Neurological Complications Research Articles

PTPN2 dephosphorylates STAT3 to ameliorate anesthesia-induced cognitive decline in aged rats by altering the microglial phenotype and inhibiting inflammation

Perioperative neurocognitive disorders (PNDs) are common neurological complications after anesthesia in the elderly. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates signal transducer and activator of transcription protein 3 (STAT3) signaling to control inflammation in certain organs, but its role in PNDs remains unknown. Herein, we constructed a PND model in 18-month-old rats by treating them with sevoflurane. PND rats developed neuroinflammation, along with a significant decrease in PTPN2 expression and a rise in STAT3 phosphorylation in the hippocampus. Ptpn2 overexpression alleviated the behavioral disorders of PND rats, ameliorated neuronal injury, inhibited neuroinflammation, inflammasome activation, microglial activation, and microglial phenotype switching. Similar results were observed in sevoflurane-treated HMC3 microglia with PTPN2 overexpression, while PTPN2 silencing showed the opposite results. Additionally, PTPN2 seems to be a target of T-box transcription factor 2 (TBX2). These results contribute to the evidence supporting the idea that PTPN2 is a regulatory factor in PND progression.

Efficacy of Levetiracetam vs Phenobarbital as First Line Therapy for the Treatment of Neonatal Seizures

OBJECTIVE Seizures are one of the most common neurologic complications seen in a neonate. Historically, phenobarbital has been the agent of choice, but can lead to adverse neurologic outcomes, which has contributed to the use of other agents. Levetiracetam has proven great efficacy with an excellent safety profile in older patients, causing interest of its use in neonates. The objective of this study was to determine if levetiracetam would provide similar neonatal seizure resolution rates as phenobarbital. METHODS The study was a single-center, retrospective, cohort study from August 1, 2020 to August 31, 2022 investigating the efficacy and safety of using levetiracetam compared with phenobarbital as a first line treatment for neonatal seizures. The primary outcome was to assess overall seizure resolution after administration of levetiracetam or phenobarbital, without addition of a second antiseizure medication. RESULTS There were 87 patients included in the study. Fifteen neonates (27.78%) achieved seizure resolution with phenobarbital compared with 9 neonates (27.27%) who received levetiracetam first line (p = 0.959). Neonates who received phenobarbital had higher rates of adverse effects. Neonates who received a benzodiazepine prior to administration of levetiracetam had lower seizure resolution rates (p = 0.021). CONCLUSIONS These findings suggest there is no difference in using phenobarbital over levetiracetam to achieve complete seizure resolution in a neonate. Higher rates of adverse events were seen in the phenobarbital group. The use of a benzodiazepine prior to administration of levetiracetam may reduce the efficacy of levetiracetam.

ID: 328666 Neurological Complications After Paddle Lead SCS Placement: An Analysis of 800 Consecutive Patients

ID: 328666 Neurological Complications After Paddle Lead SCS Placement: An Analysis of 800 Consecutive Patients

Yap1 alleviates sepsis associated encephalopathy by inhibiting hippocampus ferroptosis via maintaining mitochondrial dynamic homeostasis.

Sepsis-associated encephalopathy (SAE) is a serious neurological complication accompanied by acute and long-term cognitive dysfunction. Ferroptosis is a newly discovered type of cell death that is produced by iron-dependent lipid peroxidation. As a key transcriptional coactivator in the Hippo signalling pathway, Yes-associated protein 1 (YAP1) could target ferroptosis-related genes. This study was aimed to determine whether Yap1 protects against SAE and inhibits ferroptosis via maintaining mitochondrial dynamic homeostasis. Caecal ligation puncture (CLP) was used to establish the SAE model, and LPS was applied in hippocampal cells to mimic the inflammatory model invitro. The results showed that Yap1 conditional knockout in hippocampal caused lower survival in SAE mice and cognitive dysfunction, as proved by Morri's water maze (MWM) task, tail suspension test (TST), open field test (OFT) and elevated plus maze test (EPMT). After Yap1 knockout, the production of ROS, MDA and Fe2+ and proinflammatory cytokines in the hippocampus were increased, indicating that Yap1 deficiency exacerbates CLP-induced brain injury and hippocampus ferroptosis. Meanwhile, GPX4, SLC7A11, ferritin (FTH1) and GSH levels were decreased in the Yap1 knockout group. Invitro, Yap1 overexpression mitigated LPS-induced hippocampal cell ferroptosis and improved mitochondrial function by inhibiting mitochondrial fission, as evidenced by lower mitochondrial ROS, cell viability, Fe2+ and the expression of Fis1 and Drp1. Further, the present study suggested that Yap1 could inhibit ferritinophagy-mediated ferroptosis in the hippocampus via inhibiting mitochondrial fission, thus reducing cognitive dysfunction in SAE mice.

Neuroprotective effects of whey and buttermilk-based formulas on a DSS-induced colitis murine model.

Inflammatory bowel disease is a gut-brain axis disorder that comprises chronic inflammatory conditions affecting the gastrointestinal tract, where alterations in the mood of patients are common. Gut-brain axis is a bidirectional communication that link gut and brain. The close association between inflammatory bowel disease and neuroinflammation has far-reaching implications, as is increasingly recognized as a contributing factor to neuropsychiatric and neurodegenerative diseases. The increasing prevalence and high economic cost, together with the loss of life quality of people suffering from these diseases, point to the need to find alternatives to alleviate them. Exploring new therapeutic avenues prompts us to consider the potential benefits of milk fractions, taking advantage of the use of dairy by-products, such as whey and buttermilk. This study examines the impact of cow's whey- and buttermilk-based formulas supplemented with bovine lactoferrin and milk fat globule membrane on the expression of cytokines, as well as on the components of immune and serotonergic system of the brain in a murine model of DSS-induced colitis. Our results show the potential of these dairy by-products, especially whey, as functional foods in ameliorating neuroinflammation and safeguarding the central nervous system function amid the neurological complications induced or concomitant with intestinal inflammatory processes.

Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia.

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting "brain fog" and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. HIGHLIGHTS: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated.

Minocycline mitigates sepsis-induced neuroinflammation and promotes recovery in male mice: Insights into neuroprotection and inflammatory modulation.

Sepsis is associated with brain injury and acute brain inflammation, which can potentially transition into chronic inflammation, triggering a cascade of inflammatory responses that may lead to neurological disorders. Minocycline, recognized for its potent anti-inflammatory properties, was investigated in this study for its protective effects against sepsis-induced brain injury. Adult male C57 mice pretreated with minocycline (12.5, 25, and 50 mg/kg) 3 days before sepsis induction. An intraperitoneal injection of 5 mg/kg LPS was used to induce sepsis. Spontaneous locomotor activity (SLA) and weight changes were assessed over several days post-sepsis to monitor the recovery of the mice. The expression of inflammatory mediators and oxidative stress markers was assessed 24 h post sepsis. Septic mice exhibited significant weight loss and impaired SLA. Initially, minocycline did not attenuate the severity of weight loss (1 day) or SLA (4 h post-sepsis), but it significantly accelerated the recovery of the mice in later days. Minocycline dose-dependently mitigated sepsis-induced brain inflammation and oxidative stress. Our findings demonstrate that pretreatment with minocycline has the potential to prevent brain tissue damage and accelerate recovery from sepsis in mice, suggesting that minocycline may serve as a promising therapeutic intervention to protect against sepsis-induced neurological complications.

Effects of EEG-Neurofeedback in children with Down syndrome

Background. Down syndrome (DS) is a genetic disorder characterized by varying degrees of mental retardation and neurological complications. Children with DS often experience difficulties with attention, concentration, learning, memory, speech, language, behavior, and physical balance. Methods. This study included 11 children with DS and 10 children with ADHD, aged 6 to 10 years who received treatment at the private clinic “Neyromed Servis” in Tashkent, Uzbekistan. Cognitive functions were analyzed by using Electroencephalography-neurofeedback (EEG-NFB) and the Forbrain headsets. The Wechsler Preschool and Primary Scale of Intelligence and Schulte table were used to assess the effectiveness of non-drug treatment. Results. The utilization of Forbrain headsets enhanced children’s attentiveness as listeners and improved the quality of their voice and speaking. Positive changes in EEG parameters were also registered: theta wave amplitude and theta-tobeta ratio in the frontal lobes decreased significantly. Conclusion. EEG-NFB treatment significantly improved cognitive function, particularly attention, without any side effects in observed children. Moreover, impulsivity as well as hyperactivity decreased gradually. Additionally, after using of the Forbrain method, vocabulary in children improved by 20-40% across all groups.

Evaluation of the Relationship Between Bacterial Infection and Immunological Factors with Diabetic Foot Ulcer

Diabetes represent a chronic disorder that involve the decline in the levels of insulin produced by the pancreas due to many genetic and environmental factors. The disease involves the elevation of blood sugar in the circulation which may lead to vascular, neurological, ocular and renal complications. In addition, diabetic patients tend to develop ulceration due to wound infection swiftly in the lower limbs due to the reduce in the neurological sensation as well as to elevated sugar circulation which may greatly provoke wound infection and diabetic foot ulcerations. The current study aimed at isolation of the common causes of bacterial infection associated with diabetic foot ulcer as well as the assessment of IL-17 and IL-18 and in those patients and in control healthy group. The present study was conducted in Salah Aldeen province during the period from 1st of November 2023 to 15th of May 2024 and included 150 patients with diabetic foot infection who attended Salah-Alden Hospitals: (Tikrit Teaching Hospital, Balad General Hospital and private surgery clinics). Swabs and whole blood from patients with diabetic foot ulcer were taken and submitted to routine culture and identification of the causative bacterial infection followed by biochemical identification and antibiotics susceptibility test for the isolated microbe. The serum specimens from those positive bacterial isolates were submitted for IL17 and IL-18 ELISA assessment. IL-17, significant elevation P<0.05 of this cytokine was recorded in diabetic patients with foot ulcer with mean 21.94 pg/ml compared to control group. In the same way significant increase of IL-18 (P<0.05) was noted in diabetic patients with foot ulcer with mean 347.15 pg/ml in comparison to control group. In conclusion, diabetic foot ulceration is the result of in controlled elevation of blood glucose and bacterial infection with various pathogens can complicate the scenario, and the significant elevation of IL17 and IL18 in those patients can insight the role played by these cytokines in signaling the immune to recruit cellular and humoral response.

Extra-pulmonary manifestations of COVID-19: A comprehensive review

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has predominantly been recognized for its respiratory impact. However, as the pandemic has progressed, it has become evident that SARS-CoV-2 affects multiple organ systems beyond the lungs, resulting in a wide array of extra-pulmonary manifestations. These manifestations encompass cardiovascular, neurological, gastrointestinal, hepatic, renal, dermatological, hematological, endocrine, musculoskeletal, ocular, immunological, and psychiatric complications. This review aims to provide a comprehensive understanding of these extra-pulmonary manifestations, highlighting their clinical significance, underlying mechanisms, and implications for patient management. Recognizing these manifestations is critical for improving patient outcomes and informing ongoing research and therapeutic strategies.

Emergency Surgical Management of Meningiomas: Factors Affecting Early Outcomes and Complications

Abstract Objective Intracranial meningiomas constitute a third of all brain tumors and are among the most common indications for neurosurgical procedures performed worldwide. Most meningiomas present with an indolent, longstanding history. However, the data on outcomes of emergency surgeries for meningioma is limited. This study aims to present our experience of urgent surgical intervention in patients with meningiomas presenting acutely. We also analyze the factors influencing early neurological outcomes and complications. Materials and Methods All nonelective meningioma surgeries done on an emergency basis between January 2015 and December 2019 were retrospectively reviewed. Patients' demography, clinical, and radiological details were recorded for analysis. The surgical procedure, complications, and follow-up outcomes were also included for statistical comparison. Results Forty-four patients qualified for the study with a mean age of 49.4 ± 13.4 years. The average presenting Glasgow Coma Scale (GCS) was 13; 47.7% of cases presented with altered sensorium. The most common lesion location was convexity (25, 56.8%), and the mean tumor volume was 74.1 ± 36.5 mL. Gross peritumor edema with mass effect was seen in 16 patients (36.4%). The mean Karnofsky Performance Status at 3 months' follow-up was 89.3 ± 18.2. Patient age and tumor size did not affect outcomes. The presenting GCS of < 15 (odds ratio [OR] 8.8, confidence interval [CI] 0.95–80.72, p 0.03) and the occurrence of postoperative complications (OR 25.71, CI 2.65–249.2, p 0.001) were associated with unfavorable outcomes. Although not statistically significant, a poor tumor grade was also associated with worse clinical outcomes (p 0.20). Conclusion Emergency meningioma surgery has comparable outcomes and complication rates with routine elective procedures. Grade II/III meningiomas are more likely to present with acute neurological deterioration and carry a relatively worse prognosis. Poor presenting GCS and postoperative complications are the most critical factors associated with poor patient outcomes in our study.

Periprocedural clinical outcomes of stenting and endarterectomy in patients with carotid artery stenosis

Purpose: To identify the chief pathological cause of extracranial cerebrovascular disease, which is atherosclerosis, we analyzed and compared the early and 6-month morbidity and mortality rates of patients who underwent carotid endarterectomy (CEA) and carotid artery stenting (CAS) for carotid artery stenosis. Materials and Methods: We retrospectively included patients who had undergone surgical endarterectomy and endovascular carotid stent implantation for carotid artery stenosis between April 2019 and August 2022. We evaluated neurological examinations, routine blood tests, neurological and systemic complications, mortality rates, and follow-up colour Doppler ultrasonography 6 months post-discharge. Results: The study included a total of 300 patients, with 52.7% (n = 158) undergoing CEA and 47.3% (n = 142) undergoing endovascular stent implantation (CAS). The patients’ average ages were 66±8 years in the CEA group and 70±7.4 years in the CAS group, suggesting that those undergoing CAS were generally older. Notably, there were significantly more instances of congestive heart failure and a history of cerebrovascular disease within the CAS group compared to the CEA group. However, no significant difference was observed in the rates of postprocedural complications. Furthermore, there were no cases of mortality reported in either group. Conclusion: The preferred method for treating severe carotid artery stenosis should be determined by considering patient characteristics and preferences, as well as the complication rates in the centre.

The Impact of Covid-19 on Lower Urinary Tract Symptoms (LUTS) in Patients Treated Conservatively for Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a non-malignant urological pathology characterized by a progressive increase in the volume of the prostate gland and one of the important diseases which affect lower urinary tract symptoms (LUTS). Covid-19 is a new viral infection with epidemiological characteristics of a pandemic. The disease is presented as a respiratory, cardiovascular, and neurological late complication. There is limited data that low urinary tract can be affected and aggravate symptoms and quality of life (QoL). Our pilot study describes a male population treated with conservative methods for BPH and the effect of Covid-19 infection on their LUTS and QoL. This was a case-control study between April 2021 and November 2021. The study included 33 patients with a history of Covid-19 infection. The assessment of LUTS was carried out by processing the data obtained from the completed by the patients IPSS questionnaires (the last one before, immediately, and five months after Covid-19). The control group consisted of 50 patients, which for the management of the selection bias, matched according to demographic and clinical features of the group. All patients underwent ultrasound diagnostics giving information about the volume of the prostate gland and the amount of residual urine. Two years after the beginning of the Covid-19 pandemic, we can confidently say that not all characteristics of this type of infection are sufficiently clear. More in-depth studies on Covid-19 as a cause of worsening LUTS and overall progression of BPH could help identify new aspects of infection leading to significant improvements in its treatment.

Could Timed Targeting of the Circadian-Controlled NLRP3 Inflammasome Be a Potential Therapeutic Strategy for Treatment of COVID-19–Induced Encephalitis?

The new coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has several manifestations including neurological complications like encephalitis. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes, which are regulated by the circadian clock genes, are key signaling proteins that detect pathogenic microorganisms and sterile stressors and activate the pro-inflammatory cytokines such as interleukin-1β and -18 (IL-1β and IL-18). The disruption of circadian rhythms following SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) receptors in the capillary endothelium could lead to hyperactivation of the NLRP3 inflammasome, contributing to an enhanced inflammatory response in the central nervous system, thereby increasing susceptibility to or severity of coronavirus disease 2019 (COVID-19)-induced encephalitis. This review highlights the role of the circadian-controlled NLRP3 inflammasome in the pathogenesis of COVID-19-induced encephalitis and suggests targeting the NLRP3 circadian axis for timely intervention as a potential therapeutic target for the treatment of COVID-19-induced encephalitis.

Neurodevelopmental outcome in preterm infants

Background and objectives. Preterm is defined as babies born alive before 37 weeks of pregnancy are completed. It is one of the world's critical health problems because it may be a significant cause of long-term neurodevelopmental disability. The purpose of this work was to evaluate the impact of premature birth and brain injuries on neurological development and to identify problems as soon as possible in order to prevent or minimize sequelae as much as possible. Materials and methods. Between June 2022 and July 2024, 374 infants were examined at “Prof. Dr. Panait Sarbu” Clinical Hospital of Obstetrics and Gynecology. Each baby's gross and fine motor development was assessed, cognitive acquisitions were evaluated using an adapted Denver Developmental Screening Test, and where needed, physical therapy, head ultrasound/MRI, EEG, or genetic tests were recommended. Results. From the 374 infants evaluated (M/F: 142/232), 72 were excluded considering the normal term of birth. Of the other 302, 23 did not present for follow-up checks after one or two appointments, and 54 completed all evaluations up to 21-24 months (the study is ongoing). 5/54 had poor neurodevelopmental outcomes, almost all due to very preterm birth. From the remaining 225 babies, with a few exceptions with variable neurological damage (13/225), no motor or cognitive development abnormalities have been observed in the evaluations carried out so far. Conclusions. In our cohort, almost all babies who completed or did not the follow-up program had normal development (261/279), but in some cases, prematurity, brain lesions, or genetic causes remain associated with a poor long-term outcome. Establishing a follow-up system for premature infants is necessary because early management during the period of higher brain plasticity may prevent neurological complications and improve the quality of life.

The effect of low-intensity intradialytic cycling aerobic exercise on cognitive function in patients undergoing continuous hemodialysis

Background. End-stage renal disease (ESRD) patients often experience neurological complications. Mounting evidence suggests cognitive impairment associated with end-stage renal disease is likely related to vascular disruption in the brain, particularly in white matter integrity. Hemodialysis is an independent risk factor for mild cognitive decline (MCD) of ESRD patients and have serious implications for the quality of life. Intradialysis training is the most ideal choice for hemodialysis patients, because not requiring extra time and the patient is also under the supervision of a doctor when doing the exercises. Method. Eighteen patients with end-stage renal disease (ESRD) were randomized into two groups: a treatment group and a control group, with 9 patients in each group. The treatment group participated in low-intensity aerobic exercise on a cycle ergometer, consisting of two 30-minute sessions per week for 12 weeks. Both groups were instructed to continue their regular hemodialysis and medication regimen. MoCA-INA scores were measured before the intervention and again after 12 weeks for both groups. Comparisons of MoCA-INA scores were made within each group as well as between the two groups before and after the 12-week intervention. Results. In the treatment group, the MoCA-INA scores showed a significant improvement from baseline to after the intervention (p < 0.001; effect size = 1.88). In contrast, the control group did not exhibit a significant change in MoCA-INA scores (p = 0.468). Additionally, there was a significant difference in the change in MoCA-INA scores between the treatment and control groups after 12 weeks of intervention (p = 0.001).

EFFECTS OF HUMAN CYTOMEGALOVIRUS ON SOME HEMATOLOGICAL PARAMETERS AND LIVER FUNCTION IN PREGNANT WOMEN, YEMEN

Human Cytomegalovirus (HCMV) infection is a common congenital infection that affects approximately 0.7%–1% of all live births worldwide. Approximately 11% of newborns who are infected show symptoms at birth, and of these, between 30% and 40% are at a risk of experiencing long-term neurological complications. This study aimed to evaluate the effect of HCMV on hematological parameters and liver function in pregnant women in Hajjah governorate, Yemen. This study is a cross-section study that conducted in the Hajjah governorate of Yemen during a period of March to June 2023. A total of 108 blood specimens were collected from participants; 78 from patients group and 30 health group. Hematological parameters, such as total red blood cell count (RBC), hemoglobin (HB), platelet count (PLT), and white blood cells (WBC), as well as liver function tests, such as total protein, albumin, alkaline phosphatase (ALP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), total bilirubin, and direct bilirubin, were measured. Majority of participant patients aged between 16–21 years 27 (34.7%), studied at secondary schools (46.2%), in their second trimester 51 (65.4%), those with multigravida 54 (69.2%), and those with no history of congenital diseases 60 (76.9%). Compared with the control group, the mean WBC levels were significantly lower in HCMV patients (P < 0.05), whereas PLT levels were higher among HCMV patients (P < 0.05). Additionally, the mean levels of total bilirubin, direct bilirubin, SGOT, ALP, and albumin were significantly lower in patients with HCMV than in HC (P < 0.05). Furthermore, there were no significant differences between the patient and healthy groups in terms of HB, RBC counts, SGPT, and total protein (P > 0.05). It can be concluded that HCMV infection had a statistically significant effect on WBC, PLT, total bilirubin, direct bilirubin, SGOT, ALP, and albumin levels in pregnant women. Consequently, further studies are needed to define the role of HCMV in liver disorders.

Advancement and Challenges in Monitoring of CAR-T Cell Therapy: A Comprehensive Review of Parameters and Markers in Hematological Malignancies.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment for relapsed/refractory B-cell lymphomas. Despite its success, this therapy is accompanied by a significant frequency of adverse events, including cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), or cytopenias, reaching even up to 80% of patients following CAR-T cell therapy. CRS results from the uncontrolled overproduction of proinflammatory cytokines, which leads to symptoms such as fever, headache, hypoxia, or neurological complications. CAR-T cell detection is possible by the use of flow cytometry (FC) or quantitative polymerase chain reaction (qPCR) assays, the two primary techniques used for CAR-T evaluation in peripheral blood, bone marrow (BM), and cerebrospinal fluid (CSF). State-of-the-art imaging technologies play a crucial role in monitoring the distribution and persistence of CAR-T cells in clinical trials. Still, they can also be extended with the use of FC and digital PCR (dPCR). Monitoring the changes in cell populations during disease progression and treatment gives an important insight into how the response to CAR-T cell therapy develops on a cellular level. It can help improve the therapeutic design and optimize CAR-T cell therapy to make it more precise and personalized, which is crucial to overcoming the problem of tumor relapse.

Protective role of antibodies in enteric virus infections: Lessons from primary and secondary immune deficiencies.

Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus.

Brain microbleeds resulting from presumed extensive fat emboli in a patient with bone marrow necrosis following a sickle cell disease vaso-occlusive crisis.

Acute manifestations of sickle cell disease (SCD) are numerous and multisystemic.Cerebral fat embolism (CFE) is a rare but serious complication of SCD caused by bone marrow necrosis (BMN) during vaso-occlusive crises (VOC). We present the case of a41-year-old man with SCD who developed severe VOC and multi-organ dysfunction.He subsequently experienced neurological deterioration with decreased consciousness and diffuse encephalopathy on serial electroencephalograms. Bone marrow aspiration confirmed BMN. Brain MRI revealed extensive diffuse leukoencephalopathy, vasogenic and cytotoxic edema in the white matter, patchy edema in the cranial vault bone marrow on fat-suppressed FLAIR sequence (a finding consistent with the confirmed BMN), and multiple cerebral microbleeds on susceptibility-weighted imaging consistent with CFE. The management of acute neurological complications of SCD varies depending on the specific complication. Brain MRI plays a crucial role in the accurate diagnosis of these complications to guide appropriate treatment.