the growing challenges of content moderation on social media platforms: the immense scale of the data, the relentlessness of the violations, and the need for human judgments without wanting humans to have to make them. The push toward automated content moderation is often justified as a necessary response to the scale: the enormity of social media platforms like Facebook and YouTube stands as the reason why AI approaches are desirable, even inevitable. But even if we could effectively automate content moderation, it is not clear that we should.
Patient-Reported Outcomes Following Inpatient Multimodal Treatment Approach in Chronic Pain-Related Rheumatic Diseases
Authors: Romeyke Tobias , Noehammer Elisabeth , Stummer Harald
Published: August 2020

Introduction

Musculoskeletal disorders may cause chronic pain, which is associated with deterioration in physical well-being, functions, and quality of life. There are worldwide shortfalls in the care that is provided to the affected patients. Holistic, interdisciplinary care is rare. Monomodal therapeutic approaches dominate when health-care resources are scarce. In this study, we test the patient-relevant outcomes of multimodal treatment for rheumatic diseases that are associated with pain and check for remuneration.

Methods

We performed a retrospective data analysis of an inpatient multimodal treatment. The target parameter was the patient perspective, which we assessed by means of Patient-Reported Outcomes (PRO). We applied the Visual Analogue Scale (mental and physical condition), the Heidelberg Short Early Risk Assessment Questionnaire, the Pain Disability Index, and the pain grading according to Kohlmann/Raspe (N = 375 patients). We also investigated compensation for inpatient treatments with and without multimodal treatments. Moreover, we compared Diagnosis-Related Group remuneration with and without complex treatment.

Results

After implementing a multimodal treatment, improved mental (mood) status was significantly better (Wilcoxon signed-rank test, P < . 001), despite high levels of pain (Kohlmann/Raspe) reported on admission. Apart from the underlying rheumatic disease, 111 patients also reported chronic back pain, which was improved following the treatment ( t test, P < . 001). Subjective impairments associated with pain were significantly lower at the end of the hospital stay (Wilcoxon signed-rank test, P < . 001). Compensation for inpatient treatments with multimodal treatments increased noticeably in German hospitals in 2016 to 2019, while remunerations for monomodal treatments show mixed results.

Conclusion

PROs regarding mood, pain, and perceived impairments improved following the multimodal complex treatment. Compensation of hospitals should take into account additional performance requirements of holistic treatments, whereby the promotion and further studies of PROs are recommended.
Ethnicity and Elections in Eastern Turkey: What do the Kurds Want?
Authors: Yeğen Mesut , Tol Uğraş Ulaş , Çalışkan Mehmet Ali
Published: August 2020

Relying on a survey conducted in 2014 in 12 provinces in eastern Turkey, this article analyses the extent to which (a) ethnicity and religiosity shape Kurds’ electoral choices and (b) the Kurds in the East support the demand for education in Kurdish and the demand for self-rule for Kurds. The findings demonstrate that ethnicity is an important factor in shaping Kurds’ electoral choices and that the demands for education in Kurdish language and self-rule are backed not only by the vast majority of those Kurds who support the pro-Kurdish party but also by a significant number of those Kurds who support the AK Party.
Ranking Candidates: An Experiential Exercise in Personnel Selection
Authors: Bérubé Nicole
Published: August 2020

Personnel selection is a key topic in Human Resource Management (HRM) courses. Many selection exercises focus on management situations that are unfamiliar to students who are taking introductory HRM courses. In contrast, this exercise introduces students to the pre-interview steps in the personnel selection process by asking them to determine the knowledge, skills, and abilities of potential adjunct instructors for a future offering of an HRM course. Groups of students act as management teams to determine the suitability of four applicants. Tasks include determining desirable qualifications, and then developing and ranking selection criteria based on the job posting. Subsequently, each group reviews the resumes of the four applicants and ranks them based on their selection criteria. A plenary discussion follows, during which students compare their choices and provide their rationale for their rankings. A discussion based on key questions concludes the activity. The exercise may be conducted in class or online.
Exploring Fetal Sex as a Risk Factor for Sleep Disordered Breathing and Its Complications in Pregnancy
Authors: Bublitz Margaret H. , Salameh Myriam , Sanapo Laura , Bourjeily Ghada
Published: August 2020

Sleep disordered breathing (SDB) is a common, yet under-recognized and undertreated condition in pregnancy. Sleep disordered breathing is associated with pregnancy complications including preeclampsia, gestational diabetes, preterm birth, as well as severe maternal morbidity and mortality. The identification of risk factors for SDB in pregnancy may improve screening, diagnosis, and treatment of SDB prior to the onset of pregnancy complications. The goal of this study was to determine whether fetal sex increases risk of SDB in pregnancy. A cohort of singleton (N = 991) pregnant women were recruited within 24 to 48 hours of delivery and answered questions regarding SDB symptoms by questionnaire. Women who reported frequent loud snoring at least 3 times a week were considered to have SDB. Hospital records were reviewed to extract information on fetal sex and pregnancy complications including preeclampsia, pregnancy-induced hypertension, gestational diabetes, preterm delivery, and low birth weight. Women carrying male fetuses were significantly more likely to have SDB (β = .37, P = .01, OR: 1.45 [95% CI: 1.09-1.94]). Fetal sex was associated with increased risk of hypertensive disorders of pregnancy (defined as preeclampsia and/or pregnancy-induced hypertension) among women with SDB in pregnancy (β = .41, P = .02, OR: 1.51 [95% CI: 1.08-2.11]). Fetal sex did not increase risk of preterm birth, low birth weight, or gestational diabetes among women with SDB in pregnancy. Women carrying male fetuses were approximately 1.5 times more likely to report SDB in pregnancy compared to women carrying female fetuses, and women with pregnancy-onset SDB carrying male fetuses were 1.5 times more likely to have hypertensive disorders of pregnancy compared to women with SDB carrying female fetuses. Confirmation of fetal sex as a risk factor may, with other risk factors, play a role in identifying women at highest risk of SDB complications in pregnancy.
The effect of intraoperative goal-directed crystalloid versus colloid administration on perioperative inflammatory markers - a substudy of a randomized controlled trial
Authors: Obradovic Mina , Kurz Andrea , Kabon Barbara , Roth Georg , Kimberger Oliver , Zotti Oliver , Bayoumi Ahamed , Reiterer Christian , Stift Anton , Fleischmann Edith
Published: August 2020

Background

Excessive perioperative fluid administration may result in iatrogenic endothelial dysfunction and tissue edema, transducing inflammatory markers into the bloodstream. Colloids remain longer in the circulation, requiring less volume to reach similar hemodynamic endpoints compared to crystalloids. Thus, we tested the hypothesis that a goal-directed colloid regimen attenuates the inflammatory response compared to a goal-directed crystalloid regime.

Methods

Patients undergoing moderate- to high-risk open abdominal surgery were randomly assigned to goal-directed lactated Ringer’s solution (n = 58) or a hydroxyethyl starch 6% 130/0.4 (n = 62) fluid regimen. Our primary outcome was perioperative levels of pro- and anti-inflammatory cytokines. Secondary outcome was perioperative levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP). Measurements were performed preoperatively, immediate postoperatively, on postoperative day one, two and four.

Results

The areas under the curve of Interleukin (IL) 6 (p = 0.60), IL 8 (p = 0.46), IL 10 (p = 0.68) and tumor necrosis factor α (p = 0.47) levels did not differ significantly between the groups. WBC, CRP and PCT values were also comparable. LBP, although significantly higher in the crystalloid group, remained in the normal range. Patients assigned to crystalloids received a median (IQR) amount of 3905 mL (2880–5288) of crystalloid. Patients assigned to colloids received 1557 mL (1207–2116) of crystalloid and 1250 mL (750–1938) of colloid.

Conclusion

Cytokine and inflammatory marker levels did not differ between goal-directed crystalloid and colloid administration after moderate to high-risk abdominal surgery.

Trial registration

ClinicalTrials.gov (NCT00517127). Registered 16th August 2007.
Late stage diagnosis of mucinous adenocarcinoma of the appendix: a case report of an unusual tumor with a rare presentation
Authors: Roma Katerina , Baldwin Mark , Sedmak Daniel , Silva Matthew , Stellar William , Many Gina
Published: August 2020

Background

The incidence of mucinous appendiceal adenocarcinomas (MAA) has increased over the past three decades. Advanced stage tumor diagnosis is likely attributable to non-specific findings. Here we describe advanced stage appendiceal MAA presenting as inguinal ulcers, scrotal abscesses, and other nonspecific symptoms. To our knowledge, this is the first report of MAA presenting as inguinal pain with inflamed phlegmonous tissue and scrotal abscess.

Case presentation

A 67-year-old male presented to a rural facility complaining of weight-loss, fatigue, hematuria, dysuria, painful right inguinal ulceration, and right scrotal abscess drainage. Computed tomography of the abdomen and pelvis revealed a distended appendix (> 1.3 cm) and a fistula between the appendix, urinary bladder, right scrotum, and right groin. Laparoscopic appendectomy was performed and diagnosed as MAA. After a right hemicolectomy, the MAA was staged as pT3b pN0 M0 G2.

Conclusion

This case highlights a unique presentation of late stage appendiceal MAA. Due to the increased incidence of appendiceal MAAs, reports of unique clinical features are needed to facilitate early diagnosis and intervention, especially in rural settings with limited access to specialists.
Economics of the Management of Craniospinal Chordoma and Chondrosarcoma and the feasibility of the bundled payment model
Authors: Aljuboori Zaid , Ugiliweneza Beatrice , Wang Dengzhi , Andaluz Norberto , Boakye Maxwell , Williams Brian
Published: August 2020

Background

The Centers for Medicare and Medicaid Services (CMS) created a new reimbursement model “Bundled Payment for Care Improvement (BPCI)” which reimburses providers a predetermined payment in advance to cover all possible services rendered within a certain time window. Chordoma and Chondrosarcoma are locally aggressive malignant primary bony tumors. Treatment includes surgical resection and radiotherapy with substantial risk for recurrence which necessitates monitoring and further treatment. We assessed the feasibility of the BPCI model in these neurosurgical diseases.

Methods

We selected patients with chordoma/chondrosarcoma from inpatient admission table using the International Classification of Disease, 9th (ICD-9), and 10th (ICD-10) revision codes. We collected the patients’ demographics and insurance type at the index hospitalization. We recorded the following outcomes length of stay, total payment, discharge disposition, and complications for the index hospitalization. For post-discharge, we collected the 30 days and 3/6/12 months inpatient admission, outpatient service, and medication refills. Continuous variables were summarized by means with standard deviations, median with interquartile and full ranges (minimum-maximum); Continuous outcomes were compared by nonparametric Wilcoxson rank-sum test. All tests were 2-sided with a significance level of 0.05. Statistical data analysis was performed in SAS 9.4 (SAS Institute, Inc, Cary, NC).

Results

The population size was 2041 patients which included 1412 patients with cranial (group1), 343 patients with a mobile spine (group 2), and 286 patients with sacrococcygeal (group 3) chordoma and chondrosarcoma. For index hospitalization, the median length of stay (days) was 4, 6, and 7 for groups 1, 2, and 3 respectively (P<.001). The mean payments were ($58,130), ($84,854), and ($82,440), for groups 1, 2, and 3 respectively (P=.02). The complication rates were 30%, 35%, and 43% for groups 1, 2, and 3 respectively (P<.001). Twelve months post-discharge, the hospital readmission rates were 44%, 53%, and 65% for groups 1, 2, and 3, respectively (P<.001). The median payments for this period were ($72,294), ($76,827), and ($101,474), for groups 1, 2, and 3, respectively (P <.001).

Conclusion

The management of craniospinal chordoma and chondrosarcoma is costly and may extend over a prolonged period. The success of BPCI requires a joint effort between insurers and hospitals. Also, it should consider patients’ comorbidities, the complexity of the disease. Finally, the adoptionof quality improvement programs by hospitals can help with cost reduction.
Health may be compromised by social interactions depending on culture among postpartum Arab and Jewish Israeli women
Authors: Puddister Sadie , Ali-Saleh Ola , Cohen-Dar Michal , Baron-Epel Orna
Published: August 2020

Background

Social support is generally perceived to facilitate health in postpartum women; however, previous research shows that this is not always true. Social interactions intended to provide support can be perceived as negative and in turn, may have negative impacts on maternal health. The purpose of the present study was to asses if social support and negative interactions at one month after childbirth can predict maternal health four months after childbirth, and if this relationship is influenced by culture.

Methods

This prospective longitudinal cohort study included randomly selected Arab (n = 203) and Jewish (n = 202) women who attended Mother and Child Health Clinics in Northern Israel one month after giving birth. The women were interviewed at one and four months after childbirth using a questionnaire including measures of health (self-reported health (SRH) and health problems), socioeconomic and demographic status, obstetric characteristics, social support, negative social interactions and perceptions of customs and traditions intended to help the mother cope after childbirth. Multivariable regressions were run to identify the variables predicting health four months after childbirth.

Results

The response rate for both interviews was 90%. Negative social interactions one month after childbirth significantly predicted health problems in Arab and Jewish women (Beta 0.20 and 0.37 respectively) and SRH among Arab women only (odds ratio (OR) 0.32, confidence interval (CI) 0.19–0.54) four months after childbirth. Social support at one month after childbirth significantly predicted better SRH in both Jewish and Arab women four months after childbirth (OR 2.33, CI 1.38–3.93 and 1.59, CI 1.01–2.46 respectively) and fewer health problems only among Jewish women (Beta − 0.37).

Conclusions

Social support and negative social interactions appear to be predictive of health in postpartum women. Associations varied between Arabs and Jews, indicating that social support may be more important for predicting health among Jewish women and negative interactions may be more important among Arab women. Healthcare practitioners should be aware of the cultural context and social circumstances of postpartum women to ensure they receive the social support and care they need.
Posterior short segment fixation including the fractured vertebra combined with kyphoplasty for unstable thoracolumbar osteoporotic burst fracture
Authors: Hu Xudong , Ma Weihu , Chen Jianming , Wang Yang , Jiang Weiyu
Published: August 2020

Background

Various studies have described the efficacy and safety of the treatment for unstable thoracolumbar osteoporotic burst fracture, however, there is still no consensus on the optimal treatment regimen. The aim of this study was to evaluate the clinical and radiographic results of posterior short segment fixation including the fractured vertebra (PSFFV) combined with kyphoplasty (KP) for unstable thoracolumbar osteoporotic burst fracture.

Methods

Forty-three patients with unstable thoracolumbar osteoporotic burst fracture underwent PSFFV combined with KP from January 2015 to December 2017 were analyzed retrospectively. Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) was used to evaluate the clinical outcome, radiological parametres including local kyphotic Cobb angle, percentage of the anterior, middle and posterior height of the fractured vertebra were measured and compared pre-operation, post-operation and at final follow-up.

Results

All patients underwent surgery successfully and with an average follow-up of 19.2 ± 6.7 months (rang 15–32). The VAS decreased from 7.1 ± 2.3 pre-operation to 1.6 ± 0.4 at the final follow-up (p < 0.05). The ODI decreased from 83.1 ± 10.5 pre-operation to 19.2 ± 7.3 (P < 0.05) at the final follow-up. The correction of local kyphotic angle was 16.9° ± 5.3° (p < 0.05), and the loss of correction was 3.3° ± 2.6° (p > 0.05), the correction of anterior vertebral height was 30.8% ± 8.6% (p < 0.05), and the loss of correction was 4.5% ± 3.9% (p > 0.05), the correction of middle vertebral height was 26.4% ± 5.8% (p < 0.05), and the loss of correction was 2.0% ± 1.6% (p > 0.05), the correction of posterior vertebral height was 9.4% ± 6.9% (p < 0.05), and the loss of correction was 1.6% ± 1.3% (p > 0.05). Two cases of screw pullout and 8 cases of cement leakage were observed, but without clinical consequence.

Conclusions

PSFFV combined with KP is a reliable and safe procedure with satisfactory clinical and radiological results for the treatment of unstable thoracolumbar osteoporotic burst fracture.
Traumatic brain injury neuroelectrochemical monitoring: behind-the-ear micro-instrument and cloud application
Authors: Tageldeen Momen K. , Gowers Sally A. N. , Leong Chi L. , Boutelle Martyn G. , Drakakis Emmanuel M.
Published: August 2020

Background

Traumatic Brain Injury (TBI) is a leading cause of fatality and disability worldwide, partly due to the occurrence of secondary injury and late interventions. Correct diagnosis and timely monitoring ensure effective medical intervention aimed at improving clinical outcome. However, due to the limitations in size and cost of current ambulatory bioinstruments, they cannot be used to monitor patients who may still be at risk of secondary injury outside the ICU.

Methods

We propose a complete system consisting of a wearable wireless bioinstrument and a cloud-based application for real-time TBI monitoring. The bioinstrument can simultaneously record up to ten channels including both ECoG biopotential and neurochemicals (e.g. potassium, glucose and lactate), and supports various electrochemical methods including potentiometry, amperometry and cyclic voltammetry. All channels support variable gain programming to automatically tune the input dynamic range and address biosensors’ falling sensitivity. The instrument is flexible and can be folded to occupy a small space behind the ear. A Bluetooth Low-Energy (BLE) receiver is used to wirelessly connect the instrument to a cloud application where the recorded data is stored, processed and visualised in real-time. Bench testing has been used to validate device performance.

Results

The instrument successfully monitored spreading depolarisations (SDs) - reproduced using a signal generator - with an SNR of 29.07 dB and NF of 0.26 dB. The potentiostat generates a wide voltage range from -1.65V to +1.65V with a resolution of 0.8mV and the sensitivity of the amperometric AFE was verified by recording 5 pA currents. Different potassium, glucose and lactate concentrations prepared in lab were accurately measured and their respective working curves were constructed. Finally,the instrument achieved a maximum sampling rate of 1.25 ksps/channel with a throughput of 105 kbps. All measurements were successfully received at the cloud.

Conclusion

The proposed instrument uniquely positions itself by presenting an aggressive optimisation of size and cost while maintaining high measurement accuracy. The system can effectively extend neuroelectrochemical monitoring to all TBI patients including those who are mobile and those who are outside the ICU. Finally, data recorded in the cloud application could be used to help diagnosis and guide rehabilitation.
Sternal reconstruction using locking compression plates (LCP): our experience in Egypt, a case series
Authors: Ahmed Kareem , Nady Mohamed Alaa
Published: August 2020

Background

Sternal fractures are rare accounting for about 3–8% of traumatic chest. There are many lines of treatments for sternal fractures which can be classified as conservative or surgical. Surgical techniques include wire fixation and sternal plating. There are no standardization of indications for each line of management.

We explore if sternal reconstruction using locking titanium plates and self-tapping screws provide the patient with the best chance of proper sternal healing avoiding chronic pain and its complications and allow the patient early mobilization and rapid restoring of his normal life at its maximum.

Methods

Our inclusion criteria are patients of both gender from 20 to 60 years of age presented with traumatic sternal fracture at any site or pathological fracture due to metastatic or primary tumors infiltrating the sternum. High Associated Injury Scale scores were excluded. Exclusion criteria also included patients younger than 20 years or older than 60 years. Primary outcome is post-operative pain score and is measured using numerical pain scale ranging from zero to 10 where zero means there is no pain at all and ten is the worst imaginable pain ever.

Results

Sternal reconstruction using titanium plates has proven to be an efficient method of stabilization with tremendous immediate relief of pain showed by the differences between pre-operative and post-operative pain scale scores in our patients (n = 5) with Median scores being 7 and 1.5 with range being from 7 to 9 and 1 to 3 respectively (p-value = .039). Operative time range between 150 min and 90 min with median of 120 min. Extubation of patients was smooth with no events with median time of extubation being 120 min. From our experience, there were no observed wound complications except at the third patient who suffered a small wound hematoma that was resolved by gentle compressing only and needed no further intervention.

Conclusion

We recommend adopting sternal reconstruction using titanium plating systems more readily encouraging even larger clinical trials on the way to a clear guidelines. Plating systems show promising results with least pain, better stability, less complications and rapid, smooth recovery.

Trial registration

NCT04092374
Applying Experiential Learning to Career Development Training for Biomedical Graduate Students and Postdocs: Perspectives on Program Development and Design
Authors: Van Wart Audra , O'Brien Theresa C. , Varvayanis Susi , Alder Janet , Greenier Jennifer , Layton Rebekah L. , Stayart C. Abigail , Wefes Inge , Brady Ashley E.
Published: August 2020

Four types of experiential learning approaches used for predoctoral graduate students and postdoctoral scholars in the biomedical sciences are described and associated learning objectives and evaluation strategies are compared. This framework will help other institutions design and deliver experiential learning programs for career training.
MILO/ENGOT-ov11: Binimetinib Versus Physician’s Choice Chemotherapy in Recurrent or Persistent Low-Grade Serous Carcinomas of the Ovary, Fallopian Tube, or Primary Peritoneum
Authors: Monk Bradley J. , Grisham Rachel N. , Banerjee Susana , Kalbacher Elsa , Mirza Mansoor Raza , Romero Ignacio , Vuylsteke Peter , Coleman Robert L. , Hilpert Felix , Oza Amit M. , Westermann Anneke , Oehler Martin K. , Pignata Sandro , Aghajanian Carol , Colombo Nicoletta , Drill Esther , Cibula David , Moore Kathleen N. , Christy-Bittel Janna , del Campo Josep M. , Berger Regina , Marth Christian , Sehouli Jalid , O’Malley David M. , Churruca Cristina , Boyd Adam P. , Kristensen Gunnar , Clamp Andrew , Ray-Coquard Isabelle , Vergote Ignace
Published: August 2020

PURPOSE

Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC.

METHODS

This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician’s choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety.

RESULTS

A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent.

CONCLUSION

Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.
LONG-TERM ATHLETIC DEVELOPMENT AS A FRAMEWORK TO INFLUENCE WELLNESS DURING CHILDHOOD AND ADOLESCENCE
Authors: Eisenmann Joey C. , Howard Rick , Moreno Tony
Published: August 2020

Apply It!

• Health and fitness professionals working with children and adolescents should first understand normal growth, maturation, and development (the “business of growing up”) when considering the implementation and effect of lifestyle behaviors.

• Fundamental movement skills provide the foundation or building blocks for developing confidence and competency in sports, games, play, and physical activity and, along with developing muscular fitness, should be the focus of youth physical development.

• Along with physical activity, sleep and nutrition also serve as a polypill for optimal growth, maturation, and development. Youth programs should provide education and intervention on these key behaviors as well.

• Quality instruction and supervision of youth programs should include assessment and monitoring of growth and maturation, fundamental movement skill acquisition, physical performance, injury prevention, nutrition, sleep, and psychosocial well-being.
Effect of 6-Month Exercise Training on Neurovascular Function in Spinal Cord Injury
Authors: OZTURK ERIN D. , LAPOINTE MATTHEW S. , KIM DONG-IL , HAMNER J. W. , TAN CAN OZAN
Published: August 2020

Introduction

Although previous data show exacerbated incidence of cognitive impairment after spinal cord injury (SCI), the physiology that underlies this postinjury cognitive decline is unknown. One potential culprit is impairment in the ability of cerebral vasculature to alter regional flow to sustain neural metabolism (i.e., “neurovascular coupling”). We hypothesized that cerebrovascular responses to a working memory task are impaired in individuals with SCI and can be improved by aerobic exercise training.

Methods

We assessed the effect of injury and 6-month full-body aerobic exercise training on the cerebral blood flow response to cognitive demand (i.e., neurovascular coupling) in 24 individuals with SCI and 16 controls. Cognitive demand was introduced in a graded fashion using a working memory task.

Results

Reaction time tended to be higher in individuals with SCI, especially those with high-level (≥T4) injuries, possibly due to upper motor impairments. Neurovascular coupling was graded across task difficulty (P < 0.01) and followed cognitive demand, and injury itself did not have a significant effect (group effect P = 0.99, interaction P = 0.70). Individuals with low-level injuries (<T4) had higher aerobic capacity than high-level injuries (P < 0.01). Aerobic capacity increased significantly with training in both groups (P < 0.01). Although there was no overall significant improvement in neurovascular coupling with training at the group level, the degree of improvement was closely related to that in aerobic fitness in individuals with high-level injuries (R2
= 0.19, P = 0.03) but not low-level injuries (R2
= 0.04, P = 0.46). Importantly, improvement in neurovascular coupling translated to an increase in reaction time (R2
= 0.16, P = 0.05).

Conclusion

Previously reported cognitive impairment after SCI may reflect a decline in neurovascular coupling primarily due to physical deconditioning rather than injury itself. The latter can be mitigated by aerobic exercise training.
Novel CPET Reference Values in Healthy Adults: Associations with Physical Activity
Authors: WAGNER JONATHAN , KNAIER RAPHAEL , INFANGER DENIS , KÖNIGSTEIN KARSTEN , KLENK CHRISTOPHER , CARRARD JUSTIN , HANSSEN HENNER , HINRICHS TIMO , SEALS DOUGLAS , SCHMIDT-TRUCKSÄSS ARNO
Published: August 2020

Purpose

Cardiopulmonary exercise testing (CPET) is an important measurement in clinical practice, and its primary outcome, maximal oxygen uptake (V˙O2peak), is inversely associated with morbidity and mortality. The purposes of this study are to provide CPET reference values for maximal and submaximal parameters across the adult age spectrum of a healthy European cohort, to compare V˙O2peak values with other reference data sets, and to analyze the associations between physical activity (PA) levels and CPET parameters.

Methods

In this cross-sectional study, we prospectively recruited 502 participants (47% female) from 20 to 90 yr old. The subjects performed a CPET on a cycle ergometer using a ramp protocol. PA was objectively and continuously measured over 14 d using a triaxial accelerometer. Quantile curves were calculated for CPET parameters. To investigate the associations between CPET parameters and PA levels, linear regression analysis was performed.

Results

V˙O2peak values observed in the group of 20–29 yr were 46.6 ± 7.9 and 39.3 ± 6.5 mL·kg−1⋅min−1 for males and females, respectively. On average, each age category (10-yr increments) showed a 10% lower V˙O2peak relative to the next younger age category. V˙O2peak values of previous studies were on average 7.5 mL·kg−1⋅min−1 (20%) lower for males and 6.5 mL·kg−1⋅min−1 (21%) lower for females. There was strong evidence supporting a positive association between the V˙O2peak (mL·kg−1⋅min−1) and the level of habitual PA performed at vigorous PA (estimate, 0.26; P < 0.001].

Conclusion

Maximal and submaximal CPET reference values over a large age range are novel, and differences to other studies are clinically highly relevant. Objectively measured vigorous-intensity PA showed a strong positive association with higher V˙O2peak and other performance-related CPET parameters, supporting the implementation of higher-intensity aerobic exercise in health promotion.
Effects of BMI on Walking Speed and Gait Biomechanics after Anterior Cruciate Ligament Reconstruction
Authors: DAVIS-WILSON HOPE C. , JOHNSTON CHRISTOPHER D. , YOUNG EMMA , SONG KYEONGTAK , WIKSTROM ERIK A. , BLACKBURN J. TROY , PIETROSIMONE BRIAN
Published: August 2020

Purpose

History of an anterior cruciate ligament reconstruction (ACLR) and high body mass index (BMI) are strong independent risk factors for knee osteoarthritis (KOA) onset. The combination of these risk factors may further negatively affect joint loading and KOA risk. We sought to determine the combined influence of BMI and ACLR on walking speed and gait biomechanics that are hypothesized to influence KOA onset.

Methods

Walking speed and gait biomechanics (peak vertical ground reaction force [vGRF], peak vGRF instantaneous loading rate [vGRF-LR], peak knee flexion angle, knee flexion excursion [KFE], peak internal knee extension moment [KEM], and peak internal knee abduction moment [KAM]) were collected in 196 individuals with unilateral ACLR and 106 uninjured controls. KFE was measured throughout stance phase, whereas all other gait biomechanics were analyzed during the first 50% of stance phase. A 2 × 2 ANOVA was performed to evaluate the interaction between BMI and ACLR and main effects for both BMI and ACLR on walking speed and gait biomechanics between four cohorts (high BMI ACLR, normal BMI ACLR, high BMI controls, and normal BMI controls).

Results

History of an ACLR and high BMI influenced slower walking speed (F
1,298 = 7.34, P = 0.007), and history of an ACLR and normal BMI influenced greater peak vGRF-LR (F
1,298 = 6.56, P = 0.011). When evaluating main effects, individuals with an ACLR demonstrated lesser KFE (F
1,298 = 7.85, P = 0.005) and lesser peak KEM (F
1,298 = 6.31, P = 0.013), and individuals with high BMI demonstrated lesser peak KAM (F
1,297 = 5.83, P = 0.016).

Conclusion

BMI and history of ACLR together influence walking speed and peak vGRF-LR. History of an ACLR influences KFE and peak KEM, whereas BMI influences peak KAM. BMI may need to be considered when designing interventions aimed at restoring gait biomechanics post-ACLR.
Long-Term and Acute Benefits of Reduced Sitting on Vascular Flow and Function
Authors: HARTMAN YVONNE A. W. , TILLMANS LAURA C. M. , BENSCHOP DAVID L. , HERMANS ASTRID N. L. , NIJSSEN KEVIN M. R. , EIJSVOGELS THIJS M. H. , WILLEMS PETER H. G. M. , TACK CEES J. , HOPMAN MARIA T. E. , CLAASSEN JURGEN A. H. R. , THIJSSEN DICK H. J.
Published: August 2020

Purpose

Sedentary behavior increases the risk for cardiovascular and cerebrovascular disease. To understand potential benefits and underlying mechanisms, we examined the acute and long-term effect of reduced sitting intervention on vascular and cerebrovascular function.

Methods

This prospective study included 24 individuals with increased cardiovascular risk (65 ± 5 yr, 29.8 ± 3.9 kg·m−2). Before and after 16-wk reduced sitting, using a mobile health device with vibrotactile feedback, we examined (i) vascular function (flow-mediated dilation [FMD]), (ii) cerebral blood flow velocity (CBFv, transcranial Doppler), and (iii) cerebrovascular function (cerebral autoregulation [CA] and cerebral vasomotor reactivity [CVMR]). To better understand potential underlying mechanisms, before and after intervention, we evaluated the effects of 3 h sitting with and without light-intensity physical activity breaks (every 30 min).

Results

The first wave of participants showed no change in sedentary time (n = 9, 10.3 ± 0.5 to 10.2 ± 0.5 h·d−1, P = 0.87). Upon intervention optimization by participants’ feedback, the subsequent participants (n = 15) decreased sedentary time (10.2 ± 0.4 to 9.2 ± 0.3 h·d−1, P < 0.01). This resulted in significant increases in FMD (3.1% ± 0.3% to 3.8% ± 0.4%, P = 0.02) and CBFv (48.4 ± 2.6 to 51.4. ±2.6 cm·s−1, P = 0.02), without altering CA or CVMR. Before and after the 16-wk intervention, 3-h exposure to uninterrupted sitting decreased FMD and CBFv, whereas physical activity breaks prevented a decrease (both P < 0.05). CA and CVMR did not change (P > 0.20).

Conclusion

Long-term reduction in sedentary behavior improves peripheral vascular function and cerebral blood flow and acutely prevents impaired vascular function and decreased cerebral blood flow. These results highlight the potential benefits of reducing sedentary behavior to acutely and chronically improve cardio- or cerebrovascular risk.
Timing of Rectus Femoris and Biceps Femoris Muscle Activities in Both Legs at Maximal Running Speed
Authors: KAKEHATA GAKU , GOTO YUTA , ISO SHIGEO , KANOSUE KAZUYUKI
Published: August 2020

Purpose

The purpose of this study was to investigate the relationship between spatiotemporal variables of running and onset/offset timing of rectus femoris (RF) and biceps femoris (BF) muscle activities in both legs.

Methods

Eighteen male well-trained athletes (age = 20.7 ± 1.8 yr) were asked to run 50 m at maximal speed. The spatiotemporal variables (running speed, step frequency, and step length) over the distance from 30 to 50 m were measured. In addition, RF and BF muscle activities were obtained from both legs using wireless EMG sensors. To quantify the onset and offset timing of muscle activity, the band-pass filtered (20–450 Hz) EMG signal was processed using a Teager–Kaiser energy operator filter. We calculated RF and BF onset/offset timings (%) in both legs (e.g., ipsilateral leg RF [iRF] and contralateral leg BF [cBF]) during running cycle. Based on those timings, we obtained the EMG timing variables (%) as follows: “Switch1 (iBF-offset to iRF-onset),” “Switch2 (iRF-offset to iBF-onset),” “Scissors1 (cBF-onset to iRF-onset),” and “Scissors2 (iRF-offset to cBF-offset).

Results

We found that “Switch2” had positive (r = 0.495, P = 0.037), “Scissors1” had negative (r = −0.469, P = 0.049), and “Scissors2” had positive (r = 0.574, P = 0.013) correlations with step frequency. However, these variables had no significant correlations with running speed or step length.

Conclusions

These results indicate that higher step frequency would be achieved by smoother switching of the agonist–antagonist muscle activities and earlier iRF activation relative to the cBF activity. To improve sprint performance, athletes and coaches should consider not only muscle activities in one leg but also coordination of muscle activities in both legs.
Dynamic Changes of Performance Fatigability and Muscular O2 Saturation in a 4-km Cycling Time Trial
Authors: AZEVEDO RAFAEL A. , MILIONI FABIO , MURIAS JUAN M. , BERTUZZI ROMULO , MILLET GUILLAUME Y.
Published: August 2020

Exercise intensity variations throughout a cycling time trial (TT) might be influenced by subject’s functional state.

Purpose

The current study characterized the performance fatigability etiology, immediately after exercise cessation, and its relation to the dynamic changes in muscle O2 saturation (SmO2) at different TT phases.

Methods

Twelve males performed three separated TT of different distances, in a crossover counterbalanced design, until the end of the fast-start (FS, 827 ± 135 m), even-pace (EP, 3590 ± 66 m), or end-spurt (ES, 4000 m) TT phases. Performance fatigability was characterized by using isometric maximal voluntary contractions (IMVC), whereas the maximal voluntary activation (VA) and contractile function of knee extensors (e.g., peak torque of potentiated twitches [TwPt]) were evaluated using electrically evoked contractions performed before and immediately after each exercise bouts. SmO2, power output (PO), and EMG were also recorded.

Results

Immediately after the FS phase, there were lower values for IMVC (−23%), VA (−8%), and TwPt (−43%) (all P < 0.001), but no further changes were measured after EP (IMVC, −28%; VA, −8%; TwPt, −38%). After the ES phase, IMVC (−34%) and TwPt (−59%) further decreased compared with the previous phases (P < 0.05). There were lower SmO2 and higher EMG/PO values during FS and ES compared with EP phase.

Conclusion

FS and EP phases had similar performance fatigability etiology, but ES showed further impairments in contractile function. This later finding might be due to the abrupt changes in SmO2 and EMG/PO because of the high exercise intensity during the ES, which elicited maximal decline in contractile function at the finish line.
Effects of Horizontal Impeding Force Gait Training on Older Adult Push-Off Intensity
Authors: CONWAY KATIE A. , CRUDUP KEYAIRA L. , LEWEK MICHAEL D. , FRANZ JASON R.
Published: August 2020

Introduction

Aging and many gait pathologies are often characterized by deficits in push-off intensity (i.e., propulsive ground reaction forces and peak ankle moment and power output) during walking. Unfortunately, conventional interventions such as progressive resistance training, designed to enhance calf muscle mechanical output, generally fail to translate strength gains to functional improvements in habitual push-off intensity.

Methods

Horizontal impeding forces applied to the body’s center of mass systematically augment the mechanical output required from muscle–tendon units spanning the ankle during the push-off phase of walking, which could convey long-term benefits via training. Therefore, the purpose of this study was to investigate the preliminary efficacy of a 6-wk horizontal impeding force training paradigm on improving habitual push-off intensity in 11 healthy but not physically active older adults (age = 76 ± 4 yr, 6 females and 5 males).

Results

We found that older adults significantly (P < 0.05) increased measures of isometric strength by 18%, maximum walking speed by 10%, and 6-min walk test distance by 9% as a result of horizontal impeding force training. As a more clinically significant contribution of this work, we found that those subjects also increased habitual peak ankle moment and peak ankle power during push off after training by a significant 10% and 15%, respectively (P ≤ 0.036).

Conclusions

We conclude that the use of horizontal impeding forces in older adults improves their maximum muscular and walking capacities while encouraging access to newfound strength gains, thereby improving habitual push-off intensity during walking.
Identifying corpus luteum rupture as the culprit for haemoperitoneum
Authors: Pulappadi Vishnu Prasad , Manchanda Smita , SK Pritviraj , Hari Smriti
Published: August 2020

Corpus luteum rupture presenting as acute abdomen is an underdiagnosed condition. Though a self-limiting entity, its differentiation from other causes is essential to prevent unnecessary surgical procedures. The radiologist should be aware of the possibility of a ruptured haemorrhagic ovarian cyst in a female of reproductive age group presenting with pelvic pain and a large amount of haemorrhagic ascites. Imaging characteristically reveals a thick-walled cystic structure in the adnexa with internal echoes, focal discontinuity or irregularity of its wall with haemoperitoneum. While sonography is usually indicative of corpus luteum rupture, cross-sectional imaging (CT/MRI) can be used to confirm the diagnosis.