Long-term efficacy (at and beyond 1 year) of gastric peroral endoscopic myotomy for refractory gastroparesis: A systematic review and meta-analysis.

Introduction: Although gastric peroral endoscopic myotomy (G-POEM) has shown substantial efficacy in patients with medically refractory gastroparesis (GP), comprehensive long-term data on its effectiveness are lacking. Methods: We conducted a systematic review and meta-analysis including observational studies assessing long-term efficacy after G-POEM in patients with refractory GP. Our primary outcome was the pooled rate of clinical success 1-year after G-POEM. Secondary outcomes included clinical success at 2 and 3 years and the rate of adverse events according to the American Society for Gastrointestinal Endoscopy classification. Results: Thirteen studies, involving 952 patients with refractory GP undergoing G-POEM, were eligible. The pooled 1 year-clinical success was 0.72 (95% confidence interval [CI]: 0.56, 0.85, I2 = 94.9%). The clinical success was 0.67 (95% CI: 0.47, 0.97, I2 = 95.8%) when considering only studies defining success as 1 point decrease in Gastroparesis Cardinal Symptoms Index score and at least 25% decrease in two subscales. For patients who had 1-year success, the pooled clinical success at 2 and 3 years were 0.71 (95% CI: 0.45, 0.92, I2 = 94.9%) and 0.58 (95% CI: 0.19, 0.92, I2 = 97.1%), respectively. The pooled rate of adverse events was 0.08 (95% CI: 0.06, 0.10, I2 = 0%). Conclusion: G-POEM is associated with successful outcomes in about 70% of treated cases after 1 year, with durable long-term effects lasting up to 3 years. In the future, new uniform outcome definitions and strict patient selection criteria are warranted to delineate G-POEM outcomes more accurately.

Effectiveness of Changing Drug Classes in Patients With Refractory Laryngopharyngeal Reflux Disease.

OBJECTIVE: To investigate the effectiveness of drug class changes in patients with refractory laryngopharyngeal reflux disease (LPRD). STUDY DESIGN: Retrospective case series with prospective data. SETTING: Multicenter study. METHODS: The data of patients treated for a refractory LPRD from September 2017 to December 2023 were collected. The effectiveness of drug class changes was assessed through the reflux symptom score (RSS) change. Signs were evaluated with the Reflux Sign Assessment. The RSS reduction was used to categorize the therapeutic responses as mild (20%-40% RSS reduction), moderate (40.1%-60% RSS reduction), high (60.1%-80%), and complete (>80%). RESULTS: Among the 334 medical records, 74 (22.2%) patients had refractory LPRD defined as no RSS change in the pre- to 3-month posttreatment. The mean age was 52.6 ± 15.5 years. Changing drug class was associated with significant 3- to 6-month posttreatment reductions of RSS and RSA. Thirty patients (39%) did not experience symptom reduction after changing drugs. Changing alginate to magaldrate and magaldrate to alginate was associated with the highest responder rate (76.9%). Changing PPI and alginate/magaldrate molecules led to a response rate of 62.5%. In patients initially treated with a combination of PPI and alginate or magaldrate, changing PPI without changing alginate/magaldrate led to a 37.5% response rate. The baseline RSS was predictive of the 3- and 6-month RSS (therapeutic response). CONCLUSION: Changing drug class, especially alginate-to-magaldrate, may be an effective therapeutic approach for patients with a refractory LPRD.

Efficacy Analysis of Temporary Spinal Cord Stimulation in the Treatment of Refractory Postherpetic Neuralgia.

BACKGROUND: Spinal cord stimulation can be considered in PHN patients if conservative treatment is not effective. However, the long-term pain outcomes of temporary (7-14 days) spinal cord stimulation (tSCS) in refractory PHN patients with a course of more than 3 months have not been  documented. OBJECTIVES: To investigate the efficacy of tSCS as a treatment for refractory PHN. STUDY DESIGN: Retrospective study. SETTING: Pain Department in a university hospital. METHODS: A total of 52 patients with refractory PHN were treated with tSCS between March 2018 and February 2021. Their medical records were collected, and the patients were divided into 3 groups according to the course of their disease into the medium-term group, long-term group and ultra-long-term group. The changes in the numeric rating scale (NRS) scores, Pittsburgh sleep quality index (PSQI) responses, pain relief rate, postoperative efficiency and patients' use of analgesics were recorded before the operation, 3 days, 10 days, one month, 3 months, 6 months and 12 months after the operation. RESULTS: The average NRS scores, the maximum NRS scores and the PSQI scores at 3 days, 10 days, one month, 3 months, 6 months and 12 months after the operation were significantly lower than those before the operation (P < 0.05). The average NRS scores and the maximum NRS scores of all groups increased significantly from one month to 6 months compared to those at 10 days after the tSCS treatment, and they decreased significantly at 12 months compared with 6 months post-operation. The average NRS scores of the medium-term and long-term group were significantly lower than that of the ultra-long-term group at 1-3 months after the operation, and the maximum NRS scores at one month, 3 months and 12 months after the operation were also significantly lower in the medium-term and long-term group compared to the ultra-long-term group. The average PSQI scores at 1-12 months after the operation were not significantly higher than that at 10 days after the operation, but it decreased significantly at 12 months compared with 6 months after the operation. Among the 3 groups, the PSQI scores of the medium-term and long-term group were significantly lower than those of the ultra-long-term group at 6 months after the operation. The postoperative pain relief rate ranged from 41.51%-59.81%, and the total effective rate was 42.31%-69.23%, and there was no significant difference among the 3 groups. Some patients still needed analgesics at 12 months after the operation, but the number of patients who were taking medications post-operation was significantly lower than that before the operation. LIMITATIONS: This is a single-center retrospective study with the inability to completely control for variables. Additionally, the number of cases is small and the follow-up duration is short. CONCLUSION: tSCS can be used as a safe and effective method to relieve refractory PHN, and the curative effect is substantially higher in patients with a disease course of 3-12 months compared to that in patients with a course of more than 12 months.

Unveiling post-COVID-19 Rasmussen's encephalitis: a case report of rare neurological complication.

Introduction and importance: Rasmussen encephalitis (RE) is a rare autoimmune disorder that causes unilateral inflammation of the cerebral cortex and can lead to drug-resistant epilepsy and progressive neurological decline. Although the emergence of RE following COVID-19 has not been well documented, it emphasizes the need to understand the impact of COVID-19 on neurological health. This case emphasizes the importance of early recognition and intervention to prevent adverse outcomes related to post-COVID-19 neurological complications. Case presentation: A 30-year-old woman, recently diagnosed with COVID-19, experienced recurrent seizures that primarily affected the left side of her body. Despite medical management, signs of progressive weakness and altered consciousness were observed. Neurological examination, imaging, and electroencephalography confirmed a diagnosis of post-COVID-19 RE. Despite conservative management, the patient's condition continued to deteriorate, ultimately resulting in fatal outcomes. Clinical discussion: The relationship between COVID-19 and autoimmune responses, which can lead to neurological complications, such as RE, is a matter of concern. Accurate diagnosis of RE depends on imaging and EEG studies; however, a definitive diagnosis often requires histopathological examination. The management of RE involves the use of anti-seizure medications and surgical interventions to control symptoms and improve outcomes. However, the unusual presentation of this case, along with challenges in diagnosis and treatment, underscores the need for increased awareness and extensive research on the neurological consequences of COVID-19. Conclusion: This case underscores the severe neurological consequences that can emerge after COVID-19, emphasizing the need for prompt identification and intervention. Additional research is essential to improve the comprehension and management of the neurological aftermath of COVID-19 with the ultimate goal of enhancing patient outcomes.

Severe Epilepsy in an Individual With a TSC2 R905Q Variant Prompting Late Diagnosis in Affected Family Members.

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitor genes TSC1 and TSC2. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in TSC2 are typically associated with a more severe phenotype compared with TSC1; the TSC2 R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected. METHODS: We studied the TSC phenotype of a 13-year-old individual and three family members with a TSC2 c.2714G>A (R905Q) pathogenic variant. RESULTS: Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3-diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4-diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis. CONCLUSIONS: This study expands the possible phenotypic spectrum of TSC2 R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur.

Extracorporeal photopheresis vs. systemic immunosuppression for immune-related adverse events: Interim analysis of a prospective two-arm study.

BACKGROUND: Checkpoint inhibitor-induced steroid-refractory (sr) and steroid-dependent (sd) immune-related adverse events (irAE) account for about 11 % of irAE. Although these patients face worse outcomes due to irAE mortality and/or sustained immunosuppression, which impairs anti-tumor response, there is no established second-line treatment based on prospective trial data. METHODS: This prospective comparative study investigates outcomes of extracorporeal photopheresis (ECP), an immunomodulating therapy, versus second-line immunosuppressants (SLI) in sr/sd-irAE. The primary endpoint was longitudinal change in immunophenotype; secondary endpoints were outcome of irAE and tumor response. Patient demographics, quality of life (EORTC QLQ-C30; global health status (GHS/QoL)) and longitudinal blood samples were analyzed at baseline; in weeks 1, 4, 8, and 12. RESULTS: At interim analysis, 21 patients (11 ECP, 10 SLI) with 7 different sr/sd-irAE were included. Compared with the SLI group, the ECP group demonstrated a higher clinical response rate of irAE (93 % vs. 80 %; 95 % CI 0.83-1.92; P = 0.54) and a better GHS/QoL score throughout all follow-up visits. ECP patients showed a numerically higher overall survival (23 vs. 12 months; 95 % CI 0.02-3.02; P = 0.27) and lower cancer progression rates (33 % vs. 67 %; 95 % CI 0.09-1.60; P = 0.52). Immunophenotyping revealed changes in immune cell populations and the regulation of immune checkpoints. There were no significant safety issues in either treatment group. CONCLUSION: This prospective comparative study supports the clinical efficacy of ECP in the treatment of sr/sd-irAE in comparison to the SLI cohort. Thus, ECP represents a potential treatment option for this indication, given its good safety profile while maintaining anti-tumor response. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05700565, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05700565.

Patient-reported outcomes in patients with relapsed or refractory follicular lymphoma treated with zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy: results from the ROSEWOOD trial.

OBJECTIVE: We report patient-reported outcomes (PROs) measuring health-related quality of life (HRQoL) from the ROSEWOOD trial (NCT03332017), which demonstrated superior efficacy and a manageable safety profile with zanubrutinib plus obinutuzumab (ZO) versus obinutuzumab (O) in patients with heavily pretreated relapsed/refractory follicular lymphoma (R/R FL). METHODS: PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) and EQ-5D-5L questionnaires at baseline and subsequently every 12 weeks. All QLQ-C30 domains and EQ-5D-5L visual analog scale (VAS) scores were analyzed descriptively. At the key clinical timepoints (weeks 12 and 24), a mixed model for repeated measures (MMRM) analysis was used to evaluate the key PRO endpoints, including global health status, physical and role functioning, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting. Clinically meaningful change was defined as a ≥5-point mean difference from baseline and between the ZO and O arms. RESULTS: Patients were randomized to ZO (n = 145) or O (n = 72). By week 48, descriptive analysis results indicated that patients in the ZO arm demonstrated improved outcomes in role functioning and fatigue and nausea/vomiting symptoms, compared with those in the O arm. Both groups experienced improvements in pain symptoms. EQ-5D-5L VAS scores showed no observable differences between treatment arms through week 48. MMRM analysis revealed that the global health status/quality of life of patients treated with ZO improved, as did fatigue, at week 12. At week 24, patients in the ZO arm experienced a clinically meaningful improvement in role functioning, pain, and fatigue. CONCLUSIONS: In patients with R/R FL, ZO was associated with improved PROs compared with O. These findings suggest that zanubrutinib contributed clinically meaningful benefits to patient HRQoL when added to obinutuzumab.

Follicular lymphoma (or FL) is a common blood cancer where abnormal white blood cells form lumps in organs and glands in the body that normally help fight infection (lymph nodes). Zanubrutinib selectively blocks Bruton tyrosine kinase, which can prevent cancer cells growing and lead to their death. Obinutuzumab binds to a protein called CD20 on cancer cells, facilitating their removal using the body's natural defense system. Previous results from the ROSEWOOD trial showed that zanubrutinib plus obinutuzumab had improved cancer-fighting effects versus obinutuzumab alone, with manageable side effects in patients whose cancer returned after treatment or when treatment had failed.

Therapeutic potential of ketamine in management of epilepsy: Clinical implications and mechanistic insights.

Epilepsy, a widespread neurological disorder, affects approximately 50 million people worldwide. This disorder is typified by recurring seizures due to abnormal neuron communication in the brain. The seizures can lead to severe ischemia and hypoxia, potentially threatening patients' lives. However, with proper diagnosis and treatment, up to 70 % of patients can live without seizures. The causes of epilepsy are complex and multifactorial, encompassing genetic abnormalities, structural brain anomalies, ion channel dysfunctions, neurotransmitter imbalances, neuroinflammation, and immune system involvement. These factors collectively disrupt the crucial balance between excitation and inhibition within the brain, leading to epileptic seizures. The management of treatment-resistant epilepsy remains a considerable challenge, necessitating innovative therapeutic approaches. Among emerging potential treatments, ketamine-a drug traditionally employed for anesthesia and depression-has demonstrated efficacy in reducing seizures. It is noteworthy that, independent of its anti-epileptic effects, ketamine has been found to improve the balance between excitatory and inhibitory (E/I) activities in the brain. The balance is crucial for maintaining normal neural function, and its disruption is widely considered a key driver of epileptic seizures. By acting on N-methyl-D-aspartate (NMDA) receptors and other potential mechanisms, ketamine may regulate neuronal excitability, reduce excessive synchronized neural activity, and counteract epileptic seizures. This positive impact on E/I balance reinforces the potential of ketamine as a promising drug for treating epilepsy, especially in patients who are insensitive to traditional anti-epileptic drugs. This review aims to consolidate the current understanding of ketamine's therapeutic role in epilepsy. It will focus its impact on neuronal excitability and synaptic plasticity, its neuroprotective qualities, and elucidate the drug's potential mechanisms of action in treating epilepsy. By scrutinizing ketamine's impact and mechanisms in various types of epilepsy, we aspire to contribute to a more comprehensive and holistic approach to epilepsy management.

The effect of deep brain stimulation on cortico-subcortical networks in Parkinson's disease patients with freezing of gait: Exhaustive exploration of a basic model.

Current treatments of Parkinson's disease (PD) have limited efficacy in alleviating freezing of gait (FoG). In this context, concomitant deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) has been suggested as a potential therapeutic approach. However, the mechanisms underlying this approach are unknown. While the current rationale relies on network-based hypotheses of intensified disinhibition of brainstem locomotor areas to facilitate the release of gait motor programs, it is still unclear how simultaneous high-frequency DBS in two interconnected basal ganglia nuclei affects large-scale cortico-subcortical network activity. Here, we use a basic model of neural excitation, the susceptible-excited-refractory (SER) model, to compare effects of different stimulation modes of the network underlying FoG based on the mouse brain connectivity atlas. We develop a network-based computational framework to compare subcortical DBS targets through exhaustive analysis of the brain attractor dynamics in the healthy, PD, and DBS states. We show that combined STN+SNr DBS outperforms STN DBS in terms of the normalization of spike propagation flow in the FoG network. The framework aims to move toward a mechanistic understanding of the network effects of DBS and may be applicable to further perturbation-based therapies of brain disorders.

Parkinson's disease patients with freezing of gait (FoG) may be treated by deep brain stimulation, which produces effects mediated by brain networks. Currently, the approach of combined DBS of the subthalamic nucleus and the substantia nigra pars reticulata is investigated for being particularly beneficial for patients with axial symptoms, but the exact mechanisms of this effect are unknown. Here, we present a network-based computational framework using a basic excitable model that enables us to simulate the complete activity patterns of the brain network involved in FoG. These simulations reveal network mechanisms underlying STN+SNr DBS and its efficacy in alleviating FoG. The proposed framework can capture the influence of the DBS target sites on cortico-subcortical networks and help to identify suitable stimulation targets.

Neurosimilator for Undergraduate Biophysics and Neurophysiology Courses.

Stringent animal welfare principles are forcing undergraduate instructors to avoid the use of animals. Therefore, many hands-on lab sessions using laboratory animals are progressively replaced by computer simulations. These versatile software simulations permit the observation of the behavior of biological systems under a great variety of experimental conditions. While this versatility is important, computer simulations often work even when a student makes wrong assumptions, a situation that poses its own pedagogical problem. Hands-on learning provides pupils with the opportunity to safely make mistakes and learn organically through trial and error and should therefore still be promoted. We propose an electronic model of an excitable cell composed of different modules representing different parts of a neuron - dendrites, soma, axon and node of Ranvier. We describe a series of experiments that allow students to better understand differences between passive and active cell responses and differences between myelinated and demyelinated axons. These circuits can also be used to demonstrate temporal and spatial summation of signals coming to the neuron via dendrites, as well as the neuron coding by firing frequency. Finally, they permit experimental determination along with theoretical calculations of important biophysical properties of excitable cells, such as rheobase, chronaxie and space constant. This open-source model has been successfully integrated into an undergraduate course of the physiology of excitable cells and student feedback assessment reveals that it helped students to understand important notions of the course. Thus, this neuromorphic circuit could be a valuable tool for biophysics and neuroscience courses in other universities.

A comprehensive prediction model of drug-refractory epilepsy based on combined clinical-EEG microstate features.

Background: Epilepsy is a chronic neurological disorder characterized by recurrent seizures that significantly impact patients' quality of life. Identifying predictors is crucial for early intervention. Objective: Electroencephalography (EEG) microstates effectively describe the resting state activity of the human brain using multichannel EEG. This study aims to develop a comprehensive prediction model that integrates clinical features with EEG microstates to predict drug-refractory epilepsy (DRE). Design: Retrospective study. Methods: This study encompassed 226 patients with epilepsy treated at the epilepsy center of a tertiary hospital between October 2020 and May 2023. Patients were categorized into DRE and non-DRE groups. All patients were randomly divided into training and testing sets. Lasso regression combined with Stepglm [both] algorithms was used to screen independent risk factors for DRE. These risk factors were used to construct models to predict the DRE. Three models were constructed: a clinical feature model, an EEG microstate model, and a comprehensive prediction model (combining clinical-EEG microstates). A series of evaluation methods was used to validate the accuracy and reliability of the prediction models. Finally, these models were visualized for display. Results: In the training and testing sets, the comprehensive prediction model achieved the highest area under the curve values, registering 0.99 and 0.969, respectively. It was significantly superior to other models in terms of the C-index, with scores of 0.990 and 0.969, respectively. Additionally, the model recorded the lowest Brier scores of 0.034 and 0.071, respectively, and the calibration curve demonstrated good consistency between the predicted probabilities and observed outcomes. Decision curve analysis revealed that the model provided significant clinical net benefit across the threshold range, underscoring its strong clinical applicability. We visualized the comprehensive prediction model by developing a nomogram and established a user-friendly website to enable easy application of this model (https://fydxh.shinyapps.io/CE_model_of_DRE/). Conclusion: A comprehensive prediction model for DRE was developed, showing excellent discrimination and calibration in both the training and testing sets. This model provided an intuitive approach for assessing the risk of developing DRE in patients with epilepsy.

Healthcare resource utilization and costs of chronic lymphocytic leukemia/small lymphocytic lymphoma patients who relapse or are refractory to ibrutinib.

Aim: Evaluate healthcare resource utilization (HRU) and costs in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who relapsed or are refractory to (R/R) ibrutinib.Methods: All-cause and CLL/SLL-related HRU and healthcare costs were evaluated in adult patients with CLL/SLL who received ibrutinib (2/2014-3/2020) as single-agent or combination therapy and discontinued/switched to another antineoplastic agent (R/R) vs. all other (non-R/R) ibrutinib users.Results: Compared with the non-R/R patients (N = 919), R/R patients (N = 207) had higher all-cause HRU (inpatient, outpatient and emergency room visits; rate ratios [95% CIs]: 1.51 [1.38, 1.65]-1.92 [1.57, 2.37]; all P < 0.001) and healthcare costs ($81,645 vs. $34,717; cost difference [95% CI] = $50,170 [$40,555, $61,383]; P < 0.001).Conclusion: CLL/SLL patients who are R/R to ibrutinib bear a substantial economic burden.

Ibrutinib is a drug often prescribed for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)­two similar types of blood cancer-that returns/does not show improvement after a previous treatment (i.e., to patients who relapse after/are refractory to [R/R] the treatment). CLL/SLL that is R/R to ibrutinib can be costly because patients are left with fewer options for treatment and their cancer is likely to worsen. Knowing how much medical services are used and their cost when treating CLL/SLL that is R/R to ibrutinib can help patients, doctors and policy makers make informed decisions. In this study, the authors compared the use of healthcare resources-which included visits to the hospital, emergency room and doctor's office­and associated costs between patients with CLL/SLL in the United States who were R/R to ibrutinib and those who were not (non-R/R patients). The study showed that healthcare resource use and CLL/SLL-related medical costs were approximately two-times higher in R/R patients than in non-R/R patients. Thus, there is a substantial economic burden associated with R/R CLL/SLL.

Serum IFN-γ Predicts the Therapeutic Effect of Belimumab in Refractory Lupus Nephritis Patients.

Objective: To evaluate belimumabf's efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response. Methods: In this single-arm retrospective study, we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment. Results: Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70-1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001). Conclusion: Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.

Impact of pre-infusion disease burden on outcomes in pediatric relapsed/refractory B-cell lymphoblastic leukemia following anti-CD19 CAR T-cell therapy.

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have demonstrated high efficacy in pediatric patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Despite this success, the challenge of post-infusion relapse persists. In our study, we evaluate 116 children with R/R B-ALL who received anti-CD19 CAR T-cell therapy at our center. All patients were included in the response analysis and assessed for survival and toxicity. The CR rate was 98.3%, with 90.5% achieving minimal residual disease negative (MRD)- CR by day 28 (d28). The overall survival (OS) and event-free survival (EFS) were 69.3%±4.5% and 59.0%±4.6%, respectively, with a median follow-up duration of 47.9 months. The patients with pre-infusion MRD ≥ 1% was associated with lower 4-year OS (p = 0.006) and EFS (p = 0.027) comparing to those with MRD < 1%. The incidences of grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were21.6 and 5.0%, respectively. Therefore, pre-infusion disease burden is a predictor of long-term outcome following anti-CD19 CAR T-cell therapy for pediatric R/R B-ALL.

Successful Treatment of Refractory Cutaneous Manifestations of Dermatomyositis With Intravenous Immunoglobulin: A Case Report.

Dermatomyositis is a connective tissue disorder with dermatological and extracutaneous manifestations. Multiple treatment modalities have been used to treat dermatomyositis, and there have been cases with resistant disease refractory to conventional therapies. Corticosteroids are usually used to achieve remission, and from then, steroid-sparing agents such as azathioprine are used to maintain remission. However, in this report, we present a case of dermatomyositis with refractory cutaneous manifestation. The patient's muscular pain had subsided with the use of corticosteroids, but the dermatological lesions did not respond to multiple treatment modalities, responding only to intravenous immunoglobulins (IVIG).

Efficacy of Ruxolitinib with corticosteroids in idiopathic pneumonia syndrome post-allogeneic hematopoietic stem cell transplantation: A single-center experience and systematic review.

BACKGROUND: Idiopathic Pneumonia Syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-threatening complication with high morbidity and mortality. IPS is thought to arise from damage caused by various inflammatory mediators. This study assesses the effectiveness of Ruxolitinib, a Janus Kinase (JAK) 1 and 2 inhibitor that blocks cytokine production, in combination with corticosteroids (CS) for managing IPS after allo-HSCT, compared to the conventional use of CS alone in a case series and a systematic review of previously published literature. METHODS: The study includes a retrospective case series of three patients treated for IPS with Ruxolitinib and CS from the University of Kansas Medical Center and a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement 2020 guidelines. The systematic review encompassed seven studies involving 346 cases including three cases from the case series. Statistical analyses were conducted using SPSS v.25. RESULTS: The case series included three patients with IPS after allo-HSCT who received ruxolitinib and CS with favorable results. All patients showed substantial improvement with no IPS-associated mortality. Two of the three patients in the case series were discharged on a 2 L nasal cannula, which was later discontinued during follow-up visits, while the third was discharged on room air. There was marked improvement observed on the computed tomography (CT) following the use of ruxolitinib. Of the total 346 cases included in the systematic review, the median age was 46.6 years (Range 5-72), and 62 % were males. The primary disorders were acute leukemia (52 %), chronic myeloid leukemia (12 %), myelodysplastic syndrome (11 %), Lymphoma (10 %), and others (21 %). Stem cell sources were peripheral blood (45 %), bone marrow (49 %), and cord blood (6 %). Donor types involved match unrelated (55 %), match related (36 %), and mismatched related (4.5 %). Most patients received myeloablative conditioning (81 %). Acute GVHD was observed in 47 %, and chronic GVHD in 38 %. The primary treatment was CS (96 %), with limited use of ruxolitinib (1 %) and etanercept (9.5 %). The mortality rate was 63.3 %, whereas in our case series with the use of ruxolitinib, it was zero. CONCLUSION: The combination of Ruxolitinib and CS for treating IPS post-allo-HSCT suggested promising results in the case series, with favorable response and improved survival by blocking the cytokine production contributing to IPS. The significant mortality difference in the systematic review supports the need for innovative treatment approaches, highlighting the potential role of Ruxolitinib in CS-refractory cases. Despite the positive outcomes in the case series, the absence of randomized controlled trials emphasizes the necessity for further research.

Confined Gelation Synthesis of Flexible Barium Aluminate Nanofibers as a High-Performance Refractory Material.

Barium aluminate (BAO) ceramics are highly sought after as a kind of high-temperature refractory material due to their exceptional thermal stability in both vacuum and oxygen atmospheres, but their inherent brittleness results in rapid hardening, imposing a negative impact on the overall construction performance. Here, we report a strategy to synthesize flexible BAO nanofibers with a needle-like structure through confined-gelation electrospinning followed by in situ mineralization. The confined gelation among the colloidal particles promotes the formation of precursor nanofibers with high continuity and a large aspect ratio. The resulting flexible BAO nanofiber membranes are bendable, stretchable, and can even be woven, exhibiting a softness (12 mN) that is lower than that of tissue paper (27 mN). Additionally, they are capable of withstanding hundreds to thousands of continuous buckling and bending at 50% deformation without tearing. More importantly, the low emissivity of the flexible BAO nanofiber membranes ensures excellent thermal insulation at 1300 °C while preserving structural integrity and performance stability. In this sense, our strategy can be easily scaled up to produce flexible yet tough oxide ceramic membranes for a wider range of applications.

Refractory Hyperinsulinemic Hypoglycemia as a Complication of Roux-en-Y Gastric Bypass Surgery.

This case involves a 45-year-old woman with severe obesity who underwent Roux-en-Y gastric bypass (RYGB) surgery. After one year, she developed daily episodes of severe hypoglycemia, presenting with symptoms of palpitations, diaphoresis, and syncope. The patient was diagnosed with endogenous hyperinsulinemic hypoglycemia, a condition characterized by abnormally high insulin levels leading to low blood glucose, commonly associated with insulinoma. In rare instances, this can be due to nesidioblastosis, an overgrowth of pancreatic beta cells, which is more prevalent in individuals who have undergone bariatric surgery. Diagnostic evaluations included blood tests, abdominal computed tomography and magnetic resonance imaging, continuous glucose monitoring, and hepatic venous sampling to exclude insulinoma. This report details the diagnosis and unsuccessful treatment of endogenous hyperinsulinemic hypoglycemia following RYGB surgery. Interventions included dietary modifications (small, frequent, low-carbohydrate meals), medical management with acarbose 100 mg three times daily, diazoxide 150 mg three times daily, verapamil 40 mg twice daily, and surgical reversal of the RYGB. Ultimately, a percutaneous gastrostomy tube was placed for 24-hour continuous parenteral feeding. Despite these extensive treatment efforts, the patient continues to experience frequent hypoglycemic episodes four years after the bariatric procedure.

Clinical outcomes in peritoneal dialysis with refractory peritonitis: significance of the day 5 cell count.

BACKGROUND: Peritoneal dialysis-associated peritonitis is a common and severe complication of peritoneal dialysis, associated with high morbidity and mortality. However, there's a lack of research on refractory peritonitis, which is difficult to manage and has a poor prognosis. Our study aimed to investigate factors affecting clinical outcomes in peritoneal dialysis patients with refractory peritonitis over a 12-year period at a medical faculty hospital in Turkey. METHODS: We conducted a retrospective study at a single center from January 2009 to December 2020, involving 135 patients with 236 episodes of refractory peritonitis. The average age of the patient cohort was 53.0 ± 15.9 years, and 72 (53.4%) of the patients were male. The leading identified causes of end-stage kidney disease were glomerulonephritis, hypertensive glomerulosclerosis, and diabetic nephropathy. Data on microbiological etiology, dialysate white blood cell counts, and patient demographics were analyzed to identify catheter removal risk factors. Statistical significance was set at p ≤ 0.05. RESULTS: Comparative analysis between patients with and without catheter loss revealed no significant differences in gender, age, presence of diabetes, prior hemodialysis, or duration of peritoneal dialysis. However, multivariate logistic regression analysis showed that a dialysate white blood cell count exceeding 1000/mm3 on day 5 and hospitalization had a positive association with catheter loss, while the presence of gram-positive bacterial growth had an inverse correlation. CONCLUSION: Our study shows that fifth-day dialysate white blood cell count predicts refractory peritonitis outcomes. Future research should focus on developing tools to manage catheter removal proactively and enhance patient prognosis.

Efficacy of pharmacological treatment in OCD comorbid with tic disorder: Systematic review and meta-analysis.

Up to 30% of subjects with obsessive compulsive disorder (OCD) also have a lifetime tic disorder. Several meta-analyses of pharmaceutical or psychotherapeutic interventions for the management of OCD have been published, but none specifically on patients with OCD comorbid with tics. The literature regarding pharmacological treatments of patients with this condition is mainly focused on studies of OCD. After a search of the Cochrane, EMBASE, PubMed, PsychINFO and Science Direct databases, we performed a proportion meta-analysis of the percentage of patients whose condition improved and a paired meta-analysis of the change in the OCD score (Y-BOCS). Twelve case reports were retained for qualitative analysis and 14 articles for meta-analysis. Case reports showed better efficacy of combined antidepressant-antipsychotic treatment for OCD comorbid with tic disorder. The meta-analysis showed an improvement in 29% [18-42] of patients with antidepressants. Although there was no significant difference with placebo add-on, in antidepressant-resistant OCD patients, adding an antipsychotic to the antidepressant regimen led to an increase in the number of patients who improved (67% [45-86] vs 7% [0-35]) and seemed to show a decrease in the Y-BOCS score (-10.06 [-20.38; 0.26] vs (-3.61 [-9.08; 13.85]). Our study provides new evidence on the pharmacological treatment of OCD comorbid with tics. In some patients, the condition is improved by a first-line antidepressant. In case of non-response or insufficient efficacy of antidepressants, add-on treatment with certain antipsychotics can be implemented.