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Expert Review of Clinical Immunology 2023Chimeric antigen receptor (CAR) T-cell is among the most prevalent approaches that act by directing T-cells toward cancer; however, they need to be optimized to minimize... (Review)
Review
INTRODUCTION
Chimeric antigen receptor (CAR) T-cell is among the most prevalent approaches that act by directing T-cells toward cancer; however, they need to be optimized to minimize side effects and maximize efficacy before being used as standard treatment for malignancies. Neurotoxicity associated with CAR T-cell therapy has been well-documented in recent works.
AREAS COVERED
In this regard, two established syndromes exist. Immune effector cell-associated neurotoxicity syndrome (ICANS), previously called cytokine release encephalopathy syndrome (CRES), is a neuropsychiatric condition which can occur after therapy by immune effector cells (IEC) and T-lymphocytes utilizing treatments. Another syndrome is cytokine release syndrome (CRS), which may overlap with ICANS.
EXPERT OPINION
ICANS clinical manifestations include cerebral edema, mild lethargy, aphasia, and seizures. Notably, ICANS is associated with changes to EEG and neuroradiological findings. Therefore, it is necessary to make a timely and accurate diagnosis of neurological complications of CAR T-cells by clinical presentations, neuroimaging, and EEG. Since neurological events by different CAR T-cell products are heterogeneous, guides should be developed according to each product. Here, we provide an updated review of general information on CAR T-cell therapies and applications, neurological syndromes associated with their use, and risk factors contributing to ICANS.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Neurotoxicity Syndromes; Cytokine Release Syndrome; Cell- and Tissue-Based Therapy; Receptors, Antigen, T-Cell
PubMed: 37578341
DOI: 10.1080/1744666X.2023.2248390 -
Endocrine, Metabolic & Immune Disorders... Oct 2023Citrullinemia type I (CTLN1) is a rare autosomal recessive metabolic disorder. Symptoms typically include vomiting, lethargy, seizures and coma. In neonatal...
INTRODUCTION
Citrullinemia type I (CTLN1) is a rare autosomal recessive metabolic disorder. Symptoms typically include vomiting, lethargy, seizures and coma. In neonatal presentation, death occurs in days if untreated. Survivors may evolve with neurocognitive dysfunction.
RESULTS/CASE REPORT
Two 10 years old, non-identical, twin sisters (S1; S2) with CTLN1 were born after a 36W gestation: S1 by eutocic delivery and S2 by cesarean section with nuchal cord (Apgar score 5/10). On day four, S2 presented hyperammonemia with coma. S1 had no complications. Diagnosis followed that of S2. Neurocognitive development was monitored at 3 months - 4 years of age with Griffiths Scales: global development quotient kept within the average, but S2 had a deficit in language and eye and hand coordination. At 5 years, the neurocognitive abilities were evaluated using Wechsler Preschool and Primary Scale of Intelligence - Revised (WPPSI-R). S2 revealed difficulties in verbal area (vocabulary, comprehension and memorizing sentences), with a lower average verbal intelligence quotient (IQ). S1 had high average IQ. Due to learning difficulties, S2 was reassessment at 8 years old with Wechsler Intelligence Scale for Children - Third edition (WISC-III): full-scale IQ -"extremely low".
CONCLUSION
These non-identical twin sisters share the same citrullinemia type 1 causing variants in the ASS1 gene. Nevertheless, their clinical presentation and neurocognitive evolution are diverse. Other factors, like the different genetic background and perinatal issues such as the type of delivery and its circumstances and the neonatal coma episode of S2 may explain the dissimilar evolution. Maximum ammonium levels (and its duration) are critical for the patients' neurodevelopment: 131 in S1 and 546 umol/l in S2.
PubMed: 37859410
DOI: 10.2174/0118715303280142231006103019 -
Veterinary Medicine and Science Nov 2023Six 100-day-old mixed-breed lambs were examined in a farm with a semi-intensive system due to neurologic signs. Cachexia, bilateral blindness, stupor, severe drowsiness...
Six 100-day-old mixed-breed lambs were examined in a farm with a semi-intensive system due to neurologic signs. Cachexia, bilateral blindness, stupor, severe drowsiness and lethargy with left and right movements of the head and neck were recorded after awakening and stimulation. Lambs died 10 days after the onset of the clinical signs. The lambs were necropsied, and after routine parasitology, bacteriology and histopathology, the occurrence of acute coenurosis was confirmed due to finding multiple cystic structures in the brain tissue. All lambs of the herd were treated with albendazole (orally, 25 mg/kg, two doses with an interval of 14 days). All shepherd dogs were treated with popantel (orally, one tablet/10 kg, two doses with an interval of 14 days). The affected lambs died despite this treatment. No new case of the disease was observed after the initiation of control measures. The present study shows the importance of preventive measure against coenurosis in a semi-intensive sheep farming system that includes implementing consistent parasite control programme in dogs being in contact with sheep.
Topics: Animals; Sheep; Dogs; Sheep Diseases; Cestode Infections; Cysticercosis; Brain; Dog Diseases
PubMed: 37725338
DOI: 10.1002/vms3.1278 -
World Journal of Clinical Cases Apr 2024Splenic hamartomas (SHs) are uncommon, benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images, at surgery, or at autopsy.... (Review)
Review
Splenic hamartomas (SHs) are uncommon, benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images, at surgery, or at autopsy. Since the first case description, in 1861, less than 50 pediatric SH cases have been reported in the literature. In this article, we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with SH. These lesions in children were shown to cause symptoms more often than in the adult population. The observed SH sizes in children ranged from a few millimeters to 18 cm, and the symptomatic lesions were mostly larger or multiple. The most common clinical finding was splenomegaly. Signs of hypersplenism were present in children with a single SH larger than 4.5 cm (diameter range: 4.5-18.0 cm) and in those with multiple hamartomas, ranging from a few millimeters to 5 cm. Eighty percent of patients with available laboratory findings had hematological abnormalities such as anemia, thrombocytopenia, or pancytopenia. Other symptoms and signs included abdominal pain, recurrent infections, fever, night sweats, lethargy, growth retardation, and weight loss. The use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic approach. However, the final diagnosis of SH relies on histopathological evaluation. Surgery, including total or partial splenectomy (PS), is the mainstay of SH management. Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with SH. In the majority of pediatric patients with symptomatic SH, resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.
PubMed: 38660549
DOI: 10.12998/wjcc.v12.i11.1909 -
Toxicon : Official Journal of the... Nov 2023Sodium monensin is the most frequently used ionophore as a growth promoter in ruminant diets. It has numerous benefits; however its toxic effects have also been observed...
Sodium monensin is the most frequently used ionophore as a growth promoter in ruminant diets. It has numerous benefits; however its toxic effects have also been observed in several animal species. Naturally occurring cases have not yet been reported in goats. This study describes an outbreak of accidental poisoning, characterizing its clinical, laboratory and pathological findings. Thirty-seven of 40 Anglo Nubian goat kids became intoxicated after receiving a diet that was erroneously supplemented with sodium monensin. They ingested an estimated toxic dose between 25 and 39 mg/kg BW. Clinical evolution was monitored (n = 27), followed by serum creatine kinase (CK) and aspartate aminotransferase (AST) activities measurements, and blood gas analysis. Postmortem examinations were performed between 1 and 8 days of evolution (n = 14). Clinical signs began 5 h after ingestion and included reticuloruminal hypomotility, lethargy, anorexia, tachycardia, cardiac arrhythmia, wet cough, pulmonary and tracheal crackles, and serous nasal discharge. The morbidity and lethality rates were 92.5 and 62.1%, respectively. CK and AST activities increased, reaching median values of 10,860 and 1596 U/L, respectively; the hyperchloremic metabolic acidosis was mild. The lesions were characterized by degeneration and necrosis of the cardiac and skeletal muscles, pulmonary congestion and edema, and passive liver congestion. The kids essentially developed cardiomyopathy with left and right congestive heart failures. Unlike in other ruminant species, skeletal muscle functional disability was infrequent. It can be concluded that monensin is toxic to goats and should be used with caution in their diet.
Topics: Animals; Monensin; Goats; Heart; Muscle, Skeletal; Sodium
PubMed: 37857004
DOI: 10.1016/j.toxicon.2023.107314 -
Neurological Sciences : Official... Jan 2024A 65-years-old woman with bipolar affective disorder presented to our ED with a severe lithium intoxication and the recent onset of confusion, clumsiness, and tremors....
A 65-years-old woman with bipolar affective disorder presented to our ED with a severe lithium intoxication and the recent onset of confusion, clumsiness, and tremors. Symptoms worsened to stupor and anarthria immediately after hospital admission. Gadolinium-enhanced brain Magnetic Resonance Imaging (MRI) showed signal hyperintensity involving both thalami in T2weighted (T2w)/Fluid Attenuated Inversion Recovery sequences (right > left), restricted areas of proton diffusivity at the level of both occipital lobes and a sharp contrast enhancement of thalami, rhombencephalon, and of leptomeninges from either the temporal, parietal, occipital lobes as well as from the cerebellar folia (right > left). These findings were consistent with a severe form of Posterior Encephalopathy known as Subacute Diencephalic Angio Endotheliopahty (SDAE). In addition, Magnetic Resonance Angiography revealed thrombosis of the right transverse and sigmoidal sinuses up to confluence with the jugular vein. The MRI picture resolved one month later after a course of high dosage dexamethasone. The patient deceased one month after discharge, mainly due to Diabetes Insipidusassociated hypernatremia. Dissecting the "Pandora's box" represented by complex MRI findings (SDAE and sinus thrombosis) in lithium-induced neurotoxicity is fundamental in timely recognizing this threating but potentially reversible clinical picture.
Topics: Female; Humans; Aged; Lithium; Posterior Leukoencephalopathy Syndrome; Brain; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging
PubMed: 37775617
DOI: 10.1007/s10072-023-07097-w -
Journal of Avian Medicine and Surgery Apr 2024Diabetes mellitus (DM) is an uncommon, poorly documented metabolic disorder of birds. Extrapolating knowledge from DM in mammals is challenging because of marked... (Review)
Review
Diabetes mellitus (DM) is an uncommon, poorly documented metabolic disorder of birds. Extrapolating knowledge from DM in mammals is challenging because of marked differences in avian physiology and metabolism. A literature review from December 1991 to January 2022 identified 14 publications covering 16 diabetic birds, 63% (10/16) of which belonged to the order Psittaciformes with as the predominant genus. No sex predilection was noted, but males generally presented at a younger age. Commonly reported clinical signs included polyuria 94% (15/16), polydipsia 88% (14/16), weight loss 75% (12/16), lethargy 63% (10/16), and polyphagia 38% (6/16). Diagnosis of DM was based on the presence of clinical signs and persistent hyperglycemia 100% (16/16), often with glucosuria 93% (13/14), response to insulin therapy 80% (8/10), and pancreatic pathology 90% (9/10). Specific treatment for DM was initiated in 14 patients, but blood glucose regulation for 6 months or longer was only achieved in 6 birds. Five of the regulated birds were managed with injectable long-acting insulin and 1 with oral glipizide combined with dietary modifications. However, glipizide yielded poor results in other cases, likely attributable to a lack of functional beta cells. Three diabetic birds progressed to remission. Treatment proved unsuccessful for 7 patients with a mean survival time of 36 days from diagnosis. One patient was lost to follow-up, and 2 were euthanized immediately following diagnosis. Histological examination of the pancreas frequently (90%, 9/10) revealed abnormalities including atrophy, fibrosis, and vacuolization of the endocrine islets with or without lymphoplasmacytic pancreatitis. Comorbidities, including hemosiderosis and infection, were common. This review suggests that birds diagnosed with DM are primarily affected by a type I diabetes as observed in dogs and humans. In contrast to mammalian species, avian DM is often associated with underlying disease and a complete clinical workup is essential to diagnose and address secondary disease conditions prior to initiating long-term insulin therapy.
Topics: Animals; Bird Diseases; Birds; Diabetes Mellitus
PubMed: 38686885
DOI: 10.1029/AVIANMS-D-22-00057 -
Microorganisms Jan 2024First recognized 15 years ago, Heartland virus disease (Heartland) is a tickborne infection contracted from the transmission of Heartland virus (HRTV) through tick bites... (Review)
Review
First recognized 15 years ago, Heartland virus disease (Heartland) is a tickborne infection contracted from the transmission of Heartland virus (HRTV) through tick bites from the lone star tick () and potentially other tick species. Heartland symptoms include a fever <100.4 °F, lethargy, fatigue, headaches, myalgia, a loss of appetite, nausea, diarrhea, weight loss, arthralgia, leukopenia and thrombocytopenia. We reviewed the existing peer-reviewed literature for HRTV and Heartland to more completely characterize this rarely reported, recently discovered illness. The absence of ongoing serosurveys and targeted clinical and tickborne virus investigations specific to HRTV presence and Heartland likely contributes to infection underestimation. While HRTV transmission occurs in southern and midwestern states, the true range of this infection is likely larger than now understood. The disease's proliferation benefits from an expanded tick range due to rising climate temperatures favoring habitat expansion. We recommend HRTV disease be considered in the differential diagnosis for patients with a reported exposure to ticks in areas where HRTV has been previously identified. HRTV testing should be considered early for those matching the Heartland disease profile and nonresponsive to initial broad-spectrum antimicrobial treatment. Despite aggressive supportive therapy, patients deteriorating to sepsis early in the course of the disease have a very grim prognosis.
PubMed: 38399689
DOI: 10.3390/microorganisms12020286