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Biomedicines May 2024This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We... (Review)
Review
Clinical Outcomes and Molecular Predictors of Pembrolizumab (Keytruda) as a PD-1 Immune Checkpoint Inhibitor in Advanced and Metastatic Cervical Cancer: A Systematic Review and Meta-Analysis.
This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We adhered to the PRISMA guidelines for systematic reviews, conducting a database search in PubMed, Scopus, and Embase. The eligibility criteria centered on clinical outcomes, including the overall survival (OS), progression-free survival (PFS), and immune-related biomarkers post-pembrolizumab therapy. We included both prospective and retrospective studies that detailed clinical outcomes and molecular characteristics predictive of therapeutic response. Our search yielded six studies involving 846 patients treated with pembrolizumab from 2017 to 2022. The meta-analysis of these studies showed that pembrolizumab, used as monotherapy or in combination with chemotherapy, extended the OS by a weighted median of 10.35 months and the PFS by 8.50 months. The treatment demonstrated a pooled objective response rate (ORR) of 22.39%, although the I test result of 67.49% showed a high heterogeneity among the studies. Notably, patients with high PD-L1 expression (CPS ≥ 10) experienced improved outcomes in terms of the PFS and OS. The most common complications were fatigue, diarrhea, and immune-related adverse events. Pembrolizumab significantly enhances clinical outcomes in metastatic cervical cancer, particularly among patients with high PD-L1 expression. The drug maintains a good safety profile, reinforcing its treatment potential for patients with advanced and metastatic cervical cancer. Future studies should explore long-term effects and strategies to integrate pembrolizumab optimally into current treatment regimens, aiming to maximize patient benefits and effectively manage side effects.
PubMed: 38791070
DOI: 10.3390/biomedicines12051109 -
BMC Infectious Diseases Feb 2024Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic... (Meta-Analysis)
Meta-Analysis
Diagnosis of human leptospirosis: systematic review and meta-analysis of the diagnostic accuracy of the Leptospira microscopic agglutination test, PCR targeting Lfb1, and IgM ELISA to Leptospira fainei serovar Hurstbridge.
BACKGROUND
Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic reference standard remains the microscopic agglutination test (MAT) on paired serum samples. However, reported estimates of MAT's sensitivity vary. We evaluated the accuracy of four index tests, MAT on paired samples as well as alternative standards for leptospirosis diagnosis: MAT on single acute-phase samples, polymerase chain reaction (PCR) with the target gene Lfb1, and ELISA IgM with Leptospira fainei serovar Hurstbridge as an antigen.
METHODS
We performed a systematic review of studies reporting results of leptospirosis diagnostic tests. We searched eight electronic databases and selected studies that tested human blood samples and compared index tests with blood culture and/or PCR and/or MAT (comparator tests). For MAT selection criteria we defined a threshold for single acute-phase samples according to a national classification of leptospirosis endemicity. We used a Bayesian random-effect meta-analysis to estimate the sensitivity and specificity of MAT in single acute-phase and paired samples separately, and assessed risk of bias using the Quality Assessment of Studies of Diagnostic Accuracy Approach- 2 (QUADAS-2) tool.
RESULTS
For the MAT accuracy evaluation, 15 studies were included, 11 with single acute-phase serum, and 12 with paired sera. Two included studies used PCR targeting the Lfb1 gene, and one included study used IgM ELISA with Leptospira fainei serovar Hurstbridge as antigen. For MAT in single acute-phase samples, the pooled sensitivity and specificity were 14% (95% credible interval [CrI] 3-38%) and 86% (95% CrI 59-96%), respectively, and the predicted sensitivity and specificity were 14% (95% CrI 0-90%) and 86% (95% CrI 9-100%). Among paired MAT samples, the pooled sensitivity and specificity were 68% (95% CrI 32-92%) and 75% (95% CrI 45-93%) respectively, and the predicted sensitivity and specificity were 69% (95% CrI 2-100%) and 75% (2-100%).
CONCLUSIONS
Based on our analysis, the accuracy of MAT in paired samples was not high, but it remains the reference standard until a more accurate diagnostic test is developed. Future studies that include larger numbers of participants with paired samples will improve the certainty of accuracy estimates.
Topics: Humans; Serogroup; Bayes Theorem; Antibodies, Bacterial; Leptospira; Leptospirosis; Agglutination Tests; Sensitivity and Specificity; Enzyme-Linked Immunosorbent Assay; Immunoglobulin M; Polymerase Chain Reaction
PubMed: 38326762
DOI: 10.1186/s12879-023-08935-0 -
Journal of the European Academy of... Jun 2024The standard of care for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) involves excision by conventional surgery (CS) with a predefined safety margin of... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Efficacy of micrographic surgery versus conventional excision in reducing recurrence for basal cell carcinoma and squamous cell carcinoma: A systematic review and meta-analysis.
The standard of care for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) involves excision by conventional surgery (CS) with a predefined safety margin of resection or micrographic surgery (MS) with microscopic margin control. Previous studies have reported the superiority of MS in reducing recurrences for high-risk BCC and SCC. This systematic review aimed to assess MS and CS recurrence rates by including randomized clinical trials (RCTs) and cohort studies. A systematic review and meta-analysis were conducted for related studies in PubMed, LILACS, Embase, Scopus, Web of Science, CINHAL and Cochrane until May 2023. RCTs and cohorts involving patients with BCC or SCC submitted to MS and CS were included. Risk of bias assessment followed Cochrane-recommended tools for RCTs and cohorts, and certainty of evidence followed the GRADE approach. Pooled estimates were used to determine the relative risk (RR) and absolute risk difference (RD) using a random-effects model. Seventeen studies were included, two RCTs and fifteen cohorts. There were 82 recurrences in 3050 tumours submitted to MS, with an overall recurrence rate of 3.1% (95% CI 2.0%-4.7%). For CS, there were 209 recurrences in 3453 tumours, with a recurrence rate of 5.3% (95% CI 2.9%-9.3%). The combined estimate of RR was 0.48 (95% CI 0.36-0.63), without heterogeneity nor evidence of publication bias (p > 0.3). The RD resulted in 2.9% (95% CI 1.0%-4.9%; NNT = 35). Regarding subgroup analysis, the RR for BBC was 0.37 (95% CI 0.25-0.54), and RD was 3.7% (95% CI 0.8%-6.5%; NNT = 28). For SCC, RR was 0.57 (95% CI 0.29-1.13), and RD was 1.9% (95% CI 0.8%-4.7%; NNT = 53). Among primary tumours, RR was 0.39 (95% CI 0.28-0.54), and for recurrent tumours was 0.67 (95% CI 0.30-1.50). There is moderate evidence based on two RCTs, and low evidence based on 15 cohort studies that MS is superior to CS in reducing recurrences of BCCs and primary tumours. The development of protocols that maximize the cost-effectiveness of each method in different clinical scenarios is paramount.
Topics: Humans; Carcinoma, Basal Cell; Skin Neoplasms; Mohs Surgery; Neoplasm Recurrence, Local; Carcinoma, Squamous Cell
PubMed: 38116955
DOI: 10.1111/jdv.19743 -
The Laryngoscope Feb 2024Endoscopic ear surgery is no longer a promising technique, but a well-established one. This study aims to compare endoscopic and microscopic tympanoplasty based on... (Review)
Review
OBJECTIVE
Endoscopic ear surgery is no longer a promising technique, but a well-established one. This study aims to compare endoscopic and microscopic tympanoplasty based on current literature evidence, in terms of their efficacy and safety characteristics.
DATA SOURCES
We conducted a systematic literature search of four medical databases (Pubmed, Cochrane Library, Scopus, ClinicalTrials.gov), focusing on randomized controlled or observational studies comparing microscopic to endoscopic tympanoplasty.
REVIEW METHODS
Data related to the efficacy and safety of each technique were extracted. Outcome data were summarized using pooled mean differences or pooled odds ratio along with their 95% confidence intervals. The risk of bias was estimated, by using the ROBINS-I and RoB-II assessment tools, while the overall quality of evidence was evaluated according to the GRADE working group.
RESULTS
Thirty-three studies, with 2646 patients in total, were included in the meta-analysis. Success rate was evaluated by estimating tympanic graft failure (pooled mean difference:-0.23; 95% CI: -0.61, 0.14, I = 33.42%), and air-bone gap improvement (pooled mean difference:-0.05; 95% CI:-0.23, 0.13, I = 52.69%), resulting in comparable outcomes for the two techniques. A statistically significant difference favoring the endoscopic technique was detected regarding postoperative wound infection (OR: -1.72; 95% CI: -3.39, -0.04, I = 0%), dysgeusia (OR: -1.47; 95% CI: -2.47, -0.47, I = 0%), otitis externa development (OR: -1.96; 95% CI: -3.23, -0.69, I = 0%), auricular numbness (OR: -2.56; 95% CI: -3.93, -1.19, I = 0%), as well as surgical duration (OR: -1.86; 95% CI: -2.70, -1.02, I = 43.95%), when compared to the postauricular microscopic approach.
CONCLUSION
Endoscopic tympanoplasty is an innovative alternative to the microscopic technique, resulting in commensurate outcomes regarding success rate. Furthermore, it offers superior results concerning postoperative complications, while it presents a significant reduction in the duration of surgery, mainly when it is compared to the postauricular microscopic approach.
LEVEL OF EVIDENCE
NA Laryngoscope, 2024.
PubMed: 38415937
DOI: 10.1002/lary.31365 -
International Journal of Molecular... Jan 2024Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype-phenotype correlation, which is useful for clinical research.
Topics: Humans; Cardiomyopathy, Hypertrophic; Genetic Testing; Arrhythmias, Cardiac; Autopsy; Fibrosis; Phenotype; Death, Sudden, Cardiac
PubMed: 38279275
DOI: 10.3390/ijms25021275 -
The Spine Journal : Official Journal of... Jun 2024Symptomatic lumbar spinal stenosis is routinely treated with spinal decompression surgery, with an increasing trend towards minimally invasive techniques. Endoscopic... (Meta-Analysis)
Meta-Analysis
BACKGROUND CONTEXT
Symptomatic lumbar spinal stenosis is routinely treated with spinal decompression surgery, with an increasing trend towards minimally invasive techniques. Endoscopic decompression has emerged as a technique which minimizes approach-related morbidity while achieving similar clinical outcomes to conventional open or microscopic approaches.
PURPOSE
To assess the safety and efficacy of endoscopic versus microscopic decompression for treatment of lumbar spinal stenosis.
STUDY DESIGN
Systematic review and meta-analysis.
METHODS
A systematic review on randomized and nonrandomized studies comparing endoscopic versus microscopic decompression was conducted, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Treatment effects were computed using pairwise random-effects meta-analysis. Risk of bias was assessed using the Cochrane Risk-of-bias and ROBINS-I tools for randomized and nonrandomized trials respectively. Quality of the overall body of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
RESULTS
A total of 19 primary references comprising 1,997 patients and 2,132 spinal levels were included. Endoscopic decompression was associated with significantly reduced intraoperative blood-loss (weighted mean differences [WMD]=-33.29 mL, 95% CI:-51.80 to -14.78, p=.0032), shorter duration of hospital stay (WMD=-1.79 days, 95% CI: -2.63 to 0.95, p=.001), rates of incidental durotomy (RR = 0.63, 95% CI: 0.43 to 0.91, p=.0184) and surgical site infections (RR=0.23, 95% CI: 0.10 to-0.51, p=.001), and a nonsignificant trend towards less back pain, leg pain, and better functional outcomes compared to its microscopic counterpart up to 2-year follow up.
CONCLUSIONS
Endoscopic and microscopic decompression are safe and effective techniques for treatment of symptomatic lumbar spinal stenosis. Prospective studies of larger power considering medium to long-term outcomes and rates of iatrogenic instability are warranted to compare potential alignment changes and destabilization from either techniques.
Topics: Humans; Decompression, Surgical; Endoscopy; Lumbar Vertebrae; Microsurgery; Spinal Stenosis; Treatment Outcome
PubMed: 38190892
DOI: 10.1016/j.spinee.2023.12.009 -
Brain Sciences Dec 2023In the field of minimally invasive neurosurgery, microscopic transsphenoidal surgery (MTS) and endoscopic transsphenoidal surgery (ETS) have been widely accepted as a... (Review)
Review
In the field of minimally invasive neurosurgery, microscopic transsphenoidal surgery (MTS) and endoscopic transsphenoidal surgery (ETS) have been widely accepted as a safe approach for pituitary lesions and, more recently, their indications have been extended to lesions at various skull base regions. It is mandatory during transsphenoidal surgery (TS) to identify key anatomical landmarks in the sphenoid sinus and distinguish them from the lesion. Over the years, many intraoperative tools have been introduced to improve the neuronavigation systems aiming to achieve safer and more accurate neurosurgical interventions. However, traditional neuronavigation systems may lose the accuracy of real-time location due to the discrepancy between the actual surgical field and the preoperative 2D images. To deal with this, augmented reality (AR)-a new sophisticated 3D technology that superimposes computer-generated virtual objects onto the user's view of the real world-has been considered a promising tool. Particularly, in the field of TS, AR can minimize the anatomic challenges of traditional endoscopic or microscopic surgery, aiding in surgical training, preoperative planning and intra-operative orientation. The aim of this systematic review is to analyze the potential future role of augmented reality, both in endoscopic and microscopic transsphenoidal surgeries.
PubMed: 38137143
DOI: 10.3390/brainsci13121695 -
World Neurosurgery Apr 2024Exoscopes were recently developed as an alternative to the operative microscope (OM) and endoscope for intraoperative visualization during neurosurgery. Prior reviews... (Review)
Review
BACKGROUND
Exoscopes were recently developed as an alternative to the operative microscope (OM) and endoscope for intraoperative visualization during neurosurgery. Prior reviews studying mixed cranial and spinal surgical cohorts reported advantages with exoscope use, including improved ergonomics and teaching. In recent years, there has been an increase in exoscope research, with no updated systematic review focused exclusively on the benefits and limitations of exoscope use in spine surgery. Thus, we sought to systematically synthesize the literature related to exoscope-assisted spine surgery.
METHODS
A literature search was conducted using the PubMed, Embase, Scopus, Cochrane, and Web of Science databases to identify relevant studies reported between 2010 and September 2023. Data, such as the exoscope model used, procedure types performed, and user observations, were then collected.
RESULTS
A total of 31 studies met our inclusion criteria, including 481 patients with spine pathologies who underwent a surgical procedure using 1 of 9 exoscope models. The lumbar region was the most frequently operated area (n = 234; 48.6%), and discectomies comprised the most overall procedures (n = 273; 56.8%). All patients benefited clinically. The reported advantages of exoscopes compared with OMs or endoscopes were improved focal distance, surgeon posture, trainee education, compactness, and assistant participation. Other aspects such as stereopsis, illumination, and cost had various observations.
CONCLUSIONS
Exoscopes have advantages compared with OMs or endoscopes during spine surgery. The user learning curve is minimal, and no negative patient outcomes have been reported. However, some aspects of exoscope use necessitate longer term prospective research before exoscopes can be considered a standard tool in the armamentarium of intraoperative visualization strategies.
Topics: Humans; Prospective Studies; Neurosurgical Procedures; Spine; Skull; Microscopy; Microsurgery
PubMed: 38154686
DOI: 10.1016/j.wneu.2023.12.102 -
European Journal of Obstetrics,... May 2024The rate of caesarean section (CS) is increasing worldwide. Defects in uterine healing have a major gynaecological and obstetric impact (uterine rupture, caesarean scar...
The rate of caesarean section (CS) is increasing worldwide. Defects in uterine healing have a major gynaecological and obstetric impact (uterine rupture, caesarean scar defect, caesarean scar pregnancy, placenta accreta spectrum). The complex process of cellular uterine healing after surgery, and specifically after CS, remains poorly understood in contrast to skin wound healing. This literature review on uterine wound healing was mainly based on histological observations, particularly after CS. The primary objective of the review was to examine the effects of CS on uterine tissue at the cellular level, based on histological observations. The secondary objectives were to describe the biomechanical characteristics and the therapies used to improve scar tissue after CS. This review was performed using PRISMA criteria, and PubMed was the data source. The study included all clinical and animal model studies with CS and histological analysis of the uterine scar area (macroscopic, microscopic, immunohistochemical and biomechanical). Twenty studies were included: 10 human and 10 animal models. In total, 533 female humans and 511 female animals were included. Review articles, meeting abstracts, case series, case reports, and abstracts without access to full-text were excluded. The search was limited to studies published in English. No correlation was found between cutaneous and uterine healing. The histology of uterine scars is characterized by disorganized smooth muscle, fibrosis with collagen fibres and fewer endometrial glands. As for skin healing, the initial inflammation phase and mediation of some growth factors (particularly connective tissue growth factor, vascular endothelial growth factor, platelet-derived growth factor, tumour necrosis factor α and tumour necrosis factor β) seem to be essential. This initial phase has an impact on the subsequent phases of proliferation and maturation. Collagen appears to play a key role in the initial granulation tissue to replace the loss of substance. Subsequent maturation of the scar tissue is essential, with a decrease in collagen and smooth muscle restoration. Unlike skin, the glandular structure of uterine tissue could be responsible for the relatively high incidence of healing defects. Uterine scar defects after CS are characterized by an atrophic disorganized endometrium with atypia and a fibroblastic highly collagenic stromal reaction. Concerning immunohistochemistry, one study found a decrease in tumour necrosis factor β in uterine scar defects. No correlation was found between biomechanical characteristics (particularly uterine strength) and the presence of a collagenous scar after CS. Based on the findings of this review, an illustration of current understanding about uterine healing is provided. There is currently no validated prevention of caesarean scar defects. Various treatments to improve uterine healing after CS have been tested, and appeared to have good efficacy in animal studies: alpha lipoic acid, growth factors, collagen scaffolds and mesenchymal stem cells. Further prospective studies are needed.
Topics: Animals; Female; Humans; Pregnancy; Cesarean Section; Cicatrix; Collagen; Lymphotoxin-alpha; Uterine Diseases; Vascular Endothelial Growth Factor A; Wound Healing
PubMed: 38417279
DOI: 10.1016/j.ejogrb.2024.02.045 -
World Journal of Methodology Mar 2024Inflammatory bowel disease, including ulcerative colitis, microscopic colitis, and Crohn's disease (CD), has a global impact. This review focuses on duodenal CD (DCD), a...
BACKGROUND
Inflammatory bowel disease, including ulcerative colitis, microscopic colitis, and Crohn's disease (CD), has a global impact. This review focuses on duodenal CD (DCD), a rare subtype affecting the duodenum. DCD's rarity and asymptomatic nature create diagnostic challenges, impacting prognosis and patient well-being. Delayed diagnosis can worsen DCD outcomes.
AIM
To report a rare case of DCD and to discuss the diagnostic challenges and its implications on prognosis.
METHODS
A systematic literature search, following the PRISMA statement, was conducted. Relevant studies were identified and analysed using specific Medical Subject Terms (MeSH) from PubMed/MEDLINE, American Journal of Gastroenterology, and the University of South Wales database. Data collection included information from radiology scans, endoscopy procedures, biopsies, and histopathology results.
RESULTS
The review considered 8 case reports and 1 observational study, involving 44 participants diagnosed with DCD, some of whom developed complications due to delayed diagnosis. Various diagnostic methods were employed, as there is no gold standard workup for DCD. Radiology scans [magnetic resonance imaging (MRI), computed tomography (CT), and upper gastrointestinal X-ray], endoscopy procedures (colonoscopy and esophagogastroduodenoscopy), biopsies, and clinical suspicions were utilized.
CONCLUSION
This review discusses DCD diagnosis challenges and the roles of CT, MRI, and fluoroscopy. It notes their limitations and compares findings with endoscopy and histopathology studies. Further research is needed to improve diagnosis, emphasizing scan interpretation, endoscopy procedures, and biopsies, especially in high-risk patients during routine endoscopy.
PubMed: 38577197
DOI: 10.5662/wjm.v14.i1.88619