Viltolarsen: First Approval.

Viltolarsen (Viltepso in Japan) is a phosphorodiamidate morpholino antisense oligonucleotide being developed by Nippon Shinyaku, in collaboration with the National Center of Neurology and Psychiatry (NCNP), for the treatment of Duchenne muscular dystrophy (DMD). Viltolarsen binds to exon 53 of the dystrophin mRNA precursor and restores the amino acid open-reading frame by skipping exon 53, resulting in the production of a shortened dystrophin protein that contains essential functional portions. In March 2020, intravenous viltolarsen received its first global approval in Japan for the treatment of DMD in patients with confirmed deletion of the dystrophin gene that is amenable to exon 53 skipping.

Short-term effects of Lumacaftor/Ivacaftor (Orkambi™) on exertional symptoms, exercise performance, and ventilatory responses in adults with cystic fibrosis.

Rationale: Lumacaftor/ivacaftor (LUM/IVA) modestly improves lung function following 1 month of treatment but it is unknown if this translates into improvements in exercise endurance and exertional symptoms.

Methods: Adult CF participants completed a symptom-limited constant load cycling test with simultaneous assessments of dyspnea and leg discomfort ratings pre- and 1 month post-initiation of LUM/IVA.

Results: Endurance time, exertional dyspnea and leg discomfort ratings at submaximal exercise did not change significantly.

Ultrasensitive Photoresponse of Graphene Quantum Dots in the Coulomb Blockade Regime to THz Radiation.

Graphene quantum dots (GQDs) have recently attracted considerable attention, with appealing properties for terahertz (THz) technology. This includes the demonstration of large thermal bolometric effects in GQDs when illuminated by THz radiation. However, the interaction of THz photons with GQDs in the Coulomb blockade regime, i.

Cytomegalovirus Proctitis in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib Therapy: A Case Report.

Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor that has shown significant efficacy in patients with lymphoid carcinomas, mostly chronic lymphocytic leukemia (CLL). Cytomegalovirus (CMV) infection is not a common infectious complication associated with ibrutinib. To increase the clinical awareness about this rare entity, we present the first case of CMV proctitis in an immunocompromised host who was being treated with ibrutinib.

Lipopolysaccharide-induced changes in the neurovascular unit in the preterm fetal sheep brain.

Background: Exposure to inflammation during pregnancy can predispose to brain injury in premature infants. In the present study, we investigated the effects of prolonged exposure to inflammation on the cerebrovasculature of preterm fetal sheep.

Methods: Chronically instrumented fetal sheep at 103-104 days of gestation (full term is ~ 147 days) received continuous low-dose lipopolysaccharide (LPS) infusions (100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h plus boluses of 1 μg LPS at 48, 72, and 96 h) or the same volume of normal saline (0.

Does aerobic fitness moderate age-related cognitive slowing? Evidence from the P3 and lateralized readiness potentials.

Reaction time (RT) slowing occurs among older adults, although it remains unclear whether general or specific aspects of information-processing are implicated in this phenomenon. Aerobic fitness moderates age-related RT slowing, although it is unknown whether fitness benefits earlier versus later stages of information-processing. To test these hypotheses, 40 younger and 43 older adults classified by level of aerobic fitness were tested using a visual oddball paradigm to assess behavioral measures of RT and accuracy along with the P3 wave and lateralized readiness potential (LRP) to index stimulus categorization and response selection and execution processes, respectively.

Correction to: Isatuximab: First Approval.

In the table 'Key clinical trials of isatuximab (Sanofi)', in the left-hand column.

Genetics and the Elite Athlete: Our Understanding in 2020.

Modern competitive sport has evolved so much that athletes would go to great extremes to develop themselves into champions; medicine has also evolved to the point that many genetic elements have been identified to be associated with specific athletic traits, and genetic alterations are also possible. The current review examines the published literature and looks at three important factors: genetic polymorphism influencing sporting ability, gene doping and genetic tendency to injury. The ACTN3 gene has an influence on type II muscle fibres, with the R allele being advantageous to power sports like sprinting and the XX genotype being associated with lower muscle strength and sprinting ability.

Rowing Injuries in Elite Athletes: A Review of Incidence with Risk Factors and the Role of Biomechanics in Its Management.

Background: Rowing is an Olympic sport gaining popularity in India and injuries are common in these athletes. Determinants of performance, injury risk and training are all interrelated in rowing. Injuries result from various risk factors including fitness issues and improper techniques.

Tirabrutinib: First Approval.

Tirabrutinib (Velexbru) is an orally administered, small molecule, Bruton's tyrosine kinase (BTK) inhibitor being developed by Ono Pharmaceutical and its licensee Gilead Sciences for the treatment of autoimmune disorders and haematological malignancies. Tirabrutinib irreversibly and covalently binds to BTK in B cells and inhibits aberrant B cell receptor signalling in B cell-related cancers and autoimmune diseases. In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma.

Isatuximab: First Approval.

Isatuximab (isatuximab-irfc; Sarclisa) is an IgG1 monoclonal antibody that binds to the glycoprotein CD38 expressed on the surface of haematopoietic and tumour cells. It is being developed by Sanofi, under a license from Immunogen, for the treatment of haematological malignancies. In March 2020, intravenous isatuximab (in combination with pomalidomide and dexamethasone) was approved in the USA for the treatment of adult patients with multiple myeloma who have received ≥ 2 prior therapies, including lenalidomide and a proteasome inhibitor.

The Effect of Size, Maturation, Global Asphyxia, Cerebral Ischemia, and Therapeutic Hypothermia on the Pharmacokinetics of High-Dose Recombinant Erythropoietin in Fetal Sheep.

High-dose human recombinant erythropoietin (rEPO) is a promising potential neuroprotective treatment in preterm and full-term neonates with hypoxic-ischemic encephalopathy (HIE). There are limited data on the pharmacokinetics of high-dose rEPO in neonates. We examined the effects of body weight, gestation age, global asphyxia, cerebral ischemia, hypothermia and exogenous rEPO on the pharmacokinetics of high-dose rEPO in fetal sheep.

Lower airway bacterial microbiome may influence recurrence after resection of early-stage non-small cell lung cancer.

Objective: The lower airway bacterial microbiome influences carcinogenesis and response to immunotherapy in non-small cell lung cancer (NSCLC). We investigated the association of this microbiome with recurrence in early NSCLC.

Methods: Microbiomes of presurgery bronchoalveolar lavage (BAL) and saliva, and resected stage I NSCLC tumor and adjacent lung tissues of 48 patients were examined by 16S gene sequencing.

Author Correction: Diffraction-limited ultrabroadband terahertz spectroscopy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tumor necrosis factor inhibition attenuates white matter gliosis after systemic inflammation in preterm fetal sheep.

Background: Increased circulating levels of tumor necrosis factor (TNF) are associated with greater risk of impaired neurodevelopment after preterm birth. In this study, we tested the hypothesis that systemic TNF inhibition, using the soluble TNF receptor Etanercept, would attenuate neuroinflammation in preterm fetal sheep exposed to lipopolysaccharide (LPS).

Methods: Chronically instrumented preterm fetal sheep at 0.

Heterotic Effect of Different Cytoplasmic Combinations in Sunflower Hybrids Cultivated Under Diverse Irrigation Regimes.

The sunflower hybrids hold a narrow cytoplasmic diversity. Besides, the heterotic effect of wild cytoplasmic combinations of sunflower on important traits under water stress has not been explored in detail. Here, we evaluated the different sunflower cytoplasmic combinations in sunflower hybrids using cytoplasmic male sterile (CMS) sources as female parents.

On the nature of objective and perceived cognitive impairments in depressive symptoms and real-world functioning in young adults.

Cognitive impairments in depression contribute to disability. According to prevailing cognitive theories, one's perception related to cognitive ability can cause and maintain depression, and related outcomes. Here, we investigate the degree to which perceived cognitive impairment predicts functional impairment above and beyond objective neurocognition.

Eptinezumab: First Approval.

Eptinezumab-jjmr (referred to as eptinezumab hereafter; Vyepti™) is a humanised monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and blocks its binding to the receptor. CGRP is believed to play a major role in the pathophysiology of migraine. Eptinezumab, delivered by intravenous (IV) administration, is being developed by Lundbeck Seattle BioPharmaceuticals for the prevention of migraine.

Ultrafast response of harmonic modelocked THz lasers.

The use of fundamental modelocking to generate short terahertz (THz) pulses and THz frequency combs from semiconductor lasers has become a routine affair, using quantum cascade lasers (QCLs) as a gain medium. However, unlike classic laser diodes, no demonstrations of harmonic modelocking, active or passive, have been shown in THz QCLs, where multiple pulses per round trip are generated when the laser is modulated at the harmonics of the cavity's fundamental round-trip frequency. Here, using time-resolved THz techniques, we show for the first time harmonic injection and mode-locking in which THz QCLs are modulated at the harmonics of the round-trip frequency.

The Impact of Music and Noise-Cancellation on Sedation Requirements During Total Knee Replacement: A Randomized Controlled Trial.

Background: Music has emerged as a well-received medical intervention. Patients may be uncomfortable during total joint replacement, which can result in high sedation requirements. These requirements place elderly patients at risk for delirium.

Delgocitinib: First Approval.

Delgocitinib, a janus kinase (JAK) inhibitor, is being developed by Japan Tobacco for the treatment of autoimmune disorders and hypersensitivity, including inflammatory skin conditions. The JAK family of tyrosine kinases plays an important role in mediating the biological effects of several inflammatory cytokines, e.g.

Practice Variation Among Canadian Pediatric Cardiologists in Medical Management of Dilated Ascending Aorta in Patients With Bicuspid Aortic Valve.

Background: Medical therapy is often prescribed to reduce the rate of aortic dilatation and prevent aortic dissection in patients with bicuspid aortic valve (BAV) despite a lack of evidence. We conducted an anonymous survey to gain insight into Canadian clinical practice regarding medical therapy used to slow the progression of aortic dilatation in patients with BAV.

Methods: A questionnaire was sent to 115 paediatric cardiologists and 18 adult congenital heart disease specialists in Canada.

Tricuspid Intervention Following Pulmonary Valve Replacement in Adults With Congenital Heart Disease.

Background: Tricuspid regurgitation (TR) is common among adults with corrected tetralogy of Fallot (TOF) or pulmonary stenosis (PS) referred for pulmonary valve replacement (PVR). Yet, combined valve surgery remains controversial.

Objectives: This study sought to evaluate the impact of concomitant tricuspid valve intervention (TVI) on post-operative TR, length of hospital stay, and on a composite endpoint consisting of 7 early adverse events (death, reintervention, cardiac electronic device implantation, infection, thromboembolic event, hemodialysis, and readmission).

Avapritinib: First Approval.

Avapritinib (AYVAKIT™) is a potent and selective tyrosine kinase inhibitor of platelet-derived growth factor receptor alpha (PDGFRA) and KIT activation loop mutants. It is being developed by Blueprint Medicines for the treatment of gastrointestinal stromal tumours (GIST), solid tumours and systemic mastocytosis. Avapritinib is approved in the USA for PDGFRA exon 18 (including D842V) mutant GIST and is undergoing regulatory assessment in the USA as a 4th-line treatment for GIST.