-
Head and Neck Pathology Mar 2022The 5 edition of the World Health Organization (WHO) Classification of Head and Neck Tumours (2022) comes out only five years after the previous edition, however it...
The 5 edition of the World Health Organization (WHO) Classification of Head and Neck Tumours (2022) comes out only five years after the previous edition, however it presents important updates that run in parallel with the rapid progression involving the increasingly sophisticated molecular investigation and its interpretation, some of which already have therapy-related impact. This manuscript provides an overview of the leading changes introduced in the classification of Odontogenic and Maxillofacial Bone Tumours that encompasses cysts of the jaws, odontogenic tumours, giant cell lesions and bone cysts, and bone and cartilage tumours. This is the first edition that Essential and Desirable Diagnostic Features were added for each entity, so that the most important clinical, microscopic and/or radiologic features were encapsulated and briefly highlighted. Surgical ciliated cyst was added to the group of odontogenic cysts, adenoid ameloblastoma was a newly recognized benign epithelial odontogenic tumour, and segmental odontomaxillary dysplasia was introduced in the group of fibro-osseous tumours and dysplasia. In addition, rhabdomyosarcoma with TFCP2 rearrangement, was introduced into the group of malignant jawbone tumours. The unique genetic aberrations distinguish it from other types of rhabdomyosarcomas. On the other hand, melanotic neuroectodermal tumour of infancy and osteoid osteoma were deleted from the benign bone and cartilageneous tumours, as was the hematolymphoid tumour of solitary plasmacytoma of bone. We systematically reviewed each entity in this chapter and provided important updated findings for selected topics that can further aid in the diagnostic process for challenging cases, broaden insights on the logic of the present classification, and finally, emphasize the potential that some of the molecular results may have in the near future to set new treatment approaches.
Topics: Bone Neoplasms; DNA-Binding Proteins; Head and Neck Neoplasms; Humans; Odontogenic Cysts; Odontogenic Tumors; Transcription Factors; World Health Organization
PubMed: 35312978
DOI: 10.1007/s12105-021-01404-7 -
The Cochrane Database of Systematic... Oct 2016When primary root canal therapy fails, periapical lesions can be retreated with or without surgery. Root canal retreatment is a non-surgical procedure that involves... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
When primary root canal therapy fails, periapical lesions can be retreated with or without surgery. Root canal retreatment is a non-surgical procedure that involves removal of root canal filling materials from the tooth, followed by cleaning, shaping and obturating of the canals. Root-end resection is a surgical procedure that involves exposure of the periapical lesion through an osteotomy, surgical removal of the lesion, removal of part of the root-end tip, disinfection and, commonly, retrograde sealing or filling of the apical portion of the remaining root canal. This review updates one published in 2008.
OBJECTIVES
To assess effects of surgical and non-surgical therapy for retreatment of teeth with apical periodontitis.To assess effects of surgical root-end resection under various conditions, for example, when different materials, devices or techniques are used.
SEARCH METHODS
We searched the following electronic databases: the Cochrane Oral Health Trials Register (to 10 February 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE Ovid (1946 to 10 February 2016) and Embase Ovid (1980 to 10 February 2016). We searched the US National Registry of Clinical Trials (ClinicalTrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (to 10 February 2016). We placed no restrictions regarding language and publication date. We handsearched the reference lists of the studies retrieved and key journals in the field of endodontics.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) involving people with periapical pathosis. Studies could compare surgery versus non-surgical treatment or could compare different types of surgery. Outcome measures were healing of the periapical lesion assessed after one-year follow-up or longer; postoperative pain and discomfort; and adverse effects such as tooth loss, mobility, soft tissue recession, abscess, infection, neurological damage or loss of root sealing material evaluated through radiographs.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from included studies and assessed their risk of bias. We contacted study authors to obtain missing information. We combined results of trials assessing comparable outcomes using the fixed-effect model, with risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, and 95% confidence intervals (CIs). We used generic inverse variance for split-mouth studies.
MAIN RESULTS
We included 20 RCTs. Two trials at high risk of bias assessed surgery versus a non-surgical approach: root-end resection with root-end filling versus root canal retreatment. The other 18 trials evaluated different surgical protocols: cone beam computed tomography (CBCT) versus periapical radiography for preoperative assessment (one study at high risk of bias); antibiotic prophylaxis versus placebo (one study at unclear risk); different magnification devices (loupes, surgical microscope, endoscope) (two studies at high risk); types of incision (papilla base incision, sulcular incision) (one study at high risk and one at unclear risk); ultrasonic devices versus handpiece burs (one study at high risk); types of root-end filling material (glass ionomer cement, amalgam, intermediate restorative material (IRM), mineral trioxide aggregate (MTA), gutta-percha (GP), super-ethoxy benzoic acid (EBA)) (five studies at high risk of bias, one at unclear risk and one at low risk); grafting versus no grafting (three studies at high risk and one at unclear risk); and low energy level laser therapy versus placebo (irradiation without laser activation) versus control (no use of the laser device) (one study at high risk).There was no clear evidence of superiority of the surgical or non-surgical approach for healing at one-year follow-up (RR 1.15, 95% CI 0.97 to 1.35; two RCTs, 126 participants) or at four- or 10-year follow-up (one RCT, 82 to 95 participants), although the evidence is very low quality. More participants in the surgically treated group reported pain in the first week after treatment (RR 3.34, 95% CI 2.05 to 5.43; one RCT, 87 participants; low quality evidence).In terms of surgical protocols, there was some inconclusive evidence that ultrasonic devices for root-end preparation may improve healing one year after retreatment, when compared with the traditional bur (RR 1.14, 95% CI 1.00 to 1.30; one RCT, 290 participants; low quality evidence).There was evidence of better healing when root-ends were filled with MTA than when they were treated by smoothing of orthograde GP root filling, after one-year follow-up (RR 1.60, 95% CI 1.14 to 2.24; one RCT, 46 participants; low quality evidence).There was no evidence that using CBCT rather than radiography for preoperative evaluation was advantageous for healing (RR 1.02, 95% CI 0.70 to 1.47; one RCT, 39 participants; very low quality evidence), nor that any magnification device affected healing more than any other (loupes versus endoscope at one year: RR 1.05, 95% CI 0.92 to 1.20; microscope versus endoscope at two years: RR 1.01, 95% CI 0.89 to 1.15; one RCT, 70 participants, low quality evidence).There was no evidence that antibiotic prophylaxis reduced incidence of postoperative infection (RR 0.49, 95% CI 0.09 to 2.64; one RCT, 250 participants; low quality evidence).There was some evidence that using a papilla base incision (PBI) may be beneficial for preservation of the interdental papilla compared with complete papilla mobilisation (one RCT (split-mouth), 12 participants/24 sites; very low quality evidence). There was no evidence of less pain in the PBI group at day 1 post surgery (one RCT, 38 participants; very low quality evidence).There was evidence that adjunctive use of a gel of plasma rich in growth factors reduced postoperative pain compared with no grafting (measured on visual analogue scale: one day postoperative MD -51.60 mm, 95% CI -63.43 to -39.77; one RCT, 36 participants; low quality evidence).There was no evidence that use of low energy level laser therapy (LLLT) prevented postoperative pain (very low quality evidence).
AUTHORS' CONCLUSIONS
Available evidence does not provide clinicians with reliable guidelines for treating periapical lesions. Further research is necessary to understand the effects of surgical versus non-surgical approaches, and to determine which surgical procedures provide the best results for periapical lesion healing and postoperative quality of life. Future studies should use standardised techniques and success criteria, precisely defined outcomes and the participant as the unit of analysis.
Topics: Humans; Periapical Periodontitis; Randomized Controlled Trials as Topic; Retreatment; Root Canal Therapy
PubMed: 27759881
DOI: 10.1002/14651858.CD005511.pub3 -
Pain Physician 2016Lumbar muscle dysfunction due to pain might be related to altered lumbar muscle structure. Macroscopically, muscle degeneration in low back pain (LBP) is characterized... (Review)
Review
BACKGROUND
Lumbar muscle dysfunction due to pain might be related to altered lumbar muscle structure. Macroscopically, muscle degeneration in low back pain (LBP) is characterized by a decrease in cross-sectional area and an increase in fat infiltration in the lumbar paraspinal muscles. In addition microscopic changes, such as changes in fiber distribution, might occur. Inconsistencies in results from different studies make it difficult to draw firm conclusions on which structural changes are present in the different types of non-specific LBP. Insights regarding structural muscle alterations in LBP are, however, important for prevention and treatment of non-specific LBP.
OBJECTIVE
The goal of this article is to review which macro- and/or microscopic structural alterations of the lumbar muscles occur in case of non-specific chronic low back pain (CLBP), recurrent low back pain (RLBP), and acute low back pain (ALBP).
STUDY DESIGN
Systematic review.
SETTING
All selected studies were case-control studies.
METHODS
A systematic literature search was conducted in the databases PubMed and Web of Science. Only full texts of original studies regarding structural alterations (atrophy, fat infiltration, and fiber type distribution) in lumbar muscles of patients with non-specific LBP compared to healthy controls were included. All included articles were scored on methodological quality.
RESULTS
Fifteen studies were found eligible after screening title, abstract, and full text for inclusion and exclusion criteria. In CLBP, moderate evidence of atrophy was found in the multifidus; whereas, results in the paraspinal and the erector spinae muscle remain inconclusive. Also moderate evidence occurred in RLBP and ALBP, where no atrophy was shown in any lumbar muscle. Conflicting results were seen in undefined LBP groups. Results concerning fat infiltration were inconsistent in CLBP. On the other hand, there is moderate evidence in RLBP that fat infiltration does not occur, although a larger muscle fat index was found in the erector spinae, multifidus, and paraspinal muscles, reflecting an increased relative amount of intramuscular lipids in RLBP. However, no studies were found investigating fat infiltration in ALBP. Restricted evidence indicates no abnormalities in fiber type in the paraspinal muscles in CLBP. No studies have examined fiber type in ALBP and RLBP.
LIMITATIONS
Lack of clarity concerning patient definitions, exact LBP symptoms, and applied methods.
CONCLUSIONS
The results indicate atrophy in CLBP in the multifidus and paraspinal muscles but not in the erector spinae. No atrophy was shown in RLBP and ALBP. Fat infiltration did not occur in RLBP, but results in CLBP were inconsistent. No abnormalities in fiber type in the paraspinal muscles were found in CLBP.
KEY WORDS
Low back pain, non-specific, chronic, recurrent, acute, muscle structure, fat infiltration, cross-sectional area, fiber type, review.
Topics: Humans; Low Back Pain; Lumbar Vertebrae; Lumbosacral Region; Muscle, Skeletal; Paraspinal Muscles
PubMed: 27676689
DOI: No ID Found -
The Cochrane Database of Systematic... Dec 2015After the introduction of microsurgical principles in endodontics involving new techniques for root canal treatment, there has been a drive to enhance the visualisation... (Comparative Study)
Comparative Study Review
BACKGROUND
After the introduction of microsurgical principles in endodontics involving new techniques for root canal treatment, there has been a drive to enhance the visualisation of the surgical field. It is important to know if the technical advantages for the operator brought in by magnification devices such as surgical microscopes, endoscopes and magnifying loupes, are also associated with advantages for the patient in terms of improvement of clinical and radiographic outcomes. This version updates the review published in 2009.
OBJECTIVES
To evaluate and compare the effects of endodontic treatment performed with the aid of magnification devices versus endodontic treatment without magnification devices. We also aimed to compare the different magnification devices used in endodontics with one another.
SEARCH METHODS
The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 13 October 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 9), MEDLINE via OVID (1946 to 13 October 2015) and EMBASE via OVID (1980 to 13 October 2015). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
We considered all randomised controlled trials (RCTs) and quasi-randomised controlled trials comparing endodontic therapy performed with versus without one or more magnification devices, as well as randomised and quasi-randomised trials comparing two or more magnification devices used as an adjunct to endodontic therapy.
DATA COLLECTION AND ANALYSIS
We conducted screening of search results independently and in duplicate. We obtained full papers for potentially relevant trials. The Cochrane Collaboration statistical guidelines were to be followed for data synthesis.
MAIN RESULTS
No trials met the inclusion criteria for this review.
AUTHORS' CONCLUSIONS
No article was identified in the current literature that satisfied the criteria for inclusion. It is unknown if and how the type of magnification device affects the treatment outcome, considering the high number of factors that may have a significant impact on the success of endodontic surgical procedure. This should be investigated by further long-term, well-designed RCTs that conform to the CONSORT statement (www.consort-statement.org/).
Topics: Endodontics; Endoscopes; Humans; Lenses; Microscopy; Root Canal Therapy
PubMed: 26650099
DOI: 10.1002/14651858.CD005969.pub3 -
Cancer Treatment Reviews Sep 2022Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management.
METHODS
Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis.
RESULTS
The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis.
CONCLUSION
Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.
Topics: Colitis; Diarrhea; Humans; Immune Checkpoint Inhibitors; Incidence; Ipilimumab; Prospective Studies
PubMed: 35917654
DOI: 10.1016/j.ctrv.2022.102440 -
Autoimmunity Reviews Jun 2021The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood... (Review)
Review
The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood vessels affected (Chapel Hill classification). In recent years, several drugs with well-characterized immunological targets have been tested in clinical trials in large vessel vasculitis and small vessel vasculitis. Such trials provide "reverse translational" or bedside to bench information about underlying pathogenic mechanisms. Therefore, the aim of this systematic literature review was to examine the evidence base for a more refined mechanistic immunological classification of vasculitis. A total of 40 studies (20 randomized controlled trials (RCTs), 16 prospective studies, 1 retrospective cohort study and 3 case series) were included for full qualitative assessment. RCTs concerning biologic therapy for large vessel vasculitis mainly supports interleukin 6 receptor inhibition (tocilizumab). RCTs concerning biologic therapy for granulomatosis with polyangiitis and microscopic polyangiitis mainly support anti-CD20 treatment (rituximab) and complement inhibition with a small molecule C5a receptor antagonist (avacopan) is an emerging treatment option. The biologic treatment of eosinophilic granulomatosis with polyangiitis is centered around interleukin 5 inhibition (mepolizumab). Studies on tumor necrosis factor alpha inhibition (adalimumab, infliximab, and etanercept) showed negative results in giant cell arteritis but some effect in Takayasu arteritis. Taken together, clinical studies with cytokine and cell specific drugs are dissecting the heterogeneous immunopathogenic mechanisms of vasculitis and support a mechanistic immunological classification. Especially, cytokine antagonism is pointing towards immunological distinctions between eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis/microscopic polyangiitis and differences between giant cell arteritis and Takayasu arteritis.
Topics: Churg-Strauss Syndrome; Etanercept; Giant Cell Arteritis; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis; Randomized Controlled Trials as Topic; Rituximab; Takayasu Arteritis
PubMed: 33872767
DOI: 10.1016/j.autrev.2021.102829 -
Apoptosis : An International Journal on... Aug 2022Programmed cell death is considered a key player in a variety of cellular processes that helps to regulate tissue growth, embryogenesis, cell turnover, immune response,... (Review)
Review
Programmed cell death is considered a key player in a variety of cellular processes that helps to regulate tissue growth, embryogenesis, cell turnover, immune response, and other biological processes. Among different types of cell death, apoptosis has been studied widely, especially in the field of cancer research to understand and analyse cellular mechanisms, and signaling pathways that control cell cycle arrest. Hallmarks of different types of cell death have been identified by following the patterns and events through microscopy. Identified biomarkers have also supported drug development to induce cell death in cancerous cells. There are various serological and microscopic techniques with advantages and limitations, that are available and are being utilized to detect and study the mechanism of cell death. The complexity of the mechanism and difficulties in distinguishing among different types of programmed cell death make it challenging to carry out the interventions and delay its progression. In this review, mechanisms of different forms of programmed cell death along with their conventional and unconventional methods of detection of have been critically reviewed systematically and categorized on the basis of morphological hallmarks and biomarkers to understand the principle, mechanism, application, advantages and disadvantages of each method. Furthermore, a very comprehensive comparative analysis has been drawn to highlight the most efficient and effective methods of detection of programmed cell death, helping researchers to make a reliable and prudent selection among the available methods of cell death assay. Conclusively, how programmed cell death detection methods can be improved and can provide information about distinctive stages of cell death detection have been discussed.
Topics: Apoptosis; Biomarkers; Cell Death; Signal Transduction
PubMed: 35713779
DOI: 10.1007/s10495-022-01735-y -
Neonatology 2021The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related...
BACKGROUND
The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related normal values for CSF findings in neonates, and many previous studies have included infants in whom antibiotics were administered before lumbar puncture or in whom viral meningitis was not excluded.
METHODS
A systematic search was done using MEDLINE and EMBASE to identify original studies which investigated CSF normal values in either healthy neonates or febrile neonates in whom bacterial and viral meningitis were reliably excluded.
RESULTS
We identified seven studies investigating 270 term and 96 preterm neonates. There were minimal differences between preterm and term neonates in the CSF white blood cell (WBC) count and glucose concentration. In contrast, the CSF neutrophil count and protein concentration were influenced by gestational and chronological age. In the four studies that reported individual patient data, in 95% of cases the CSF WBC count was <12 cells/μL in preterm and <10 cells/μL in term neonates, the neutrophil count was <16 and 8 cells/μL, and the protein concentration was <210 and 110 mg/dL, respectively.
CONCLUSION
The normal range for CSF parameters in neonates is different to that in older infants, and some parameters are influenced by gestational and chronological age. CSF parameters alone are not sufficiently reliable to exclude meningitis.
Topics: Aged; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Meningitis; Reference Values; Retrospective Studies; Spinal Puncture
PubMed: 34818234
DOI: 10.1159/000517630 -
The Cochrane Database of Systematic... Jul 2023Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of... (Review)
Review
BACKGROUND
Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of EoE requires a constellation of clinical symptoms of esophageal dysfunction and histologic findings (at least 15 eosinophils/high-powered microscope field (eos/hpf)). Current guidelines no longer require the failure of response to proton pump inhibitor medications to establish a diagnosis of EoE, but continue to suggest the exclusion of other etiologies of esophageal eosinophilia. The treatment goals for EoE are improvement in clinical symptoms, resolution of esophageal eosinophilia and other histologic abnormalities, endoscopic improvement, improved quality of life, improved esophageal function, minimized adverse effects of treatment, and prevention of disease progression and subsequent complications. Currently, there is no cure for EoE, making long-term treatment necessary. Standard treatment modalities include dietary modifications, esophageal dilation, and pharmacologic therapy. Effective pharmacologic therapies include corticosteroids, rapidly emerging biological therapies, and proton pump inhibitor medications.
OBJECTIVES
To evaluate the efficacy and safety of medical interventions for people with eosinophilic esophagitis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP to 3 March 2023.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing any medical intervention or food elimination diet for the treatment of eosinophilic esophagitis, either alone or in combination, to any other intervention (including placebo).
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as a risk ratio (RR) and as the mean or standardized mean difference (MD/SMD) with 95% confidence interval (CI). We assessed the certainty of the evidence using GRADE. Our primary outcomes were: clinical, histological, and endoscopic improvement, and withdrawals due to adverse events. Secondary outcomes were: serious and total adverse events, and quality of life.
MAIN RESULTS
We included 41 RCTs with 3253 participants. Eleven studies included pediatric patients while the rest recruited both children and adults. Four studies were in patients with inactive disease while the rest were in patients with active disease. We identified 19 intervention comparisons. In this abstract we present the results of the primary outcomes for the two main comparisons: corticosteroids versus placebo and biologics versus placebo, based on the prespecified outcomes defined of the primary studies. Fourteen studies compared corticosteroids to placebo for induction of remission and the risk of bias for these studies was mostly low. Corticosteroids may lead to slightly better clinical improvement (20% higher), measured dichotomously (risk ratio (RR) 1.74, 95% CI 1.08 to 2.80; 6 studies, 583 participants; number needed to treat for an additional beneficial outcome (NNTB) = 4; low certainty), and may lead to slightly better clinical improvement, measured continuously (standard mean difference (SMD) 0.51, 95% CI 0.17 to 0.85; 5 studies, 475 participants; low certainty). Corticosteroids lead to a large histological improvement (63% higher), measured dichotomously (RR 11.94, 95% CI 6.56 to 21.75; 12 studies, 978 participants; NNTB = 3; high certainty), and may lead to histological improvement, measured continuously (SMD 1.42, 95% CI 1.02 to 1.82; 5 studies, 449 participants; low certainty). Corticosteroids may lead to little to no endoscopic improvement, measured dichotomously (RR 2.60, 95% CI 0.82 to 8.19; 5 studies, 596 participants; low certainty), and may lead to endoscopic improvement, measured continuously (SMD 1.33, 95% CI 0.59 to 2.08; 5 studies, 596 participants; low certainty). Corticosteroids may lead to slightly fewer withdrawals due to adverse events (RR 0.64, 95% CI 0.43 to 0.96; 14 studies, 1032 participants; low certainty). Nine studies compared biologics to placebo for induction of remission. Biologics may result in little to no difference in clinical improvement, measured dichotomously (RR 1.14, 95% CI 0.85 to 1.52; 5 studies, 410 participants; low certainty), and may result in better clinical improvement, measured continuously (SMD 0.50, 95% CI 0.22 to 0.78; 7 studies, 387 participants; moderate certainty). Biologics result in better histological improvement (55% higher), measured dichotomously (RR 6.73, 95% CI 2.58 to 17.52; 8 studies, 925 participants; NNTB = 2; moderate certainty). We could not draw conclusions for this outcome when measured continuously (SMD 1.01, 95% CI 0.36 to 1.66; 6 studies, 370 participants; very low certainty). Biologics may result in little to no difference in endoscopic improvement, measured dichotomously (effect not estimable, low certainty). We cannot draw conclusions for this outcome when measured continuously (SMD 2.79, 95% CI 0.36 to 5.22; 1 study, 11 participants; very low certainty). There may be no difference in withdrawals due to adverse events (RR 1.55, 95% CI 0.88 to 2.74; 8 studies, 792 participants; low certainty).
AUTHORS' CONCLUSIONS
Corticosteroids (as compared to placebo) may lead to clinical symptom improvement when reported both as dichotomous and continuous outcomes, from the primary study definitions. Corticosteroids lead to a large increase in histological improvement (dichotomous outcome) and may increase histological improvement (continuous outcome) when compared to placebo. Corticosteroids may or may not increase endoscopic improvement (depending on whether the outcome is measured dichotomously or continuously). Withdrawals due to adverse events (dichotomous outcome) may occur less frequently when corticosteroids are compared to placebo. Biologics (as compared to placebo) may not lead to clinical symptom improvement when reported as a dichotomous outcome and may lead to an increase in clinical symptom improvement (as a continuous outcome), from the primary study definitions. Biologics lead to a large increase in histological improvement when reported as a dichotomous outcome, but this is uncertain when reported as a continuous outcome, as compared to placebo. Biologics may not increase endoscopic improvement (dichotomous outcome), but this is uncertain when measured as a continuous outcome. Withdrawals due to adverse events as a dichotomous outcome may occur as frequently when biologics are compared to placebo.
Topics: Adult; Child; Humans; Adrenal Cortex Hormones; Biological Products; Chronic Disease; Eosinophilic Esophagitis; Proton Pump Inhibitors; Remission Induction; Randomized Controlled Trials as Topic
PubMed: 37470293
DOI: 10.1002/14651858.CD004065.pub4 -
Biology Dec 2022: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease developed by autoantibody production against human... (Review)
Review
: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease developed by autoantibody production against human neutrophilic granulocytes, including proteinase-3 (PR3) and myeloperoxidase (MPO). The management of AAV patients is difficult due to the multiorgan involvement, high rate of relapse, and complications of immunosuppressive agents that make it challenging. This study aims to investigate the efficacy and safety of rituximab (RTX) therapy in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) subtypes. : The PubMed/Medline database was searched for any studies related to RTX therapy in ANCA-associated vasculitis (GPA and MPA subtypes), from inception to 1 August 2022, and proceeded in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). : Our search resulted in 1082 initial records. After the elimination of review papers, irrelevant studies, and non-English records, 223 articles were included, and the data related to the efficacy and safety of RTX therapy were extracted. Several randomized and non-randomized studies showed that RTX is an effective treatment option for patients with AAV. Most of the studies showed the very effective effect of RTX in controlling disease in AAV patients, including pediatrics, adults, and elderlies, although RTX cannot completely prevent relapse. However, maintenance therapy helps delay the disease's relapse and causes sustained remission. Not only the licensed dose (375 mg/m intravenous per week for 4 weeks) could induce disease remission, but studies also showed that a single infusion of RTX could be effective. Although RTX could resolve many rare manifestations in AAV patients, there are few reports showing treatment failure. Additionally, few sudies have reported the unexpeted worsening of the disease after RTX administration. Generally, RTX is relatively safe compared to conventional therapies, but some serious adverse effects, mainly infections, cytopenia, hypogammaglobinemia, malignancy, and hypersensitivity have been reported. : RTX is an effective and relatively safe therapeutic option for AAV. Studies on the evaluation of the safety profiles of RTX and the prevention of severe RTX-related side effects in AAV patients are required.
PubMed: 36552276
DOI: 10.3390/biology11121767