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International Journal of Molecular... Nov 2023Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's... (Review)
Review
Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's pathogenesis, focusing on established genetic factors. Studies reveal that is the primary genetic risk factor, but non-HLA genes (, , ), as well as innate immunity genes (, , ), also contribute. Genome-wide studies emphasize the significance of and HLA-I epistasis. These variants influence antigen presentation, enzymatic activity, and HLA-I peptidomes, potentially leading to distinct autoimmune responses. We conducted a systematic review of the literature to identify studies exploring the association between and BD and further highlighted the roles of innate and adaptive immunity in BD. Dysregulations in Th1/Th2 and Th17/Th1 ratios, heightened clonal cytotoxic (CD8+) T cells, and reduced T regulatory cells characterize BD's complex immune responses. Various immune cell types (neutrophils, γδ T cells, natural killer cells) further contribute by releasing cytokines (IL-17, IL-8, GM-CSF) that enhance neutrophil activation and mediate interactions between innate and adaptive immunity. In summary, this review advances our understanding of BD pathogenesis while acknowledging the research limitations. Further exploration of genetic interactions, immune dysregulation, and immune cell roles is crucial. Future studies may unveil novel diagnostic and therapeutic strategies, offering improved management for this complex disease.
Topics: Humans; Behcet Syndrome; Antigen Presentation; Genetic Predisposition to Disease; HLA-B Antigens; Risk Factors; Aminopeptidases; Minor Histocompatibility Antigens
PubMed: 38003572
DOI: 10.3390/ijms242216382 -
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 -
International Journal of Colorectal... Nov 2023Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate... (Meta-Analysis)
Meta-Analysis Review
Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials.
INTRODUCTION
Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME.
METHODS
A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes.
RESULTS
A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001).
CONCLUSION
NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.
Topics: Humans; Rectum; Neoadjuvant Therapy; Treatment Outcome; Rectal Neoplasms; Disease-Free Survival; Chemoradiotherapy; Neoplasm Recurrence, Local; Neoplasm Staging; Randomized Controlled Trials as Topic
PubMed: 37924372
DOI: 10.1007/s00384-023-04558-8 -
Blood Purification 2024Therapeutic apheresis (TA) is commonly used for cryoglobulinemic vasculitis (CV) patients, but its efficacy remains uncertain. This systematic review aimed to assess the...
INTRODUCTION
Therapeutic apheresis (TA) is commonly used for cryoglobulinemic vasculitis (CV) patients, but its efficacy remains uncertain. This systematic review aimed to assess the efficacy of different TA modalities, such as plasma exchange (PE), plasmapheresis (PP), and cryofiltration (CF), in treating CV patients with renal involvement.
METHODS
Literature search of MEDLINE, EMBASE, and Cochrane Databases was conducted up to December 2022. Studies that reported the outcomes of TA in adult CV patients with renal involvement were assessed. The protocol for this systematic review has been registered with PROSPERO (No. CRD42023417727). The quality of each study was evaluated by the investigators using the validated methodological index for non-randomized studies (minors) quality score.
RESULTS
154 patients who encountered 170 episodes of serious events necessitating TA were evaluated across 76 studies. Among them, 51% were males, with a mean age ranging from 49 to 58 years. The CV types included 15 type I, 97 type II, and 13 type III, while the remaining patients exhibited mixed (n = 17) or undetermined CV types (n = 12). Among the treatment modalities, PE, PP, and CF were performed in 85 (56%), 52 (34%), and 17 patients (11%), respectively, with no identical protocol for TA treatment. The overall response rate for TA was 78%, with response rates of 84%, 77%, and 75% observed in type I, II, and III patients respectively. Most patients received steroids, immunosuppressants, and treatment targeting the underlying causative disease. The overall long-term renal outcome rate was 77%, with type I, II, and III patients experiencing response rates of 89%, 76%, and 90%, respectively. The renal outcomes in patients receiving PE, PP, and CF were comparable, with rates of 78%, 76%, and 81%, respectively.
CONCLUSIONS
This study presents compelling evidence that combination of TA with other treatments, especially immunosuppressive therapy, is a successful strategy for effectively managing severe renal involvement in CV patients. Among the TA modalities studied, including PE, PP, and CF, all demonstrated efficacy, with PE being the most frequently employed approach.
Topics: Adult; Female; Humans; Male; Middle Aged; Blood Component Removal; Cryoglobulinemia; Immunosuppressive Agents; Plasma Exchange; Plasmapheresis; Vasculitis
PubMed: 37852193
DOI: 10.1159/000534102 -
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 -
Telemedicine Journal and E-health : the... Mar 2024Telemedicine systems were rapidly implemented in response to COVID-19. However, little is known about their effectiveness, acceptability, and sustainability for safety...
Telemedicine systems were rapidly implemented in response to COVID-19. However, little is known about their effectiveness, acceptability, and sustainability for safety net populations. This study systematically reviewed primary care telemedicine implementation and effectiveness in safety net settings. We searched PubMed for peer-reviewed articles on telemedicine implementation from 2013 to 2021. The search was done between June and December 2021. Included articles focused on health care organizations that primarily serve low-income and/or rural populations in the United States. We screened 244 articles from an initial search of 343 articles and extracted and analyzed data from = 45 articles. Nine (20%) of 45 articles were randomized controlled trials. = 22 reported findings for at least one marginalized group (i.e., racial/ethnic minority, 65 years+, limited English proficiency). Only = 19 (42%) included African American/Black patients in demographics descriptions, = 14 (31%) LatinX/Hispanic patients, = 4 (9%) Asian patients, = 4 (9%) patients aged 65+ years, and = 4 (9%) patients with limited English proficiency. Results show telemedicine can provide high-quality primary care that is more accessible and affordable. Fifteen studies assessed barriers and facilitators to telemedicine implementation. Common barriers were billing/administrative workflow disruption ( = 9, 20%), broadband access/quality ( = 5, 11%), and patient preference for in-person care ( = 4, 9%). Facilitators included efficiency gains ( = 6, 13%), patient acceptance ( = 3, 7%), and enhanced access ( = 3, 7%). Telemedicine is an acceptable care modality to deliver primary care in safety net settings. Future studies should compare telemedicine and in-person care quality and test strategies to improve telemedicine implementation in safety net settings.
Topics: Humans; Ethnicity; Minority Groups; Poverty; Telemedicine; United States; Safety-net Providers
PubMed: 37707997
DOI: 10.1089/tmj.2023.0260 -
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 -
Journal of Surgical Education Dec 2023Transgender and gender diverse (TGD) individuals in the U.S. face significant healthcare disparities, which can be further exacerbated by providers' unfamiliarity with...
OBJECTIVES
Transgender and gender diverse (TGD) individuals in the U.S. face significant healthcare disparities, which can be further exacerbated by providers' unfamiliarity with this population's specific needs. ACGME currently does not have requirements for gender-affirming surgery (GAS) in the residency programs of surgical specialties that are responsible for providing this care. This systematic review evaluates gender-affirming care (GAC) and GAS training in surgical residency programs in the U.S. through the analysis of survey respondent data.
METHODS
Six databases (PubMed, Embase, Web of Science and Scopus, Cochrane Library and Google Scholar) were searched in December 2022 and May 2023. The search process ultimately yielded 22 survey-based studies, published between 2015 and 2023, with responses from 3020 respondents (2582 trainees and/or attending physicians, 438 program directors).
RESULTS
Six different surgical specialties were the focus of included studies, and common questions revolved around GAS training availability, comfort in treating TGD patients, and the importance of GAS in graduate surgical education (GSE). Less than half of trainees indicated that they received some form of previous GAC or GAS training, and less than half of program directors indicated that their residency or fellowship program offered such training.
CONCLUSIONS
While comfort levels around treating TGD patients ranged, the studies indicated an overall perceived importance of GAS training. These findings highlight the need to incorporate GAS training into graduate surgical education to improve access to and quality of care for TGD patients.
Topics: Humans; Transgender Persons; Internship and Residency; Curriculum; Health Personnel; Surveys and Questionnaires
PubMed: 37658003
DOI: 10.1016/j.jsurg.2023.08.007 -
Trauma, Violence & Abuse Apr 2024Informal supporters (friends, family, colleagues, and community members) play a crucial role in societal-wide responses to victim-survivors of domestic violence and... (Review)
Review
Informal supporters (friends, family, colleagues, and community members) play a crucial role in societal-wide responses to victim-survivors of domestic violence and abuse. Familial and social networks, however, report a sense of helplessness and difficulties in knowing how to respond. This mixed method systematic review examines the effectiveness, and perceived effectiveness, of training informal supporters to improve their responses to victim-survivors. A novel conceptual framework was developed to underpin the review. A systematic search of four electronic databases, specialist repositories, and websites were used to identify empirical research (in academic or gray literature). Eleven included studies examined educational interventions that aimed to improve responses from informal supporters. Quality appraisal was undertaken, and studies were judged to be "good enough" for synthesis. The studies in the review indicated that informal supporters recognized the value of training for building understanding and equipping them with the skills to respond to victim-survivors. The synthesis identified statistically significant improvements in the knowledge and attitudes of informal supporters in the immediate and short-term following training. Using a behavior change model to frame the evidence, the review found that training/educational activities prime informal supporters to respond to victim-survivors, as well as enhancing their capacity and motivation to do so. This increases the likelihood that informal supporters will take action to support victim-survivors of abuse. We don't know, however, what type of support they will provide and/or whether it would be judged to be helpful by victim-survivors.
Topics: Humans; Domestic Violence; Attitude; Friends; Survivors; Empirical Research
PubMed: 37649408
DOI: 10.1177/15248380231189191 -
Frontiers in Immunology 2023Previous studies revealed that Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents had extensive... (Meta-Analysis)
Meta-Analysis
The benefit and risk of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small-cell lung cancer: a systematic review and single-arm meta-analysis of prospective clinical trials.
BACKGROUND
Previous studies revealed that Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents had extensive anti-tumor activities. However, almost all studies on the efficacy and safety of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small cell lung cancer are non-randomized controlled trials with small sample sizes, which might lead to a lack of effective metrics to assess the effectiveness and safety of the therapeutic regimen. Here, this meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small cell lung cancer.
METHODS
A single-arm meta-analysis was performed, and published literature from PubMed, Web of Science and Embase databases as of January 13, 2023, was systematically retrieved. We used the Cochrane risk of bias tool and methodological index for non-randomized studies (MINORS) Methodological items to evaluate the quality of eligible clinical trials. Outcomes including overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted for further analysis. The random effect model is used to calculate the pooled parameters.
RESULTS
19 studies (16 were non-comparative single-arm clinical trials and 3 were randomized controlled trials) were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 22.4% (95% CI, 16.6-28.1%) and 76.8% (95% CI, 72.6-81.1%), respectively. With regard to survival analysis, the pooled PFS and OS were 5.20 (95% CI, 4.46-5.93) months and 14.09 (95% CI, 13.20-14.97) months, respectively. The pooled grade ≥3 adverse effect (AE) rate was 47.6% (95% CI, 33.1-62.0%).
CONCLUSION
PD-1/PD-L1 inhibitors plus anti-angiogenic agents has promising efficacy and safety as second or later-line treatment in patients with advanced non-small cell lung cancer.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023407559.
Topics: Humans; Angiogenesis Inhibitors; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Programmed Cell Death 1 Receptor; Prospective Studies; Clinical Trials as Topic
PubMed: 37614237
DOI: 10.3389/fimmu.2023.1218258