bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and functional alterations in heart and skeletal muscle following severe TAC in mice: impact of moderate exercise training
Authors: Böttner Julia , Werner Sarah , Adams Volker , Knauth Sarah , Kricke Angela , Thiele Holger , Büttner Petra
Published: September 2021

Background

Heart failure (HF) is the leading cause of death in western countries. Cardiac dysfunction is accompanied by skeletal alterations resulting in muscle weakness and fatigue. Exercise is an accepted interventional approach correcting cardiac and skeletal dysfunction, thereby improving mortality, re-hospitalization and quality of life. Animal models are used to characterize underpinning mechanisms. Transverse aortic constriction (TAC) results in cardiac pressure overload and finally HF. Whether exercise training improves cardiac remodeling and peripheral cachexia in the TAC mouse model was not analyzed yet. In this study, 2 weeks post TAC animals were randomized into two groups either performing a moderate exercise program (five times per week at 60% VO2 max for 40 min for a total of 8 weeks) or staying sedentary.

Results

In both TAC groups HF characteristics reduced ejection fraction (− 15% compared to sham, p < 0.001), cardiac remodeling (+ 22.5% cardiomyocyte cross sectional area compared to sham; p < 0.001) and coronary artery congestion (+ 34% diameter compared to sham; p = 0.008) were observed. Unexpectedly, peripheral cachexia was not detected. Furthermore, compared to sedentary group animals from the exercise group showed aggravated HF symptoms [heart area + 9% (p = 0.026), heart circumference + 7% (p = 0.002), right ventricular wall thickness − 30% (p = 0.003)] while muscle parameters were unchanged [Musculus soleus fiber diameter (p = 0.55), Musculus extensor digitorum longus contraction force (p = 0.90)].

Conclusion

The severe TAC model is inappropriate to study moderate exercise effects in HF with respect to cardiac and skeletal muscle improvements. Further, the phenotype induced by different TAC procedures should be well documented and taken into account when planning experiments.
Ixekizumab improves spinal pain, function, fatigue, stiffness, and sleep in radiographic axial Spondyloarthritis: COAST-V/W 52-week results
Authors: Deodhar Atul A. , Mease Philip J. , Rahman Proton , Navarro-Compán Victoria , Strand Vibeke , Hunter Theresa , Bolce Rebecca , Leon Luis , Lauzon Steve , Marzo-Ortega Helena
Published: September 2021

Background

This analysis assessed improvements in patients with radiographic axial spondyloarthritis (r-axSpA) treated with ixekizumab in the Assessment of Spondyloarthritis International Society (ASAS) treatment response domains and additional patient-reported outcomes at 1 year of treatment.

Methods

COAST-V and COAST-W were 52-week, phase 3, randomized controlled trials evaluating the efficacy and safety of ixekizumab in biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with radiographic spondyloarthritis, respectively. Patients were treated with 80-mg ixekizumab either every 2 weeks or every 4 weeks. Patient-reported outcomes included Patient Global Disease Activity, Spinal Pain, stiffness as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6, function as measured by the Bath Ankylosing Spondylitis Functional Index, fatigue as measured by the Fatigue Numeric Rating Scale and BASDAI question 1, Spinal Pain at Night, and sleep quality as measured by the Jenkins Sleep Evaluation Questionnaire. Mixed-effects models for repeated measures were used to analyze changes from baseline in patient-reported outcomes from weeks 1 to 16, and descriptive statistics were reported from weeks 20 to 52. Analysis of covariance with Scheffé’s method was used for the ASAS response association analyses.

Results

This study assessed 341 bDMARD-naïve and 316 TNFi-experienced patients in the placebo-controlled blinded treatment dosing period (weeks 1–16) as well as 329 bDMARD-naïve and 281 TNFi-experienced patients in the dose double-blind extended treatment period (weeks 20–52). bDMARD-naïve or TNFi-experienced patients treated with ixekizumab every 2 weeks and every 4 weeks reported improvements in patient global disease activity, spinal pain, function, stiffness, fatigue, spinal pain at night, and sleep quality through week 52. Greater correlations with improvements in all response domains were seen when comparing ASAS40 responders to ASAS20 non-responders (p < 0.001), with up to 10.5-fold greater improvements observed in ASAS40 responses compared with ASAS20 non-responders. Function and fatigue demonstrated the highest values.

Conclusions

Ixekizumab-treated bDMARD-naïve and TNFi-experienced patients with radiographic axial spondyloarthritis achieving ASAS40 reported sustained and consistent improvement in all ASAS response domains and other patient-reported outcomes though week 52, with spinal pain, function, and stiffness as major drivers of the response.

Trial registration

NCT02696785 and NCT02696798, March 2, 2016.
One-year evaluation of the treatment of hydrocephalus associated with Galen’s vein aneurysm: about 3 cases in a country with limited health resources
Authors: Barry Louncény Fatoumata , Cisse Yakhya , Faye Mohameth , Ndongo Mouhamadou Moustapha , Malangu Mhaks , Adjamou Amidou , Ba Momar Codé , Badiane Seydou Boubakar
Published: September 2021

Background

Aneurysm of vein of Galen is a rare congenital arteriovenous malformation. Clinical manifestations depend on the age of discovery. Endovascular embolization is currently the treatment of choice. This technique is not always available in developing countries. We report 3 cases treated symptomatically by endoscopic third ventriculostomy and ventriculoperitoneal shunt.

Cases presentation

Three patients, 7 months, 15 years, and 26 years old, received in a table of acute intracranial hypertension, associated for the first one with convulsions and for the second one with moderate heart failure. Bain CT scan revealed triventricular hydrocephalus secondary to sacciform dilatation of the Galen’s vein in all three patients, requiring symptomatic treatment by endoscopic third ventriculostomy for the first patient and ventriculoperitoneal shunt for the other two in the absence of an adequate clinical platform for endovascular embolization. The evolution was favorable at 1 year’s follow-up.

Conclusion

Galen’s vein aneurysm is a rare vascular malformation. It mainly affects newborns and small children but can be discovered in adulthood. Endovascular embolization is its treatment of choice. This technique is not always available in some countries, which makes it necessary to resort to symptomatic treatment by ventricular shunt.
Comparison of pretreatment with low-dose midazolam in combination with fentanyl and midazolam alone on the occurrence of etomidate-induced myoclonus—a randomized, double-blind study
Authors: Hareed Khaise , Kachru Nisha , Yadav Rupesh
Published: September 2021

Background

Myoclonus is reported to occur in 50–80% of patients receiving etomidate in the absence of pretreatment. The study aimed to evaluate the efficacy of pretreatment with low-dose midazolam and fentanyl, and midazolam alone to reduce the occurrence of etomidate-induced myoclonus. Sixty patients were randomly divided into 2 groups. In group MF, patients received pretreatment with intravenous (IV) midazolam 0.015mg/kg in a volume of 5 ml normal saline, followed by IV fentanyl 1μg/kg in a volume of 5 ml normal saline. In group M, patients received pretreatment with IV midazolam 0.03mg/kg in a volume of 5 ml normal saline, followed by 5ml of IV normal saline. The test drug was injected over 30 s, and after 120 s, IV etomidate 0.3 mg/kg was injected over 30 s. The patients were observed for 120 s for myoclonus and graded as mild, moderate, or severe. Heart rate, blood pressure, and oxygen saturation were recorded immediately after test drug injection and at every minute for 5 min.

Results

The demographic parameters and hemodynamic parameters were comparable between the two groups. In group M, the incidence of myoclonus was 36.67% (26.67% mild and 10% moderate) whereas, in the group MF, the incidence of myoclonus was 26.67% (3.33% mild, 16.67% moderate, and 6.67% severe). This incidence of myoclonus was significantly lower in group MF (p=0.030).

Conclusions

The incidence of etomidate-induced myoclonus is significantly lower in patients pretreated with midazolam and fentanyl combination as compared to midazolam alone.

Trial registration

Clinical Trial Registry Details:CTRI/2019/05/018920
Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis
Authors: Fu Yu , Lin Qing , Zhang Zhi-rong
Published: September 2021

Objective

To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility, we performed a meta-analysis on the association of the following single nucleotide polymorphisms (SNPs) of TNFSF4 with SLE: rs1234315, rs844648, rs2205960, rs704840, rs844644, rs10489265.

Methods

A literature-based search was conducted using PubMed, MEDLINE, Embase, Web of Science databases, and Cochrane Library databases to identify all relevant studies. And the association of TNFSF4 gene polymorphisms and SLE susceptibility was evaluated by pooled odds ratio (OR) with 95% confidence interval (CI).

Results

The meta-analysis produced overall OR of 1.42 (95% CI 1.36–1.49, P < 0.00001), 1.41 (95% CI 1.36–1.46, P < 0.00001) and 1.34 (95% CI 1.26–1.42, P < 0.00001) for the rs2205960, rs1234315 and rs704840 polymorphisms respectively, confirming these three SNPs confer a significant risk for the development of SLE. On the other hand, the meta-analysis produced overall OR of 0.92 (95% CI 0.70–1.21, P = 0.54) for the rs844644 polymorphism, suggesting no significant association. And no association was also found between either rs844648 1.11 (OR 1.11, 95% CI 0.86–1.43, P = 0.41) or rs10489265 (OR 1.17, 95% CI 0.94–1.47, P = 0.17) polymorphism with SLE susceptibility, respectively.

Conclusions

Our meta-analysis demonstrated that the TNFSF4 rs2205960, rs1234315 and rs844840 SNPs was significantly associated with an increased risk of SLE.
The vital importance of a web of prevention for effective biosafety and biosecurity in the twenty-first century
Authors: Novossiolova Tatyana A. , Whitby Simon , Dando Malcolm , Pearson Graham S.
Published: September 2021

Biological threats are complex and multifaceted, as evidenced by the ongoing COVID-19 pandemic. Their effective prevention and countering require multiple lines of collaborative action and sustained cross-sectorial coordination. This paper reviews the conclusions of Graham Pearson’s 1997JAMAarticle titled ‘The Complementary Role of Environmental and Security Biological Control Regimes in the 21st Century’, taking into account the international policy developments that have occurred over the past two decades. The paper underscores the utility of the concept of a ‘web of prevention’ for elucidating the need for continuous interaction between the international biosafety and international biosecurity regimes, in order to ensure that the life sciences are used only for peaceful purposes. The terms ‘biosafety’ and ‘biosecurity’ are used to denote the primary purpose of the two regimes: the international biosafety regime seeks to prevent the unintentional (accidental) release of pathogens and toxins, including naturally occurring disease, whereas the biosecurity regime seeks to prevent the deliberate release and misuse of pathogens and toxins. The paper concludes by recommending practical steps for strengthening the implementation of all elements of the web of prevention and upholding the norms against the hostile misuse of life sciences.
Effect of maternal separation and transportation stress on the bovine upper respiratory tract microbiome and the immune response to resident opportunistic pathogens
Authors: Malmuthuge Nilusha , Howell Angela , Arsic Natasa , Prysliak Tracy , Perez-Casal Jose , Griebel Philip
Published: September 2021

Background

The bovine upper respiratory tract (URT) microbiome includes opportunistic pathogens that cause respiratory disease and stress associated with maternal separation and transportation contributes to the severity of this respiratory disease. Stress is known to alter the gut microbiome but little is known regarding the effect of stress on the URT microbiota. This study used six-month old suckling beef calves to investigate whether maternal separation (weaned), by itself or combined with transportation (weaned + transport), altered the URT microbiome and host immune responses to resident opportunistic pathogens.

Results

Taxonomic and functional composition of the URT microbiome in suckling and weaned beef calves did not change significantly when serially sampled over a one-month period. Subtle temporal changes in the URT microbiome composition were observed in weaned + transport calves. Total bacterial density was lower (p < 0.05) on day 4 post-weaning in both the weaned and weaned + transport groups when compared to suckling calves. In addition, significant (p < 0.05) temporal changes in the density of the opportunistic pathogens,M. haemolyticaandP. multocida, were observed independent of treatment but these changes did not correlate with significantly increased (p < 0.05) serum antibody responses to both of these bacteria in the weaned and weaned + transport groups. Serum antibody responses toMy. bovis, another opportunistic pathogen, remained unchanged in all treatment groups. Weaning, by itself and in combination with transportation, also had significant (p < 0.05) short- (2 to 8 days post-weaning) and long-term (28 days post-weaning) effects on the expression of adrenergic receptor genes in blood leukocytes when compared to age-matched suckling beef calves.

Conclusions

Maternal separation (weaning) and transportation has minor effects on the taxonomic and functional composition of the URT microbiome and temporal changes in the density of opportunistic pathogen residing in the URT did not correlate with significant changes in immune responses to these bacteria. Significant changes in adrenergic receptor expression in blood leukocytes following weaning, with or without transportation, suggests altered neuroimmune regulation should be further investigated as a mechanism by which stress can alter host-microbiome interactions for some opportunistic respiratory pathogens that reside in the URT.
Prognostic factors and outcome of pineoblastoma: 10 years single-center experience
Authors: Elhemaly Ahmed , Zaghloul Mohamed S. , Ahmed Soha , Taha Hala , Refaat Amal , Maher Eslam , El-Beltagy Mohamed , Zekry Wael
Published: September 2021

Background

The survival of pineoblastoma patients is low, particularly in infants and those with metastatic disease. This study aimed to analyze the prognostic factors affecting the outcome of Pineoblastoma in different age groups.

Methods

A retrospective study included 33 patients. Twenty-two patients older than 3 years had upfront surgery, followed by induction CSI then 6 cycles of chemotherapy.

Eleven patients younger than 3 years underwent surgery, followed by induction chemotherapy then radiation therapy. Focal irradiation (54 Gy) was administrated in six patients, and CSI (23.4 Gy) with booster dose 30.6 Gy to the tumor bed in two patients followed by 4 cycles of chemotherapy.

Results

Patient’s age showed a significant impact on the outcome (P value = 0.001 for EFS and 0.002 for OS). The metastases’ presence did not impact the outcome negatively. The survival of patients with metastatic disease did not differ between age groups. However, age had a significant impact on the outcome of M0 disease, with 3-year EFS and OS of 65.3% and 74%, respectively, in the older group compared to 0% for both rates in younger patients. CSI showed a positive impact on survival. For all cases, the 3-year OS and EFS were 46.7% and 44.4%, respectively.

Conclusions

A multimodality approach is needed to treat this aggressive disease. Inadequate dose intensity affected our patients’ outcome negatively. A more aggressive approach using high-dose chemotherapy or CSI may be required to improve infantile pineoblastoma’s dismal outcome. Focal radiotherapy is not an efficacious treatment in infants due to its high-metastatic potential. Molecular typing should be considered to label patients who need a more intensified approach.
Necrotizing descending mediastinitis by Acinetobacter Baumannii in an out-patient: a case report
Authors: Cherrabi Kaoutar , Ouattassi Naouar , Tinni Omar , Kamal Dounia , Elalami Mohamed Noureddine
Published: September 2021

Background

Complicated cervico-facial cellulitis is an infectious disease which can have fatal prognosis. Necrotizing descending mediastinitis is a rare and fatal complication of cervico-thoracic cellulitis. This is the case of necrotizing descending mediastinitis complicating by a multi-resistant Acinetobacter Baumannii in a 27-year-old female, with early management of hemodynamic, respiratory and surgical emergencies, and very careful post-operative care, resulting in very satisfying outcome.

Case presentation

The patient presented was first treated with broad spectrum antibiotics for Ludwig’s angina for 10 days, then presented with a swelling of sub-mandibular, sub-mental, and cervical regions, a mild respiratory distress, with clinical enhancement of dyspnea in proclive position, tachycardia of 100 beats per minute, and arterial blood pressure of 10/5.

Clinical exam showed a tight trismus, with oral opening inferior to 1 cm, no inflammatory signs in facial and cervical swollen areas, and a saturation of 95% in proclive position. Auscultation suspected a pericardial effusion.

CT scan with and without injected contrast medium showed diffuse abscesses of sub-mental, sub-mandibular, retro-pharyngeal, para-pharyngeal regions, along with mediastinal abscesses and pericardial effusion. Trans-thoracic ultrasound showed 2 cm pericardial effusion, preserved function of myocardium, and without signs of tamponade.

The diagnosis of necrotizing descending mediastinitis with pericardial effusion was established.

The patient underwent a course of wide spectrum antibiotic therapy, low doses of cathecholamine, and a surgical drainage through cervical approach of all implicated zones. The surgical dissection was thorough and difficult due to diffuse fibrosis found in tissues of cervical regions. Two hundred milliliters of pus was evacuated, with a placement of surgical drains and Delbet blades.

Bacteriological exam found an Acinetobacter Baumannii sensitive to colistin only.

The post-operative outcome showed clinical and biological enhancement; however, a residual mediastinal collection appeared in control CT scan after 48 h, which indicated a surgical revision through mediastinoscopy.

The post-operative outcome was satisfying with stabilized clinical, biological, and radiological aspects.

Conclusions

Necrotizing descending mediastinitis is an infectious disease correlated with a very elevated mortality rate, and management is based on airway control, antibiotic therapy, and surgical treatment, as well as the post-operative intensive unit care.

Early diagnosis and appropriate management enhances outcome and decreases mortality significantly.
A common symptom with an uncommon diagnosis
Authors: Velayutham Prabu , Davis Prem , Savery Nishanth , Vaigundavasan Ramprasath
Published: September 2021

Background

Nasopharyngeal carcinoma is one of the uncommon tumours and the most difficult tumour to diagnose at an earlier stage due to the clandestine and deceptive nature. The incidence is more common in men with a peak incidence of 50 to 60 years. The suspicion of tumour at the earliest stage is very helpful in reducing morbidity and mortality.

Case presentation

A 45-year-old female presented with right hemi cranial headache for 2years without any comorbidities for that she consulted many hospitals and got symptomatic and empherical treatment in which her symptoms resolved temporarily and recurred. We did diagnostic nasal endoscopy and found a smooth globular mass in the right nasopharynx with contrast enhanced computerised tomography mass extending into the muscle plane which was found with the confirmation of diagnosis as undifferentiated nasopharyngeal carcinoma by histopathological examination and treated accordingly.

Conclusion

Although the diagnosis of the nasopharyngeal carcinoma in the earlier stage is difficult, it is an imperative one because the prognosis depends upon the stage of the disease in which it has been diagnosed. The clinicians always should have a suspicion of the rare disease for a day-to-day unresolved symptom, because the earlier diagnosis and appropriate management helps in the prevention of the life-threatening complications of any disease.
Factors favoring neck metastasis in patients underwent laryngectomy for laryngeal cancer
Authors: Sabaa Mohamed Abd Elmottaleb , El Batawi Ahmed Mahmoud
Published: September 2021

Background

One third of all head and neck cancers are caused by laryngeal cancer. However, the incidence and prevalence rates have decreased over the past 3 decades. Neck metastasis from cancer larynx is important to be addressed as its presence greatly reduces the probability of survival. However, quality of life should be taken into consideration. Hence, it was important to analyze factors related to neck metastasis from primary laryngeal cancer to detect any change of tumor behavior with time.

Results

One hundred thirty-eight patients underwent concomitant neck dissection with laryngectomy (total or partial). Supraglottic tumors had the greatest share in the neck metastasis with a count of 11 (of 26 neck metastasis), representing 42% and a total value of 11 (of 30 total supraglottic cancer) representing a tendency of spread in 37% of the total case number. Tumor midline crossing was present in 77% cases (20 of 26) with positive nodes, representing a P value 0.05.

Conclusion

This study investigated different factors related to lymph node metastasis from primary laryngeal tumor. The most important factors were the site of the tumor and its relation to the midline.
Computationally repurposed drugs and natural products against RNA dependent RNA polymerase as potential COVID-19 therapies
Authors: Piplani Sakshi , Singh Puneet Kumar , Winkler David A. , Petrovsky Nikolai
Published: September 2021

Repurposing of existing drugs and drug candidates is an ideal approach to identify new potential therapies for SARS-CoV-2 that can be tested without delay in human trials of infected patients. Here we applied a virtual screening approach using Autodock Vina and molecular dynamics simulation in tandem to calculate binding energies for repurposed drugs against the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). We thereby identified 80 promising compounds with potential activity against SARS-Cov2, consisting of a mixture of antiviral drugs, natural products and drugs with diverse modes of action. A substantial proportion of the top 80 compounds identified in this study had been shown by others to have SARS-CoV-2 antiviral effects in vitro or in vivo, thereby validating our approach. Amongst our top hits not previously reported to have SARS-CoV-2 activity, were eribulin, a macrocyclic ketone analogue of the marine compound halichondrin B and an anticancer drug, the AXL receptor tyrosine kinase inhibitor bemcentinib. Our top hits from our RdRp drug screen may not only have utility in treating COVID-19 but may provide a useful starting point for therapeutics against other coronaviruses. Hence, our modelling approach successfully identified multiple drugs with potential activity against SARS-CoV-2 RdRp.
Clinical Utility of Anti-Mullerian Hormone in Pediatrics
Authors: Kanakatti Shankar Roopa , Dowlut-McElroy Tazim , Dauber Andrew , Gomez-Lobo Veronica
Published: September 2021

Context

Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females. In this mini-review, we offer an updated synopsis on AMH and its clinical utility in pediatric patients.

Design and Results

A systematic search was undertaken for studies related to the physiology of AMH, normative data, and clinical role in pediatrics. In males, AMH, secreted by Sertoli cells, is found at high levels prenatally and throughout childhood and declines with progression through puberty to overlap with levels in females. Thus, serum AMH has clinical utility as a marker of testicular tissue in males with differences in sexual development and cryptorchidism and in the evaluation of persistent Mullerian duct syndrome. In females, serum AMH has been used as a predictive marker of ovarian reserve and fertility, but prepubertal and adolescent AMH assessments need to be interpreted cautiously. AMH is also a marker of tumor burden, progression, and recurrence in germ cell tumors of the ovary.

Conclusions

AMH has widespread clinical diagnostic utility in pediatrics but interpretation is often challenging and should be undertaken in the context of not only age and sex but also developmental and pubertal stage of the child. Nonstandardized assays necessitate the need for assay-specific normative data. The recognition of the role of AMH beyond gonadal development and maturation may usher in novel diagnostic and therapeutic applications that would further expand its utility in pediatric care.
Associations of Age at Menopause With Postmenopausal Bone Mineral Density and Fracture Risk in Women
Authors: Shieh Albert , Ruppert Kristine M , Greendale Gail A , Lian Yinjuan , Cauley Jane A , Burnett-Bowie Sherri-Ann , Karvonen-Guttierez Carrie , Karlamangla Arun S
Published: September 2021

Context

Menopause before age 45 is a risk factor for fractures, but menopause occurs at age ≥45 in ~90% of women.

Objective

To determine, in women with menopause at age ≥45, whether (1) years since the final menstrual period (FMP) is more strongly associated with postmenopausal bone mineral density (BMD) than chronological age and (2) lower age at FMP is related to more fractures.

Design and Setting

The Study of Women’s Health Across the Nation, a longitudinal cohort study of the menopause transition (MT).

Participants

A diverse cohort of ambulatory women (pre- or early perimenopausal at baseline, with 15 near-annual follow-up assessments).

Main Outcome Measures

Postmenopausal lumbar spine (LS) or femoral neck (FN) BMD (n = 1038) and time to fracture (n = 1554).

Results

Adjusted for age, body mass index (BMI), cigarette use, alcohol intake, baseline LS or FN BMD, baseline MT stage, and study site using multivariable linear regression, each additional year after the FMP was associated with 0.006 g/cm2 (P < 0.0001) and 0.004 g/cm2 (P < 0.0001) lower postmenopausal LS and FN BMD, respectively. Age was not related to FN BMD independent of years since FMP. In Cox proportional hazards regression, accounting for race/ethnicity, BMI, cigarette use, alcohol intake, prior fracture, diabetes status, exposure to bone-modifying medications/supplements, and study site, the hazard for incident fracture was 5% greater for each 1-year decrement in age at FMP (P = 0.02).

Conclusions

Years since the FMP is more strongly associated with postmenopausal BMD than chronological age, and earlier menopause is associated with more fractures.
The Relationship Between Continuous Glucose Monitoring and OGTT in Youth and Young Adults With Cystic Fibrosis
Authors: Chan Christine L , Pyle Laura , Vigers Tim , Zeitler Philip S , Nadeau Kristen J
Published: September 2021

Context

Early glucose abnormalities in people with cystic fibrosis (PwCF) are commonly detected by continuous glucose monitoring (CGM). Relationships between these CGM abnormalities and oral glucose tolerance testing (OGTT) in PwCF have not been fully characterized.

Objective

This work aimed to determine the relationship between CGM and common OGTT-derived estimates of β-cell function, including C-peptide index and oral disposition index (oDI) and to explore whether CGM can be used to screen for OGTT-defined prediabetes and cystic fibrosis–related diabetes (CFRD).

Methods

PwCF not on insulin and healthy controls aged 6 to 25 years were enrolled in a prospective study collecting OGTT and CGM. A subset underwent frequently sampled OGTTs (fsOGTT) with 7-point glucose, insulin, and C-peptide measurements. Pearson correlation coefficient was used to test the association between select CGM and fsOGTT measures. Receiver operating curve (ROC) analysis was applied to CGM variables to determine the cutoff optimizing sensitivity and specificity for detecting prediabetes and CFRD.

Results

A total of 120 participants (controls = 35, CF = 85), including 69 with fsOGTTs, were included. CGM coefficient of variation correlated inversely with C-peptide index (Cpeptide30-Cpeptide0/Glucose30-Glucose0) (r = –0.45, P < .001) and oDIcpeptide (C-peptide index)(1/cpep0) (r = –0.48, P < .0001). In PwCF, CGM variables had ROC – areas under the curve ranging from 0.43 to 0.57 for prediabetes and 0.47 to 0.6 for CFRD.

Conclusion

Greater glycemic variability on CGM correlated with reduced β-cell function. However, CGM performed poorly at discriminating individuals with and without OGTT-defined CFRD and prediabetes. Prospective studies are now needed to determine how well the different tests predict clinically relevant nonglycemic outcomes in PwCF.
Divergent Patterns of Antifracture Medication Use Following Fracture on Therapy: A Population-Based Cohort Study
Authors: Kline Gregory A , Morin Suzanne N , Lix Lisa M , Leslie William D
Published: September 2021

Context

Fracture on therapy should motivate better antifracture medication adherence.

Objective

This study aimed to describe osteoporosis medication adherence in women before and following a fracture.

Methods

This retrospective cohort analysis of antifracture medication possession ratios (MPR) among women in the Manitoba BMD Registry (1996-2013) included menopausal women who started antifracture drug therapy after a dual-energy x-ray absorptiometry (DXA)-BMD assessment with follow-up for 5 years during which a nontraumatic fracture occurred at least 1 year after starting treatment. Linked prescription records determined medication adherence (estimated by MPR) in 1-year intervals. The variable of interest was MPR in the year before and after the year in which the fracture occurred, with subgroup analyses according to duration of treatment pre-fracture. We chose an MPR of ≥ 0.50 to indicate minimum adherence needed for drug efficacy.

Results

There were 585 women with fracture on therapy, 193 (33%) had hip or vertebral fracture. Bisphosphonates accounted for 82.2% of therapies. Median MPR the year prior to fracture was 0.89 (IQR, 0.49-1.0) and 0.69 (IQR, 0.07-0.96) the year following the year of fracture (P < 0.0001). The percentage of women with MPR ≥ 0.5 pre-fracture was 73.8%, dropping to 57.3% post-fracture (P < 0.0001); when restricted to hip/vertebral fracture, results were similar (58.2% to 33.3%; P < 0.002). Among those with pre-fracture MPR < 0.5, only 21.7% achieved a post-fracture MPR ≥ 0.5.

Conclusions

Although fracture on therapy may motivate sustained/improved adherence, MPR remains low or even declines after fracture in many. This could reflect natural decline in MPR with time but is paradoxical to expectations. Fracture on therapy represents an important opportunity for clinicians to reemphasize treatment adherence.
Mask, the Drosophila ankyrin repeat and KH domain-containing protein, affects microtubule stability
Authors: Martinez Daniel , Zhu Mingwei , Guidry Jessie J. , Majeste Niles , Mao Hui , Yanofsky Sarah T. , Tian Xiaolin , Wu Chunlai
Published: September 2021

Proper regulation of microtubule (MT) stability and dynamics is vital for essential cellular processes, including axonal transportation and synaptic growth and remodeling in neurons. In the present study, we demonstrate that the Drosophila ankyrin repeat and KH domain-containing protein Mask negatively affects MT stability in both larval muscles and motor neurons. In larval muscles, loss-of-function of mask increases MT polymer length, and in motor neurons, loss of mask function results in overexpansion of the presynaptic terminal at the larval neuromuscular junctions (NMJs). mask genetically interacts with stathmin (stai), a neuronal modulator of MT stability, in the regulation of axon transportation and synaptic terminal stability. Our structure–function analysis of Mask revealed that its ankyrin repeats domain-containing N-terminal portion is sufficient to mediate Mask's impact on MT stability. Furthermore, we discovered that Mask negatively regulates the abundance of the MT-associated protein Jupiter in motor neuron axons, and that neuronal knocking down of Jupiter partially suppresses mask loss-of-function phenotypes at the larval NMJs. Taken together, our studies demonstrate that Mask is a novel regulator for MT stability, and such a role of Mask requires normal function of Jupiter.
Functional imaging of COPD by CT and MRI
Authors: Lynch David A
Published: September 2021

This commentary reviews the contribution of imaging by CT and MRI to functional assessment in chronic obstructive pulmonary disease (COPD). CT can help individualize the assessment of COPD by quantifying emphysema, air trapping and airway wall thickening, potentially leading to more specific treatments for these distinct components of COPD. Longitudinal changes in these metrics can help assess progression or improvement. On hyperpolarized gas MRI, the apparent diffusion coefficient of provides an index of airspace enlargement reflecting emphysema. Perfusion imaging and measurement of pulmonary vascular volume on non-contrast CT provide insight into the contribution of pulmonary vascular disease to pulmonary impairment. Functional imaging is particularly valuable in detecting early lung dysfunction in subjects with inhalational exposures.
Physical density estimations of single- and dual-energy CT using material-based forward projection algorithm: a simulation study
Authors: Li Kai-Wen , Fujiwara Daiyu , Haga Akihiro , Liu Huisheng , Geng Li-Sheng
Published: September 2021

Objectives:

This study aims to evaluate the accuracy of physical density prediction in single-energy CT (SECT) and dual-energy CT (DECT) by adapting a fully simulation-based method using a material-based forward projection algorithm (MBFPA).

Methods:

We used biological tissues referenced in ICRU Report 44 and tissue substitutes to prepare three different types of phantoms for calibrating the Hounsfield unit (HU)-to-density curves. Sinograms were first virtually generated by the MBFPA with four representative energy spectra (i.e. 80 kVp, 100 kVp, 120 kVp, and 6 MVp) and then reconstructed to form realistic CT images by adding statistical noise. The HU-to-density curves in each spectrum and their pairwise combinations were derived from the CT images. The accuracy of these curves was validated using the ICRP110 human phantoms.

Results:

The relative mean square errors (RMSEs) of the physical density by the HU-to-density curves calibrated with kV SECT nearly presented no phantom size dependence. The kV–kV DECT calibrated curves were also comparable with those from the kV SECT. The phantom size effect became notable when the MV X-ray beams were employed for both SECT and DECT due to beam-hardening effects. The RMSEs were decreased using the biological tissue phantom.

Conclusion:

Simulation-based density prediction can be useful in the theoretical analysis of SECT and DECT calibrations. The results of this study indicated that the accuracy of SECT calibration is comparable with that of DECT using biological tissues. The size and shape of the calibration phantom could affect the accuracy, especially for MV CT calibrations.

Advances in knowledge:

The present study is based on a full simulation environment, which accommodates various situations such as SECT, kV–kV DECT, and even kV–MV DECT. In this paper, we presented the advances pertaining to the accuracy of the physical density prediction when applied to SECT and DECT in the MV X-ray energy range. To the best of our knowledge, this study is the first to validate the physical density estimation both in SECT and DECT using human-type phantoms.
Zonal anatomy of the prostate using magnetic resonance imaging, morphometrics, and radiomic features: impact of age-related changes
Authors: Laschkar Sophie , Montagne Sarah , De Kerviler Eric , Roupret Morgan , Lucidarme Olivier , Cussenot Olivier , Renard Penna Raphaele
Published: September 2021

Objective:

To evaluate the impact of age on the zonal anatomy of the prostate by MRI using morphometric and textural analysis.

Methods:

A total of 154 men (mean age: 63 years) who underwent MRI due to a high prostate-specific antigen (PSA) level were included retrospectively. At each MRI examination the following variables were measured: overall dimensions of the prostate (whole gland (WG), transitional zone (TZ), and peripheral zone (PZ)), and thickness of the anterior fibromuscular stroma (AFMS) and the periprostatic venous plexus (PPVP) on T  2 weighted images. Identical regions of interest (ROIs) were delineated on the apparent diffusion coefficient (ADC) map on the anterior (horn) and posterior part of the PZ. Textural (TexRAD®) parameter differences between TZ and PZ ROIs on T  2 weighted images were analyzed by linear regression. Results were correlated with age (distributed into five decades from 22 to 89 years).

Results:

Age was positively correlated with PSA level and glandular volumes (WG, TZ, and TZ/WG ratio; p < 0.0001) and was negatively correlated with AFSM and PPVP thickness (p < 0.0001). There was a positive correlation between ADC values of the PZ and age (p = 0.003) and between entropy of the TZ and PZ and age (p < 0.001).

Conclusion:

Gradual variations in morphologic and textural features of the prostate were observed with age, mainly due to the increase in TZ volume while PZ volume tended to decrease. These modifications resulted in textural changes mainly at the expense of entropy.

Advances in knowledge:

Entropy could be relevant for studying the process of aging of the prostate.
Imaging evaluation of lung cancer treated with PD-1/PD-L1 inhibitors
Authors: Mohammed Nader , Zhou Rong Rong , Xiong Zeng
Published: September 2021

Immunotherapy (PD-1/PD-L1 inhibitors) has attracted attention for lung cancer treatment and recasted the administration of immunotherapeutics to patients who have advanced/metastatic diseases. Whether in combination or as monotherapy, these medications have become common therapies for certain patients with lung cancer. Moreover, their usage is expected to expand widely in the future. This review aims to discuss the imaging evaluation of lung cancer response to PD-1/PD-L1 therapy with focus on new radiological criteria for immunotherapy response. Abnormal radiological responses (pseudoprogression, dissociative responses, and hyperprogression) and immune-related adverse events are also described.
Outcome-based multiobjective optimization of lymphoma radiation therapy plans
Authors: Modiri Arezoo , Vogelius Ivan , Rechner Laura Ann , Nygård Lotte , Bentzen Søren M , Specht Lena
Published: September 2021

At its core, radiation therapy (RT) requires balancing therapeutic effects against risk of adverse events in cancer survivors. The radiation oncologist weighs numerous disease and patient-level factors when considering the expected risk–benefit ratio of combined treatment modalities. As part of this, RT plan optimization software is used to find a clinically acceptable RT plan delivering a prescribed dose to the target volume while respecting pre-defined radiation dose–volume constraints for selected organs at risk. The obvious limitation to the current approach is that it is virtually impossible to ensure the selected treatment plan could not be bettered by an alternative plan providing improved disease control and/or reduced risk of adverse events in this individual. Outcome-based optimization refers to a strategy where all planning objectives are defined by modeled estimates of a specific outcome’s probability. Noting that various adverse events and disease control are generally incommensurable, leads to the concept of a Pareto-optimal plan: a plan where no single objective can be improved without degrading one or more of the remaining objectives. Further benefits of outcome-based multiobjective optimization are that quantitative estimates of risks and benefit are obtained as are the effects of choosing a different trade-off between competing objectives. Furthermore, patient-level risk factors and combined treatment modalities may be integrated directly into plan optimization. Here, we present this approach in the clinical setting of multimodality therapy for malignant lymphoma, a malignancy with marked heterogeneity in biology, target localization, and patient characteristics. We discuss future research priorities including the potential of artificial intelligence.
Use of weight-based vs age-based groupings in the study of typical values of air kerma area product (PKA) for paediatric radiographs of chest and abdomen
Authors: Delakis Ioannis , Kelly Charlotte
Published: September 2021

Objective:

To compare age groupings versus weight groupings in the calculation of typical air kerma area product (PKA) values in paediatric X-ray exams of chest and abdomen in our hospital.

Methods:

Data were analysed from 687 abdominal and 1374 chest X-ray examinations. The PKA of exams was extracted with Radimetrics, and patient weights were collected from electronic records. Data were organised in different age groups and typical PKA values were estimated. The process was repeated by organising data in different weight groups.

Results:

Typical PKA values for the four younger age groups (<1m, 1m - < 4y, 4y - < 10y and 10y - < 14y) were comparable to typical values for their equivalent weight groups (<5 kg, 5–15 kg, 15–30 kg and 30–50 kg, respectively). However, typical PKA values at the late adolescent age group (14y - < 18y) were much lower than its equivalent weight group (>50 kg).

Conclusions:

Age and weight groupings were found at our site to be interchangeable for the calculation of typical paediatric PKA values. The only exception was the late adolescent group, whose weight distribution can account for the difference in typical PKA results within its equivalent weight group.

Advances in knowledge:

In calculating typical PKA values for radiological paediatric body examinations, departments must ascertain if using age groups, which is typical practice, is equivalent to using weight groups. Otherwise, results may misrepresent local practice.
Hemostasis using re-radiofrequency ablation for hepatic tract bleeding after ultrasound-guided percutaneous radiofrequency ablation of hepatic tumors
Authors: Song Kyoung Doo , Lee Min Woo , Rhim Hyunchul , Kang Tae Wook
Published: September 2021

Objective:

To evaluate the hemostatic efficacy of re-radiofrequency ablation (re-RFA) for hepatic tract bleeding after ultrasound-guided RFA of hepatic tumors.

Methods:

A total of 4679 percutaneous ultrasound-guided RFA procedures were performed for hepatic tumors at Samsung Medical Center between January 2012 and December 2020. We identified patients who had hepatic tract bleeding after RFA by reviewing radiologic reports and ultrasound images and investigated the measures taken to control the bleeding and their outcomes. We also identified patients who had a significant peritoneal hematoma on immediate post-RFA CT or underwent transarterial embolization to control hepatic bleeding after RFA of hepatic tumors.

Results:

In total, 91 patients with tract bleeding after RFA were identified. As initial measures to control the bleeding, external compression, re-RFA, and observation were performed in 71 (78%), 17 (19%), and 3 (3%) patients, respectively. Hemostasis using re-RFA was attempted to control tract bleeding in 40 patients as an initial measure or an additional measure after other initial efforts. In all 40 patients, the bleeding stopped after re-RFA on Doppler ultrasound, and there was no active bleeding on the immediate follow-up CT. During the study period, in the years when re-RFA was performed frequently, the number of transarterial embolizations to control tract bleeding and significant peritoneal hematoma formation tended to be low.

Conclusion:

Hemostasis using re-RFA of the needle tract is effective in controlling tract bleeding after ultrasound-guided RFA of hepatic tumors.

Advances in knowledge:

Re-RFA is a simple, safe, and effective method to control tract bleeding.
Tarlov cysts in back pain patients: prevalence, measurement method and reporting points
Authors: Shoyab Muhammad
Published: September 2021

Objective:

Determining the prevalence of Tarlov cysts in low back pain patients.

Methods and materials:

The picture archiving & communication system (PACS) & hospital information system (HIS) of a corporate hospital were retrospectively analyzed to determine the percentage of Tarlov cysts among patients undergoing spinal MRI for back pain over 3 years (January 2017 to December 2019).

Results:

384 patients had undergone spinal MRI for back pain over the study period, and 25 of them (6.51%) had Tarlov cysts. Vast majority (15 cases) showed cysts located at S2/S3 level, and few were found at S1/S2 and other levels. Single cysts were found in most (=18) of the cases, while 7 cases of multiple / bilateral cysts were found. Cyst dimensions were higher in craniocaudal than anteroposterior or transverse directions. In case of multiple cysts, one or two cysts were noted as dominant, having higher dimensions than the others. The study data revealed no gender or age predilection.

Conclusions:

We conclude that including the entire sacrum with a T2 sagittal sequence in all MRI for low back pain can increase detection of Tarlov cysts, and thereby provide more data for further analysis.

Advances in knowledge:

We propose the concept of one “dominant” cyst when there are multiple Tarlov cysts. We recommend that diameter or size of Tarlov cysts be specified to their craniocaudal dimension. We also suggest reporting points for contextual structured reporting, viz. presence or absence of bony scalloping, neural foraminal narrowing, nerve root compression or extraforaminal extension.
Prenatal prediction of respiratory distress syndrome by multimodality approach using 3D lung ultrasound, lung-to-liver intensity ratio tissue histogram and pulmonary artery Doppler assessment of fetal lung maturity
Authors: Khalifa Yasmin Essameldin abdalla , Aboulghar Mona M , Hamed Soha T , Tomerak Rania H , Asfour Ahmed M , Kamal Eman F
Published: September 2021

Objective:

Studying the correlation of different lung parameters, using three-dimensional ultrasound (3D US) with fetal lung maturity (FLM) to predict the development of neonatal respiratory distress syndrome (RDS).

Methods:

Three-dimensional ultrasound was done to record the fetal lung volume (FLV), fetal lung-to-liver intensity ratio (FLLIR) and the main pulmonary artery (MPA) blood flow parameters; pulsatility index (PI), resistive index (RI) and acceleration time-to-ejection time ratio (At/Et), to 218 women between 32 and 40 weeks gestational age within 24 h from labor.

Results:

Of 218 fetuses examined, final analysis was done for 143 fetuses. Thirty eight (26.5%) were diagnosed with RDS. The MPA PI and RI were significantly higher in fetuses diagnosed with RDS compared with those without (2.51 ± 0.33 and 0.90 ± 0.03 cm/s versus 1.96 ± 0.20 and 0.84 ± 0.01 cm/s; p value < 0.001 and <0.001 respectively). MPA At/Et was significantly lower (0.24 ± 0.04 vs 0.35 ± 0.04; p value < 0.001). FLLIR was significantly lower (1.04 ± 0.07 vs 1.18 ± 0.11; p value < 0.001), and the mean FLV was significantly smaller (28.23 ± 5.63, vs 38.87 ± 4.68 cm3; p value < 0.001).

Conclusion:

Main pulmonary artery (PI, RI, At/Et ratio), FLIIR, and mean FLV can be used as reliable predictors of neonatal RDS.

Advances in knowledge:

3D ultrasound VOCAL technique, ultrasound tissue histogram and pulmonary artery Doppler are reliable tools for prenatal prediction of fetal lung maturity.