Surgical tool entrapment in a young patient with recurrent lumbar spinal stenosis: a case report.

Lumbar spinal stenosis (LSS) is a prevalent cause of leg and back pain. In the youth, LSS is not common and mainly results from hereditary musculoskeletal disorders. Moreover, spinal fusion is a surgical approach to the treatment of LSS. Entrapment of surgical tools due to breakage is a rare yet important phenomenon in such operations. Therefore, neurological sequelae of these events need to be explored. The case was a 24-year-old male complaining of local back pain. Initially, he was diagnosed with LSS at L4 and L5. After the fusion of the vertebrae by the posterior spinal fusion (PSF) method, the patient's pain was resolved. However, the subject complained of worsening local back pain limiting his ability to do routine tasks. A few years later, radiographical evaluations indicated the possible presence of a surgical tool that could not be removed via surgery. During a third operation, the object was removed, and the patient's symptoms recovered. Immediate removal of entrapped surgical objects is necessary due to risks associated with migration and central nervous system damage. Comparing our results to other similar reports, we conclude that in cases of foreign object entrapment, neurological sequelae may be nonexistent or progressively worsen. Also, sequelae emerge either soon after the operation or emerge later. This complicates the diagnosis of such events and the decision of whether to subject the patient to additional neurosurgical operations to remove the tool. These variations may be observed due to the moving of the entrapped tool. Follow-up of neurological sequelae in spinal surgery patients is recommended.

Empagliflozin treatment of cardiotoxicity: A comprehensive review of clinical, immunobiological, neuroimmune, and therapeutic implications.

Cancer and cardiovascular disorders are known as the two main leading causes of mortality worldwide. Cardiotoxicity is a critical and common adverse effect of cancer-related chemotherapy. Chemotherapy-induced cardiotoxicity has been associated with various cancer treatments, such as anthracyclines, immune checkpoint inhibitors, and kinase inhibitors. Different methods have been reported for the management of chemotherapy-induced cardiotoxicity. In this regard, sodium-glucose cotransporter-2 inhibitors (SGLT2i), a class of antidiabetic agents, have recently been applied to manage heart failure patients. Further, SGLT2i drugs such as EMPA exert protective cardiac and systemic effects. Moreover, it can reduce inflammation through the mediation of major inflammatory components, such as Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, Adenosine 5'-monophosphate-activated protein kinase (AMPK), and c-Jun N-terminal kinase (JNK) pathways, Signal transducer and activator of transcription (STAT), and overall decreasing transcription of proinflammatory cytokines. The clinical outcome of EMPA administration is related to improving cardiovascular risk factors, including body weight, lipid profile, blood pressure, and arterial stiffness. Intriguingly, SGLT2 suppressors can regulate microglia-driven hyperinflammation affecting neurological and cardiovascular disorders. In this review, we discuss the protective effects of EMPA in chemotherapy-induced cardiotoxicity from molecular, immunological, and neuroimmunological aspects to preclinical and clinical outcomes.

Neurological adverse effects of chimeric antigen receptor T-cell therapy.

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.

The effect of cannabidiol on seizure features and quality of life in drug-resistant frontal lobe epilepsy patients: a triple-blind controlled trial.

Background: Treatment-resistant epileptic seizures are associated with reduced quality of life (QoL). As polypharmacy with routine antiseizure medications has many side effects, novel add-on treatments are necessary. Recent research showed the efficacy of add-on therapy by cannabidiol (CBD) on refractory epilepsy. We attempted to extend data on the efficacy and safety profile of CBD in patients with frontal lobe treatment-resistant epilepsy. Methods: A total of 27 patients were recruited into two CBD (n = 12) and placebo (n = 15) groups. The CBD group received a highly purified liposomal preparation of the drug in addition to routine antiseizure medications. The placebo group only received antiseizure medications. This experiment followed a triple-blinding protocol. Outcome measures were seizure frequency, the Chalfont seizure severity scale (CSSS), and the quality of life questionnaire score (QOLIE-31) assessed at baseline, 4 weeks, and 8 weeks. Results: At 4 weeks, results indicated that a higher fraction of patients in the CBD group (66.67%) showed improvement in seizure, compared to the placebo group (20.00%). Before-after comparison revealed that CBD, unlike routine ADEs, was effective in reducing the occurrence of seizures at the study's final timepoint [mean difference 45.58, 95% CI (8.987 to 82.18), p = 0.009]. Seizure severity was not affected by study groups or time intervals (repeated-measures ANOVA p > 0.05). Post-hoc tests found that the QoLI-31 score was improved at 8 weeks compared to baseline [mean diff. -5.031, 95% CI (-9.729 to -0.3328), p = 0.032]. The difference in cases who experienced enhanced QoL was meaningful between the CBD and placebo groups at 8 weeks [RR: 2.160, 95% CI (1.148 to 4.741), p = 0.018] but not at 4 weeks (p = 0.653). A positive finding for QoL improvement was associated with a positive finding for seizure frequency reduction [r = 0.638, 95% CI (0.296 to 0.835), p = 0.001]. Interestingly, limiting the correlation analysis to cases receiving CBD indicated that QoL improvement was not linked with seizure parameters such as severity and frequency (p > 0.05). Conclusion: The present study suggests the benefit of a purified and highly efficient preparation of CBD for seizure frequency reduction and improvement of QoL in refractory frontal lobe epilepsy. Further study with longer follow-ups and larger sample size is advised. Clinical trial registration: https://www.irct.ir/trial/56790, identifier: IRCT20210608051515N1.

Serum soluble Fas ligand is a severity and mortality prognostic marker for COVID-19 patients.

Finding cytokine storm initiator factors associated with uncontrolled inflammatory immune response is necessary in COVID-19 patients. The aim was the identification of Fas/Fas Ligand (FasL) role in lung involvement and mortality of COVID-19 patients. In this case-control study, mild (outpatient), moderate (hospitalized), and severe (ICU) COVID-19 patients and healthy subjects were investigated. RNA isolated from PBMCs for cDNA synthesis and expression of mFas/mFasL mRNA was evaluated by RT-PCR. Serum sFas/sFasL protein by ELISA and severity of lung involvement by CT-scan were evaluated. Also, we docked Fas and FasL via Bioinformatics software (in silico) to predict the best-fit Fas/FasL complex and performed molecular dynamics simulation (MDS) in hyponatremia and fever (COVID-19 patients), and healthy conditions. mFasL expression was increased in moderate and severe COVID-19 patients compared to the control group. Moreover, mFas expression showed an inverse correlation with myalgia symptom in COVID-19 patients. Elevation of sFasL protein in serum was associated with reduced lung injury and mortality. Bioinformatics analysis confirmed that blood profile alterations of COVID-19 patients, such as fever and hyponatremia could affect Fas/FasL complex interactions. Our translational findings showed that decreased sFasL is associated with lung involvement; severity and mortality in COVID-19 patients. We think that sFasL is a mediator of neutrophilia and lymphopenia in COVID-19. However, additional investigation is suggested. This is the first report describing that the serum sFasL protein is a severity and mortality prognostic marker for the clinical management of COVID-19 patients.

Triangle of cytokine storm, central nervous system involvement, and viral infection in COVID-19: the role of sFasL and neuropilin-1.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is identified as the cause of coronavirus disease 2019 (COVID-19), and is often linked to extreme inflammatory responses by over activation of neutrophil extracellular traps (NETs), cytokine storm, and sepsis. These are robust causes for multi-organ damage. In particular, potential routes of SARS-CoV2 entry, such as angiotensin-converting enzyme 2 (ACE2), have been linked to central nervous system (CNS) involvement. CNS has been recognized as one of the most susceptible compartments to cytokine storm, which can be affected by neuropilin-1 (NRP-1). ACE2 is widely-recognized as a SARS-CoV2 entry pathway; However, NRP-1 has been recently introduced as a novel path of viral entry. Apoptosis of cells invaded by this virus involves Fas receptor-Fas ligand (FasL) signaling; moreover, Fas receptor may function as a controller of inflammation. Furthermore, NRP-1 may influence FasL and modulate cytokine profile. The neuroimmunological insult by SARS-CoV2 infection may be inhibited by therapeutic approaches targeting soluble Fas ligand (sFasL), cytokine storm elements, or related viral entry pathways. In the current review, we explain pivotal players behind the activation of cytokine storm that are associated with vast CNS injury. We also hypothesize that sFasL may affect neuroinflammatory processes and trigger the cytokine storm in COVID-19.

Pathophysiological roles of chronic low-grade inflammation mediators in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common hormonal imbalance disease in reproductive-aged women. Its basic characteristics are ovulatory dysfunction and ovarian overproduction of androgens that lead to severe symptoms such as insulin resistance, hirsutism, infertility, and acne. Notwithstanding the disease burden, its underlying mechanisms remain unknown, and no causal therapeutic exists. In recent years, further studies showed that inflammation processes are involved in ovulation and play a key role in ovarian follicular dynamics. Visceral adipose tissue can cause inflammatory response and maintenance of the inflammation state in adipocytes by augmented production of inflammatory cytokines, monocyte chemoattractant proteins, and recruitment of the immune cell. Therefore, the PCOS can be related to a low-grade inflammation state and inflammatory markers. Investigating the inflammatory processes and mediators that contribute to the commencement and development of PCOS can be a critical step for better understanding the pathophysiology of the disease and its treatment through inhibition or control of related pathways. In the present review, we discuss the pathophysiological roles of chronic low-grade inflammation mediators including inflammasome-related cytokines, interleukin-1ß (IL-1ß), and IL-18 in PCOS development.

Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke.

Stem cell-based treatments have been suggested as promising candidates for stroke. Recently, mesenchymal stem cells (MSCs) have been reported as potential therapeutics for a wide range of diseases. In particular, clinical trial studies have suggested MSCs for stroke therapy. The focus of MSC treatments has been directed towards cell replacement. However, recent research has lately highlighted their paracrine actions. The secretion of extracellular vesicles (EVs) is offered to be the main therapeutic mechanism of MSC therapy. However, EV-based treatments may provide a wider therapeutic window compared to tissue plasminogen activator (tPA), the traditional treatment for stroke. Exosomes are nano-sized EVs secreted by most cell types, and can be isolated from conditioned cell media or body fluids such as plasma, urine, and cerebrospinal fluid (CSF). Exosomes apply their effects through targeting their cargos such as microRNAs (miRs), DNAs, messenger RNAs, and proteins at the host cells, which leads to a shift in the behavior of the recipient cells. It has been indicated that exosomes, in particular their functional cargoes, play a significant role in the coupled pathogenesis and recovery of stroke through affecting the neurovascular unit (NVU). Therefore, it seems that exosomes could be utilized as diagnostic and therapeutic tools in stroke treatment. The miRs are small endogenous non-coding RNA molecules which serve as the main functional cargo of exosomes, and apply their effects as epigenetic regulators. These versatile non-coding RNA molecules are involved in various stages of stroke and affect stroke-related factors. Moreover, the involvement of aging-induced changes to specific miRs profile in stroke further highlights the role of miRs. Thus, miRs could be utilized as diagnostic, prognostic, and therapeutic tools in stroke. In this review, we discuss the roles of stem cells, exosomes, and their application in stroke therapy. We also highlight the usage of miRs as a therapeutic choice in stroke therapy.

The involvement of the central nervous system in patients with COVID-19.

Coronaviruses disease (COVID-19) has caused major outbreaks. A novel variant, SARS-CoV-2, is responsible for COVID-19 pandemic. Clinical presentations and pathological mechanisms of COVID-19 are broad. The respiratory aspect of the disease has been extensively researched. Emerging studies point out the possibility of the central nervous system (CNS) involvement by COVID-19. Here, we discuss the current evidence for CNS involvement in COVID-19 and highlight that the high pathogenicity of SARS-CoV-2 might be due to its neuroinvasive potential.