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Biomolecules Sep 2023Pompe disease is a lysosomal storage disease characterised by skeletal and respiratory muscle weakness. Since 2006, enzyme replacement therapy (ERT) with alglucosidase... (Review)
Review
BACKGROUND
Pompe disease is a lysosomal storage disease characterised by skeletal and respiratory muscle weakness. Since 2006, enzyme replacement therapy (ERT) with alglucosidase alfa has been available. ERT significantly improves the prognosis of patients with Pompe disease. The effect of high antibody titres on treatment response in adults with late-onset Pompe disease (LOPD) remains unclear but may contribute to interpatient variation. We therefore conducted a systematic review on this subject.
METHODS
A systematic search was performed in Embase, Medline Ovid, Web of Science, Psych Info Ovid, Cochrane (Clinical Trials only), and Google Scholar (random top-200). Articles were included if they involved adults with LOPD treated with alglucosidase alfa and mentioned anti-rhGAA antibodies or antibody titres. In addition, articles mentioning dosages different from the standard recommended dosage were included.
RESULTS
Our literature search retrieved 2562 publications, and 17 fulfilled our selection criteria, describing 443 cases. Seven publications reported on anti-rhGAA antibody titres on a group level, with the percentage of patients with a high titre as defined in the included articles ranging from 0-33%. Six publications reported on the effect of anti-rhGAA antibody titre on clinical course, and four found no correlation. Two studies reported a negative effect on treatment. The first study found a greater improvement in Medical Research Council (MRC) score in patients with no detectable antibody titre. In the second study, a patient discontinued ERT due to a declining neuromuscular state as a result of high anti-rhGAA antibody titres. Seven publications reported on 17 individual patients with a high antibody titre (range 1:12,800-1:3,906,250). In only two cases were high-sustained neutralising antibodies reported to interfere with treatment efficacy.
CONCLUSIONS
No clear effect of anti-rhGAA IgG antibodies on treatment response could be established for the majority of LOPD patients with a high antibody titre. In a minority of patients, a clinical decline related to (possible) interference of anti-rhGAA antibodies was described.
Topics: Humans; Adult; Glycogen Storage Disease Type II; alpha-Glucosidases; Treatment Outcome; Enzyme Replacement Therapy
PubMed: 37759814
DOI: 10.3390/biom13091414 -
Journal of Crohn's & Colitis Jan 2024The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation [FMT] in the treatment of chronic pouchitis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation [FMT] in the treatment of chronic pouchitis.
METHODS
A PRISMA-compliant systematic review and meta-analysis was conducted using the following databases and clinical trial registers: Medline, Embase, Scopus, Cochrane Database of Systematic Reviews [CENTRAL], clinical trials.gov, ScienceDirect, and VHL [virtual health library]. The primary outcome was clinical response/remission in patients treated with FMT. Secondary outcomes included safety profile, quality of life, and changes in the gut microbiome.
RESULTS
Seven observational cohort studies/case series and two randomised, controlled trials with a total of 103 patients were included. The route, preparation, and quantity of FMT administered varied among the included studies. Clinical response rate of 42.6% with a remission rate of 29.8% was estimated in our cohort following FMT therapy. Minor, self-limiting, adverse events were reported, and the treatment was well tolerated with good short- and long-term safety profiles. Successful FMT engraftment in recipients varied and, on average, microbial richness and diversity was lower in patients with pouchitis. In some instances, shifts with specific changes towards abundance of species, suggestive of a 'healthier' pouch microbiota, were observed following treatment with FMT.
CONCLUSION
The evidence for FMT in the treatment of chronic pouchitis is sparse, which limits any recommendations being made for its use in clinical practice. Current evidence from low-quality studies suggests a variable clinical response and remission rate, but the treatment is well tolerated, with a good safety profile. This review emphasises the need for rationally designed, well-powered, randomised, placebo-controlled trials to understand the efficacy of FMT for the treatment of pouchitis.
Topics: Humans; Fecal Microbiota Transplantation; Pouchitis; Quality of Life; Remission Induction; Gastrointestinal Microbiome; Treatment Outcome; Feces; Randomized Controlled Trials as Topic
PubMed: 37450947
DOI: 10.1093/ecco-jcc/jjad120 -
Cancers Sep 2023Recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has poor survival rates. Immunotherapy is the standard of care for R/M HNSCC, but objective... (Review)
Review
BACKGROUND
Recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has poor survival rates. Immunotherapy is the standard of care for R/M HNSCC, but objective responses occur in a minority of patients. Toll-like receptor (TLR) agonists promote antitumor immune responses and have been explored in clinical trials.
METHODS
A search for clinical trials using TLR agonists in HNSCC was performed under PRISMA guidelines. Data on patient characteristics, safety, and efficacy were collected and analyzed.
RESULTS
Three phase 1b trials with 40 patients and three phase 2 trials with 352 patients studying TLR8 and TLR9 agonists in combination with other treatment regimens for HNSCC were included. In phase 2 trials, there was no significant change in the objective response rate (RR = 1.13, CI 0.80-1.60) or association with increased grade 3+ adverse events (RR = 0.91, CI 0.76-1.11) associated with TLR agonist use.
CONCLUSION
TLR agonists do not appear to provide additional clinical benefits or increase adverse events in the treatment of HNSCC. Given these results across multiple clinical trials and drug regimens, it is unlikely that additional trials of TLR agonists will demonstrate clinical benefits in HNSCC.
PubMed: 37686661
DOI: 10.3390/cancers15174386 -
Sports Health Jan 2024Running is one of the most popular sports worldwide. However, controversies exist regarding how running affects runner's intervertebral discs (IVD). (Review)
Review
CONTEXT
Running is one of the most popular sports worldwide. However, controversies exist regarding how running affects runner's intervertebral discs (IVD).
OBJECTIVE
The purpose of this study was to systematically review studies that evaluated IVD morphology or composition changes in response to running exercise, to determine the impact of running exercise on IVD.
DATA SOURCES
A systematic literature search was performed for 4 major databases: PubMed, Cochrane, Embase, and Web of Science.
STUDY SELECTION
Inclusion criteria were as follows: (1) healthy people without known IVD disease or major complications such as tuberculosis (IVD degeneration or low back pain are considered as minor complications); (2) subjects performed 1-time or regular running exercises; (3) pre and post comparison of runners or comparison between runners and healthy control subjects; (4) direct or indirect IVD morphology or composition measured; (5) IVD assessed before and after either acute or chronic running exercise, or compared cross-sectionally between runners and controls. Exclusion criteria were as follows: (1) reviews, editorials, letters or abstracts only; (2) animal studies; (3) subjects performed exercise other than running.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 3.
DATA EXTRACTION
The extracted data included study design and primary outcomes of the included studies. The Newcastle-Ottawa scale (NOS) was used to evaluate study quality and risk of bias.
RESULTS
A total of 13 studies with 632 participants were included in the final analysis; 4 studies measured IVD changes using stature or spinal height, and the other 9 measured IVD changes using magnetic resonance imaging; 6 studies found that running acutely and negatively impacts IVD; 3 out of 5 cross-sectional studies found that IVD parameters are better for runners than controls; 1 longitudinal study found no significant difference in IVD before and after training for marathon in runners; 1 longitudinal study found no significant difference in changes of IVD between runners and controls after 15 years of follow-up.
CONCLUSION
Negative changes in IVD exist for a short period of time after running, which may be due to the temporary compression pushing water content out of the disc. Cross-sectional studies suggest that long-term running exerts a mild positive effect on IVD; however, this inference has not been confirmed by high-quality longitudinal studies.
PubMed: 38204324
DOI: 10.1177/19417381231221125 -
European Journal of Gastroenterology &... Jan 2024Our study aimed to evaluate the efficacy and safety of Lenvatinib compared with Sorafenib for treating hepatocellular carcinoma (HCC) patients under real-world setting. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Our study aimed to evaluate the efficacy and safety of Lenvatinib compared with Sorafenib for treating hepatocellular carcinoma (HCC) patients under real-world setting.
METHODS
We retrieved relevant literature through the PubMed, Embase, Web of Science, and Cochrane Library databases from 1 January 2000 to 25 June 2022. The differences in overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) as well as treatment adverse related events were evaluated between HCC patients treated with Lenvatinib and Sorafenib using fixed or random-effects models. The MINORS evaluation questionnaire was used to assess the quality of the included literature.
RESULTS
This meta-analysis included a total of 9 single-arm studies and 6 comparative studies. In the meta-analysis, Lenvatinib showed significantly longer median OS than Sorafenib ( P < 0.01, MD = 1.20, 95% CI [0.92-1.48]), as well as median PFS ( P < 0.01, OR = 2.68, 95% CI [1.59-3.76]), and higher ORR( P < 0.01, OR = 5.36, 95% CI [3.42-8.40]), DCR( P < 0.01, OR = 2.17, 95% CI [1.64-2.86]). The occurrence of Hypertension was higher in Lenvatinib than in Sorafenib treatment ( P < 0.01, MD = 5.27, 95% CI [2.38-11.66]), and there was no significant difference in Hand-foot syndrome between Lenvatinib and Sorafenib.
CONCLUSION
We found that treatment with Lenvatinib in HCC patients resulted in better OS, PFS, and higher ORR and DCR compared to Sorafenib. However, safety data indicated that Lenvatinib did not exhibit a significant advantage.
Topics: Humans; Sorafenib; Carcinoma, Hepatocellular; Antineoplastic Agents; Liver Neoplasms
PubMed: 37942731
DOI: 10.1097/MEG.0000000000002668 -
Cureus Mar 2024Vertebrobasilar insufficiency (VBI) is a significant medical condition that results from a lack of adequate blood flow to the posterior circulation of the brain. The... (Review)
Review
Vertebrobasilar insufficiency (VBI) is a significant medical condition that results from a lack of adequate blood flow to the posterior circulation of the brain. The first-line treatment involves the use of antiplatelet therapy, but in cases where patients are not responsive to drug therapy, surgical management is the next viable option. In the past, open endarterectomy was the preferred surgical approach for treating critical VBI patients. However, due to its high mortality rates and severe peri-procedural complications, its usage has decreased. Instead, the endovascular approach has emerged as an alternative surgical option for resolving VBI. This review explores the current literature to assess the effectiveness of endovascular interventions in treating VBI patients. It also highlights potential complications and adverse effects associated with these treatments while identifying gaps in the current research that warrant further investigation. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to extensively search relevant literature on endovascular approaches for treating VBI patients on PubMed, BioMed Central, and ClinicalTrials.gov. The findings suggest that endovascular treatments have demonstrated significant technical success in treating VBI, with low mortality rates and minor adverse effects, such as intracranial hemorrhage and restenosis. The overall incidence of these complications is relatively low. Combining medical therapies with endovascular interventions has improved outcomes and reduced restenosis rates. However, there are methodological limitations and inconsistencies in the current literature that necessitate further investigation. Future research should focus on larger, randomized clinical trials and direct comparisons with other treatment options to obtain more conclusive evidence.
PubMed: 38510521
DOI: 10.7759/cureus.56479 -
Virology Journal May 2024Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and... (Meta-Analysis)
Meta-Analysis Review
Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis.
BACKGROUND
Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients.
RESULTS
This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn't respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%.
CONCLUSION
While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses.
Topics: Humans; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Hematopoietic Stem Cell Transplantation; Antibodies, Viral; Vaccination; Immunotherapy, Adoptive; Cell- and Tissue-Based Therapy
PubMed: 38702752
DOI: 10.1186/s12985-024-02375-1 -
Sports Medicine - Open Apr 2024Increases in maximal strength and muscle volume represent central aims of training interventions. Recent research suggested that the chronic application of stretch may...
BACKGROUND
Increases in maximal strength and muscle volume represent central aims of training interventions. Recent research suggested that the chronic application of stretch may be effective in inducing hypertrophy. The present systematic review therefore aimed to syntheisize the evidence on changes of strength and muscle volume following chronic static stretching.
METHODS
Three data bases were sceened to conduct a systematic review with meta-analysis. Studies using randomized, controlled trials with longitudinal (≥ 2 weeks) design, investigating strength and muscle volume following static stretching in humans, were included. Study quality was rated by two examiners using the PEDro scale.
RESULTS
A total of 42 studies with 1318 cumulative participants were identified. Meta-analyses using robust variance estimation showed small stretch-mediated maximal strength increases (d = 0.30 p < 0.001) with stretching duration and intervention time as significant moderators. Including all studies, stretching induced small magnitude, but significant hypertrophy effects (d = 0.20). Longer stretching durations and intervention periods as well as higher training frequencies revealed small (d = 0.26-0.28), but significant effects (p < 0.001-0.005), while lower dosage did not reach the level of significance (p = 0.13-0.39).
CONCLUSIONS
While of minor effectiveness, chronic static stretching represents a possible alternative to resistance training when aiming to improve strength and increase muscle size. As a dose-response relationship may exist, higher stretch durations and frequencies as well as long program durations should be further elaborated.
PubMed: 38637473
DOI: 10.1186/s40798-024-00706-8 -
European Review For Medical and... Jan 2024Hepatocellular carcinoma (HCC) represents a highly lethal and recurrent neoplasm, with limited effective treatment regimens available. Camrelizumab, as a novel PD1... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hepatocellular carcinoma (HCC) represents a highly lethal and recurrent neoplasm, with limited effective treatment regimens available. Camrelizumab, as a novel PD1 inhibitor combined with transcatheter arterial chemoembolization (TACE), has been widely used in the treatment of HCC. However, there remains a contentious debate regarding the clinical value of the TACE and camrelizumab combination. This study seeks to investigate the efficacy and safety of this combination treatment regimen in patients with HCC.
MATERIALS AND METHODS
The related studies were retrieved from four online databases, including Pubmed, Cochrane Library, EMBASE, and Web of Science, up to June 1, 2023. The selection of studies was based on screening of titles, abstracts, and full-texts. The primary efficacy outcomes included complete response (CR), objective response rate (ORR), and disease control rate (DCR), while safety outcomes evaluated all treatment-related adverse events (AEs). Additionally, secondary outcomes such as overall (OS) and progression-free survival (PFS) were extracted for further survival analysis. The quality of the included trials was assessed using the MINORS tool. Publication bias was evaluated through funnel plot and Egger's test.
RESULTS
A total of 17 publications involving 1,377 cases were included. The pooled CR rate, ORR, and DCR of the patients treated with TACE plus camrelizumab had a pooled CR rate of 8% (95% CI: 0.01-0.15, p=0.03), ORR of 47% (95% CI: 0.42-0.52, p<0.00001) and DCR of 82% (95% CI: 0.77-0.88, p<0.00001), respectively. Compared with a control group that did not receive TACE or camrelizumab, the pooled RR of CR rate, ORR, and DCR were 1.61 (95% CI: 1.27-2.04, p<0.0001), 1.56 (95% CI: 1.19-2.05, p=0.001) and 1.55 (95% CI: 1.19-2.03, p=0.001), respectively. Besides, the combination regimen can prolong the OS (HR=2.60, 95% CI: 2.25-3.02, p<0.00001) and PFS (HR=4.90, 95% CI: 1.94-12.38, p=0.0008). However, the incidence of treatment-related AEs was relatively high (77%), with 29% for grade 3 AEs. The most common AEs observed were pain (47%), fever (46%), hepatic function abnormalities (44%), hypoalbuminemia (39%), and hypertension (37%). The combination treatment did not increase the incidence of AEs compared to the control group, except for the hand-foot skin reaction (RR=0.85, 0.74-0.97, p=0.01), hepatic encephalopathy (RR=4.29, 2.51-7.35, p<0.00001) and nausea (RR=1.35, 1.13-1.61, p=0.001).
CONCLUSIONS
Combination therapy of TACE plus camrelizumab has shown notable clinical benefits, improved survival, and a manageable safety profile in patients with HCC, but it is essential to monitor and manage the specific toxicities, especially for the camrelizumab-related AEs.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Neoplasm Recurrence, Local; Pathologic Complete Response; Antibodies, Monoclonal, Humanized
PubMed: 38305611
DOI: 10.26355/eurrev_202401_35066 -
Journal of Neurology, Neurosurgery, and... Nov 2023The literature on predictors of persistent postural-perceptual dizziness (PPPD) following peripheral vestibular insults has not been systematically reviewed.
BACKGROUND
The literature on predictors of persistent postural-perceptual dizziness (PPPD) following peripheral vestibular insults has not been systematically reviewed.
METHODS
We systematically reviewed studies on predictors of PPPD and its four predecessors (phobic postural vertigo, space-motion discomfort, chronic subjective dizziness and visual vertigo). Investigations focused on new onset chronic dizziness following peripheral vestibular insults, with a minimum follow-up of 3 months. Precipitating events, promoting factors, initial symptoms, physical and psychological comorbidities and results of vestibular testing and neuroimaging were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
We identified 13 studies examining predictors of PPPD or PPPD-like chronic dizziness. Anxiety following vestibular injury, dependent personality traits, autonomic arousal and increased body vigilance following precipitating events and visual dependence, but not the severity of initial or subsequent structural vestibular deficits or compensation status, were the most important predictors of chronic dizziness. Disease-related abnormalities of the otolithic organs and semi-circular canals and age-related brain changes seem to be important only in a minority of patients. Data on pre-existing anxiety were mixed.
CONCLUSIONS
After acute vestibular events, psychological and behavioural responses and brain maladaptation are the most likely predictors of PPPD, rather than the severity of changes on vestibular testing. Age-related brain changes appear to have a smaller role and require further study. Premorbid psychiatric comorbidities, other than dependent personality traits, are not relevant for the development of PPPD.
PubMed: 36941047
DOI: 10.1136/jnnp-2022-330196