bluuebunny/crossref_metadata_2025 huggingface dataset:
Geochemical Evolution of Arc and Slab Following Subduction Initiation: a Record from the Bonin Islands, Japan
Authors: Ishizuka Osamu , Taylor Rex N , Umino Susumu , Kanayama Kyoko
Published: April 2020

Volcanism following the initiation of subduction is vital to our understanding of this specific magma-generation environment. This setting is represented by the first development of the Izu–Bonin–Mariana arc system as subduction commenced along the Western Pacific margin in the Eocene. A new collection of volcanic rocks recovered from the islands and exposed crustal sections of the Bonin Ridge spans the first 10 Myr of arc evolution. An elemental and radiogenic isotope dataset from this material is presented in conjuction with new 40Ar/39Ar ages and a stratigraphic framework developed by a detailed mapping campaign through the volcanic sections of the Bonin Islands. The dating results reveal that both the locus and type of magmatism systematically changed with time in response to the progressive sinking of the slab until the establishment of steady-state subduction at around 7–8 Ma. Following initial mid-ocean ridge basalt (MORB)-like spreading-related basalt magmatism, volcanic centres migrated away from the trench and changed from high-Si boninite to low-Si boninite or high-Mg andesite, then finally tholeiitic or calcalkaline arc magma. Subducting pelagic sediment combined with Pacific-type igneous ocean crust dominates the slab input to the shallow source of high-Si boninites at 49 Ma, but high-precision Pb isotope data show that this sediment varies in composition along the subducting plate. At around 45 Ma, volcanism switched to low-Si boninite and the pelagic sediment signature was almost entirely replaced by volcanic or volcaniclastic material originating from a HIMU ocean island source. These low-Si boninites are isotopically consistent with a slab component comprising variable proportions of HIMU volcaniclastic rocks and Pacific MORB. In turn, this signature was replaced by a Pacific MORB-dominated flux in the post 45 Ma tholeiite and calcalkaline volcanic rocks. Notably, each change in slab-derived flux coincided with a change in the magma type. Fluctuations in the slab-derived geochemical signature were superimposed on a change in the mantle wedge source from highly depleted harzburgite to a depleted MORB-type mantle-type source. In turn, this may correspond to the increasing depth of the leading edge of the slab through this 5 Myr period.
The Effectiveness of Platelet-Rich Plasma Injection for the Treatment of Suspected Sacroiliac Joint Complex Pain; a Systematic Review
Authors: Burnham Taylor , Sampson Josh , Speckman Rebecca A , Conger Aaron , Cushman Daniel M , McCormick Zachary L
Published: April 2020

Objective

To determine the effectiveness of platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) for the treatment of suspected sacroiliac joint complex (SIJC) pain.

Design

Systematic review.

Subjects

Persons aged ≥18 with suspected SIJC pain.

Comparison

Sham, placebo procedure, or active standard of care treatment.

Outcomes

The primary outcome was ≥50% pain improvement, and the secondary outcome was functional improvement of ≥30% at three or more months after the treatment intervention.

Methods

Publications in PubMed, MEDLINE, Embase, Scopus, and Cochrane Databases were reviewed up to April 3, 2019. Randomized or nonrandomized comparative studies and nonrandomized studies without internal controls were included. The Grades of Recommendation, Assessment, Development, and Evaluation system and the joint consensus American Academy of Orthopedic Surgery/National Institutes of Health recommendations were used for quality assessment and reporting standards.

Results

Query identified 151 publications; three were appropriate for inclusion. There were no studies of BMAC that met inclusion criteria. There were three eligible PRP studies: one randomized comparative trial (RCT) and two case series. In the single RCT comparing ultrasound-guided PRP with corticosteroid injection for suspected SIJC pain, the PRP group had a significantly increased likelihood of achieving ≥50% improvement of pain at three months (adjusted odds ratio = 37, 95% confidence interval [CI] = 4.65–298.69). Pooled pain outcomes from two studies showed that 28/30, 93% (95% CI = 93–100%), experienced ≥50% pain improvement at three months.

Conclusions

The literature supporting the effectiveness of PRP for SIJC pain is very low-quality according to the GRADE system. Well-designed RCTs and large cohort studies with consistent selection protocols and reporting characteristics are needed to determine the effectiveness of PRP and BMAC for the treatment of SIJC pain.
Block Extensions, Local Categories and Basic Morita Equivalences
Authors: Coconeţ Tiberiu , Marcus Andrei , Todea Constantin-Cosmin
Published: April 2020

Let $(\mathcal{K},\mathcal{O},k)$ be a $p$-modular system where $p$ is a prime and $k$ algebraically closed, let $b$ be a $G$-invariant block of the normal subgroup $H$ of a finite group $G$, having defect pointed group $Q_\delta$ in $H$ and $P_\gamma$ in $G$ and consider the block extension $b\mathcal{O}G$. One may attach to $b$ an extended local category $\mathcal{E}_{(b,H,G)}$, a group extension $L$ of $Z(Q)$ by $N_G(Q_\delta )/C_H(Q)$ having $P$ as a Sylow $p$-subgroup, and a cohomology class $[\alpha ]\in H^2(N_G(Q_\delta )/QC_H(Q),k^\times )$. We prove that these objects are invariant under the $G/H$-graded basic Morita equivalences. Along the way, we give alternative proofs of the results of Külshammer and Puig (1990), and Puig and Zhou (2012) on extensions of nilpotent blocks. We also deduce by our methods a result of Zhou (2016) on $p^{\prime}$-extensions of inertial blocks.
Gene expression analysis in the mouse brainstem identifies Cart and Nesfatin as neuropeptides coexpressed in the Calbindin-positive neurons of the Nucleus papilio
Authors: Girard Franck , von Siebenthal Michelle , Davis Fred P , Celio Marco R
Published: April 2020

Study Objectives: The brainstem contains several neuronal populations, heterogeneous in terms of neurotransmitter/neuropeptide content, which are important for controlling various aspects of the rapid eye movement (REM) phase of sleep. Among these populations are the Calbindin (Calb)-immunoreactive NPCalb neurons, located in the Nucleus papilio, within the dorsal paragigantocellular nucleus (DPGi), and recently shown to control eye movement during the REM phase of sleep. Methods: We performed in-depth data mining of the in situ hybridization data collected at the Allen Brain Atlas, in order to identify potentially interesting genes expressed in this brainstem nucleus. Our attention focused on genes encoding neuropeptides, including Cart (Cocaine and Amphetamine Regulated Transcripts) and Nesfatin 1. Results: While nesfatin 1 appeared ubiquitously expressed in this Calb-positive neuronal population, Cart was coexpressed in only a subset of these glutamatergic NPCalb neurons. Furthermore, an REM sleep deprivation and rebound assay performed with mice revealed that the Cart-positive neuronal population within the DPGi was activated during REM sleep (as measured by c-fos immunoreactivity), suggesting a role of this neuropeptide in regulating some aspects of REM sleep. Conclusions: The assembled information could afford functional clues to investigators, conducive to further experimental pursuits.
Identifying and Characterizing Stress Pathways of Concern for Consumer Safety in Next-Generation Risk Assessment
Authors: Hatherell Sarah , Baltazar Maria T , Reynolds Joe , Carmichael Paul L , Dent Matthew , Li Hequn , Ryder Stephanie , White Andrew , Walker Paul , Middleton Alistair M
Published: April 2020

Many substances for which consumer safety risk assessments need to be conducted are not associated with specific toxicity modes of action, but rather exhibit nonspecific toxicity leading to cell stress. In this work, a cellular stress panel is described, consisting of 36 biomarkers representing mitochondrial toxicity, cell stress, and cell health, measured predominantly using high content imaging. To evaluate the panel, data were generated for 13 substances at exposures consistent with typical use-case scenarios. These included some that have been shown to cause adverse effects in a proportion of exposed humans and have a toxicological mode-of-action associated with cellular stress (eg, doxorubicin, troglitazone, and diclofenac), and some that are not associated with adverse effects due to cellular stress at human-relevant exposures (eg, caffeine, niacinamide, and phenoxyethanol). For each substance, concentration response data were generated for each biomarker at 3 timepoints. A Bayesian model was then developed to quantify the evidence for a biological response, and if present, a credibility range for the estimated point of departure (PoD) was determined. PoDs were compared with the plasma Cmax associated with the typical substance exposures, and indicated a clear differentiation between “low” risk and “high” risk chemical exposure scenarios. Developing robust methods to characterize the in vitro bioactivity of xenobiotics is an important part of non-animal safety assessment. The results presented in this work show that the cellular stress panel can be used, together with other new approach methodologies, to identify chemical exposures that are protective of consumer health.
Comparison of Early Definitive Fusion and Traditional Growing Rods in Early-onset Dystrophic Scoliosis in Neurofibromatosis Type 1: A Preliminary Report
Authors: Tauchi Ryoji , Kawakami Noriaki , Suzuki Teppei , Uno Koki , Yamaguchi Toru , Yanagida Haruhisa , Yamamoto Takuya , Murakami Hideki , Demura Satoru , Kotani Toshiaki
Published: April 2020

Background:

Early definitive spinal fusion (EF) has been widely recommended to avoid spinal deformity progression for early-onset scoliosis (EOS) with neurofibromatosis type 1 (NF-1). In contrast, growing rod (GR) procedure has recently been recommended for EOS associated with the dystrophic type NF-1. However, no studies have compared the surgical outcomes between EF and GR procedure for EOS with NF-1. The purpose of this study was to compare the surgical outcomes of EF versus GR for early onset and dystrophic scoliosis with NF-1.

Methods:

This was a retrospective multicenter study; 26 EOS patients with dystrophic type of NF-1 who underwent EF (16 patients) or GR (10 patients) were investigated. We compared age at first surgery, fused levels, total number of surgeries, coronal major curve, complication rates, spinal height (T1-T12 and T1-S1 length), and forced vital capacity between the 2 groups.

Results:

The mean age at first surgery was 7.3 years in the EF and 5.8 years in the GR (P<0.05). The mean follow-up period was 12.8 and 10.5 years, respectively. The 2 groups did not show significant differences in preoperative major Cobb angle (75.1 vs. 83.1 degrees), complication rate (53% vs. 60%), and increase rate of T1-T12 (20.0% vs. 30.4%). However, significant differences (P<0.05) were recognized in fusion segments (13.9 vs. 15.8), total numbers of surgery (2.6 vs. 10.1), correction rate of major curve (59.0% vs. 40.6%), increase rate of T1-S1 (19.0% vs. 33.9%), body height at final follow-up (151 vs. 142 cm), and forced vital capacity at final follow-up (2.23 vs. 1.46 L).

Conclusions:

Early fusion is still a viable option for progressive EOS with dystrophic type of NF-1 even in the growth-friendly era. Surgeons should consider the best procedure for each patient taking into account the severity of dystrophic change when treating EOS with NF-1.

Level of Evidence:

Level IV.
30-Day Recurrence, Readmission Rate, and Clinical Outcome After Emergency Lumbar Discectomy
Authors: Reito Aleksi , Kyrölä Kati , Pekkanen Liisa , Paloneva Juha
Published: April 2020

Study Design.

A retrospective cohort study.

Objective.

To investigate the 30-day recurrence rate after emergency lumbar discectomy. Secondary aims were to investigate the factors affecting the 30-day recurrence and readmission rates and clinical outcome.

Summary of Background Data.

Excluding cauda equine syndrome (CES) due to massive intervertebral disc herniation, emergency surgery for lumbar disc herniation (LDH) is rarely required. The operation may, however, be performed for other reasons such as persistent or progressive motor paresis associated with radiculopathy or uncontrolled pain. Literature on these topics is scarce.

Methods.

All patients admitted for inpatient care after a visit to the emergency department (ED) due to acute low back pain and who had subsequently undergone an emergency lumbar discectomy during the 4-year study period were included in the study. Patients attending the ED who subsequently had a delayed discectomy formed the control group. Recurrence and readmission rates were analyzed and clinical outcome at 30 days post-surgery was assessed with the Oswestry Disability Index (ODI) and the visual analog pain scale (VAS).

Results.

One hundred thirty patients were admitted to the hospital after visiting the ED and underwent an emergency discectomy after a median of 1.0 days from admittance. Six patients in the study group [4.6% (95% CI: 2.1–9.7)] had recurrent LDH and nine patients in total [6.9% (95% CI: 3.9–12.6)] were readmitted within 30 days. None of the baseline variables clearly predicted recurrence. Mean ODI difference between the study group and controls was 8.1 (95% CI: –6.7–23.2). BMI and surgery by a non-spine surgeon were associated with higher ODI values.

Conclusion.

An emergency discectomy is associated with a higher rate than expected of both recurrent LDHs and 30-day readmissions. Surgeon experience and patient-related factors had minor effects on the 30-day clinical outcome.

Level of Evidence: 4
Preoperative Halo Traction for Severe Scoliosis
Authors: Hwang Chang Ju , Kim Dong Gyun , Lee Choon Sung , Lee Dong-Ho , Cho Jae Hwan , Park Jae-Woo , Baik Jong Min , Lee Kwan Bum
Published: April 2020

Study Design.

Retrospective case control study.

Objective.

The aim of this study was to analyze the appropriate traction period and preoperative halo traction (HT)-related factors in severe scoliosis

Summary of Background Data.

HT can reduce risks involved in severe scoliosis treatment, and its safety and efficacy are well known. However, a lack of evidence exists in guiding the appropriate traction period and other factors involved in HT.

Methods.

We retrospectively reviewed 59 patients who underwent preoperative HT, analyzed correction rate changes over time using HT, and assessed other factors by dividing the patients into two groups according to differences between the post-bending correction angle (PBC) and post-halo traction correction angle (PTC): group A (PBC ≒ PTC) and group B (PBC < PTC). The grouping was determined by whether the difference between PBC and PTC was >8°, the maximum measurement error when measuring the Cobb angle.

Results.

The mean Cobb angle improved from 96.9° preoperatively to 72.9° post-bending to 63.3° post-traction and 32.5° postoperatively. The coronal correction of the major curve (change in curve from the start to each week/total change in curve after traction) was 28.2% at 1 week (n = 59), 34.0% at 2 weeks (n = 58), 33.8% at 3 weeks (n = 41), and 32.2% at 4 weeks (n = 13); a difference was noted between the first and second weeks (P < 0.001, <0.001, 0.244, and 0.082, respectively). Compared with group A, group B had a lower height (154.9 vs. 144.4 cm, P = 0.029), lower body weight (49.1 vs. 39.4 kg, P = 0.017), higher traction/body weight ratio (0.41 vs. 0.47, P = 0.025), and more halo-femoral traction (0 vs. 6, P = 0.018).

Conclusion.

Traction for ≥3 weeks was unnecessary for optimal traction. In patients with low height and weight, halo-femoral traction with a heavy traction weight was effective.

Level of Evidence: 4
Cervical Decompression Surgery Normalizes Gait Ground Reaction Forces in Patients With Cervical Spondylotic Myelopathy
Authors: Haddas Ram , Derman Peter B.
Published: April 2020

Study Design.

Prospective cohort study.

Objective.

Investigate the effect of surgical decompression and fusion on gait ground reaction forces (GRFs) parameters in patients with cervical spondylotic myelopathy (CSM) and to compare these values to those of healthy controls.

Summary of Background Data.

Surgical intervention to alleviate spinal cord compression is typically recommended in cases of CSM. While the primary aim of surgery is to halt disease progression, the literature suggests that some symptomatic improvement is often observed postoperatively. Gait analysis via measurement of GRFs is a particularly sensitive means of quantifying changes in ambulatory function, but no comprehensive analysis has been published in the setting of CSM.

Methods.

Forty patients with symptomatic CSM underwent gait analysis with measurement of horizontal and vertical GRFs before and 3 months after surgery. Thirty healthy controls (H) underwent the same battery of tests. Comparisons were made between the pre- and postoperative profiles of patients with CSM as well as to that of the control group.

Results.

Before surgery, patients with CSM exhibited disturbances in GRF magnitudes: significantly greater maximum weight acceptance (Pre: 113.7 vs. H: 101.1% body weight [BW], P = 0.040) and push off forces (Pre: 112.2 vs. H: 101.4% BW, P = 0.044), and timing: maximum weight acceptance occurred earlier while mid-stance (Pre: 15.8 vs. H: 17.8% gait cycle [GC], P = 0.018), toe-off (Pre: 65.0 vs. H: 62.9% GC, P = 0.001), braking (Pre: 55.6 vs. H: 54.2% GC, P = 0.003), and propulsion occurred (Pre: 11.9 vs. H: 10.6% GC, P = 0.011) later compared with healthy controls. Surgery improved all GRF parameters (P < 0.039), but postoperative gait profiles did not completely normalize to levels observed in the control group.

Conclusion.

These observations combined with published data on gait muscle activation and gait patterns in CSM patients support the idea that patients with CSM have an altered gait profile consistent with a series of poorly controlled near falls. Surgical intervention was observed to produce improvements in but not complete resolution of these gait disturbances. These data provide a more comprehensive understanding of gait in the setting of CSM.

Level of Evidence: 3
Predictors for Deformity Progression in a Spinal Muscular Atrophy Cohort After Scoliosis Correction Surgery
Authors: Shen Po-Chih , Lu Cheng-Chang , Liang Wen-Chen , Tien Yin-Chun , Jong Yuh-Jyh , Lu Yen-Mou , Liu Zi-Miao , Shih Chia-Lung , Chou Shih-Hsiang
Published: April 2020

Study Design:

This was a single-center, retrospective study.

Objective:

The objective of this study was to assess the risk factors for deformity progression after scoliosis correction surgery in spinal muscular atrophy (SMA) patients.

Summary of Background Data:

Moderate residual postoperative scoliosis curve is common in SMA populations; however, the acceptable postoperative scoliosis curve for preventing deformity progression remains uncertain.

Materials and Methods:

Twenty-nine SMA patients undergoing scoliosis correction surgery were included. Scoliosis progression was defined as an increase of 10 degrees in the major curve of Cobb angle (MCCA); pelvic obliquity (PO) or concave-side hip progression was arbitrarily defined as an increase of ≥1 grade after surgery. Risk factors for deformity progression were examined using Cox proportional hazard models. The cumulative incidence rate of deformity progression was performed by the Kaplan-Meier survival analysis

Results:

The mean age at surgery was 13.3 years (range: 8–25 y) and the mean follow-up time was 7 years (range: 2–22.9 y). The mean MCCA was corrected from 69 to 34.6 degrees at initial follow-up and 42.2 degrees at the final follow-up. Postoperative MCCA (P=0.002) and PO (P=0.004) at initial follow-up were the risk factors for scoliosis progression. Postoperative MCCA at initial follow-up (P=0.007) and age at the time of surgery (P=0.017) were the risk factors for PO progression. Different cutoff points of postoperative MCCA at initial follow-up were compared for predicting deformity progression. We found the patient with postoperative MCCA of <30 degrees at initial follow-up had a significantly less cumulative incidence rate of progression than their counterparts for scoliosis (P=0.005), PO (P=0.023), and concave-side hip progressions (P=0.008).

Conclusions:

We recommended that MCCA should be corrected to <30 degrees to prevent postoperative scoliosis, PO, and concave-side femoral head coverage percentage progressions. Patients receiving surgery earlier had less postoperative MCCA at initial follow-up but with no increase in the risk of postoperative scoliosis progression.
The Women's Health Initiative trials of menopausal hormone therapy: lessons learned
Authors: Manson JoAnn E. , Bassuk Shari S. , Kaunitz Andrew M. , Pinkerton JoAnn V.
Published: April 2020

Objective:

The Women's Health Initiative (WHI) assessed oral conjugated equine estrogens (CEE) taken with or without medroxyprogesterone acetate (MPA) for prevention of chronic disease in postmenopausal women aged 50-79 years.

Methods:

Women with an intact uterus (n = 16,608) were randomized to CEE+ MPA therapy or placebo for a median of 5.6 years; women with hysterectomy (n = 10,739) were randomized to CEE-alone therapy or placebo for a median of 7.2 years. Both cohorts have been followed for 18 years.

Results:

In the overall study population (mean age, 63 y), neither estrogen-progestin therapy (EPT) nor estrogen-only therapy prevented coronary heart disease or led to a favorable balance of chronic-disease benefits and risks. Subgroup analyses, however, suggest that timing of hormone therapy (HT) initiation influences the relation between HT and coronary risk, as well as its overall benefit-risk balance, with more favorable effects in women who are younger (age < 60 year) or recently menopausal (within 10 year) than in women who are older or further past the menopausal transition. In younger women who entered the trial of estrogen-only therapy with oophorectomy, the intervention was associated with a significant 32% reduction in all-cause mortality over long-term follow-up.

Conclusions:

WHI findings indicate important differences in HT-related clinical outcomes by age and time since menopause. Systemic HT has an acceptable safety profile for menopause management when initiated among healthy women who are younger (or recently menopausal) and not at elevated risk for cardiovascular disease or breast cancer. Initiation of treatment in older women who are distant from menopause onset, however, should be avoided. Other HT formulations and routes of delivery warrant further study.

(WHI clinicaltrials.gov identifier: NCT00000611)
Bacillus Calmette-Guérin Cervical Lymphadenitis in a 6-Year-Old Boy on Infliximab for Inflammatory Bowel Disease
Authors: Yoshida Michiko , Takeuchi Ichiro , Shoji Kensuke , Miyairi Isao , Arai Katsuhiro
Published: April 2020

We encountered a case of Bacillus Calmette-Guérin (BCG) cervical lymphadenitis in a patient undergoing infliximab after 6 years from BCG vaccination. Tumor necrosis factor-α inhibitors may be a risk for reactivation of BCG and serious infection even several years after vaccination.
Fundamental sex differences in morphine withdrawal-induced neuronal plasticity
Authors: Hadschieff Viktoria , Drdla-Schutting Ruth , Springer David Niklas , Siegert Anna Siobhán Maria , Schroeder Hanna , Sandkühler Jürgen
Published: April 2020

Withdrawal from systemic opioids can induce long-term potentiation (LTP) at spinal C-fibre synapses (“opioid-withdrawal-LTP”). This is considered to be a cellular mechanism underlying opioid withdrawal-induced hyperalgesia, which is a major symptom of the opioid withdrawal syndrome. Opioids can activate glial cells leading to the release of proinflammatory mediators. These may influence synaptic plasticity and could thus contribute to opioid-withdrawal-LTP. Here, we report a sexual dimorphism in the mechanisms of morphine-withdrawal-LTP in adult rats. We recorded C-fibre-evoked field potentials in the spinal cord dorsal horn from deeply anaesthetised male and female rats. In both sexes, we induced a robust LTP through withdrawal from systemic morphine infusion (8 mg·kg−1 bolus, followed by a 1-hour infusion at a rate of 14 mg·kg−1·h−1). This paradigm also induced mechanical hypersensitivity of similar magnitude in both sexes. In male rats, systemic but not spinal application of (−)naloxone blocked the induction of morphine-withdrawal-LTP, suggesting the involvement of descending pronociceptive pathways. Furthermore, we showed that in male rats, the induction of morphine-withdrawal-LTP required the activation of spinal astrocytes and the release of the proinflammatory cytokines tumour necrosis factor and interleukin-1. In striking contrast, in female rats, the induction of morphine-withdrawal-LTP was independent of spinal glial cells. Instead, blocking µ-opioid receptors in the spinal cord was sufficient to prevent a facilitation of synaptic strength. Our study revealed fundamental sex differences in the mechanisms underlying morphine-withdrawal-LTP at C-fibre synapses: supraspinal and gliogenic mechanisms in males and a spinal, glial cell-independent mechanism in females.
The bivalent ligand, MMG22, reduces neuropathic pain after nerve injury without the side effects of traditional opioids
Authors: Speltz Rebecca , Lunzer Mary M. , Shueb Sarah S. , Akgün Eyup , Reed Rachelle , Kalyuzhny Alex , Portoghese Philip S. , Simone Donald A.
Published: April 2020

Functional interactions between the mu opioid receptor (MOR) and the metabotropic glutamate receptor 5 (mGluR5) in pain and analgesia have been well established. MMG22 is a bivalent ligand containing MOR agonist (oxymorphamine) and mGluR5 antagonist (MPEP) pharmacophores tethered by a 22-atom linker. MMG22 has been shown to produce potent analgesia in several models of chronic inflammatory and neuropathic pain (NP). This study assessed the efficacy of systemic administration of MMG22 at reducing pain behavior in the spared nerve injury (SNI) model of NP in mice, as well as its side-effect profile and abuse potential. MMG22 reduced mechanical hyperalgesia and spontaneous ongoing pain after SNI, with greater potency early (10 days) as compared to late (30 days) after injury. Systemic administration of MMG22 did not induce place preference in naive animals, suggesting absence of abuse liability when compared to traditional opioids. MMG22 also lacked the central locomotor, respiratory, and anxiolytic side effects of its monomeric pharmacophores. Evaluation of mRNA expression showed the transcripts for both receptors were colocalized in cells in the dorsal horn of the lumbar spinal cord and dorsal root ganglia. Thus, MMG22 reduces hyperalgesia after injury in the SNI model of NP without the typical centrally mediated side effects associated with traditional opioids.
Objectifying the Pivot Shift Test
Authors: Horvath Alexandra , Meredith Sean J. , Nishida Kyohei , Hoshino Yuichi , Musahl Volker
Published: April 2020

The pivot shift test is utilized for assessment of rotatory instability in the anterior cruciate ligament (ACL) deficient knee. There are multiple reports of the pivot shift maneuver, and there is a lack of consensus among clinicians as to a standardized maneuver. Measurement devices are a feasible option to evaluate rotatory knee instability, objectively or quantitatively. Traditionally, measurement systems have been invasive systems. More recently, electromagnetic system, inertial sensor, or imaging analysis systems, specifically with the utilization of a tablet computer, have emerged as noninvasive, and more importantly, validated options. It is important to recognize that anatomic structures other than the ACL contribute to rotatory knee stability. Addressing the tibial slope, anterolateral structures of the knee, specifically the iliotibial band, and menisci during ACL surgery may decrease residual pivot shift in an attempt to improve clinical outcomes and prevent reinjury. This review article describes the pivot shift maneuver, objective measurement tools, and clinical applications of the pivot shift test.
Chapter 5: Techniques For ACL Revision Reconstruction
Authors: Kew Michelle E. , Miller Mark D. , Werner Brian C.
Published: April 2020

Anterior cruciate ligament (ACL) reconstruction is a commonly performed procedure, with an increasing frequency leading to an increased number of revision procedures. Etiologies for graft rupture are varied and can include technical issues, repeat trauma, and graft choice. The preoperative evaluation before a revision ACL reconstruction should include a detailed history and physical exam, as well as radiographs, magnetic resonance imaging to evaluate graft integrity and for concomitant injuries, as well as computed tomography to measure for bone tunnel osteolysis. Surgical techniques for revision ACL reconstruction include a 1-stage or 2-stage procedure with possible bone grafting and repair of associated injuries. Recent studies show worse clinical outcomes after a revision procedure; however, research continues to emerge with novel techniques and rehabilitation protocols to improve patient outcomes after revision ACL reconstruction.
Utilization and effectiveness of elbasvir/grazoprevir and adoption of resistance-associated substitutions testing in real-world treatment of hepatitis C virus genotype 1A infection: results from the German Hepatitis C-Registry
Authors: Hinrichsen Holger , Stoehr Albrecht , Cornberg Markus , Klinker Hartwig , Heyne Renate , John Christine , Simon Karl-Georg , Guenther Veronika , Martin Karen , Witte Vanessa , Zeuzem Stefan
Published: April 2020

Background

For treatment of genotype 1a (GT1a) infection with elbasvir/grazoprevir, the German guidelines recommend a differentiated approach depending on baseline viral load (BVL). For low BVL ≤800 000 IU/mL, treatment with 12 weeks elbasvir/grazoprevir should be considered, whereas for high BVL >800 000 IU/mL, this regimen is only recommended in nonstructural protein 5A (NS5A) resistance-associated substitutions (RAS) absence. With present NS5A RAS or when RAS-testing is not available, 16 weeks elbasvir/grazoprevir + ribavirin is preferred. Here, we investigated the adherence to these recommendations and the effectiveness of elbasvir/grazoprevir in a large German Hepatitis C-Registry GT1a cohort.

Methods

From September 2016 until July 2018, 195 GT1a-infected patients were treated with elbasvir/grazoprevir ± ribavirin for 12–16 weeks. The primary outcome was per protocol SVR12 or SVR24.

Results

Mean age was 50 years, 89% were male, 19% had cirrhosis, 72% were treatment-naïve. Forty-five percent had low BVL ≤800 000 IU/mL, 55% high BVL >800 000 IU/mL, of whom 49 vs. 42% were baseline RAS-tested. Four patients with high (7.7%) and two with low BVL (5%) had NS5A RAS of whom 50% received elbasvir/grazoprevir+ribavirin, respectively. Ninety-four percent of patients with low and 65% with high BVL received elbasvir/grazoprevir without ribavirin. Thirty-five percent of patients with high BVL received ribavirin, mostly without prior RAS-testing. Per protocol sustained virologic response (SVR) by low vs. high BVL was 98.8 and 95.1%. All patients with NS5A RAS achieved SVR.

Conclusions

In German, real-world most patients received elbasvir/grazoprevir without ribavirin. Ribavirin was mainly added in GT1a patients >800 000 IU/mL, who were not NS5A RAS tested. SVR rates were consistently high and comparable to clinical trial results.
Lessons from American Board of Plastic Surgery Maintenance of Certification Tracer Data: A 16-Year Review of Clinical Practice Patterns and Evidence-Based Medicine in Cleft Palate Repair
Authors: Kearney Aaron M. , Gart Michael S. , Brandt Keith E. , Gosain Arun K.
Published: April 2020

Background:

As a component of the Maintenance of Certification process from 2003 to 2019, the American Board of Plastic Surgery tracked 20 common plastic surgery operations. By evaluating the data collected over 16 years, the authors are able to examine the practice patterns of pediatric/craniofacial surgeons in the United States.

Methods:

Cumulative tracer data for cleft palate repair was reviewed as of April of 2014 and September of 2019. Evidence-based medicine articles were reviewed. Results were tabulated in three categories: pearls, or topics that were covered in both the tracer data and evidence-based medicine articles; topics that were covered by evidence-based medicine articles but not collected in the tracer data; and topics that were covered in tracer data but not addressed in evidence-based medicine articles.

Results:

Two thousand eight hundred fifty cases had been entered as of September of 2019. With respect to pearls, pushback, von Langenbeck, and Furlow repairs all declined in use, whereas intravelar veloplasty increased. For items not in the tracer, the quality of studies relating to analgesia is among the highest of all areas of study regarding cleft palate repair. In terms of variables collected by the tracer but not studied, in 2019, 41 percent of patients received more than 1 day of antibiotics.

Conclusions:

This article provides a review of cleft palate tracer data and summarizes the research in the field. Review of the tracer data enables cleft surgeons to compare their outcomes to national norms and provides an opportunity for them to consider modifications that may enhance their practice.
Neurocytoskeleton Proteins in Cerebrospinal Fluid of People With HIV-1 Subtypes B and C
Authors: de Almeida Sérgio Monteiro , Ribeiro Clea E. , Tang Bin , de Pereira Ana P. , Rotta Indianara , Vaida Florin , Letendre Scott , Potter Michael , Ellis Ronald J.
Published: April 2020

Background:

The objective was to compare the effect of HIV-1C and HIV-1B subtypes on neurofilament light (NfL) cerebrospinal fluid (CSF) levels and ratios of NfL to tau proteins. Additional comparisons were performed between people with HIV (PWH), participants with Alzheimer disease (AD), and HIV-negative controls (HIV−). We also calculated the diagnostic characteristics of CSF NfL and its ratios in HIV-associated neurocognitive disorder (HAND) diagnosis.

Methods:

CSF NfL, T-tau, and P-tau181 concentrations were measured using immunoassays in a total of 108 CSF samples, including PWH (n = 68), HIV− (n = 16), and participants with AD (n = 24). These proteins were compared between HIV-1B (n = 27) and HIV-1C (n = 26) using multiple linear regression adjusted for nadir CD4 and plasma viral load suppression. Comparisons between PWH, HIV−, and participants with AD were adjusted for gender and age.

Results:

CSF neurocytoskeleton proteins and their ratios were comparable in HIV-1B and HIV-1C. However, the HIV-1C group had a higher proportion of samples of CSF NfL above the reference value (n = 14, 53.85%) than the HIV-1B group (n = 8, 29.63%), P = 0.098. The values of CSF NfL were higher in the AD group [2578 (1864; 3500) pg/mL] than those in PWH [683 (500; 1197) pg/mL, P < 0.001] and control [660 (539; 802) pg/mL, P = 0.012] groups. The value of CSF NfL and its ratios for HAND diagnosis were poor.

Conclusion:

The effects of HIV-1B and HIV-1C on CSF NfL and tau ratios were comparable. The differences in CSF neurocytoskeleton proteins between PWH and individuals with AD suggested they might not share the same mechanisms of impairment. Further research is necessary to evaluate CSF NfL on the differential diagnoses of HAND with AD.
Diagnostic Performance of the Support Vector Machine Model for Breast Cancer on Ring-Shaped Dedicated Breast Positron Emission Tomography Images
Authors: Satoh Yoko , Tamada Daiki , Omiya Yoshie , Onishi Hiroshi , Motosugi Utaroh
Published: April 2020

Objective

The aim of this study was to evaluate the diagnostic ability of support vector machine (SVM) for early breast cancer (BC) using dedicated breast positron emission tomography (dbPET).

Methods

We evaluated 116 abnormal fluorodeoxyglucose (FDG) uptakes less than 2 cm on dbPET images in 105 women. Fluorodeoxyglucose uptake patterns and quantitative PET parameters were compared between BC and noncancer groups. Diagnostic accuracy of the SVM model including quantitative parameters was compared with that of visual assessment based on FDG-uptake pattern.

Results

Age, maximum standardized uptake value, peak standardized uptake value, total lesion glycolysis, metabolic tumor volume, and lesion-to-contralateral background ratio were significantly different between BC and noncancer groups. Area under the curve, sensitivity, specificity, and accuracy for FDG-uptake pattern of visual assessment were 0.77, 0.57, 0.77, and 0.71, respectively; those of an SVM model including age, maximum standardized uptake value, total lesion glycolysis, and lesion-to-contralateral background ratio were 0.89, 0.94, 0.77, and 0.85, respectively.

Conclusions

Support vector machine showed high diagnostic performance for BC using dbPET.
Resuscitative endovascular balloon of the aorta is feasible in penetrating chest trauma with major hemorrhage: Proposal of a new institutional deployment algorithm
Authors: Ordoñez Carlos A. , Rodríguez Fernando , Parra Michael , Herrera Juan Pablo , Guzmán-Rodríguez Mónica , Orlas Claudia , Caicedo Edgar Yaset , Serna José Julián , Salcedo Alexander , del Valle Ana Milena , Meléndez Juan José , Angamarca Edison , García Alberto , Brenner Megan
Published: April 2020

BACKGROUND

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emerging option for hemorrhage control, but its use is limited in scenarios such as penetrating chest trauma. The aim of this study was to describe the use of REBOA as a resuscitative adjunct in these cases with major hemorrhage and to propose a new clinical management algorithm.

METHODS

This was a prospective, observational study conducted at a single Level I trauma center in Colombia. We included all patients older than 14 years with severe trauma who underwent REBOA from January 2015 to December 2019. Patients received REBOA if they were in hemorrhagic shock and were unresponsive to resuscitation.

RESULTS

A total of 56 patients underwent REBOA placement of which 37 had penetrating trauma and 23 had chest trauma. All patients were hemodynamically unstable upon arrival to the emergency department, with a median systolic blood pressure of 69 mm Hg (interquartile range [IQR], 57–90 mm Hg) and median Injury Severity Score was 25 (IQR, 25–41). All REBOAs were deployed and inflated in zone 1, median inflation time was 40 minutes (IQR, 26–55 minutes), and no adverse neurologic outcomes were observed. Fifteen patients had REBOA and a median sternotomy. Eleven patients had concomitant abdominal wounds. Overall mortality was 28.6%, and there was no significant difference between penetrating versus blunt trauma patients (21.6% vs. 42.1%, p = 0.11). The survival rate of thoracic injured patients was similar to the predicted survival (65.2% vs. 63.3%).

CONCLUSION

Resuscitative endovascular balloon occlusion of the aorta can be used safely in penetrating chest trauma, and the implementation of a REBOA management algorithm is feasible with a well-trained multidisciplinary team.

LEVEL OF EVIDENCE

Therapeutic, level V.
17β-Estradiol as a New Therapy to Preserve Microcirculatory Perfusion in Small Bowel Donors
Authors: Vieira Roberta Figueiredo , Breithaupt-Faloppa Ana Cristina , Correia Cristiano Jesus , Armstrong Roberto , Coutinho-e-Silva Raphael dos Santos , Ferreira Sueli Gomes , Moreira Luiz Felipe Pinho , Sannomiya Paulina
Published: April 2020

Background.

Intestine graft viability compromises retrieval in most brain-dead donors. Small bowel transplantation is a complex procedure with worse outcomes than transplantation of other abdominal organs. The hormone 17β-estradiol (E2) has shown vascular protective effects in lung tissue of brain death (BD) male rats. Thus, estradiol might be a treatment option to improve the quality of intestinal grafts.

Methods.

Male Wistar rats were divided into 3 groups (n = 10/group): rats that were trepanned only (sham-operated), rats subjected to rapid-onset BD, and brain-dead rats treated with E2 (280 µg/kg, intravenous) (BD-E2). Experiments performed for 180 minutes thereafter are included: (a) laser-Doppler flowmetry and intravital microscopy to evaluate mesenteric perfusion; (b) histopathological analysis; (c) real-time polymerase chain reaction of endothelial nitric oxide synthase (eNOS) and endothelin-1; (d) immunohistochemistry of eNOS, endothelin-1, P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 expression; and (e) ELISA for cytokines and chemokines measurement.

Results.

17β-Estradiol improved microcirculatory perfusion and reduced intestinal edema and hemorrhage after BD. The proportions of perfused small vessels were (mean ± scanning electron microscope) BD rats (40% ± 6%), sham-operated rats (75% ± 8%), and BD-E2 rats (67% ± 5%) (P = 0.011). 17β-Estradiol treatment was associated with 2-fold increase in eNOS protein (P < 0.0001) and gene (P = 0.0009) expression, with no differences in endothelin-1 expression. BD-E2 rats exhibited a reduction in vascular cell adhesion molecule 1 expression and reduced cytokine-induced neutrophil chemoattractant 1 and interleukina-10 serum levels.

Conclusions.

17β-Estradiol was effective in improving mesenteric perfusion and reducing intestinal edema and hemorrhage associated with BD. The suggestion is that E2 might be considered a therapy to mitigate, at least in part, the deleterious effects of BD in small bowel donors.
RETRACTED: DDP-resistant ovarian cancer cells-derived exosomal microRNA-30a-5p reduces the resistance of ovarian cancer cells to DDP
Authors: Liu Ronghua , Zhang Yucan , Sun Peiwen , Wang Changxiu
Published: April 2020

Exosomes carrying microRNAs (miRNAs) have been demonstrated to play critical roles in the regulation of development, growth and metastasis of cancer. Bioinformatic predictions identified differentially expressed SRY-box 9 (SOX9) in OC, and the regulatory miRNA miR-139-5p. Here, we aim to evaluate the function of exosomal miR-139-5p in the sensitivity of ovarian cancer (OC) cells to cis-diamminedichloroplatinum(II) (DDP). Expression pattern of miR-139-5p and SOX9 in ovarian cancer cells (SKOV3) and DDP-resistant cells (SKOV3/DDP) was identified using reverse transcription quantitative polymerase chain reaction and western blot analysis. The relationship between miR-139-5p and SOX9 was validated using a dual-luciferase reporter assay. SKOV3/DDP cell line was developed and introduced with miR-30a-5p mimic to analyse the effects of miR-30a-5p on resistance to DDP. The
in vitro
and
in vivo
effects of exosomal miR-30a-5p on resistance of SKOV3 cells to DDP were assessed in a co-culture system of exosomes and OC cells as well as in tumour-bearing nude mice. High expression of SOX9 and low expression of miR-30-5p were witnessed in OC. Furthermore, miR-30-5p, a downregulated miRNA in SKOV3/DDP cells, increased the rate of cell apoptosis and enhanced the sensitivity of SKOV3/DDP cells to DDP by targeting SOX9. Moreover, exosomes carrying miR-30a-5p were identified to sensitize SKOV3/DDP cells to DDP both
in vitro
and
in vivo
. These data together supported an important conclusion that DDP-resistant OC cell-derived exosomal miR-30a-5p enhanced cellular sensitivity to DDP, highlighting a potential strategy to overcome drug resistance.
Multi-chain Fudan-CCDC model for COVID-19 in Iran
Authors: Pan Hanshuang , Shao Nian , Yan Yue , Luo Xinyue , Ahmadi Ali , Fadaei Yasin , Cheng Jin , Chen Wenbin
Published: April 2020

Background

COVID-19 has been deeply affecting people’s lives all over the world. It is significant for prevention and control to model the evolution effectively and efficiently.

Methods

We first propose the multi-chain Fudan-CCDC model which is based on the original Fudan-CCDC model to describe the revival of COVID-19 in some countries. Multi-chains are considered as the superposition of distinctive single chains. Parameter identification is carried out by minimizing the penalty function.

Results

From results of numerical simulations, the multi-chain model performs well on data fitting and reasonably interprets the revival phenomena. The band of ±25% fluctuation of simulation results could contain most seemly unsteady increments.

Conclusion

The multi-chain model has better performance on data fitting in revival situations compared with the single-chain model. It is predicted by the three-chain model with data by Apr 21 that the epidemic curve of Iran would level off on round May 10, and the final cumulative confirmed cases would be around 88820. The upper bound of the 95% confidence interval would be around 96000.
Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment
Authors: Liu Xuan , Zhang Xiaopeng , Xiao Yongjiu , Gao Ting , Wang Guangfei , Wang Zhongyi , Zhang Zhang , Hu Yong , Dong Qincai , Zhao Songtao , Yu Li , Zhang Shuwei , Li Hongzhen , Li Kaitong , Chen Wei , Bian Xiuwu , Mao Qing , Cao Cheng
Published: April 2020

Background

Coronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19.

Methods

Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors.

Findings

Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50×109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52·2% (24/46) had severe thrombocytopenia, compared to 6·7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81·3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naïve patients, suggesting that spontaneous HIT may occur in COVID-19.

Interpretation

Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition.

Funding

This investigation was supported by grants 2016CB02400 and 2017YFC1201103 from the National Major Research and Development Program of China.