bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of TNF inhibitors with bisphosphonates vs bisphosphonates alone on bone mineral density and bone and cartilage biomarkers at 1 year in patients with rheumatoid arthritis: A prospective study
Authors: Nagase Yuichi , Nagashima Masakazu , Shimane Kenichi , Nishikawa Takuji , Naito Masashi , Tanaka Sakae
Published: October 2021

Background

The present study aimed prospectively to investigate the effect of a combination of tumour necrosis factor inhibitors and bisphosphonates (TNFi with BP) on bone mineral density (BMD) and bone and cartilage biomarkers compared to that of BP alone at 1 year in patients with rheumatoid arthritis (RA).

Methods

Two groups of patients with RA and osteoporosis were enrolled. One group (37 patients) had already received BP, while the other group (37 patients) had already received TNFi with BP. The serum bone resorption and formation markers, cartilage markers, BMD in the lumbar spine, femoral neck, and distal radius were prospectively investigated at the beginning of the study and at 6 and 12 months.

Results

The percentages of change recorded for the various assessment categories were as follows in the TNFi with BP group: (1) tartrate-resistant acid phosphatase-5b had significantly decreased and osteocalcin had increased; (2) matrix metalloproteinase-3 and cartilage oligomeric matrix protein had significantly decreased; and (3) each BMD did not differ significantly between the groups.

Conclusion

Our data suggested that TNFi with BP therapy not only suppressed cartilage degradation and bone resorption but also increased bone formation; however, this treatment did not affect the BMD at 1 year.
Complexity of enthesitis and new bone formation in ankylosing spondylitis: current understanding of the immunopathology and therapeutic approaches
Authors: Kusuda Masaki , Haroon Nigil , Nakamura Akihiro
Published: October 2021

Despite increasing availability of treatments for spondyloarthritis (SpA) including tumour necrosis factor (TNF) and interleukin-17 (IL-17) inhibitors, there is no established treatment that abates new bone formation (NBF) in ankylosing spondylitis (AS), a subset of SpA. Recent research on TNF has revealed the increased level of transmembrane TNF in the joint tissue of SpA patients compared to that of rheumatoid arthritis patients, which appears to facilitate TNF-driven osteo-proliferative changes in AS. In addition, there is considerable interest in the central role of IL-23/IL-17 axis in type 3 immunity and the therapeutic potential of blocking this axis to ameliorate enthesitis and NBF in AS. AS immunopathology involves a variety of immune cells, including both innate and adoptive immune cells, to orchestrate the immune response driving type 3 immunity. In response to external stimuli of inflammatory cytokines, local osteo-chondral progenitor cells activate intra-cellular anabolic molecules and signals involving hedgehog, bone morphogenetic proteins, receptor activator of nuclear factor kappa-B ligand, and Wnt pathways to promote NBF in AS. Here, we provide an overview of the current immunopathology and future directions for the treatment of enthesitis and NBF associated with AS.
Fast interaction dynamics of G-quadruplex and RGG-rich peptides unveiled in zero-mode waveguides
Authors: Patra Satyajit , Claude Jean-Benoît , Naubron Jean-Valère , Wenger Jérome
Published: October 2021

G-quadruplexes (GQs), a non-canonical form of DNA, are receiving a huge interest as target sites for potential applications in antiviral and anticancer drug treatments. The biological functions of GQs can be controlled by specifically binding proteins known as GQs binding proteins. Some of the GQs binding proteins contain an arginine and glycine-rich sequence known as RGG peptide. Despite the important role of RGG, the GQs-RGG interaction remains poorly understood. By single molecule measurements, the interaction dynamics can be determined in principle. However, the RGG–GQs interaction occurs at micromolar concentrations, making conventional single-molecule experiments impossible with a diffraction-limited confocal microscope. Here, we use a 120 nm zero-mode waveguide (ZMW) nanoaperture to overcome the diffraction limit. The combination of dual-color fluorescence cross-correlation spectroscopy (FCCS) with FRET is used to unveil the interaction dynamics and measure the association and dissociation rates. Our data show that the RGG–GQs interaction is predominantly driven by electrostatics but that a specific affinity between the RGG sequence and the GQs structure is preserved. The single molecule approach at micromolar concentration is the key to improve our understanding of GQs function and develop its therapeutic applications by screening a large library of GQs-targeting peptides and proteins.
DNA sequence and methylation prescribe the inside-out conformational dynamics and bending energetics of DNA minicircles
Authors: Yoo Jejoong , Park Sangwoo , Maffeo Christopher , Ha Taekjip , Aksimentiev Aleksei
Published: October 2021

Eukaryotic genome and methylome encode DNA fragments’ propensity to form nucleosome particles. Although the mechanical properties of DNA possibly orchestrate such encoding, the definite link between ‘omics’ and DNA energetics has remained elusive. Here, we bridge the divide by examining the sequence-dependent energetics of highly bent DNA. Molecular dynamics simulations of 42 intact DNA minicircles reveal that each DNA minicircle undergoes inside-out conformational transitions with the most likely configuration uniquely prescribed by the nucleotide sequence and methylation of DNA. The minicircles’ local geometry consists of straight segments connected by sharp bends compressing the DNA’s inward-facing major groove. Such an uneven distribution of the bending stress favors minimum free energy configurations that avoid stiff base pair sequences at inward-facing major grooves. Analysis of the minicircles’ inside-out free energy landscapes yields a discrete worm-like chain model of bent DNA energetics that accurately account for its nucleotide sequence and methylation. Experimentally measuring the dependence of the DNA looping time on the DNA sequence validates the model. When applied to a nucleosome-like DNA configuration, the model quantitatively reproduces yeast and human genomes’ nucleosome occupancy. Further analyses of the genome-wide chromatin structure data suggest that DNA bending energetics is a fundamental determinant of genome architecture.
Integration of single cell data by disentangled representation learning
Authors: Guo Tiantian , Chen Yang , Shi Minglei , Li Xiangyu , Zhang Michael Q
Published: October 2021

Recent developments of single cell RNA-sequencing technologies lead to the exponential growth of single cell sequencing datasets across different conditions. Combining these datasets helps to better understand cellular identity and function. However, it is challenging to integrate different datasets from different laboratories or technologies due to batch effect, which are interspersed with biological variances. To overcome this problem, we have proposed Single Cell Integration by Disentangled Representation Learning (SCIDRL), a domain adaption-based method, to learn low-dimensional representations invariant to batch effect. This method can efficiently remove batch effect while retaining cell type purity. We applied it to thirteen diverse simulated and real datasets. Benchmark results show that SCIDRL outperforms other methods in most cases and exhibits excellent performances in two common situations: (i) effective integration of batch-shared rare cell types and preservation of batch-specific rare cell types; (ii) reliable integration of datasets with different cell compositions. This demonstrates SCIDRL will offer a valuable tool for researchers to decode the enigma of cell heterogeneity.
Robotic-Assisted Trajectory Into Kambin's Triangle During Percutaneous Transforaminal Lumbar Interbody Fusion—Initial Case Series Investigating Safety and Efficacy
Authors: Dalton Tara , Sykes David , Wang Timothy Y , Donnelly Dustin , Than Khoi D , Karikari Isaac O , Goodwin C Rory , Gupta Dhanesh K , Wiggins Walter F , Abd-El-Barr Muhammad M
Published: October 2021

BACKGROUND

Minimally invasive spine surgery (MISS) has the potential to further advance with the use of robot-assisted (RA) techniques. While RA pedicle screw placement has been extensively investigated, there is a lack of literature on the use of the robot for other tasks, such as accessing Kambin's triangle in percutaneous lumbar interbody fusion (percLIF).

OBJECTIVE

To characterize the surgical feasibility and preliminary outcomes of an initial case series of 10 patients receiving percLIF with RA cage placement via Kambin's triangle.

METHODS

We performed a single-center, retrospective review of patients undergoing RA percLIF using robot-guided trajectory to access Kambin's triangle for cage placement. Patients undergoing RA percLIF were eligible for enrollment. Baseline health and demographic information in addition to peri- and postoperative data was collected. The dimensions of each patient's Kambin's triangle were measured.

RESULTS

Ten patients and 11 levels with spondylolisthesis were retrospectively reviewed. All patients successfully underwent the planned procedure without perioperative complications. Four patients underwent their procedure with awake anesthesia. The average dimension of Kambin's triangle was 66.3 m2. With the exception of 1 patient who stayed in the hospital for 7 d, the average length of stay was 1.2 d, with 2 patients discharged the day of surgery. No patients suffered postoperative motor or sensory deficits. Spinopelvic parameters and anterior and posterior disc heights were improved with surgery.

CONCLUSION

As MISS continues to evolve, further exploration of robot-guided surgical practice, such as our technique, will lead to creative solutions to challenging anatomical variation and overall improved patient care.
Influence of global environmental Change on plankton
Authors: Raven John A , Beardall John
Published: October 2021

Much has been published on the effects of ocean acidification on plankton since the original Royal Society 2005 report. In addition to direct effects on primary production, it is clear that ocean acidification also has profound consequences for biogeochemistry. Furthermore, although ocean acidification can have direct effects of on grazers such as copepods, acidification induces changes in nutritional value of phytoplankton which can be passed on up the food chain. There has also been recognition of the complexity of the interactions between elevated CO2 and other environmental factors and this has seen an upsurge in climate change research involving multifactorial experiments. In particular, the interaction of ocean acidification with global warming resulting from the increasing greenhouse effect has been investigated. There has also been research on acidification and warming effects in inland water plankton. These, combined with novel experimental techniques and long term studies of genetic adaptation, are providing better insights to plankton biology and communities in a future world.
Tapering of TNF inhibitors in axial spondyloarthritis in routine care — 2-year clinical and MRI outcomes and predictors of successful tapering
Authors: Wetterslev Marie , Georgiadis Stylianos , Sørensen Inge Juul , Pedersen Susanne Juhl , Christiansen Sara Nysom , Hetland Merete Lund , Brahe Cecilie Heegaard , Bakkegaard Mads , Duer Anne , Boesen Mikael , Gosvig Kasper Kjærulf , Møller Jakob Møllenbach , Krogh Niels Steen , Jensen Bente , Madsen Ole Rintek , Christensen Jan , Hansen Annette , Nørregaard Jesper , Røgind Henrik , Østergaard Mikkel
Published: October 2021

Objectives

In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered TNF inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining clinical remission after flare and the progression on MRI/radiography were also assessed.

Methods

One-hundred-and-nine patients (78 [72%]/31 [28%] receiving standard and reduced dose, respectively) in clinical remission (BASDAI < 40, physician global score < 40) and no signs of disease activity the previous year tapered TNFi as follows: to two-thirds of standard dose at baseline, half at week 16, one-third at week 32 and discontinuation at week 48. Patients experiencing clinical, BASDAI or MRI flare (predefined criteria) stopped tapering and escalated to previous dose. Prediction analyses were performed by multivariable regression.

Results

One hundred and six patients (97%) completed 2 years’ follow-up; 55 patients (52%) had successfully tapered: 23 (22%) receiving two-thirds, 15 (14%) half, 16 (15%) one-third dose and 1 (1%) discontinued. In patients at standard dose at baseline (n = 78), lower physician global score was the only independent predictor of successful tapering (odds ratio [OR] = 0.79 [95% CI: 0.64, 0.93]; P = 0.003). In the entire patient group lower physician global score (OR = 0.86 [0.75, 0.98]; P = 0.017), lower Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Erosion score (OR = 0.78 [0.57, 0.98]; P = 0.029) and current smoker (OR = 3.28 [1.15, 10.57]; P = 0.026) were independent predictors of successful tapering. At 2 years, 97% of patients were in clinical remission. Minimal changes in imaging findings were observed.

Conclusion

After 2 years following a clinical guideline, 52% of patients with axSpA in clinical remission had successfully tapered TNFi, only 1% discontinued. Baseline physician global score was an independent predictor of successful tapering.
Asian in the Time of COVID-19: Creating a Social Work Agenda for Asian American and Pacific Islander Communities
Authors: Azhar Sameena , Farina Anne , Alvarez Antonia R. G. , Klumpner Susan
Published: October 2021

The health of Asian American and Pacific Islander (AAPI) communities remains an understudied area of racial/ethnic minority research in the United States, and even more so in the field of social work. The COVID-19 pandemic has highlighted how AAPI health and social welfare issues have not received adequate attention in social policy, social work practice, and research. Contrary to model minority myths, AAPIs are subject to racialized attitudes and discrimination, which have been associated with adverse physical and mental health outcomes, including increased anxiety, depression, and suicidality. Drawing from the theoretical framework of AsianCrit, which is grounded in critical race theory, authors analyze health disparities among AAPI communities as reflected in COVID-19 hospitalizations and fatalities, as well as increases in acts of anti-Asian racism and xenophobia. Better understanding health disparities of AAPI communities needs to be a key research issue for social workers in future years. The authors conclude by offering a short set of recommendations to improve social policy, social work practice, and research to more aptly address contemporary social issues impacting AAPI communities.
Understanding COVID-19 through a Complex Trauma Lens: Implications for Effective Psychosocial Responses
Authors: Alessi Edward J , Hutchison Courtney , Kahn Sarilee
Published: October 2021

The psychosocial impact of COVID-19 on individuals, families, and communities will likely persist for years to come. While briefing notes informed by disaster psychology and crisis management have been released to guide social workers and other mental health professionals in their work during the pandemic, the far-reaching impacts of COVID-19 may require inclusion of additional theories of trauma and resilience. Thus, this article first examines the application of complex trauma theory as an effective framework for assessing the psychosocial impacts of the pandemic, especially among individuals with prior trauma exposure, those with preexisting mental illness, and communities affected by marginalization and historical trauma. Authors then discuss the importance of using trauma-informed practice to address the effects of the pandemic on both individual and community levels during this unprecedented moment in history.
Effect of supplementing lactation and nursery pig diets with capsaicin on growth performance and gene expression of nursery pigs
Authors: Rosa-Medina Eduardo A , Urriola Pedro E , Jang Jae C , Faulk Christopher D , Johnston Lee J , Shurson Gerald C
Published: October 2021

The objective of this study was to determine the effects of supplementing capsaicin in diets for lactating sows and their offspring on the growth performance and gene expression of pigs postweaning. Twenty-eight multiparous sows were fed corn-soybean meal-based diets without (n = 14) and with (n = 14) capsaicin (2.5 mg/kg) during a 19-d lactation period. Litters from these sows (n = 288 pigs) were weaned and assigned to 36 blocks (pens) based on maternal dietary treatment and initial body weight (BW) to provide 8 pigs/pen. Blocks were assigned randomly to one of two nursery dietary treatments (control or capsaicin supplemented diets) in a 2 × 2 factorial arrangement of treatments to provide nine replications per treatment combination. A three-phase nursery feeding program was used and consisted of feeding phase 1 (weaning to d 7), phase 2 (d 8–21), and phase 3 (d 22–38) diets postweaning, without and with 1.0, 1.3, and 1.6 mg capsaicin/kg of diet, respectively. Data were analyzed using a mixed model with the effect of nursery dietary treatment nested within sow lactation treatment, the effect of time with repeated measures, and interactions between treatments and wk postweaning. On d 38 postweaning, blood samples were collected from one pig in each pen (n = 36) with BW closest to the pen average for RNA sequencing and gene expression analysis. There were no effects of feeding capsaicin diets to lactating sows and/or their weaned offspring on BW, average daily gain, or average daily feed intake of pigs during the 35-d nursery period. However, pigs weaned from sows fed capsaicin during lactation and continuing to be fed capsaicin diets during the nursery period tended (P = 0.09) to have greater gain:feed (G:F) than pigs fed the other dietary treatments. Furthermore, there was an interaction (P < 0.01) for G:F for dietary treatment and week postweaning, where the magnitude of improvement was greater during the first week postweaning than subsequent wks. There were a limited number of differentially expressed genes among dietary treatment combinations but the greatest number occurred in offspring from sows that were fed capsaicin during lactation. In conclusion, the combination of feeding capsaicin to sows during lactation and to their offspring after weaning appears to improve gain efficiency for the first wk postweaning and may alter gene expression to a greater extent than when capsaicin is supplemented only in the nursery diets.
Music in Noise: Neural Correlates Underlying Noise Tolerance in Music-Induced Emotion
Authors: Murai Shota , Yang Ae Na , Hiryu Shizuko , Kobayasi Kohta I
Published: October 2021

Music can be experienced in various acoustic qualities. In this study, we investigated how the acoustic quality of the music can influence strong emotional experiences, such as musical chills, and the neural activity. The music’s acoustic quality was controlled by adding noise to musical pieces. Participants listened to clear and noisy musical pieces and pressed a button when they experienced chills. We estimated neural activity in response to chills under both clear and noisy conditions using functional magnetic resonance imaging (fMRI). The behavioral data revealed that compared with the clear condition, the noisy condition dramatically decreased the number of chills and duration of chills. The fMRI results showed that under both noisy and clear conditions the supplementary motor area, insula, and superior temporal gyrus were similarly activated when participants experienced chills. The involvement of these brain regions may be crucial for music-induced emotional processes under the noisy as well as the clear condition. In addition, we found a decrease in the activation of the right superior temporal sulcus when experiencing chills under the noisy condition, which suggests that music-induced emotional processing is sensitive to acoustic quality.
Total-evidence dating and morphological partitioning: a novel approach to understand the phylogeny and biogeography of augochlorine bees (Hymenoptera: Apoidea)
Authors: Gonçalves Rodrigo Barbosa , De Meira Odair Milioni , Rosa Brunno Bueno
Published: October 2021

Augochlorini comprise 646 described bee species primarily distributed in the Neotropical region. According to molecular and morphological phylogenies, the tribe is monophyletic and subdivided into seven genus groups. Our main objective is to propose a revised phylogeny of Augochlorini based on a comprehensive data set including fossil species as terminals and new characters from the internal skeleton. We also aim to develop a total-evidence framework incorporating a morphological-partitioned homoplasy approach and molecular data and propose a detailed biogeographic and evolutionary scenario based on ancestor range estimation. Our results recovered Augochlorini and most genus groups as monophyletic, despite some uncertainties about monophyly of the Megalopta and Neocorynura groups. The position of the cleptoparasite Temonosoma is still uncertain. All analyses recovered Augochloropsis s.l. as related to the Megaloptidia group. Internal characters from the head, mesosoma and sting apparatus provided important synapomorphies for most internal nodes, genus groups and genera. Augochlorini diversification occurred in the uplands of the Neotropical region, especially the Brazilian Plateau. Multiple dispersals to Amazonia, Central America and North America with returns to the Atlantic endemism area were recovered in our analysis. Total evidence, including morphological partitioning, was shown to be a reliable approach for phylogenetic reconstruction.
Hyperparasitism on Plasmopara viticola by Simplicillium lanosoniveum
Authors: Shen Hongmiao , Shi Xiaomeng , Ran Longxian
Published: October 2021

A previously unknown association between Plasmopara viticola, the causal pathogen of grape downy mildew, and the mycoparasite strain F2 is described in this paper. F2 could be consistently isolated from the mildew of diseased spots on grape leaves of Kyoho ( Vitis labrusca × V. vinifera cv. Kyoho) infected with P. viticola but not from the surfaces of healthy grape leaves or within lesions of other diseases. It was observed that strain F2 was capable of coiling around sporangiophores and sporangia of P. viticola under a microscope, causing hyphae deformation, decreasing the pathogen growth, and reducing the number of sporangia. This fungal strain was identified as Simplicillium lanosoniveum on the basis of morphological characterizations and 28S rDNA sequencing. To our knowledge, this is the first report of S. lanosoniveum with hyperparasitic characteristics on P. viticola, and the hyperparasite has potential application in the control of grape downy mildew.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
From Raynaud Phenomenon to Systemic Sclerosis in COVID-19: A Case Report
Authors: Giuggioli Dilia , Spinella Amelia , de Pinto Marco , Mascia Maria Teresa , Salvarani Carlo
Published: October 2021

In 2019, the novel SARS-CoV-2 infection emerged, causing the disease called COVID-19, which primarily affects the respiratory tract and lung at alveolar and interstitial levels. Systemic sclerosis (SSc) is an autoimmune connective disease characterized by vascular abnormalities and diffuse and progressive fibrosis of the skin and internal organs. Raynaud phenomenon (RP) occurs in virtually all patients affected by SSc and, in most cases, is an onset symptom of the disease; that is, RP may appear several years before overt illness. Although the exact pathophysiologic pathways leading to RP and SSc are still unknown, several infectious agents, especially viruses, have been suggested as possible triggering factors. Here, the authors describe the first case of RP secondary to SSc following SARS-CoV-2 infection.
CE: Pediatric Antibiotic Stewardship
Authors: Good Amanda , Olans Rita
Published: October 2021

With the rise of antibiotic resistance, antimicrobial stewardship programs can now be found in the ambulatory setting, where nearly 95% of antibiotic prescriptions originate. Judicious use of antibiotics is of particular importance to the ambulatory pediatric provider, as the annual antibiotic prescription rate is highest among children ages two and younger and inappropriate early-life antibiotic use is associated with elevated childhood risk of several medical conditions. While most ambulatory antibiotic stewardship programs have focused on shaping clinician behaviors to prevent unnecessary antibiotic prescribing, duration of antibiotic therapy has been found to be a critical, yet underexamined, facet of antibiotic use. In the past, duration of antibiotic therapy was largely based on convention and expert opinion, with little scientific evidence supporting many of the recommendations. Research suggests that many common pediatric infections such as acute otitis media, community-acquired pneumonia, streptococcal pharyngitis, and urinary tract infections can be effectively and safely treated with reduced courses of antibiotic therapy. In addition to reducing the incidence of antibiotic resistance, a shorter duration of antibiotic therapy may help prevent many adverse effects associated with antibiotic treatment. Current studies on the duration of antibiotic therapy, especially in pediatrics, are limited as they often rely on data extrapolated from adult studies that fail to consider the effects of age-related growth and development on both pharmacokinetics and pharmacodynamics. Future investigation into this topic is also limited by researchers' reliance on subsidies from pharmaceutical companies; clinicians' fear of undertreating infection; and hesitancy to deviate from current standards of care, even when such standards are not evidence based. Despite these challenges, the dangers of inappropriate antibiotic use in the pediatric population warrant further evaluation.
Cost Reduction for Knee-Spanning External Fixation in the Staged Treatment of Tibial Plateau Fractures: A Practical Intervention
Authors: Only Arthur J. , Hayek Kevin , McCreary Dylan L. , Huyke Fernando A. , Siljander Breana , Kibble Kendra , Cunningham Brian P.
Published: October 2021

Objective:

To determine whether an educational intervention affects surgeon implant decision making measured by total implant costs for temporizing a knee-spanning external fixation construct.

Design:

A total of 24 cases were prospectively collected after an educational intervention and matched to 24 cases before intervention using Schatzker classification and by surgeon.

Setting:

A single Level 1 trauma center.

Patients/Participants:

Forty-eight patients with Schatzker II-VI tibial plateau fractures.

Intervention:

Education session to create transparency with component pricing and to provide 3 clinical cases of Orthopaedic Trauma Association/AO 41-C3 (Schatzker VI) with accompanying images and fixator construct costs. Total implant costs displayed in the session ranged from $2354 to $11,696.

Outcome Measurement:

External fixator construct cost.

Results:

The mean cost of constructs in the postintervention group was $4550.20 [95% confidence interval (CI) $3945.60–$5154.00], which was significantly different compared with the preintervention group cost of $6046.75 (95% CI = $5309.54–$6783.97, P = 0.003). After 1 year, the total implant costs of external fixation constructs were reduced by an average of almost $1500 per patient.

Conclusion:

An educational intervention created a reduction in the average total implant construction costs for temporary knee-spanning external fixation in the treatment of tibial plateau fractures. Surgical implant selection and cost variance remain an ideal area to improve value for patients and hospitals. Empowering surgeons with knowledge regarding implant prices is a critical part of working toward the cost reductions of external fixation constructs.
Prevention of Neurological Deficit With Intraoperative Neuromonitoring During Anterior Lumbar Interbody Fusion
Authors: Farooq Jeffrey , Pressman Elliot , Elsawaf Yasmeen , McBride Paul , Alikhani Puya
Published: October 2021

Study Design:

This was a retrospective cohort study.

Objective:

While intraoperative neuromonitoring (IONM) has been increasingly used in spine surgery to have a real-time evaluation of the neurological injury, we aim here to assess its utility during anterior lumbar interbody fusion (ALIF) and its association with postoperative neurological deficit.

Summary of Background Data:

ALIF is a beneficial surgical approach for patients with degenerative disease of the lower lumbar spine who would benefit from increased lordosis and restoration of neuroforaminal height. One risk of ALIF is iatrogenic nerve root injury. IONM may be useful in preventing this injury.

Materials and Methods:

We performed a retrospective cohort study of 111 consecutive patients who underwent ALIF at a tertiary care academic center by 6 spine surgeons. We aimed to describe the association between IONM, postoperative weakness, and factors that predispose our center to using IONM.

Results:

The 111 patients had a median age of 62 years [interquartile range (IQR): 53–69 y]. Neuromonitoring was used in 67 patients (60.3%) and not used in 44 patients. Seven neuromonitoring patients had IONM changes during the surgery. Three of these patients’ surgeries featured intraoperative adjustments to reduce iatrogenic neural injury. The IONM cohort underwent significantly more complex procedures [5 levels (IQR: 3–7) vs. 2 levels (IQR: 2–5), P=0.001]. There was no difference in rates of new or worsened postoperative weakness (IONM: 20.6%, non-IONM: 20.5%).

Conclusions:

We demonstrate evidence of the potential benefits of IONM for patients undergoing ALIF. Intraoperative changes in neuromonitoring signals resulted in surgical adjustments that likely prevented neurological deficits postoperatively. IONM was protective so that more complex surgeries did not have a higher rate of postoperative weakness.
Normative data of the Portuguese version of the Mini-Addenbrooke's Cognitive Examination
Authors: Peixoto Bruno , Machado António , Peixoto Miguel , Pimentel Paulo , Baeta Élia
Published: October 2021

Introduction:

Mini-Addenbrooke's Cognitive Examination (M-ACE) is a screening neurocognitive test with diagnostic accuracy for mild cognitive impairment and dementia. The present study aims to determine the construct validity, concurrent and divergent validity and to determine the normative equation for the Portuguese version of M-ACE.

Method:

The sample is composed by 130 participants without any subjective complaint of memory loss and completely independent in daily life activities, recruited in health units, day care centers and religious and civic associations, from several districts of Portugal. The ACE-III, from which the M-ACE was extracted, and the Geriatric Depression Scale (GDS) were administered to all participants.

Results:

Reliability is considered good (α = 0.844) and the item-total correlations of the M-ACE were highly significant. M-ACE showed a positive correlation with ACE-III and a negative correlation with GDS. Schooling and age were the only variables related to M-ACE performance. The obtained model from the multiple regression was significant. A normative equation was extracted from this model.

Conclusions:

The Portuguese version of M-ACE has solid psychometric properties enabling its clinical use. The availability of M-ACE normative equation based on a healthy sample according to age and education enables the use of a brief screening tool for cognitive functioning. M-ACE does not require formal specialized training, it is a quick test which can be an advantage, for instance, in primary health care consultations.
Diagnosing Pulsatile Tinnitus: A Review of 251 Patients
Authors: Lynch Patrick , Mitton Tanner , Killeen Daniel E. , Kutz Joe Walter , Newcomer Mark
Published: October 2021

Objective:

To analyze the underlying etiologies, presenting characteristics, and diagnostic workup of patients with pulsatile tinnitus (PT).

Study Design:

Retrospective review.

Setting:

Tertiary referral center.

Patients:

All patients who received a diagnostic workup for PT from January 01, 2015 and May 31, 2020.

Main Outcome Measure:

Diagnostic rate of imaging studies.

Results:

Among 251 patients with PT, the most common etiologies included neoplasms (16%), arteriopathies (14%), venopathies (8.5%), middle/inner ear pathology (9.0%), or idiopathic (50%). Patients with identifiable etiologies of PT more often had hypertension, obesity, vision changes, ipsilateral asymmetric hearing loss, or an abnormal otologic examination. Only 18.5% of patients without those characteristics had an identifiable etiology of PT. The most commonly ordered diagnostic studies were magnetic resonance imaging with contrast (n = 146), MR angiography (MRA) (n = 105), CT angiography (CTA) (n = 84), computed tomography (CT) without contrast (n = 76), and MR Venogram (MRV) (n = 62). Magnetic resonance imaging with contrast and CT without contrast preferentially identified patients with nonvascular etiologies of PT, while MRA and CTA identified patients with vascular etiologies of PT. MRV did not demonstrate high diagnostic rate for either type of PT. No difference in diagnostic rate was found between MR-based or CT-based imaging.

Conclusions:

Patients who lack a history of hypertension, obesity, vision changes, ipsilateral asymmetric hearing loss, or an abnormal otologic examination are less likely to have an identifiable cause for PT. In cases where a specific etiology was identified, MR-based imaging (MRI with contrast and MRA) or CT-based imaging (CT without contrast and CTA) were equally efficacious in identifying that etiology. MR-based imaging is preferred for neoplasms, while CT-based imaging is preferred for semicircular canal dehiscence.
Comparison of the sit-up test and head-up tilt test for assessing blood pressure and hemodynamic responses in healthy young individuals
Authors: Oyake Kazuaki , Murayama Jun , Tateishi Takaki , Mochida Ayumi , Matsumoto Mao , Tsujikawa Masahiro , Kondo Kunitsugu , Otaka Yohei , Momose Kimito
Published: October 2021

Objective

The sit-up test is used to assess orthostatic hypotension, without the use of a tilt table, in populations who are unable to stand. The primary objective of this study was to determine the differences in blood pressure and hemodynamic responses between the sit-up and head-up tilt tests. The secondary objective was to determine the hemodynamic responses related to changes in blood pressure during each test.

Methods

Nineteen healthy volunteers (nine males, aged 24.3 ± 2.4 years) underwent the sit-up and head-up tilt tests. Systolic and diastolic blood pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were measured.

Results

The increase in systolic blood pressure (15 ± 9 vs. 8 ± 8 mmHg) was greater, while the increase in heart rate (8 ± 5 vs. 12 ± 8 bpm) and reduction in stroke volume (−17 ± 10 vs. −21 ± 10 ml) were smaller during the sit-up test than during the head-up tilt test (P < 0.05). Additionally, the increases in blood pressure variables were significantly associated with the increase in total peripheral resistance (P < 0.05), but not with changes in other hemodynamic variables in both tests.

Conclusion

Although the magnitudes of changes in systolic blood pressure, heart rate, and stroke volume differed between the tests, the hemodynamic variable related to changes in blood pressure was the same for both tests. These results may contribute to the clinical application of the sit-up test for identifying the presence and hemodynamic mechanisms of orthostatic hypotension.
Epidemiology and risk factors of sudden cardiac arrest
Authors: Zimmerman Dominic S. , Tan Hanno L.
Published: October 2021

Purpose of review

Sudden cardiac arrest (SCA) remains a major health burden around the globe, most often occurring in the community (out-of-hospital cardiac arrest [OHCA]). SCA accounts for 15–20% of all natural deaths in adults in the USA and Western Europe, and up to 50% of all cardiovascular deaths. To reduce this burden, more knowledge is needed about its key facets such as its incidence in various geographies, its risk factors, and the populations that may be at risk.

Recent findings

SCA results from a complex interaction of inherited and acquired causes, specific to each individual. Resolving this complexity, and designing personalized prevention and treatment, requires an integrated approach in which big datasets that contain all relevant factors are collected, and a multimodal analysis. Such datasets derive from multiple data sources, including all players in the chain-of-care for OHCA. This recognition has led to recently started large-scale collaborative efforts in Europe.

Our insights into the causes of SCA are steadily increasing thanks to the creation of big datasets dedicated to SCA research. These insights may be used to earlier recognize of individuals at risk, the design of personalized methods for prevention, and more effective resuscitation strategies for OHCA.
Hospital-specific Template Matching for Benchmarking Performance in a Diverse Multihospital System
Authors: Vincent Brenda M. , Molling Daniel , Escobar Gabriel J. , Hofer Timothy P. , Iwashyna Theodore J. , Liu Vincent X. , Rosen Amy K. , Ryan Andrew M. , Seelye Sarah , Wiitala Wyndy L. , Prescott Hallie C.
Published: October 2021

Background:

Hospital-specific template matching is a newer method of hospital performance measurement that may be fairer than regression-based benchmarking. However, it has been tested in only limited research settings.

Objective:

The objective of this study was to test the feasibility of hospital-specific template matching assessments in the Veterans Affairs (VA) health care system and determine power to detect greater-than-expected 30-day mortality.

Research Design:

Observational cohort study with hospital-specific template matching assessment. For each VA hospital, the 30-day mortality of a representative subset of hospitalizations was compared with the pooled mortality from matched hospitalizations at a set of comparison VA hospitals treating sufficiently similar patients. The simulation was used to determine power to detect greater-than-expected mortality.

Subjects:

A total of 556,266 hospitalizations at 122 VA hospitals in 2017.

Measures:

A number of comparison hospitals identified per hospital; 30-day mortality.

Results:

Each hospital had a median of 38 comparison hospitals (interquartile range: 33, 44) identified, and 116 (95.1%) had at least 20 comparison hospitals. In total, 8 hospitals (6.6%) had a significantly lower 30-day mortality than their benchmark, 5 hospitals (4.1%) had a significantly higher 30-day mortality, and the remaining 109 hospitals (89.3%) were similar to their benchmark. Power to detect a standardized mortality ratio of 2.0 ranged from 72.5% to 79.4% for a hospital with the fewest (6) versus most (64) comparison hospitals.

Conclusions:

Hospital-specific template matching may be feasible for assessing hospital performance in the diverse VA health care system, but further refinements are needed to optimize the approach before operational use. Our findings are likely applicable to other large and diverse multihospital systems.
Current approaches to management of vocal fold scar
Authors: Allen Jacqui
Published: October 2021

Purpose of review

Vocal fold (VF) fibrosis remains an insoluble problem in most cases, with a severe impact on vocal quality and effort. This review examines current investigations and research strands that explore the understanding of VF wound healing and applied treatments for the management of VF scar.

Recent findings

Recent work focused on VF fibrosis has examined wound healing in the glottis, fibrosis-modifying medication, and tissue engineering approaches that span cytokine and growth factor therapy, scaffold and cell delivery platforms, seeded scaffolds, conditioned media and stem cell therapy. Many show promise and may deliver improvements in the wound bed favouring less fibrogenic healing patterns, ultimately with the goal of preserving or restoring VF vibration. Further collaborative research is required that examines combined approaches, long term outcomes, better three-dimensional modelling of cell-cell interactions and delivery modalities for molecular therapies.

VF fibrosis research continues to expand and explore a variety of mechanistic pathways in order to understand VF healing and identify novel and complementary targets for manipulation. Many different approaches show promise and may also offer synergistic benefits. Research continues to strive for healing that more closely resembles true VF architecture and function.
Pyruvate and Glutamine Define the Effects of Cholecystokinin and Ethanol on Mitochondrial Oxidation, Necrosis, and Morphology of Rat Pancreatic Acini
Authors: Manko Bohdan O. , Bilonoha Olha O. , Voloshyn Dariia M. , Zub Anastasiia M. , Ivasechko Iryna I. , Manko Volodymyr V.
Published: October 2021

Objectives

The objective of this study was to test whether pyruvate and glutamine affect the ethanol and cholecystokinin (CCK) effects on the mitochondrial function, viability, and morphology of rat pancreatic acini.

Methods

Respiration was measured with Clark oxygen electrode. Mitochondrial membrane potential, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), cell morphology, and viability were studied with fluorescence microscopy.

Results

In vitro, CCK (0.1 nM) caused pyruvate-dependent stimulation of basal and uncoupled respiration, and the effects were abolished by ethanol (20 mM). The combination of ethanol with CCK (2 hours) caused necrosis of approximately 40% acinar cells in medium with glucose, but not with pyruvate and/or glutamine. Cholecystokinin (10 nM) or ethanol with 0.1 nM CCK caused plasma membrane blebbing not related to apoptosis only when both glutamine and pyruvate were present. Glutamine, but not pyruvate, decreased NAD(P)H level and prevented the effects of ethanol with CCK on mitochondrial membrane potential and NAD(P)H, but, in combination with CCK and ethanol, decreased the uncoupled respiration. In vivo, the combination of ethanol (4 g/kg) and CCK (20 pmol/kg) suppressed basal and uncoupled respiration and caused acinar cell blebbing, but not necrosis.

Conclusions

The lack of sufficient substrate supply in vitro makes pancreatic acinar cells susceptible to necrosis caused by ethanol and CCK in clinically relevant concentrations.
Exome Sequencing of Pancreatic Acinar Carcinoma Identified Distinctive Mutation Patterns
Authors: Liu Yuanhang , Raimondo Massimo , Wallace Michael B. , Mody Kabir , Stauffer John A. , Zhang Lizhi , Ji Baoan , Bi Yan
Published: October 2021

Objectives

Pancreatic acinar cell carcinoma (ACC) is a rare pancreatic cancer. The advancement of treatment is hampered because of the limited knowledge of its molecular mechanism.

Methods

Whole-exome sequencing was performed on DNA extracted from 11 pure ACC surgical samples. Potential germline variants were removed on the basis of polymorphic databases, alternative allele frequency, coverage depth, and Catalogue of Somatic Mutations in Cancer (COSMIC) annotations after variant calling procedure. Mutation profiles and signatures were assessed through the Mutational Patterns package.

Results

A median of 34 somatic mutations were detected (range, 19–60). Three novel recurrent small deletions were identified. Common pancreatic ductal adenocarcinoma mutations or neuroendocrine tumor mutants were not found. FAT atypical cadherin 4, mucin 5B, titin, and zinc finger homeobox 3 were consistently mutated across 4 independent ACC studies. A high contribution of COSMIC mutational signature 1 was seen in ACC, indicating deamination of 5-methylcytosine. The majority of the patients had COSMIC signatures 6, 15, or 20, relating to defective DNA mismatch repair. Six patients showed COSMIC mutational signature 10 because of the altered activity of DNA polymerase epsilon.

Conclusions

Distinct mutational signatures pathways were found in ACC and targeting them may improve clinical outcome.
Rectally Administered Low-Dose Diclofenac Has No Effect on Preventing Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis
Authors: Takaori Ayaka , Ikeura Tsukasa , Hori Yuichi , Ito Takashi , Nakamaru Koh , Masuda Masataka , Mitsuyama Toshiyuki , Miyoshi Hideaki , Shimatani Masaaki , Takaoka Makoto , Okazaki Kazuichi , Naganuma Makoto
Published: October 2021

Objectives

We evaluated the preventive effect of low-dose diclofenac (25–50 mg) on post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) by propensity score matching analysis.

Methods

We retrospectively analyzed the data of 515 patients who underwent ERCP for the first time with or without the rectal administration of low-dose diclofenac before the procedure. For the purpose of minimization of the intrinsic selection bias, we compared the incidence rate of PEP between the diclofenac and control group after propensity score matching.

Results

Post-ERCP pancreatitis developed in 15 patients (2.9%). There was no significant difference in the incidence of PEP between the diclofenac (2.4%) and control group (3.3%) (P = 0.608). One hundred ninety matched pairs were generated by propensity score matching and analyzed; however, the incidence rate of PEP was the same in both groups (2.1%, P = 1.000). In the subgroup analysis using data of patients with high-risk factors for developing PEP, the incidence rate of PEP was comparable between the diclofenac (3.8%) and control groups (4.0%) (P = 0.917).

Conclusions

In our propensity score analysis, rectal administration of low-dose diclofenac was not shown to be useful in preventing PEP.
Impact of Renal Function on S-1 + Radiotherapy for Locally Advanced Pancreatic Cancer
Authors: Kobayashi Satoshi , Ueno Makoto , Ogawa Gakuto , Fukutomi Akira , Ikeda Masafumi , Okusaka Takuji , Sato Tosiya , Ito Yoshinori , Kadota Tomohiro , Ioka Tatsuya , Sugimori Kazuya , Sata Naohiro , Nakamori Shoji , Shimizu Kyoko , Mizuno Nobumasa , Ishii Hiroshi , Furuse Junji
Published: October 2021

Objectives

S-1 monotherapy with concurrent radiotherapy (RT) is a standard of care for patients with locally advanced pancreatic cancer (LAPC). Although renal dysfunction increases S-1 monotherapy toxicity, its effect in S-1 with concurrent RT remains unknown. We evaluated the effect of renal function on the safety of S-1 with RT for LAPC.

Methods

We performed an integrated exploratory post hoc analysis of data from 2 prospective studies (JCOG1106 and LAPC-S1RT), where patients with LAPC received RT (50.4 Gy/28 fraction for 5.5 weeks) and concurrent S-1 (40 mg/m2 per dose, twice daily on the day of irradiation). We split the patients into high creatinine clearance (CCr; ≥80 mL/min) and low CCr (<80 mL/min) groups and compared the findings to determine treatment safety.

Results

The high and low CCr groups showed a median of 97.5 (range, 80.0–194.6) and 64.4 (range, 50.0–78.3) mL/min, respectively. The low CCr group presented more adverse reactions (ARs) of grade 3 or higher and gastrointestinal ARs of grade 2 or higher than the high CCr group (30.8% vs 15.8% and 51.9% vs 36.8%).

Conclusions

The incidence of ARs associated with concurrent S-1 and RT increases in patients with low CCr; therefore, ARs should be duly considered in such patients.