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Monoclonal Antibodies: Leading Actors in the Relapsed/Refractory Multiple Myeloma Treatment.

Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and immunotherapy is becoming the mainstay of the therapeutic armamentarium of Multiple Myeloma (MM), starting with monoclonal antibodies (MoAbs) as elotuzumab, daratumumab and isatuximab. Elotuzumab, the first in class targeting SLAMF7, in combination with lenalidomide and dexamethasone and

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… These results are consistent with the most recent knowledge on genomic and molecular characterization of MM by next generation sequencing (NGS), showing a lack of universal driver mutation, presence of coexistent subclones and oligoclonality in MM, leading to different type of evolution of the disease … It binds to a specific epitope on the human cell surface antigen CD38, which is widely and uniformely expressed on myeloma cells, and it leads to apoptosis of MM cells without crosslinking of the Fc receptors of the antibody [ 65 ]. …

Conductive heating mattress leads to ECG changes that mimic pacemaker spikes.

Hypothermia is a common perioperative complication. To prevent perioperative hypothermia amongst other things electrical heating mattresses are used. We have made an observation with the use of an electrical heating mattress that may confuse users. In this case the ECG monitoring suddenly showed spikes that looked like spikes from an implanted pacemaker. When turning off the heating mattress the spikes disappeared and returned after turning on the heating mattress again.

Prolonged inflammation leads to ongoing damage after spinal cord injury.

The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates that post-SCI inflammation is severe but the role of reactive astrogliosis not well understood given its implication in ongoing inflammation as damaging or neuroprotective. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting da

Heterologous Expression Leads to Discovery of Diversified Lobophorin Analogues and a Flexible Glycosyltransferase.

The heterologous expression of the lobophorin biosynthetic gene cluster from marine-derived Streptomyces pactum SCSIO 02999 has led to the discovery of new analogues that carry d-kijanose (or its variants with a 3-amino or hydroxyl group) at C-9. The identification of intermediates resulting from the inactivation of lobG1 (encoding C-17 kijanosyltransferase) and lobG3 (encoding C-9 digitoxosyltransferase) demonstrates the substrate flexibility of LobG3 to also accept d-kijanose and its variants. Notably, two lobophorins with d-kijanose at C-9 show improved bioactivities.

Pharmacological Inhibition of MALT1 Protease Leads to a Progressive IPEX-Like Pathology.

Genetic disruption or short-term pharmacological inhibition of MALT1 protease is effective in several preclinical models of autoimmunity and B cell malignancies. Despite these protective effects, the severe reduction in regulatory T cells (Tregs) and the associated IPEX-like pathology occurring upon congenital disruption of the MALT1 protease in mice has raised concerns about the long-term safety of MALT1 inhibition. Here we describe the results of a series of toxicology studies in rat and dog species using MLT-943, a novel potent and selective MALT1 protease inhibitor. While MLT-943 effective

Delaying reclosure of bladder exstrophy leads to gradual decline in bladder capacity.

INTRODUCTION: After unsuccessful repair of bladder exstrophy, when to repeat surgical intervention is unclear. One must balance time required for tissue healing with the damaging effects of an exposed urothelium to the environment. OBJECTIVE: The authors aim to study whether a relationship exists between bladder growth/capacity and time till eventual successful closure. STUDY DESIGN: An institutional database of exstrophy-epispadias complex patients was queried for failed exstrophy closure with successful repeat reconstruction, at least three consecutive bladder capacity measurements, and me

An Unusual Case of Placenta Abruption Leading to Couvelaire Uterus in a Previable Pregnancy.

Couvelaire uterus or uteroplacental apoplexy is a rare complication of abruptio placentae whose etiology is unknown. It is a clinical diagnosis made during visual inspection of the uterus. Immediate management is usually conservative and hysterectomy is usually not required. Our case highlights the importance of early recognition of a clinically unstable previable pregnant patient with suspected placenta abruption and early surgical recourse with successful emergency hysterotomy.

Identification of metabolic changes leading to cancer susceptibility in Fanconi anemia cells.

Fanconi anemia (FA) is a chromosomal instability disorder of bone marrow associated with aplastic anemia, congenital abnormalities and a high risk of malignancies. The identification of more than two dozen FA genes has revealed a plethora of interacting proteins that are mainly involved in repair of DNA interstrand crosslinks (ICLs). Other important findings associated with FA are inflammation, oxidative stress response, mitochondrial dysfunction and mitophagy. In this work, we performed quantitative proteomic and metabolomic analyses on defective FA cells and identified a number of metabolic

Extended regorafenib treatment can be linked with mitochondrial damage leading to cardiotoxicity.

Regorafenib (RGF) has a great success in the treatment of colorectal cancer, gastrointestinal stromal tumours and hepatocellular carcinoma by inhibiting angiogenic, stromal and oncogenic kinases. However, RGF can induce life-threatening cardiotoxicity including hypertension and cardiac ischemia/infarction. The molecular mechanism of the adverse effects has not been elucidated. Mitochondrial dysfunction is one of the major causes of cardiac diseases since cardiac cells highly need ATP for their contractility. Therefore, we aimed to investigate molecular mechanisms of RGF-induced cardiac adverse

Arsenite induces testicular oxidative stress in vivo and in vitro leading to ferroptosis.

Ferroptosis is a newly identified form of cell death characterized by accumulation of intracellular iron and requirement of lipid peroxidati … e effect in cells. These findings together indicate that arsenite can trigger oxidative stress thus leading to testicular cell death by ferroptosis, suggesting that inhibition of ferroptosis would be a potential strategy for treatment of arsenite-related male reproductive toxicity.

The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse.

OBJECTIVE: Type 2 diabetes (T2D) occurs by deterioration in pancreatic β-cell function and/or progressive loss of pancreatic β-cell mass under the context of insulin resistance. α7 nicotinic acetylcholine receptor (nAChR) may contribute to insulin sensitivity but its role in the pathogenesis of T2D remains undefined. We investigated whether the systemic lack of α7 nAChR was sufficient to impair glucose homeostasis. METHODS: We used an α7 nAChR knock-out (α7-/-) mouse model fed a standard chow diet. The effects of the lack of α7 nAChR on islet mass, insulin secretion, glucose and insulin toler

Pyridaben induces mitochondrial dysfunction and leads to latent male reproductive abnormalities.

As an organochloride pesticide, pyridaben (PDB) has been used on various plants, including fruiting plants and other crops. Because of emerging concerns regarding exposure to pesticides, the deleterious effects of PDB, including neuronal disease and reproductive abnormalities, have been determined. However, the intracellular mechanisms that contribute to the effects of PDB on the male reproductive system are still unknown. Therefore, we investigated the effects of PDB on the male reproductive organ, focusing on the testes using mouse testicular cells. We demonstrated that PDB suppressed cellul

Laparoscopic Resection of a Left Upper Quadrant Mass Leading to a Surprise Diagnosis.

Background. Resplenectomy is most commonly done for the treatment of recurrent idiopathic thrombocytopenic purpura (ITP) refractory to medical management due to the regrowth of a missed accessory spleen. Case Report. A 66-year-old male had undergone open splenectomy for traumatic rupture 40 years ago. He presented with a leiomyosarcoma of his leg, which was surgically removed. When he developed metastatic disease, chemotherapy was started. He developed left upper quadrant pain, and on CT scan, a 5 cm mass compatible with a sarcoma was found between the tail of the pancreas and the left adrenal

Disseminated Cryptococcosis in An Immunocompetent Host Presenting As Osteomyelitis and Leading to Adrenal Insufficiency.

Disseminated cryptococcosis infection typically occurs in immunocompromised patients, often through pneumonia or meningoencephalitis. Cases in immunocompetent patients are uncommon, and presentation in either bone or adrenal glands are rare. We describe a case of a previously healthy immunocompetent 50-year-old woman who presented with lytic bone lesions followed by meningoencephalitis, dermatologic involvement, and adrenal insufficiency from disseminated cryptococcus. To our knowledge, this is the first case report of an immunocompetent patient with cryptococcus in the combination of blood, b

First report of Lyme borreliosis leading to cardiac bradydysrhythmia in two cats.

CASE SERIES SUMMARY: Two cats were presented for investigation of bradyarrhythmia detected by their referring veterinarians during routine examination. Both cats had extensive investigations, including haematology, serum biochemistry with electrolytes and thyroxine concentrations, systolic blood pressure measurement, echocardiography, electrocardiography and infectious disease testing. Infectious disease testing included serology for Toxoplasma gondii, Ehrlichia canis, Anaplasma phagocytophilum and Borrelia burgdorferi, and PCR for B burgdorferi antigen in both cats. Case 1 was also assessed b

HMG-CoA Reductase Inhibitors as Drug Leads against Naegleria fowleri.

Primary amebic meningoencephalitis (PAM), caused by the free-living ameba Naegleria fowleri, has a fatality rate of over 97%. Treatment of PAM relies on amphotericin B in combination with other drugs, but few patients have survived with the existing drug treatment regimens. Therefore, development of effective drugs is a critical unmet need to avert deaths from PAM. Since ergosterol is one of the major sterols in the membrane of N. fowleri, disruption of isoprenoid and sterol biosynthesis by small-molecule inhibitors may be an effective intervention strategy against N. fowleri. The genome of N.

Koebner phenomenon leading to the formation of new psoriatic lesions: evidences and mechanisms.

Koebner phenomenon refers to the emergence of new psoriatic lesions in the healthy skin regions following an injury/trauma to psoriatic patients. The occurrence of psoriatic lesions at unusual areas of the body regions such as on penis, around eyes and on keloids suggest that the Koebner phenomenon may be responsible for these lesions. A number of agents/triggers have been reported to induce the development of new psoriatic lesions in healthy skin areas and these include, tattooing skin, radiations, skin incision, viral infections and striae etc. The different mechanisms that contribute in ind

Novel Molecular Leads for the Prevention of Damage and the Promotion of Repair in Neuroimmunological Disease.

Neuroinflammation is a prominent pathological feature of all neuroimmunological diseases, including, but not limited to, multiple sclerosis … c, neurodegenerative phase, which is characterized by oligodendrocyte damage and axonal destruction leading to brain atrophy and an accumulation of disability. Recent work has shown that rather than occurring independently, both the inflammatory and degenerative phases may run concurrently. This, combined with evidence that early therapeutic interventi …