bluuebunny/crossref_metadata_2025 huggingface dataset:
Proximal Fixation in Adolescent Scoliosis Lenke 1 and 3 Treated by Posteromedial Translation Using Sublaminar Bands
Authors: Langlais Tristan , Rougereau Grégoire , Bruncottan Baptiste , Bolzinger Manon , Accadbled Franck , Compagnon Roxane , Sales de Gauzy Jérôme
Published: March 2021

Study Design:

This is retrospective comparative study.

Summary or Background Data:

Numerous studies have focused on the efficacy, safety, and restoration of thoracic kyphosis in adolescent idiopathic scoliosis surgery using posteromedial translation method with sublaminar bands and hook claws at the top. The relevance of exchanging the penultimate anchor, that is, the pedicle hook with a pedicle screw in a hybrid construction has not yet been assessed.

Objective:

Our objective was to assess, in adolescent scoliosis Lenke 1 and 3 operated by posteromedial translation using sublaminar bands, the proximal fixation claw influence (transverse-pedicular hook vs. transverse hook-pedicular screw) for postoperative correction and the proximal junctional kyphosis (PJK) at 2 years follow-up.

Materials and Methods:

A comparative monocentric retrospective study included adolescent idiopathic scoliosis thoracic requiring surgery, between 2015 and 2017, with 2 years follow-up. Clinical (complications, revision surgery, and scoliosis research society-30) and radiographic (coronal and sagittal parameters) assessment were reported. Radiologic PJK was defined by a proximal junctional angle increase of 10 degrees or more between postoperative period and the last follow-up.

Results:

Sixty patients (age at surgery=16±2 y; mean Cobb angle=58.2±12 degrees) were divided into 2 similar groups according to upper fixation: transverse-pedicular hook (H-H) and transverse hook-pedicle screw (S-H). No statistical differences were found for correction parameters (P>0.05). We reported 2 cases of PJK in H-H group (N=2/30=6.6%) and none in S-H group (N=0/30) (P=0.1) none requiring revision. No infectious or neurological events were reported. Mean scoliosis research society-30 was 126±12.7 in H-H group whereas 129.3±10 in S-H group (P=0.4).

Conclusions:

No differences in postoperative correction and clinical results at 2 years follow-up were found. A claw with transverse-pedicular hook increase proximal junctional angle without significant increase on radiographic PJK incidence compared with a claw with transverse hook and pedicle screws.
Clinical Comparison of Combined Cortical Bone Trajectory and Transarticular Surface Screw Versus Standard Pedicle Screw Insertion by Wiltse Approach for L5 Isthmic Spondylolisthesis
Authors: Terai Hidetomi , Tamai Koji , Takahashi Shinji , Umano Masayuki , Iwamae Masayoshi , Toyoda Hiromitsu , Suzuki Akinobu , Hoshino Masatoshi , Nakamura Hiroaki
Published: March 2021

Study Design:

This was a retrospective cohort study.

Objective:

The objective of this study was to assess the effectiveness and invasiveness of a combined screw insertion technique [using cortical bone trajectory (CBT) screw and transarticular surface screw (TASS)] for patients with L5 isthmic spondylolisthesis.

Summary of Background Data:

Lumbosacral posterior fixation using TASS is safe, with high biomechanical strength. However, data regarding its clinical outcomes, effectiveness, and invasiveness, are lacking.

Materials and Methods:

This study included 111 patients who underwent single-level L5–S1 posterior lumbar interbody fusion (PLIF) for L5 isthmic spondylolisthesis. The cohort was stratified into 2 groups: the Wiltse group included patients who underwent PLIF between 2008 and 2013 with standard pedicle screw fixation via Wiltse approach and the CBT/TASS group included those who underwent PLIF from 2014 onward with CBT/TASS fixation. After propensity score matching of the CBT/TASS and Wiltse groups, the surgical times, estimated blood loss (EBL), length of in-hospital stays, clinical scores, serum creatine kinase concentration, radiographic parameters, and bone union rate were compared using the χ2 test or Mann-Whitney U test. In addition, multivariate linear regression analyses, with surgical time and EBL as objective variables applied after Box-Cox transformation, were performed.

Results:

The matched CBT/TASS group showed significantly shorter surgical times (P<0.001), lower EBL (P=0.032), shorter in-hospital stays (P=0.005), and lower 3-day postoperative serum creatine kinase concentrations (P=0.014) than the matched Wiltse group. However, neither the postoperative grade of spondylolisthesis, the L5–S1 lordotic angle, nor the clinical scores were significantly different between matched groups. The bone union rates were 94.7% and 96.2% in the matched CBT/TASS and Wiltse groups, respectively (P=1.000). Regression analysis showed that CBT/TASS was an independent factor significantly related to shorter surgical times and lower EBL (P<0.001 and P=0.001, respectively).

Conclusion:

Compared with Wiltse approach, CBT/TASS is a less invasive technique, with a shorter surgical time and sufficient clinical outcomes for patients with L5 isthmic spondylolisthesis.

Level of Evidence:

Level III—treatment benefits.
Hybrid Therapy for Metastatic Disease
Authors: Pennington Zach , Ehresman Jeff , Szerlip Nicholas J. , Sciubba Daniel M.
Published: March 2021

Metastatic spine disease represents a complex clinical entity, requiring a multidisciplinary treatment team to formulate treatment plans that treat disease, palliate symptoms, and give patients the greatest quality-of-life. With the improvement in focused radiation technologies, the role of surgery has changed from a standalone treatment to an adjuvant supporting other treatment modalities. As patients within this population are often exceptionally frail, there has been increased emphasis on the smallest possible surgery to achieve the team’s treatment goals. Surgeons have increasingly turned to more minimally invasive techniques for treating spinal metastases. The use of these procedures, called separation surgery, centers around the goal of decompressing the neural elements, creating or maintaining mechanical stability, and allowing enough room for high-dose radiation to minimize cord dose.
A Novel Technique for Protecting Cartilage Repairs
Authors: Mazek Jacek , Gnatowski Maciej , Porthos Salas Antonio , Domżalski Marcin
Published: March 2021

Despite the considerable progress made in the last years with conservative and surgical orthopedic treatment methods, damage to the acetabular cartilage of the hip remains a challenging clinical issue. The development of new arthroscopic techniques and the use of biomaterials shows excellent promise in the regeneration of cartilaginous damage in young patients. It often delays the onset of degenerative joint lesions by postponing the moment where the patient will require arthroplasty. The presented technique shows promising results to serve as a bioabsorbable spacer and ensure the offloading of the operated hip joint surfaces during the postoperative period that is needed for the restoration of the cartilage and as a support of the biological scaffolds.
Genome-wide long non-coding RNA association study on Han Chinese women identifies lncHSAT164 as a novel susceptibility gene for breast cancer
Authors: Xu Jing-Kai , Li Guo-Zheng , Li Zhi , Li Wen-Jing , Chen Run-Sheng , Zhang Bo , Zhang Xue-Jun
Published: March 2021

Background:

Single-nucleotide polymorphisms (SNPs)-associated genes and long non-coding RNAs (lncRNAs) can contribute to human disease. To comprehensively investigate the contribution of lncRNAs to breast cancer, we performed the first genome-wide lncRNA association study on Han Chinese women.

Methods:

We designed an lncRNA array containing >800,000 SNPs, which was incorporated into a 96-array plate by Affymetrix (CapitalBio Technology, China). Subsequently, we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals (5634 breast cancer patients and 6308 healthy controls). Additionally, in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene.

Results:

We identified a novel breast cancer-associated susceptibility SNP, rs11066150 (P
meta = 2.34 × 10−8), and a previously reported SNP, rs9397435 (P
meta = 4.32 × 10−38), in Han Chinese women. rs11066150 is located in NONHSAT164009.1 (lncHSAT164), which is highly expressed in breast cancer tissues and cell lines. lncHSAT164 overexpression promoted colony formation, whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle.

Conclusions:

Based on our lncRNA array, we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle. These findings suggest a potential therapeutic target in breast cancer.
Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor
Authors: Brown Ryanne A. , Cloutier Jeffrey M. , Bahrani Eman , Liman Agnes , Tasso David , Palmer Adrian , Manning Melanie A. , Galperin Ilana , Rieger Kerri E. , Novoa Roberto A. , Lau Hubert , Louie Christine Y.
Published: March 2021

Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harborsALKrearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of anALKrearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.
Novel Approach to Removal of Rectal Foreign Bodies
Authors: Chilakamarry Sitaram , Klipfel Adam A.
Published: March 2021

BACKGROUND:

Retained rectal foreign bodies are a common concern in patients presenting to the emergency department. Thankfully, the rates of injury from these retained objects are low. Numerous techniques have been described for the extraction of these foreign bodies, including using endoscopic snares, Foley catheters to break suction mechanisms, and various kinds of clamps to grasp the objects. Some foreign bodies may not be amenable to snaring or grasping with forceps. We describe the use of laparoscopic specimen extraction bags to remove such objects.

TECHNIQUE:

The patient is placed in the lithotomy position under the appropriate level of anesthesia. The extraction bag is opened out of the pouch, and the metallic ring is lubricated. The ring is then compressed with 1 hand and gently guided into the rectum between the rectal wall and the foreign body with the other hand. The ring is then allowed to expand, and the foreign body is encircled. The bag is then closed around it, and the object is removed.

RESULTS:

The specimen-extraction bag works especially well for spherical objects and objects that are hard to grasp with clamps. We were able to extract a billiard ball and a glitter ball with this technique. It has minimal risk of injury to the rectum.

CONCLUSIONS:

Colorectal surgeons have a wide array of tools to use, and it is prudent to cater the tool to the task at hand. We can refashion the laparoscopic specimen extraction bag for removal of certain foreign bodies. It behooves the surgeon to consider all the tools at his or her disposal and to consider the best one for the job.
Prenatal Exposure to Mixtures of Persistent Endocrine-disrupting Chemicals and Birth Size in a Population-based Cohort of British Girls
Authors: Marks Kristin J. , Howards Penelope P. , Smarr Melissa M. , Flanders W. Dana , Northstone Kate , Daniel Johnni H. , Sjödin Andreas , Calafat Antonia M. , Hartman Terryl J.
Published: March 2021

Background:

Previous studies of endocrine-disrupting chemicals have examined one of these chemicals at a time in association with an outcome; studying mixtures better approximates human experience. We investigated the association of prenatal exposure to mixtures of persistent endocrine disruptors (perfluoroalkyl and polyfluoroalkyl substances [PFAS], polychlorinated biphenyls [PCBs], and organochlorine pesticides) with birth size among female offspring in the Avon Longitudinal Study of Parents and Children (ALSPAC), based in the United Kingdom in 1991–1992.

Methods:

We quantified concentrations of 52 endocrine-disrupting chemicals in maternal serum collected during pregnancy at median 15-week gestation. Birth weight, crown-to-heel length, and head circumference were measured at birth; ponderal index and small for gestational age were calculated from these. We used repeated holdout Weighted Quantile Sum (WQS) regression and Bayesian kernel machine regression to examine mixtures in 313 mothers.

Results:

Using WQS regression, all mixtures (each chemical class separately and all three together) were inversely associated with birth weight. A one-unit increase in WQS index (a one-decile increase in chemical concentrations) for all three classes combined was associated with 55 g (β = −55 g, 95% confidence interval [CI] = −89, −22 g) lower birth weight. Associations were weaker but still inverse using Bayesian kernel machine regression. Under both methods, PFAS were the most important contributors to the association with birth weight. We also observed inverse associations for crown-to-heel length.

Conclusions:

These results are consistent with the hypothesis that prenatal exposure to mixtures of persistent endocrine-disrupting chemicals affects birth size.
Results from the MemoryGel Post-approval Study
Authors: Short Kimberly K. , Wixtrom Roger N. , Estes Megan M. , Leopold John , Canady John W.
Published: March 2021

Background:

The approval of Mentor MemoryGel Breast Implants in November 2006 was conditional on conducting a 10-year study designed to collect long-term experience in US women with MemoryGel Breast Implants, known as the MemoryGel Post-Approval Study.

Methods:

This prospective, observational 10-year follow-up study used a current cohort design that began in 2007, which included both MemoryGel Breast Implant participants and concurrent saline controls to assess rheumatologic and neurologic signs and symptoms. The protocol was amended in 2015, which limited the scope of further data collection for the study to only secondary procedure/re-operation data for MemoryGel participants.

Results:

Primary augmentation (n = 6743), revision augmentation (n = 2071), primary reconstruction (n = 1763), and revision reconstruction (n = 557) participants were enrolled in the Re-operation Phase Safety Set. Kaplan-Meier–estimated 10-year cumulative incidence of re-operation and explantation on a participant-level were 10.5% and 4.2% (primary augmentation), 14.1% and 7.7% (revision augmentation), 20.8% and 12.8% (primary reconstruction), and 25.0% and 16.6% (revision reconstruction).

Conclusions:

The Re-operation Phase of the post-approval study addressed the Kaplan-Meier implant removal and re-operation rates over time, and provided the reasons for re-operation over time. Overall, no significant new hazards, increased risk, or unexpected adverse events were identified in the MemoryGel Post-Approval Study Re-operation Phase Safety Set.
ICG Lymphography in a 4-week Postmortem Cadaver: Implications for a Supermicrosurgery Training Model
Authors: Zolper Elizabeth G. , Bekeny Jenna C. , Fan Kenneth L. , Tzou Chieh-Han John , Song David H.
Published: March 2021

Surgical models are invaluable resources for training and for research and innovation. In the field of supermicrosurgery (SM), options for surgical models remain limited and imperfect. We report the use of a fresh, previously frozen 4-week postmortem cadaveric specimen for successful distal to proximal indocyanine green (ICG) lymphography of the upper extremity. Our technique was confirmed with handheld SPY fluorescence imaging, which visualized a clearly defined, linear lymphatic system. By outlining a straightforward, reproducible method of lymphatic mapping in cadaveric specimens, our group aims to expand the frontiers of surgical models for SM.
Genetics of dilated cardiomyopathy
Authors: Chen Suet Nee , Mestroni Luisa , Taylor Matthew R.G.
Published: March 2021

Purpose of review

Dilated cardiomyopathy (DCM), which include genetic and nongenetic forms, is the most common form of cardiomyopathy. DCM is characterized by left ventricular or biventricular dilation with impaired contraction. In the United States, DCM is a burden to healthcare that accounts for approximately 10,000 deaths and 46,000 hospitalizations annually. In this review, we will focus on the genetic forms of DCM and on recent advances in the understanding of cytoskeletal, sarcomeric, desmosomal, nuclear membrane, and RNA binding genes that contribute to the complexity and genetic heterogeneity of DCM.

Recent findings

Although mutations in TTN remain the most common identifiable cause of genetic DCM, there is a growing appreciation for arrhythmogenic-prone DCM due to mutations in LMNA, desmosomal genes, and the recently described FLNC gene encoding the structural filamin C protein. Mutations in RBM20 highlight the relevance of RNA splicing regulation in the pathogenesis of DCM. Although expanded genetic testing has improved access to genetic diagnostic studies for many patients, the molecular mechanisms in the pathogenesis of the disease remained largely unknown.

: The identification of the molecular causes and subsequent insight into the molecular mechanisms of DCM is expanding our understanding of DCM pathogenesis and highlights the complexity of DCM and the need to develop multifaceted strategies to treat the various causes of DCM.
Disparities in acute decompensated heart failure
Authors: Miller Tamari , Carter Spencer V. , Smith Bryan A.
Published: March 2021

Purpose of review

The aim of this review is to discuss racial and sex disparities in the management and outcomes of patients with acute decompensated heart failure (ADHF).

Recent findings

Race and sex have a significant impact on in-hospital admissions and overall outcomes in patients with decompensated heart failure and cardiogenic shock. Black patients not only have a higher incidence of heart failure than other racial groups, but also higher admissions for ADHF and worse overall survival, while women receive less interventions for cardiogenic shock complicating acute myocardial infarction. Moreover, White patients are more likely than Black patients to be cared for by a cardiologist than a noncardiologist in the ICU, which has been linked to overall improved survival. In addition, recent data outline inherent racial and sex bias in the evaluation process for advanced heart failure therapies indicating that Black race negatively impacts referral for transplant, women are judged more harshly on their appearance, and that Black women are perceived to have less social support than others. This implicit bias in the evaluation process may impact appropriate timing of referral for advanced heart failure therapies.

Though significant racial and sex disparities exist in the management and treatment of patients with decompensated heart failure, these disparities are minimized when therapies are properly utilized and patients are treated according to guidelines.
Drug-related adverse effects of antivascular endothelial growth factor agents
Authors: Iyer Prashanth G. , Albini Thomas A.
Published: March 2021

Purpose of review

Antivascular endothelial growth factor (VEGF) agents have provided historic therapeutic breakthroughs in the treatment of retinal disease. New anti-VEGF agents are emerging for the treatment of retinal vascular diseases. Both systemic and ocular adverse effect need to be understood in managing patients. This review aims to highlight the adverse effects seen with routine use of bevacizumab, ranibizumab and aflibercept, as well as with new medications such as brolucizumab and abicipar.

Recent findings

We review the recent findings of intraocular inflammation (IOI) of brolucizumab and abicipar in the context of the efficacy and safety reported with the routine anti-VEGF agents. Specifically, brolucizumab has been reported to cause occlusive retinal vasculitis in the setting of IOI, which has not been seen in other anti-VEGF medications. In addition, abicipar appears to cause IOI at a higher rate of patients than other anti-VEGF agents have previously.

Newer anti-VEGF agents pose a significant risk of adverse events not seen with routine anti-VEGF agents.
Accuracy of IOL power calculation formulas in Marfan lens subluxation patients with in-the-bag IOLs and implantation of scleral-sutured single-eyelet modified capsular tension rings
Authors: Zhang Min , Chen Tianhui , Deng Michael , Chen Zexu , Jiang Yongxiang
Published: March 2021

Purpose:

To investigate the accuracy of intraocular lens (IOL) formulas for the prediction of postoperative refraction in lens subluxation in Marfan syndrome.

Setting:

Eye and ENT Hospital of Fudan University, Shanghai, China.

Design:

Consecutive retrospective clinical observational case series.

Methods:

60 eligible eyes with lens subluxation from 39 young patients with Marfan syndrome (8.53 ± 4.38 years) underwent phacoemulsification combined with single-eyelet modified capsular tension ring (MCTR) and IOL implantation. The prediction error values with mean zero out (relative prediction error) and their absolute values (AE) were calculated.

Results:

Generally, the SRK/T formula with Wang-Koch (WK) adjustment had the lowest median AE at 0.418 diopters (D), and the Holladay 1 with WK adjustment had the lowest mean AE at 0.499 D. The median AE of the other 10 formulas, in order from lowest to highest, were Haigis with WK (0.494 D), Holladay 1 with WK (0.495 D), Hoffer Q with WK (0.508 D), Haigis (0.525 D), T2 (0.542 D), Hoffer Q (0.624 D), SRK/T and Holladay 1 (0.660 D), Super (0.680 D), and Barrett Universal II (0.714 D) formulas. Haigis formula was found to be statistically significantly different from SRK/T, Holladay 1, and Barrett Universal II (all 3 P < .001) but not Hoffer Q (P = .236) formula.

Conclusions:

The Haigis formula was recommended for young Marfan lens subluxation patients with in-the-bag IOLs and scleral-sutured single-eyelet MCTR implantation. WK adjustments were successful in those cases where the axial length was longer than 25.0 mm.
Dry eye and inflammation of the ocular surface after cataract surgery: effectiveness of a tear film substitute based on trehalose/hyaluronic acid vs hyaluronic acid to resolve signs and symptoms
Authors: Cagini Carlo , Di Lascio Giampiero , Torroni Giovanni , Mariniello Marco , Meschini Giulia , Lupidi Marco , Messina Marco
Published: March 2021

Purpose:

To compare the effect of trehalose 3%/hyaluronic acid 0.15% vs hyaluronic acid 0.15% eyedrops in reducing ocular surface inflammation after cataract surgery.

Setting:

Perugia, Italy.

Design:

Randomized, prospective study.

Methods:

Patients with healthy ocular surface were enrolled. Tear break-up time (TBUT), Schirmer test, corneal fluorescein staining (CFS), ocular surface disease index (OSDI) and in vivo confocal microscopy (IVCM) were performed preoperatively and at 1 months, 4 months, and 8 months postoperatively. Patients were randomly assigned to receive trehalose 3%/hyaluronic acid 0.15% eyedrops (Group A), hyaluronic acid 0.15% eyedrops (Group B), or no treatment (Group C).

Results:

98 patients were randomized as follows: 33 in Group A, 33 in Group B, and 32 in Group C. Schirmer test increased at 1-month follow-up in Group A and unchanged in Groups B and C. TBUT and CFS increased at 1-month follow-up in Group A and after 8 months in Groups B and C. OSDI score decreased at 1-month follow-up in Group A and at in Groups B and C. IVCM showed a reduction in the number of nerve fibers of the subbasal nerve plexus at 1 month in all groups and progressively increased to preoperative levels at 4 months in Group A, and at 8 months in Groups B and C. Tortuosity and reflectivity of subbasal plexus progressively decreased to became significant at 4-month follow-up in Group A whereas increased at 1-month follow-up and become normal at 8-month follow-up in Groups B and C. Langerhans cells and activated stromal keratocytes were higher in Groups B and C throughout the follow-up with a significantly lower density of hyperreflective stromal cells in Group A.

Conclusions:

Trehalose 3%/hyaluronic acid 0.15% eyedrops were effective in reducing inflammation and dry-eye symptoms.
Spinoparabrachial projection neurons form distinct classes in the mouse dorsal horn
Authors: Browne Tyler J. , Smith Kelly M. , Gradwell Mark A. , Iredale Jacqueline A. , Dayas Christopher V. , Callister Robert J. , Hughes David I. , Graham Brett A.
Published: March 2021

Projection neurons in the spinal dorsal horn relay sensory information to higher brain centres. The activation of these populations is shaped by afferent input from the periphery, descending input from the brain, and input from local interneuron circuits. Much of our recent understanding of dorsal horn circuitry comes from studies in transgenic mice; however, information on projection neurons is still based largely on studies in monkey, cat, and rat. We used viral labelling to identify and record from mouse parabrachial nucleus (PBN) projecting neurons located in the dorsal horn of spinal cord slices. Overall, mouse lamina I spinoparabrachial projection neurons (SPBNs) exhibit many electrophysiological and morphological features that overlap with rat. Unbiased cluster analysis distinguished 4 distinct subpopulations of lamina I SPBNs, based on their electrophysiological properties that may underlie different sensory signalling features in each group. We also provide novel information on SPBNs in the deeper lamina (III-V), which have not been previously studied by patch clamp analysis. These neurons exhibited higher action potential discharge frequencies and received weaker excitatory synaptic input than lamina I SPBNs, suggesting this deeper population produces different sensory codes destined for the PBN. Mouse SPBNs from both regions (laminae I and III-V) were often seen to give off local axon collaterals, and we provide neuroanatomical evidence they contribute to excitatory input to dorsal horn circuits. These data provide novel information to implicate excitatory input from parabrachial projection neuron in dorsal horn circuit activity during processing of nociceptive information, as well as defining deep dorsal horn projection neurons that provide an alternative route by which sensory information can reach the PBN.
Action of mefloquine/amitriptyline THN101 combination on neuropathic mechanical hypersensitivity in mice
Authors: Letellier Baptiste , Kremer Mélanie , Becker Léa J. , Andry Virginie , Goumon Yannick , Leboulleux Quentin , Hener Pierre , Inquimbert Perrine , Couqueberg Nolwenn , Waltisperger Elisabeth , Yalcin Ipek , Mouthon Franck , Droguerre Marine , Charvériat Mathieu , Barrot Michel
Published: March 2021

Tricyclic antidepressants that inhibit serotonin and noradrenaline reuptake, such as amitriptyline, are among the first-line treatments for neuropathic pain, which is caused by a lesion or disease affecting the somatosensory nervous system. These treatments are, however, partially efficient to alleviate neuropathic pain symptoms, and better treatments are still highly required. Interactions between neurons and glial cells participate in neuropathic pain processes, and importantly, connexins—transmembrane proteins involved in cell–cell communication—contribute to these interactions. In a neuropathic pain model in rats, mefloquine, a connexin inhibitor, has been shown to potentiate the antihyperalgesic effect of amitriptyline, a widely used antidepressant. In this study, we further investigated this improvement of amitriptyline action by mefloquine, using the cuff model of neuropathic pain in mice. We first observed that oral mefloquine co-treatment prolonged the effect of amitriptyline on mechanical hypersensitivity by 12 hours after administration. In addition, we showed that this potentiation was not due to pharmacokinetic interactions between the 2 drugs. Besides, lesional and pharmacological approaches showed that the prolonged effect was induced through noradrenergic descending pathways and the recruitment of α2 adrenoceptors. Another connexin blocker, carbenoxolone, also improved amitriptyline action. Additional in vitro studies suggested that mefloquine may also directly act on serotonin transporters and on adenosine A1 and A2A receptors, but drugs acting on these other targets failed to amplify amitriptyline action. Together, our data indicate that pharmacological blockade of connexins potentiates the therapeutic effect of amitriptyline in neuropathic pain.
Cardiorespiratory Fitness in Spanish Firefighters
Authors: Vicente Miguel Madruga , Herrero David Cerro , Prieto Josué Prieto
Published: March 2021

Objective:

To evaluate the cardiorespiratory fitness and other fitness-related measures, and to analyze the differences among age groups.

Methods:

This study was conducted on 104 firefighters. Maximal oxygen uptake (VO2 max) was assessed using the Shuttle Test and fitness was evaluated using appropriate physical tests.

Results:

Mean VO2 max was 45.7 mL/kg/min and 60.6% of firefighters were over the minimum accepted standpoint to do effective work, however, the VO2 max decreased with increasing age. 35.6% of the firefighters were overweight. Age, weight, and total body fat were found to be significant predictors of VO2 max level in this population, with total body fat as strongest predictor.

Conclusions:

Healthy habits-based interventions tailored by age groups should be promoted, to improve cardiorespiratory fitness and body composition for safe work and to improve firefighters’ health.
Can Adults Recognize Concussion Symptoms? A Critical Review of Empirical Research Using the Rosenbaum Concussion Knowledge and Attitudes Survey
Authors: Sullivan Karen A.
Published: March 2021

Objective:

The correct identification of concussion symptoms is vital for mild traumatic brain injury recognition, diagnosis, and injury management. Numerous surveys of symptom recognition have been conducted, including with athletes at-risk for injury. This critical, methodologically focused review aimed to: (1) discover which concussion symptoms are recognized, and (2) provide recommendations for future research.

Data Sources:

A quasi-systematic literature search was conducted to identify studies that used the Rosenbaum Concussion Knowledge and Attitudes Survey.

Study Selection:

Eighty-five publications were identified, 8 of which were retained after screening.

Data Extraction:

The identification of individual concussion symptoms was coded as good (a correct response by >90% of the sample), moderate (a correct response by 75%–90% of the sample), or poor (a correct response by <75% of the sample).

Data Synthesis:

The pooled data comprised responses from more than 2000 individuals, most of whom were male, young adult, sport players. Overall, there was good recognition of 3 concussion symptoms (headaches, dizziness, and confusion), poor recognition of sleep disturbances, nausea, and loss of consciousness, and misattribution to concussion of 2 distractor symptoms (weakness of neck range of motion, difficulty speaking). The methodological evaluation revealed significant variability in symptom measurement.

Conclusions:

The identified trends for concussion symptom recognition must be regarded as tentative because of the significant methodological variation in the reviewed studies. This variability affected the number, wording, and classification of items, and it restricted the data synthesis. This problem must be addressed in future research and recommendations are provided.
Cannabis for medical purposes: A cross-sectional analysis of health care professionals' knowledge
Authors: Rice Jessica , Hildebrand Andrea , Waslo Carin S. , Cameron Michelle H. , Jones Kim Dupree
Published: March 2021

Background:

Legalization of cannabis use and the evidence base supporting both risks and benefits of cannabinoids are expanding, but our understanding of health care professionals' (HCPs) knowledge about cannabis for medical purposes is limited. Understanding of the knowledge base and knowledge gaps about medical cannabis use is critical to advanced practice registered nurses (APRNs) because they are increasingly called on to manage patients taking multiple drugs, including prescribed and unprescribed cannabis and prescription cannabinoids.

Purpose:

The purpose of this study was to examine HCPs' knowledge of clinical cannabis, including laws and regulations; risks and harms; pharmacology; and effects on pain, multiple sclerosis spasticity, and seizures as assessed with written tests before an in-person, continuing medical education program.

Methods:

Total scores and differences among professions and topics were compared.

Results:

A total of 178 of the 226 program attendees completed the test (79%) (107 [47%] physicians, 30 [13%] APRNs, and 18 [8%] registered nurses). The mean test score was 63.2% (SD = 12.7%) without significant differences among professions (F
(3, 174) = 1.53; p = .21) but with significant differences among topics (χ2
(7, 1068) = 201.13; p < .001). The score was lowest for effects on seizures (43.8%) and with scores below 70% for all other areas except laws and regulations (85.7%).

Implications for practice:

There are substantial gaps in HCPs' knowledge about the clinical effects of cannabis, especially about risks and harms, pharmacology, and the effects on pain, multiple sclerosis spasticity, and seizures. Further education may help HCPs to understand the risks and benefits of cannabis and cannabinoids across conditions.
Change in Renal Function and Its Impact on Survival in Chronic Kidney Disease Patients Bridged to Heart Transplantation With a Left Ventricular Assist Device
Authors: Okoh Alexis K. , Kassotis John , Shah Aakash M. , Siddiqui Emaad , Dhaduk Nehal , Hirji Sameer , Gold Justin , Mehta Harsh , Ruberwa Joseph , Soliman Fady , Tayal Rajiv , Russo Mark J , Lee Leonard Y
Published: March 2021

The study investigates the incidence of change in renal function and its impact on survival in renal dysfunction patients who were bridged to heart transplantation with a left ventricular assist device (BTT-LVAD). BTT-LVAD patients with greater than or equal to moderately reduced renal function (estimated glomerular filtration rate [eGFR] ≤ 60 ml/min/1.73 m2) at the time of listing between 2008 and 2018 were identified from a prospectively maintained database of the United Network for Organ Sharing. Patients with a baseline eGFR less than or equal to 15 ml/min/1.73 m2 or on dialysis were excluded. Patients were divided into three groups based on percent change ([Pretransplant eGFR – listing eGFR/listing glomerular filtration rate (GFR)] × 100) in eGFR: Improvement greater than or equal to 10%, no change, decline greater than or equal to 10%, and their operative outcomes were compared. Posttransplant survival was estimated and compared among the three groups with the Kaplan-Meier survival curves and the log-rank test. Cox proportional hazards modeling was used to identify predictors of posttransplant survival. Out of 14,395 LVAD patients, 1,622 (11%) met the inclusion criteria. At the time of transplant, 900 (55%) had reported an improvement in eGFR greater than or equal to 10%, 436 (27%) had no change, and 286 (18%) experienced a decline greater than or equal to 10%. Postoperatively, the incidence of dialysis was higher in the decline than in the unchanged or improved groups (22% vs. 12% vs. 12%; p = 0.002). After a median follow-up of 5 years, there was no difference in posttransplant survival among the stratified groups (improved eGFR: 24.8%, unchanged eGFR: 23.2%, declined eGFR: 20.3%; p = 0.680). On Cox proportional hazard modeling, independent predictors of worse survival were: [hazard ratio: 95% CI; p] history of diabetes (1.43 [1.13–1.81]; p = 0.002) or tobacco use (1.40 [1.11–1.79]; p = 0.005) and ischemic time greater than 4 hours (1.36 [1.03–1.76]; p = 0.027). More than half of the patients with compromised renal function who undergo BTT-LVAD demonstrate an improvement in renal function at the time of transplant. A 10% change in GFR while listed was not associated with worse posttransplant survival.
Activation of citizen responders to out-of-hospital cardiac arrest
Authors: Folke Fredrik , Andelius Linn , Gregers Mads Tofte , Hansen Carolina Malta
Published: March 2021

Purpose of review

To discuss different approaches to citizen responder activation and possible future solutions for improved citizen engagement in out-of-hospital cardiac arrest (OHCA) resuscitation.

Recent findings

Activating volunteer citizens to OHCA has the potential to improve OHCA survival by increasing bystander cardiopulmonary resuscitation (CPR) and early defibrillation. Accordingly, citizen responder systems have become widespread in numerous countries despite very limited evidence of their effect on survival or cost-effectiveness. To date, only one randomized trial has investigated the effect of citizen responder activation for which the outcome was bystander CPR. Recent publications are of observational nature with high risk of bias. A scoping review published in 2020 provided an overview of available citizen responder systems and their differences in who, when, and how to activate volunteer citizens. These differences are further discussed in this review.

Implementation of citizen responder programs holds the potential to improve bystander intervention in OHCA, with advancing technology offering new improvement possibilities. Information on how to best activate citizen responders as well as the effect on survival following OHCA is warranted to evaluate the cost-effectiveness of citizen responder programs.
The epidermal growth factor receptor axis and kidney fibrosis
Authors: Harris Raymond C.
Published: March 2021

Purpose of review

The aim of this study was to summarize recent findings about the role of the epidermal growth factor receptor (EGFR) in acute kidney injury and in progression of chronic kidney injury.

Recent findings

There is increasing evidence that EGFR activation occurs as a response to either ischemic or toxic kidney injury and EGFR signalling plays an important role in recovery of epithelial integrity. However, with incomplete recovery or in conditions predisposing to progressive glomerular and tubulointerstitial injury, aberrant persistent EGFR signalling is a causal mediator of progressive fibrotic injury. New studies have implicated activation of HIPPO/YAP signalling as a component of EGFR's actions in the kidney. There is also new evidence for sex disparities in kidney EGFR expression and activation after injury, with a male predominance that is mediated by androgens.

There is increasing evidence for an important role for EGFR signalling in mediation of kidney injury, raising the possibility that interruption of the signalling cascade could limit progression of development of progressive kidney fibrosis.
Timing of kidney replacement therapy initiation in acute kidney injury
Authors: Meraz-Muñoz Alejandro Y. , Bagshaw Sean M. , Wald Ron
Published: March 2021

Purpose of review

Over the past 5 years, four major randomized controlled trials were published informing our practice on the optimal timing for kidney replacement therapy (KRT) initiation in critically ill patients with acute kidney injury (AKI). In this review, we summarize the main findings of these trails and discuss the knowledge gaps that still need to be addressed.

Recent findings

Four recent trials compared early versus delayed initiation of KRT in critically ill patients with acute kidney injury. Though each trial had unique design features, the three largest trials showed that earlier initiation of KRT did not reduce all-cause mortality.

A preemptive strategy for initiation of kidney replacement therapy does not confer better survival in critically ill patients with severe AKI. However, early initiation of KRT was associated with a greater risk of iatrogenic complications and one trial showed a higher risk of persistent dialysis dependence. In the absence of absolute indications for KRT, clinicians should defer KRT initiation in patients with AKI. Further research is needed to examine the safety of prolonged KRT deferral and identify markers of fluid overload that may serve to trigger KRT initiation.
Novel treatment options for acute hepatic porphyrias
Authors: Wang Bruce
Published: March 2021

Purpose of review

Acute hepatic porphyrias (AHP) are a group of rare diseases that are characterized by episodic acute neurovisceral pain episodes caused by abnormal accumulation of the neurotoxic porphyrin precursor delta-aminolevulinic acid (ALA). Patient with frequent recurrent acute attacks have been difficult to treat and these patients sometimes require liver transplantation. Recent developments in small interfering RNA (siRNA)-based therapy led to the development of an effective prophylactic treatment for patients with frequent recurrent attacks. This review will describe treatment options for AHP and highlight management in light of new treatment option.

Recent findings

Givosiran is a novel siRNA-based therapy targeted specifically to hepatocytes to inhibit ALA synthase 1, the first and rate-limiting step in heme biosynthesis. Patients with frequent recurrent attacks treated with givosiran had durable normalization of ALA and significantly reduced numbers of acute attacks and need for hemin treatment. The overall safety profile for givosiran was comparable with placebo and the drug was recently approved by the Food and Drug Administration for treatment of AHP patients.

Givosiran is an effective treatment for prevention of acute porphyria attacks in AHP patients with frequent recurrent attacks.
Mouse models of vascular development and disease
Authors: Cleaver Ondine
Published: March 2021

Purpose of review

The use of genetic models has facilitated the study of the origins and mechanisms of vascular disease. Mouse models have been developed to specifically target endothelial cell populations, with the goal of pinpointing when and where causative mutations wreck their devastating effects. Together, these approaches have propelled the development of therapies by providing an in-vivo platform to evaluate diagnoses and treatment options. This review summarizes the most widely used mouse models that have facilitated the study of vascular disease, with a focus on mouse models of vascular malformations and the road ahead.

Recent findings

Over the past 3 decades, the vascular biology scientific community has been steadily generating a powerful toolkit of useful mouse lines that can be used to tightly regulate gene ablation, or to express transgenic genes, in the murine endothelium. Some of these models inducibly (constitutively) alter gene expression across all endothelial cells, or within distinct subsets, by expressing either Cre recombinase (or inducible versions such as CreERT), or the tetracycline controlled transactivator protein tTA (or rtTA). This now relatively standard technology has been used to gain cutting edge insights into vascular disorders, by allowing in-vivo modeling of key molecular pathways identified as dysregulated across the vast spectrum of vascular anomalies, malformations and dysplasias. However, as sequencing of human patient samples expands, the number of interesting candidate molecular culprits keeps increasing. Consequently, there is now a pressing need to create new genetic mouse models to test hypotheses and to query mechanisms underlying vascular disease.

The current review assesses the collection of mouse driver lines that have been instrumental is identifying genes required for blood vessel formation, remodeling, maintenance/quiescence and disease. In addition, the usefulness of these driver lines is underscored here by cataloguing mouse lines developed to experimentally assess the role of key candidate genes in vascular malformations. Despite this solid and steady progress, numerous new candidate vascular malformation genes have recently been identified for which no mouse model yet exists.
Otolaryngology education and training in the COVID-19 and post-COVID-19 digital era: a developing world perspective
Authors: Quraishi Natasha , Quraishi Shahed
Published: March 2021

Purpose of review

This article reviews the literature on the challenges to Otolaryngology training in the developing world, the solutions that have been implemented thus far and the role of technology in first the Digital, and now the Covid era.

Recent findings

There is an increasing prevalence of Otolaryngological pathology in the developing world. Efforts to treat this are hampered by multiple factors including appropriate medical training. A number of solutions have been implemented for this both in terms of face-to-face as well as virtual training.

The Covid era has created new challenges for Otolaryngology training in the developed world, sparking a huge shift in the delivery of education. Traditional forms of training have disadvantaged colleagues in the developing world and so this change in training modalities may benefit the developing world.
Durable Response in Relapsed Adolescent Peripheral T-cell Lymphoma: A Case Report and Review of the Literature
Authors: Wedekind Mary Frances , Saraf Amanda , Willen Faye , Audino Anthony N.
Published: March 2021

Peripheral T-cell lymphoma (PTCL) is an aggressive tumor, rarely seen in pediatrics or adolescent and young adults (AYAs) so there is no upfront or relapsed standard of care. The authors describe a 16-year-old with PTCL, treated with chemotherapy and autologous stem cell transplant. Upon relapse, he received ifosfamide, carboplatin, etoposide, and radiation with durable remission of 4 years. Data in pediatric/AYA PCTL continue to lack an understanding of the biology and microenvironment, the differences to adult patients, and a lack of adequate therapy. Targeted therapy may improve outcomes for children and AYAs with refractory or relapsed PTCL.
Abducted Standing in Children With Cerebral Palsy: Effects on Hip Development After 7 Years
Authors: Martinsson Caroline , Himmelmann Kate
Published: March 2021

Purpose:

The effects of abducted standing on hip migration percentage (MP) and range of hip and knee motion in children with cerebral palsy were studied for more than 7 years in 2 case-control groups. One group had adductor-psoas tenotomy and the other did not.

Methods:

Case participants performed 15° to 30° of abduction per hip. Controls performed 0° to 10° of abduction and were matched on age, surgery, and follow-up time.

Results:

Median MP decreased 7.0% in the participants without surgery, increased 6.5% in their matched participant, and decreased 3.5% in the participants who had adductor-psoas tenotomy. Migration percentage decreased 18% in participants who after surgery performed abducted standing. Range of motion was greater after surgery in participants who performed standing abduction.

Conclusions:

Standing abduction at 15° to 30° for 10 h/wk reduces MP and preserves range of motion for up to 7 years. This is a new contribution to research for children with cerebral palsy.