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International Immunopharmacology Mar 2024Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a...
INTRODUCTION
Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a risk of developing immune-related adverse events, most commonly dermatitis, colitis, hepatitis, and pneumonitis. Immune-mediated hematologic toxicities have been reported, but are less well-described in the literature. Immune thrombocytopenia (ITP) is a rare autoimmune, hematologic adverse event that has been reported with PD-1/PD-L1 inhibitors.
METHODS
We performed a retrospective observational analysis of the United States Food and Drug Administration Adverse Event Reporting System (FAERS) data. We searched for cases of ITP reported with exposure to PD-1/PD-L1 inhibitors from initial FDA approval for each agent to September 30, 2022. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). Oxaliplatin was used as a positive control for sensitivity analysis as it is an anticancer therapy that has been associated with drug-induced ITP. A systematic review of the PubMed database was also conducted to identify published cases of PD-1/PD-L1 inhibitor-induced ITP.
RESULTS
There were 329 reports of ITP with ICIs in the FAERS database that were reviewed for a disproportionality signal, including atezolizumab (n = 27), durvalumab (n = 17), nivolumab (n = 160), and pembrolizumab (n = 125). The ROR was significant for atezolizumab (ROR 5.39, 95 % CI 3.69-7.87), avelumab (ROR 10.32, 95 % CI 4.91-21.69), durvalumab (ROR 7.91, 95 % CI 4.91-12.75), nivolumab (ROR 9.76, 95 % CI 8.34-11.43), and pembrolizumab (ROR 12.6, 95 % CI 10.55-15.06). In our systematic review, we summated 57 cases of ICI-induced ITP. Nivolumab and pembrolizumab had the most reported cases of ITP in the literature. Most cases reported (53 %) included ITP-directed therapies beyond corticosteroids for the management of ICI-induced ITP.
CONCLUSION
There is a significant reporting signal of ITP with several ICI agents. Clinicians should be aware of and monitor for signs of this potentially serious adverse event.
Topics: United States; Humans; Nivolumab; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Purpura, Thrombocytopenic, Idiopathic; Pharmacovigilance; Retrospective Studies; Drug-Related Side Effects and Adverse Reactions; Thrombocytopenia
PubMed: 38359661
DOI: 10.1016/j.intimp.2024.111606 -
Blood Advances May 2023Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to... (Meta-Analysis)
Meta-Analysis
Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to response with addition of caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. In this systematic review and meta-analysis, we searched for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk of bias using the Cochrane risk-of-bias-2 tool (RCTs) and the Newcastle-Ottawa Scale (observational studies). The primary efficacy and safety outcomes were all-cause mortality and treatment-emergent bleeding, respectively. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time to response. We included 2 high-quality RCTs and 3 observational studies at high risk of bias comprising 632 total participants. Compared with SOC, caplacizumab was associated with a nonsignificant reduction in the relative risk [RR] of death in RCTs (RR, 0.21; 95% confidence interval [CI], 0.05-1.74) and observational studies (RR, 0.62; 95% CI, 0.07-4.41). Compared with SOC, caplacizumab was associated with an increased bleeding risk in RCTs (RR, 1.37; 95% CI, 1.06-1.77). In observational studies, bleeding risk was not significantly increased (RR, 7.10; 95% CI, 0.90-56.14). Addition of caplacizumab was associated with a significant reduction in refractory iTTP and exacerbation risks and shortened response time but increased relapse risk. Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time to response, and improves exacerbation rates at the expense of increased relapse and bleeding risk.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Standard of Care; Neoplasm Recurrence, Local; Hemorrhage; Purpura, Thrombocytopenic, Idiopathic
PubMed: 36053773
DOI: 10.1182/bloodadvances.2022008443 -
JSLS : Journal of the Society of... 2014The single-incision approach in laparoscopic surgery is a relatively new concept. This systematic review of the literature was performed to appraise the existing... (Review)
Review
BACKGROUND AND OBJECTIVES
The single-incision approach in laparoscopic surgery is a relatively new concept. This systematic review of the literature was performed to appraise the existing clinical evidence concerning the use of the single-incision technique for spleen resection.
METHODS
We performed a systematic search of the PubMed and Scopus databases, and the studies retrieved were included in our review. The references of the included studies were also hand searched.
RESULTS
Thirty-one relevant studies were found in the field including 81 patients with an age range from 0.6 to 90 years and a body mass index range from 18 to 36.7 kg/m2. Splenomegaly (44.6%), idiopathic thrombocytopenic purpura (31%), and immune thrombocytopenic purpura (6.8%) were the most common indications for the procedure. Concerning the applied port system, multiple single ports (5 to 12 mm) were used in 54.4% of patients, the SILS port (Covidien, Mansfield, Massachusetts) was used in 26.6%, the TriPort (Advanced Surgical Concepts, Wicklow, Ireland) was used in 7.6%, glove ports were used in 6.3%, and the GelPort (Applied Medical, Rancho Santa Margarita, California) was used in 5.1%. The median operative time was 125 minutes (range, 45-420 minutes), and the median quantity of blood loss was 50 mL (range, 10-450 mL). No conversion to open surgery and no transfusion were needed. The length of hospital stay was between 1 and 9 days. Low rates of complications and no patient deaths were found. The existing evidence on cosmesis is limited.
CONCLUSION
Single-site/single-port laparoscopic surgery is a minimally invasive procedure that seems to be a challenging alternative in the management of spleen resection.
Topics: Humans; Laparoscopy; Operative Time; Purpura, Thrombocytopenic, Idiopathic; Spleen; Splenectomy
PubMed: 25392670
DOI: 10.4293/JSLS.2014.00350 -
Journal of the European Academy of... Jul 2018Acne vulgaris is a multifaceted skin disorder, affecting more than 85% of young individuals worldwide. Pharmacological therapy is not always desirable because of the... (Review)
Review
BACKGROUND
Acne vulgaris is a multifaceted skin disorder, affecting more than 85% of young individuals worldwide. Pharmacological therapy is not always desirable because of the development of antibiotic resistance or the potential risk of adverse effects. Non-pharmacological therapies can be viable alternatives for conventional therapies. However, sufficient evidence-based support in the efficacy and safety of non-pharmacological therapies is lacking.
OBJECTIVE
To assess the efficacy and safety of several non-pharmacological therapies in the treatment of acne vulgaris.
METHODS
A systematic literature review, including a best-evidence synthesis, was performed to identify literature. Three electronic databases were accessed and searched for studies published between January 2000 and May 2017.
RESULTS
Thirty-three eligible studies were included in our systematic review. Three main types of non-pharmacological therapies were identified laser- and light-based therapies, chemical peels and fractional microneedling radiofrequency. The majority of the included studies demonstrated a significant reduction in acne lesions. However, only seven studies had a high methodologic quality. Based on these seven trials, a best-evidence synthesis was conducted. Strong evidence was found for glycolic acid (10-40%). Moderate evidence was found for amino fruit acid (20-60%), intense pulsed light (400-700 and 870-1200 nm) and the diode laser (1450 nm). Initially, conflicting evidence was found for pulsed dye laser (585-595 nm). The most frequently reported side-effects for non-pharmacological therapies included erythema, tolerable pain, purpura, oedema and a few cases of hyperpigmentation, which were in most cases mild and transient.
CONCLUSION
Circumstantial evidence was found for non-pharmacological therapies in the treatment of acne vulgaris. However, the lack of high methodological quality among included studies prevented us to draw clear conclusions, regarding a stepwise approach. Nevertheless, our systematic review including a best-evidence synthesis did create order and structure in resulting outcomes in which a first step towards future research is generated.
Topics: Acne Vulgaris; Chemexfoliation; Evidence-Based Medicine; Humans; Laser Therapy; Needles; Phototherapy; Radiofrequency Therapy
PubMed: 29444375
DOI: 10.1111/jdv.14881 -
Expert Review of Hematology Feb 2022Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP), has emerged as a significant COVID-19-associated complication. This study analyzes the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP), has emerged as a significant COVID-19-associated complication. This study analyzes the published literature of case reports and case series regarding COVID-19 infection associated with ITP.
METHODOLOGY
In this systematic review and meta-analysis, a systematic search was conducted through PubMed, Web of Science, and Medline through Clarivate and EBSCO to include the eligible studies. The authors utilized Review Manager 5.4 to conduct quantitative data synthesis for the condition of interest analysis.
RESULTS
A total of 13 eligible case reports and case series with 42 patients were included in this study; 54.8% of them were male. The pooled mean age of all participants was (59.5 ± 19) years with a median age of 63 years. The estimated mean time from diagnosis with COVID-19 to ITP development was 18.1 ± 21 days and the mean time to recovery from ITP was 5.8 ± 4.8 days. The pooled random effect of mean platelet count in the included six studies was 14.52, CI [8.79, 20.25].
CONCLUSION
Our analysis shows that ITP secondary to COVID-19 infection is slightly more prevalent among males (54.8%). Elderly patients were more vulnerable to the disease. Most cases developed ITP within 2-3 weeks after COVID-19 infection and recovered in less than one week from ITP.
Topics: Adult; Aged; COVID-19; Humans; Male; Middle Aged; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
PubMed: 35025706
DOI: 10.1080/17474086.2022.2029699 -
EJHaem Feb 2024Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening condition marked by abnormal blood clotting and organ damage. Caplacizumab is a potential... (Review)
Review
Does Caplacizumab for the management of thrombotic thrombocytopenic purpura increase the risk of relapse, exacerbation, and bleeding? An updated systematic review and meta-analysis based on revised criteria by the International Working Group for thrombotic thrombocytopenic purpura.
Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening condition marked by abnormal blood clotting and organ damage. Caplacizumab is a potential treatment for the TTP management. This systematic review and meta-analysis aimed to assess Caplacizumab's effectiveness and safety in the TTP management. A comprehensive database search identified nine studies, including randomized controlled trials and observational studies. Primary outcomes included TTP exacerbation, relapse, and major bleeding. Major bleeding risk was evaluated using updated definitions recommended by the International TTP Working Group in 2021. Revised criteria proposed by the IWG for TTP recurrence were employed for a comprehensive assessment of Caplacizumab's impact on relapse and exacerbation. Analysis revealed Caplacizumab significantly reduced all-cause mortality in TTP patients. Some studies raised concerns about bleeding risk, but overall, it did not significantly differ from standard treatment. Likewise, there was no significant difference in TTP relapse rates between Caplacizumab and standard care. This study supports Caplacizumab as a potential adjunct therapy for TTP. However, careful consideration of its advantages and risks is crucial in clinical practice. Further research is needed to address concerns related to adverse effects like bleeding risk and relapse rates associated with Caplacizumab in the TTP management. The findings emphasize the importance of weighing potential benefits and risks when considering Caplacizumab as an adjunct therapy for TTP.
PubMed: 38406548
DOI: 10.1002/jha2.833 -
Hematology Reports Aug 2022The proliferation of literature regarding the COVID-19 pandemic has served to highlight a wide spectrum of disease manifestations and complications, such as thrombotic... (Review)
Review
INTRODUCTION
The proliferation of literature regarding the COVID-19 pandemic has served to highlight a wide spectrum of disease manifestations and complications, such as thrombotic microangiopathies. Our review with a brief case presentation highlights the increasing recognition of TTP in COVID-19 and describes its salient characteristics.
METHODS
We screened the available literature in PubMed, EMBASE, and Cochrane databases from inception until April 2022 of articles mentioning COVID-19-associated TTP in English language.
RESULTS
From 404 records, we included 8 articles mentioning data of 11 patients in our review. TTP was predominantly reported in females (72%) with a mean age of 48.2 years (SD 15.1). Dyspnea was the most common symptom in one third of patients (36.6%). Neurological symptoms were reported in 27.3% of cases. The time to diagnosis of TTP was 10 days (SD 5.8) from onset of COVID-19. All 11 cases underwent plasma exchange (PLEX), with a mean of 12 sessions per patient, whereas 6 cases received Rituximab (54.5%), and 3 received Caplacizumab (27.3%). One patient died from the illness.
CONCLUSION
This review of available literature highlights the atypical and refractory nature of COVID-19-associated TTP. It required longer sessions of PLEX, with half of the patients receiving at least one immunosuppressant.
PubMed: 35997402
DOI: 10.3390/hematolrep14030035 -
Frontiers in Oral Health 2023The aim of this systematic review is to provide a clinical update of the current knowledge on COVID-19 and oral mucosal lesions, to analyze the types and prevalence of... (Review)
Review
INTRODUCTION
The aim of this systematic review is to provide a clinical update of the current knowledge on COVID-19 and oral mucosal lesions, to analyze the types and prevalence of oral mucosal lesions in patients with COVID-19, and to clarify the potential association between COVID-19 and oral mucosal lesions.
METHODS
The literature search was conducted using PubMed, Web of Science, Scopus and the Cochrane Library, as well as literatures via manual searches of the reference lists of included studies. Studies published in English that mentioned oral mucosal lesions in patients with COVID-19 were included, resulting in a total of 31 studies.
RESULTS
Most of the included studies were considered to have a moderate to high risk of bias according to the Joanna Briggs Institute bias assessment tools. Based on COVID-19 severity, the characteristics and patterns of oral mucosal lesions in COVID-19 patients were described, analyzed and synthesized. Overall, ulcers without specific diagnosis had the highest prevalence in COVID-19 patients, followed by traumatic ulcers, candidiasis, petechiae and aphthous-like lesions. Homogeneity of data cannot be achieved in statical analysis, indicating randomness of outcome (ulcers without specific diagnosis, 95% CI: 28%-96%, = 98.7%).
DISCUSSION
Given the limited evidence from currently available studies, the association between COVID-19 and oral mucosal lesions remains difficult to clarify. Healthcare professionals should be aware of the possible association between COVID-19 and oral mucosal lesions, and we hereby discuss our findings.
PubMed: 38169876
DOI: 10.3389/froh.2023.1322458 -
Rheumatology International Jun 2013Henoch-Schönlein purpura (HSP) is the most common form of systemic vasculitis of unknown etiology. This study aimed at reviewing published studies investigating the... (Meta-Analysis)
Meta-Analysis Review
Henoch-Schönlein purpura (HSP) is the most common form of systemic vasculitis of unknown etiology. This study aimed at reviewing published studies investigating the association of genetic polymorphisms with HSP and its severity. We systematically reviewed all published data on genetic risk factors for HSP by searching MEDLINE. We also performed a meta-analysis of association studies of HLA-DRB1-01, 07, and 11, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. We identified 45 studies investigating polymorphisms in 39 genes in association with HSP and/or its severity. Most of these genes are involved in immunological and/or inflammatory responses or vasomotor regulation. Most results were negative. The most convincing finding is the association of HLA-DRB1 01, 07, and 11 with HSP susceptibility. The overall odds ratios (ORs) for the three loci were significant for HSP: HLA-DRB1 01 (OR = 1.805, 95 % CI 1.259-2.588, p = 0.0012); HLA-DRB1 07 (OR = 0.671, 95 % CI 0.469-0.961, p = 0.058); HLA-DRB1 11 (OR = 2.001, 95 % CI 1.50-2.67, p = 0.027). Genetic regulation of endothelial function, such as polymorphisms in genes coding rennin-angiotensin system (RAS) components, endothelial nitric oxide synthases, Inter-Cellular Adhesion Molecule 1, and vascular endothelial growth factor, could also confer effect on HSP. In addition, MEFV, whose mutations cause familial Mediterranean fever, could be an important candidate gene for HSP. Further large studies are required to investigate the association between genetic polymorphisms and HSP. Alternative approaches, such as genome-wide association study, are necessary to help to identify genetic risks for HSP.
Topics: Cytokines; Genes, MHC Class II; Genome-Wide Association Study; Humans; IgA Vasculitis; Peptidyl-Dipeptidase A; Polymorphism, Genetic
PubMed: 23325094
DOI: 10.1007/s00296-012-2661-4 -
Bulletin of the National Research Centre 2022In 2019, a viral and respiratory pathology called COVID-19 emerged in Wuhan, China, and spread to other continents. Its main symptoms include fever, cough, dyspnea,... (Review)
Review
BACKGROUND
In 2019, a viral and respiratory pathology called COVID-19 emerged in Wuhan, China, and spread to other continents. Its main symptoms include fever, cough, dyspnea, myalgia, anorexia and respiratory distress in the most severe cases, which can lead to death. Furthermore, manifestations in the oral cavity such as ageusia and dysgeusia, as well as lesions in other regions of the oral cavity, can be observed.
MAIN BODY
This systematic review and meta-analysis aimed to critically assess the clinical evidence on the use of photobiomodulation (PBMT) and antimicrobial photodynamic therapy (aPDT) for the treatment of oral lesions in patients infected with Sars-Cov-2. The literature extracted from electronic databases such as PubMed, Medline, CINAHL, and Google Scholar was screened for eligibility, and relevant articles were included. The review is limited to manuscripts published in English, Spanish and Portuguese language between December 2019 and October 2021. A total of 5 articles with 11 cases retracting PBMT and aPDT as therapeutic strategies for the regression of oral lesions and painful symptoms. The results show favoring the associated use of PBMT with aPDT ( = 0.004), and the isolated use of PBMT with the result of significant " = 0.005" and good confidence interval (7.18, 39.20) in ulcerative lesions, herpetic, aphthous, erythematous, petechiae and necrotic areas.
CONCLUSIONS
PBMT and aPDT could be effective in the treatment of oral lesions of patients infected with Sars-Cov-2 in a short period of time; however, more long-term randomized clinical trials studies are needed to define the therapeutic strategy.
PubMed: 35601476
DOI: 10.1186/s42269-022-00830-z