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Two commercial chimeric antigen receptor (CAR) T cell products, axicabtagene-ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®), are registered for the treatment of B cell neoplasia, for which an increased supply of CAR T cell products is required.

The production of patient-specific CAR T cells as advanced therapy medicinal products (ATMPs) poses considerable challenges with respect to logistics, regulation, and manufacturing.

Review of the CAR Tcell manufacturing process and the regulatory network, the current challenges, and future development capabilities of CAR Tcells for adoptive immunotherapy.

CAR Tcells are manufactured under individualized, laborious, good manufacturing practice-conforming processes in decentralized or in specialized centers. Starting from the patient’s leukapheresis product, Tcells are genetically engineered ex vivo with aCAR, amplified, and after extensive quality control re-applied to the patient. Most CAR Tcell products are manufactured in amanual or semi-automated process; fully automated, supervised, and closed systems are increasingly applied to meet the need for agrowing number of CAR Tcell products. In this setting, research aims at providing allogeneic CAR Tcell products or non-Tcells such as natural killer cells for broad applications.

The significance of CAR Tcells in adoptive immunotherapy is continuously growing. As individualized cell products, manufacturing requires highly efficient processes under the control of harmonized protocols and regulations so as to ensure the quality of the ATMP in view of increasing demand and to develop new fields in therapy.

The significance of CAR T cells in adoptive immunotherapy is continuously growing. As individualized cell products, manufacturing requires highly efficient processes under the control of harmonized protocols and regulations so as to ensure the quality of the ATMP in view of increasing demand and to develop new fields in therapy.Hb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. CPI-455 This series shows the enormous utility of using molecular techniques for diagnosis.

Extracranial carotid artery pseudoaneurysm is a rare complication of deep neck space infection, and no evidence-based treatment guidelines are available in the literature.

To clarify the existing experience of the different treatment strategies, the authors performed a systematic literature search using the PubMed, Ovid EMBASE, and Scopus databases in accordance with PRISMA guidelines to review all reported cases of pediatric patients with infectious carotid pseudoaneurysms larger than 1 cm.

Twenty-six patients with a median age of 4 years (range 6 months-15 years) were identified. Eighteen patients (69.2%) were treated with endovascular methods, 6 patients (23.1%) with surgical methods, 1 patient (3.8%) with a hybrid endovascular/surgical approach, and 1 patient (3.8%) with conservative management. Recurrence of the pseudoaneurysm occurred in 2 cases (7.7%), both of which were successfully retreated. Of the 6 patients (23.1%) who presented with pre-procedure neurologic deficits, 3 patients had complete or near complete resolution of symptoms after intervention and 3 patients had persistent deficits at last follow-up. Four patients (15.4%) experienced new neurologic deficits post-procedure that resolved at last follow-up.

The endovascular treatment tends to be the preferred option to treat a large or giant infectious pseudoaneurysm of the carotid artery in the pediatric patient. However, more evidence is necessary to elucidate comparative safety and efficacy profiles of endovascular and surgical management strategies.

The endovascular treatment tends to be the preferred option to treat a large or giant infectious pseudoaneurysm of the carotid artery in the pediatric patient. However, more evidence is necessary to elucidate comparative safety and efficacy profiles of endovascular and surgical management strategies.

Spinal cord injuries are frequently associated with severe clinical-neurological deficits. These are evident with specific symptoms and syndromes. Hereby, athorough knowledge of spinal neuroanatomy is essential.

Spinal anatomy, examination procedures and classical spinal syndromes are presented.

Important spinal syndromes comprise the dorsal cord syndrome, spinothalamic tract syndrome, pyramidal tract syndrome, central cord syndrome, transversal and Brown-Séquard syndrome as well as combined syndromes.

Clinical examination allows assessment and anatomical classification of spinal syndromes and targeted examination of the spinal cord using additional diagnostic methods.

Clinical examination allows assessment and anatomical classification of spinal syndromes and targeted examination of the spinal cord using additional diagnostic methods.Organismal temperature tolerance and metabolic responses are correlated to recent thermal history, but responses to thermal variability are less frequently assessed. There is great interest in whether organisms that experience greater thermal variability can gain metabolic or tolerance advantages through phenotypic plasticity. We compared thermal tolerance and routine aerobic metabolism of Convict cichlid acclimated for 2 weeks to constant 20 °C, constant 30 °C, or a daily cycle of 20 → 30 °C (1.7 °C/h). Acute routine mass-specific oxygen consumption ([Formula see text]O2) and critical thermal maxima/minima (CTMax/CTMin) were compared between groups, with cycle-acclimated fish sampled from the daily minimum (20 °C, 0900 h) and maximum (30 °C, 1600 h). Cycle-acclimated fish demonstrated statistically similar CTMax at the daily minimum and maximum (39.0 °C, 38.6 °C) but distinct CTMin values, with CTMin 2.4 °C higher for fish sampled from the daily 30 °C maximum (14.8 °C) compared to the daily 20 °C minimum (12.