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Frontiers in Oncology 2024Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with...
Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.
PubMed: 38665946
DOI: 10.3389/fonc.2024.1383730 -
Frontiers in Oncology 2024The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are...
BACKGROUND
The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are yet to be optimized. The combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high clinical efficacy in several clinical trials for RRMM. We here conducted a meta-analysis to confirm its efficacy and safety.
METHODS
We collected data from Embase, Web of Science, PubMed, CNKI, Wanfang and Cochrane databases up to April 2023. We extracted and evaluated data related to the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapies in RRMM patients. The data was then analyzed using RevMan5.4 and StataSE-64 software. PROSPERO number was CRD42023455002.
RESULTS
Our meta-analysis included 12 relevant clinical trials involving 347 RRMM patients who were treated with combined anti-BCMA and anti-CD19 CAR-T cell therapies. For efficacy assessment, the pooled overall response rate (ORR) was 94% (95% CI: 91%-98%), the complete response rate (CRR) was 50% (95% CI: 29%-71%), and the minimal residual disease (MRD) negativity rate within responders was 73% (95% CI: 66%-80%). In terms of safety, the pooled all-grade cytokine release syndrome (CRS) rate was 98% (95% CI: 97%-100%), grade≥3 CRS rate was 9% (95% CI: 4%-14%), and the incidence of neurotoxicity was 8% (95% CI: 4%-11%). Of hematologic toxicity, neutropenia was 82% (95% CI: 75%-89%), anemia was 71% (95% CI: 53%-90%), thrombocytopenia was 67% (95% CI: 40%-93%) and infection was 42% (95% CI: 9%-76%). The median progression-free survival (PFS) was 12.97 months (95% CI: 6.02-19.91), and the median overall survival (OS) was 26.63 months (95% CI: 8.14-45.11).
CONCLUSIONS
As a novel immunotherapy strategy with great potential, the combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high efficacy in RRMM, but its safety needs further improvement. This meta-analysis suggests possible optimization of combined CAR-T therapy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023455002.
PubMed: 38651157
DOI: 10.3389/fonc.2024.1355643 -
Cureus Mar 2024Pain management is a critical aspect of cancer treatment and palliative care, where pain can significantly impact quality of life. Chronic pain, which affects a... (Review)
Review
Pain management is a critical aspect of cancer treatment and palliative care, where pain can significantly impact quality of life. Chronic pain, which affects a significant number of people worldwide, remains a prevalent and challenging symptom for patients. While medications and psychosocial support systems play a role in pain management, surgical and radiological interventions, including cingulotomy, may be necessary for refractory cases. Cingulotomy, a neurosurgical procedure targeting the cingulate gyrus, aims to disrupt neural pathways associated with emotional processing and pain sensation, thereby reducing the affective component of pain. Although cingulotomy has shown promise in providing pain relief, particularly in patients refractory to traditional medical treatment, its use has declined in recent years due to advancements in non-destructive therapies and concerns about long-term efficacy and patient suitability. Modern stereotactic methods have enhanced the precision and safety of cingulotomy, reducing associated complications and mortality rates. Despite these advancements, questions remain regarding its long-term efficacy and suitability for patients with limited life expectancy, particularly those with cancer. A comprehensive systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, aimed at providing insights into the efficacy, potential benefits, and limitations of this neurosurgical procedure in managing intractable pain. An electronic search of PubMed, Embase, Scopus, and Web of Science was conducted with open database coverage dates. The review focused on outcomes such as pain intensity and quality of life. The inclusion criteria encompassed human studies of any age experiencing intractable cancer or non-cancer pain, with cingulotomy as the primary intervention. Various study designs were considered, including observational studies, clinical trials, and reviews focusing on pain and cingulotomy. Exclusion criteria included non-human studies, non-peer-reviewed articles, and studies unrelated to pain or cingulotomy. This review highlights the efficacy of stereotactic anterior cingulotomy in managing intractable pain, particularly when conventional treatments fail. Advanced MRI-guided techniques enhance precision, but challenges like cost and expertise persist. Studies included in this review showed significant pain relief with minimal adverse effects, although the optimal target remains debated. Neurocognitive risks exist, but outcomes are generally favorable. Expected adverse events include transient effects like urinary incontinence and confusion. Reoperation may be necessary for inadequate pain control, with a median pain relief duration of three months to a year. A double stereotactic cingulotomy appears to be safe and effective for refractory pain.
PubMed: 38650773
DOI: 10.7759/cureus.56746 -
World Neurosurgery Apr 2024Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma that primarily affects the central nervous system. Current treatments, such as surgery,... (Review)
Review
BACKGROUND
Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma that primarily affects the central nervous system. Current treatments, such as surgery, chemotherapy, and whole-brain radiotherapy, often fail to achieve satisfactory results. The prognosis for patients with refractory or relapsed (R/R) PCNSL is bleak. The optimal treatment for refractory or relapsed PCNSL is poorly defined due to a limited number of studies in this setting. Bruton's tyrosine kinase (BTK) inhibitors, as part of targeted therapy regimens, have undergone testing in several clinical trials against PCNSL and have shown promising results in the treatment of R/R PCNSL. In this meta-analysis, we aim to explore and critically appraise the evidence regarding the efficacy of BTK inhibitors in the treatment of refractory or relapsed PCNSL.
METHODS
A systematic search was conducted on multiple databases including PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and CNKI, covering the period up to November 2023. The inclusion criteria for studies were patients with R/R PCNSL who received BTK inhibitors, and reported data on overall response rate (ORR) and complete remission (CR). The pooled rates were calculated using a random-effects or fixed-effects model with a double arcsine transformation, and 95% CIs were determined for all outcomes.
RESULTS
In total, 1 studies involving 185 patients were identified and included in the meta-analysis. The pooled complete remission (CR) rate of BTK inhibitors-based treatment for R/R PCNSL was found to be 50%. Subgroup analysis revealed that the CR rates for BTK inhibitor monotherapy, BTK inhibitor combined with chemotherapy, and BTK inhibitor combined with radiotherapy for R/R PCNSL were 7%, 68%, and 80%, respectively. The ORR for BTK inhibitors-based treatment for R/R PCNSL was 70%. Subgroup analysis showed that the ORR rates for BTK inhibitor monotherapy and BTK inhibitor combined with chemotherapy for R/R PCNSL were 55% and 83%, respectively. The most common adverse events (AEs) reported were hematologic AEs, including neutropenia, anemia, and thrombocytopenia. Severe nonhematologic AEs included rash, febrile neutropenia, increased levels of aspartate aminotransferase, and increased blood bilirubin.
CONCLUSIONS
BTK inhibitors can be regarded as a safe and effective treatment option for R/R PCNSL, thereby providing a potential new avenue for R/R PCNSL treatment. However, it is important to note that further large-sample prospective randomized controlled trials are needed to validate these findings and establish their wider applicability.
PubMed: 38641241
DOI: 10.1016/j.wneu.2024.04.066 -
World Journal of Critical Care Medicine Mar 2024Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters. Despite standard therapy, the outcomes are poor....
BACKGROUND
Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters. Despite standard therapy, the outcomes are poor. Newer adjuvant therapy, such as CytoSorb extracorporeal haemoadsorption device, has been investigated and shown promising outcome. However, there is a lack of some guidance to make clinical decisions on the use of CytoSorb haemoadsorption as an adjuvant therapy in septic shock in Indian Setting. Therefore, this expert consensus was formulated.
AIM
To formulate/establish specific consensus statements on the use of CytoSorb haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario.
METHODS
We performed a comprehensive literature on CytoSorb haemoadsorption in sepsis, septic shock in PubMed selecting papers published between January 2011 and March 2023 2021 in English language. The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps. Using a modified Delphi approach combining evidence appraisal and expert opinion, the following topics related to CytoSorb in septic shock were addressed: need for adjuvant therapy, initiation timeline, need for Interleukin -6 levels, duration of therapy, change of adsorbers, safety, prerequisite condition, efficacy endpoints and management flowchart. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question.
RESULTS
Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. All 11 experts in the consensus group (100%) participated in the first, second and third round of voting. After three iterative voting rounds and adapting two statements, consensus was achieved on nine statements out of nine statements. The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb for all indications in the open-ended question (Q10) focusing on "future recommendations for CytoSorb therapy".
CONCLUSION
This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.
PubMed: 38633478
DOI: 10.5492/wjccm.v13.i1.89026 -
Spine Surgery and Related Research Mar 2024Failed back surgery syndrome (FBSS) is a common and incapacitating condition affecting patients with previous spine surgery in whom treatment approach can be... (Review)
Review
BACKGROUND
Failed back surgery syndrome (FBSS) is a common and incapacitating condition affecting patients with previous spine surgery in whom treatment approach can be challenging. This study aimed to summarize existing secondary studies and up-to-date randomized clinical trials (RCTs) that assess the effectiveness of available treatment options for FBSS.
METHODS
Systematic searches were carried out in five databases (PubMed, Cochrane, Scielo, Epistemonikos, and Google scholar) for all systematic reviews on the effectiveness of treatment options for FBSS published after 2012. Outcomes of interest were pain levels measured through visual analog scale or numeric rating scale, Oswestry Disability Index, and quality of life. Methodological and risk of bias assessments were performed with the AMSTAR-2 tool for systematic reviews and the Joanna Briggs Institute checklist for RCT. Prospective PROSPERO registration: CRD42022307609.
RESULTS
Fifteen studies, seven systematic reviews, and eight RCTs met the inclusion criteria and fulfilled the methodological quality assessment. Of the 15 included studies, 8 were on neurostimulation, 4 on adhesiolysis, 4 on epidural or intrathecal injections, and 3 on other treatment modalities. The risk of bias was low in seven studies, moderate in five, and high in three.
CONCLUSIONS
Based on this systematic overview and the considerable heterogeneity among studies, the FBSS therapeutic approach must be individualized. FBSS treatment should start with conservative management, considering the implementation of neurostimulation, a technique with the most robust evidence of effective results, in cases of refractory axial or neuropathic pain. As the last resource, in light of the evidence found, more invasive procedures or new surgical interventions are indicated.
PubMed: 38618223
DOI: 10.22603/ssrr.2023-0032 -
Medicine Apr 2024Tyrosine kinase inhibitors (TKIs) have been approved for treating patients with clinically advanced metastatic thyroid cancer. However among the many TKIs, it remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tyrosine kinase inhibitors (TKIs) have been approved for treating patients with clinically advanced metastatic thyroid cancer. However among the many TKIs, it remains unknown which regimen is the best choice for these patients.
METHODS
We conducted a systematic review and network meta-analysis to compare the survival benefits and efficacy of the available first-line regimens. We conducted an active search for phase II, III, or IV randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to compare the effects of at least 2 drugs in the systemic treatment of advanced or metastatic thyroid cancer up to May 2023. The network meta-analysis model was adjusted using Bayesian Network model. Twelve trials with 2535 patients were included in our meta-analysis. The overall survival (OS), progression-free survival (PFS), and serious adverse events (SAEs) were taken as reference indicators. We also performed subgroup analyses of OS and PFS in medullary thyroid cancer (MTC) and radioiodine-refractory differentiated thyroid cancer (RR-DTC) to explore the variations of TKIs in different groups.
RESULTS
As a result, apatinib had the best effect on overall survival (OS) (hazards ratio [HR] = 0.42, 95% confidence interval [CI] = 0.18-0.98), lenvatinib 18 mg/d has the best effect on progression-free survival (PFS) (HR = 0.13, 95% CI = 0.064-0.27), and cabozantinib 60 mg/d has the best safety profile.
CONCLUSIONS
Our network meta-analysis showed that we believe that cabozantinib has the potential to become a widely used drug in clinical practice.
Topics: Humans; Tyrosine Kinase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Anilides; Neoplasms; Pyridines
PubMed: 38608050
DOI: 10.1097/MD.0000000000037655 -
Clinical Parkinsonism & Related... 2024Axial postural abnormalities (PA) are frequent, highly disabling, and drug-refractory motor complications affecting patients with Parkinson's disease (PD) or atypical...
Axial postural abnormalities (PA) are frequent, highly disabling, and drug-refractory motor complications affecting patients with Parkinson's disease (PD) or atypical parkinsonism. Over the past few years, advances have been reached across diagnosis, assessment, and pathophysiological mechanisms of PA. Nonetheless, their management remains a challenge, and these disturbances are generally overlooked by healthcare professionals, potentially resulting in their worsening and impact on patients' disabilities. From shared consensus-based assessment and diagnostic criteria, PA calls for interdisciplinary management based on the complexity and multifactorial pathogenesis. In this context, we conducted a systematic literature review to analyze the available pharmacological and non-pharmacological treatment options for PA in PD according to the new expert-based classification of axial PA in Parkinsonism. Different multidisciplinary approaches, including dopaminergic therapy adjustment, physiotherapy, botulinum toxin injection, and deep brain stimulation, can improve PA depending on its type and severity. An early, interdisciplinary approach is recommended in PD patients to manage PA.
PubMed: 38596537
DOI: 10.1016/j.prdoa.2024.100240 -
Heliyon Apr 2024Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit...
BACKGROUND
Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit limited efficacy in achieving remission and may result in notable adverse reactions, warranting the exploration of novel therapeutic approaches for IMN treatment. Traditional Chinese medicine (TCM), which is extensively used for kidney disease management, is a promising alternative.
OBJECTIVE
This study aimed to examine the safety and efficacy of TCM alone or in combination with Western medicine for the management of patients diagnosed with IMN.
METHODS
This study employed a systematic search of English and Chinese electronic databases to identify randomized controlled trials (RCTs) that examined the application of TCM in the treatment of IMN. RCTs that met the predetermined inclusion and exclusion criteria and assessed the safety and efficacy of TCM alone or in combination with Western medicine in patients with IMN were included in the analysis. The methodological quality of the included studies was evaluated by using a risk-of-bias tool. All statistical analyses were performed using the RevMan software (version 5.4.2). The evidence was evaluated on the https://www.gradepro.org/website.
RESULTS
This study included 29 randomized controlled trials (RCTs) involving 1982 patients with moderate methodological quality that met the inclusion criteria. The results showed that, compared to Western medicine alone therapy, the use of TCM alone or in combination with Western medicine significantly improved total remission (TR) rate (risk ratios [RR] 1.38, 95% confidence interval [CI] 1.29-1.46, I = 0%, P < 0.00001), complete remission (CR) rate (RR 1.78, 95% CI 1.48-2.15, I = 0, P < 0.00001), partial remission (PR) rate (RR 1.27, 95% CI 1.161.40, I = 0%, P < 0.00001), and serum albumin (ALB) levels (MD: 4.05, 95% CI: 3.02-5.09, I = 91%, P < 0.00001). TCM alone or in combination with Western medicine also reduced proteinuria levels (mean difference [MD]: 1.05, 95% CI: 1.30 to -0.79, I = 95%, P < 0.00001), serum creatinine (SCr) levels (MD: 7.47, 95% CI: 13.70 to -1.24, I = 97%, P = 0.02), and serum antibodies against M-type phospholipase A2 receptor levels (aPLA2Rab) (MD: 19.24, 95% CI: 33.56 to -4.93, I = 87%, P = 0.008). Moreover, the efficacy of combined TCM and Western medicine is superior to that of Western medicine alone in reducing the incidence of infection, hepatotoxicity, and thrombosis. Although the primary and secondary outcomes were consistent, the evidence was generally moderate.
CONCLUSION
The results of this study suggest that TCM alone or in combination with Western medicine may be a feasible alternative therapeutic approach for the treatment of IMN. Nevertheless, additional, rigorously designed, high-quality, and extensive clinical trials are imperative to provide substantial evidence regarding the effectiveness of TCM in managing IMN.
PubMed: 38596093
DOI: 10.1016/j.heliyon.2024.e28836 -
PloS One 2024Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its hallmark features encompass unprovoked bilateral myoclonus and tonic-clonic seizures that manifest during adolescence. While most JME patients respond favorably to anti-seizure medication (ASM), a subset experiences refractory JME, a condition where seizures persist despite rigorous ASM treatment, often termed "Drug-Resistant Epilepsy" (DRE). This systematic review and meta-analysis aims to determine the prevalence of refractory JME, and further to identify socio-demographic, electrophysiological and clinical risk factors associated with its occurrence. Pinpointing these factors is crucial as it offers the potential to predict ASM responsiveness, enabling early interventions and tailored care strategies for patients.
MATERIAL AND METHODS
The systematic review and meta-analysis followed the Cochrane Handbook and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study evaluated outcomes post ASM treatment in JME cohorts by searching papers published up to September 2023 in PubMed/MEDLINE, Scopus, and Google Scholar databases. Predefined inclusion criteria were met by 25 eligible studies, forming the basis for analysis.
RESULTS
A total of 22 potential risk factors for refractory JME were documented. Notably, robust risk factors for treatment resistance included Psychiatric Disorder (Odds Ratio (OR), 3.42 [2.54, 4.61] (95% Confidence Inverval (Cl)), Febrile Seizures (OR, 1.83 [1.14, 2.96] (95% Cl)), Alcohol Consumption (OR, 16.86 [1.94, 146.88] (95%Cl)), Aura (OR, 2.15 [1.04, 4.47] (95%Cl)), childhood absence epilepsy (CAE) evolving into JME (OR, 4.54 [1.61, 12.78] (95%CI)), occurrence of three seizure types (OR, 2.96 [1.96, 4.46] (95%CI)), and Focal EEG abnormalities (OR, 1.85 [1.13, 3.01] (95%Cl)). In addition, there were some non-significant risk factors for DRE because of noticeable heterogeneity.
CONCLUSION
In aggregate, over 36% of JME patients demonstrated drug resistance, with seven significant risk factors closely linked to this refractoriness. The interplay between these factors and whether they denote treatment non-response or heightened disease burden remains an open question and more studies would be required to fully examine their influence.
Topics: Adolescent; Humans; Child; Myoclonic Epilepsy, Juvenile; Epilepsy, Absence; Seizures; Drug Resistant Epilepsy; Risk Factors; Electroencephalography; Anticonvulsants
PubMed: 38593118
DOI: 10.1371/journal.pone.0300930