Spinal muscular atrophy is a rare, autosomal recessive, neuromuscular disease caused by biallelic loss of the survival motor neuron 1 (SMN1) gene, resulting in motor neuron dysfunction. In this ...STR1VE-EU study, we aimed to evaluate the safety and efficacy of onasemnogene abeparvovec gene replacement therapy in infants with spinal muscular atrophy type 1, using broader eligibility criteria than those used in STR1VE-US.
STR1VE-EU was a multicentre, single-arm, single-dose, open-label phase 3 trial done at nine sites (hospitals and universities) in Italy (n=4), the UK (n=2), Belgium (n=2), and France (n=1). We enrolled patients younger than 6 months (180 days) with spinal muscular atrophy type 1 and the common biallelic pathogenic SMN1 exon 7–8 deletion or point mutations, and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes vg/kg). The outpatient follow-up consisted of assessments once per week starting at day 7 post-infusion for 4 weeks and then once per month until the end of the study (at age 18 months or early termination). The primary outcome was independent sitting for at least 10 s, as defined by the WHO Multicentre Growth Reference Study, at any visit up to the 18 months of age study visit, measured in the intention-to-treat population. Efficacy was compared with the Pediatric Neuromuscular Clinical Research (PNCR) natural history cohort. This trial is registered with ClinicalTrials.gov, NCT03461289 (completed).
From Aug 16, 2018, to Sept 11, 2020, 41 patients with spinal muscular atrophy were assessed for eligibility. The median age at onasemnogene abeparvovec dosing was 4·1 months (IQR 3·0–5·2). 32 (97%) of 33 patients completed the study and were included in the ITT population (one patient was excluded despite completing the study because of dosing at 181 days). 14 (44%, 97·5% CI 26–100) of 32 patients achieved the primary endpoint of functional independent sitting for at least 10 s at any visit up to the 18 months of age study visit (vs 0 of 23 untreated patients in the PNCR cohort; p<0·0001). 31 (97%, 95% CI 91–100) of 32 patients in the ITT population survived free from permanent ventilatory support at 14 months compared with six (26%, 8–44) of 23 patients in the PNCR natural history cohort (p<0·0001). 32 (97%) of 33 patients had at least one adverse event and six (18%) had adverse events that were considered serious and related to onasemnogene abeparvovec. The most common adverse events were pyrexia (22 67% of 33), upper respiratory infection (11 33%), and increased alanine aminotransferase (nine 27%). One death, unrelated to the study drug, occurred from hypoxic-ischaemic brain damage because of a respiratory tract infection during the study.
STR1VE-EU showed efficacy of onasemnogene abeparvovec in infants with symptomatic spinal muscular atrophy type 1. No new safety signals were identified, but further studies are needed to show long-term safety. The benefit–risk profile of onasemnogene abeparvovec seems favourable for this patient population, including those with severe disease at baseline.
Novartis Gene Therapies.
Transient osteoporosis of pregnancy (TOP) is a rare and often misdiagnosed disease during pregnancy. The postpartum fatigue or stress fracture is a recognized cause of pain, the diagnosis of ...postpartum osteoporosis (PPO) should be considered in the differential diagnosis of disabling lumbalgia occurring either during pregnancy (especially in the third trimester) or immediately after delivery. We report here the case of a 31-year-old patient, primiparous with no particular history, who presented disabling radiating pubic pain on the fourth day of postpartum after her caesarean section, that pelvic MRI had shown a fracture of the left sacral fin, associated with osteopenia of the hip. Her phosphocalcic assessment had objectified a vitamin D deficiency.
Thrombocytopenia occurs in about 10% of pregnant women. This could be due to a normal variant of pregnancy (gestational thrombocytopenia), a pregnancy-specific condition (preeclampsia and HELLP ...syndrome) or a condition exacerbated by pregnancy (ITP, vasculitis, PTT). The prognosis and treatment vary enormously, based on the underlying cause. Gestational thrombocytopenia (accidental thrombocytopenia of pregnancy) is a mild, asymptomatic thrombocytopenia that usually occurs late in pregnancy. There is no association with fetal thrombocytopenia, and maternal thrombocytopenia disappears spontaneously after delivery.
The primum movens of pre-eclampsia is a systemic maternal endothelial dysfunction. Choroidal and retinal vessels are rarely affected or rarely explored, and their involvement is usually reversible in ...pre-eclampsia if the diagnosis is made in time to establish adequate surveillance and treatment for each situation. The underlying lesions to ocular disorders are retinal serous detachment (RSD), optic neuropathy and finally the most serious involvement is cortical blindness. The pathophysiological hypothesis is clearly proven by the various complementary examinations such as fundus examination, OCT (Optic Coherence Tomography), and fluorescein angiography. Clinically, there appears to be a parallelism between the clinical importance of edema and that of RSD. We report the case of a patient who presented, during a severe pre-eclampsia (in an edematous form) on twin pregnancy, a favorable postpartum DSR with suspicion of optic neuropathy. A follow-up by internists was recommended.
This observation represents an unusual clinical aspect of a rare breast cancer, mucinous carcinoma which represents 1% of all breast cancers, with its two pure and mixed forms whose treatment and ...prognosis are not identical. The pure form has a good prognosis despite the exceptional clinical presentation of this type of breast cancer hence the interest of this case study, Mrs. L, a 70 year-old without risk factors admitted for mastitis of the leftbreast with rapid installation over 2 months, suspected of malignancy, yet the couple mammography / ultrasound did not manifest this malignancy, it shows an aspect of opacity well circumscribed of sharp contours. After the needle biopsy, the diagnosis of mucinous carcinoma was made which determined a suitable management is a neoadjuvant chemotherapy followed by a radical treatment, the hormonotherapy was continued in front of the expression of the hormonal receptors. Post-treatment surveillance did not report distant recurrence or metastasis.
Endometriosis is classically defined by the ectopic presence of tissues possessing the morphological and functional characteristics of the endometrium. Ovarian endometriosis is one of the most common ...locations. Its pathogenesis remains unclear, but a multifactorial origin has been proposed. The symptomatology is dominated by pain and infertility. The clinical examination is often poor. The suprapubic pelvic ultrasound, and especially the endovaginal ultrasound, remains the examination of first intension. Laparoscopy is the only test to affirm with certainty; biopsies, classify it into stages and choose the most appropriate therapeutic strategy. The treatment of the first intension remains surgical, the medical treatments being in the majority of the cases only palliatives. The therapeutic success depends on the radicality of the surgical excision. We report the case of a postmenopausal patient with ovarian endometriosis simulating ovarian neoplastic pathology with review of the literature.
In this project we investigated the extended-gate field-effect transistor (EGFET) structure used with ITO (Indium Tin Oxide)/PET (Polyethylene Terephthalate) sensitive films acting as the ...extended-gate part of an EGFET obtained from a combination of FETs from the CD4007 chip. We tested the device as a pH sensor by immersing the ITO/PET electrode in several chemical solutions of acidic and basic nature, including hydrogen peroxide, acetic acid, sulfuric acid, and ammonium hydroxide, at different concentrations. Using a Tektronix 4200A sourcemeter, we plotted the current–voltage (I–V) characteristics for the different chemical solutions, and we established a correlation to the pH changes. Results from the plotted I–V characteristics show a great dependance of the drain current (ID) on solution concentration. Furthermore, we measured the pH of each of the used solutions, and we established a relationship between the drain current and the pH value. Our results show a consistent decrease in the current with an increase in the pH value, although with different rates depending on the solution. The device showed high voltage sensitivity at 0.23 V per pH unit when tested in sulfuric acid.
In this manuscript, we examine the existence and the Ulam stability of solutions for a class of boundary value problems for nonlinear implicit fractional differential equations with instantaneous ...impulses in Banach spaces. The results are based on fixed point theorems of Darbo and Mönch associated with the technique of measure of noncompactness. We provide some examples to indicate the applicability of our results.
The coronavirus disease 2019 (COVID-19) pandemic caused and is still causing significant mortality and economic consequences all over the globe. As of today, there are three U.S Food and Drug ...administration (FDA) approved vaccines, Pfizer-BioNTech, Moderna and Janssen COVID-19 vaccine. Also, the antiviral drug remdesivir and two combinations of monoclonal antibodies are authorized for Emergency use (EUA) in certain patients. Furthermore, baricitinib was approved in Japan (April 23, 2021). Despite available vaccines and EUA, pharmacological therapy for the prevention and treatment of COVID-19 is still highly required. There are several ongoing clinical trials investigating the efficacy of clinically available drugs in treating COVID-19. In this study, selected novel pharmacological agents for the possible treatment of COVID-19 will be discussed. Point of discussion will cover mechanism of action, supporting evidence for safety and efficacy and reached stage in development. Drugs were classified into three classes according to the phase of viral life cycle they target. Phase I, the early infective phase, relies on supportive care and symptomatic treatment as needed. In phase II, the pulmonary phase, treatment aims at inhibiting viral entry or replication. Drugs used during this phase are famotidine, monoclonal antibodies, nanobodies, ivermectin, remdesivir, camostat mesylate and other antiviral agents. Finally, phase III, the hyper-inflammatory phase, tocilizumab, dexamethasone, selective serotonin reuptake inhibitors (SSRI), and melatonin are used. The aim of this study is to summarize current findings and suggest gaps in knowledge that can influence future COVID-19 treatment study design.
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•SARS-CoV-19 can be targeted at several stages throughout its life cycle.•Viral entry can be inhibited by Nanobodies, Monoclonal antibodies, Camostat mesylate, Ivermectin, Baricitinib or SSRI.•Viral replication can be inhibited by Plitidespsin, Boceprevir, PF-07304814, Famotidine, Ivermectin and Remdesivir.•Anti-inflammatory and antioxidants that prevent cell damage are Melatonin, Baricitinib, Tocilizumab and Fluoxetine.
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