DIAGNOSTIC ACCURACY OF INTESTINAL ULTRASOUND IN THE DETECTION OF INTRA-ABDOMINAL COMPLICATIONS IN CROHN'S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Crohn's disease (CD) is frequently associated with the development of strictures and penetrating complications. Intestinal ultrasound (IUS) is a non-invasive imaging modality ideal for point-of-care assessment. In this systematic review and meta-analysis we provide a current overview on the diagnostic accuracy of IUS and its advanced modalities in the detection of intra-abdominal complications in CD compared to endoscopy, cross-sectional imaging, surgery and pathology. METHOD: We conducted a literature search for studies describing diagnostic accuracy of IUS in adult patients with CD related intra-abdominal complications. Quality of the included studies was assessed with the QUADAS-2 tool. Meta-analysis was performed for both conventional IUS (B-mode) and oral contrast IUS (SICUS). RESULTS: Of the 1498 studies we identified, 68 were included in this review and 23 studies (3863 patients) were used for the meta-analysis. Pooled sensitivities and specificities for strictures, inflammatory masses and fistulas by B-mode IUS were 0.81 and 0.90, 0.87 (sensitivities) and 0.95, and 0.67 and 0.97 (specificities), respectively. Pooled overall log diagnostic odds ratios were 3.56, 3.97 and 3.84 respectively. Pooled sensitivity and specificity of SICUS were 0.94 and 0.95, 0.91 and 0.97 (sensitivities), and 0.90 and 0.94 (specificities), respectively. Pooled overall log diagnostic odds ratio of SICUS were 4.51, 5.46 and 4.80, respectively. CONCLUSION: IUS is accurate for the diagnosis of intra-abdominal complications in CD. As a non-invasive, point-of-care modality, IUS is recommended as the first-line imaging tool if there is a suspicion of CD-related intra-abdominal complications.

The Diagnostic Value of Biomarkers in Acute Mesenteric Ischaemia Is Insufficiently Substantiated: A Systematic Review.

OBJECTIVE: There is an urgent need for accurate biomarkers to support timely diagnosis of acute mesenteric ischaemia (AMI) and thereby improve clinical outcomes. With this systematic review, the aim was to substantiate the potential diagnostic value of biomarkers for arterial occlusive AMI. DATA SOURCES: The Pubmed, Embase, and the Cochrane Library electronic databases were searched. REVIEW METHODS: A systematic review of the literature has been conducted to define the potential diagnostic value of biomarkers for arterial occlusive AMI. All studies including ≥ 10 patients describing biomarkers for macrovascular occlusive AMI between 1950 and 17 February 2023 were identified within the Pubmed, Embase, and the Cochrane Library electronic databases. There were no restrictions to any particular study design, but letters and editorials were excluded. The QUADAS-2 tool was used for the critical appraisal of quality. The study protocol was registered on Prospero (CRD42021254970). RESULTS: Fifty of 4334 studies were eligible for inclusion in this review. Ninety per cent of studies were of low quality. A total of 60 biomarkers were identified, with 24 in two or more studies and 15 in five or more studies. There was variation in reported units, normal range, and cut off values. Meta-analysis was not possible due to study heterogeneity. Biomarkers currently recommended by the European Journal of Vascular and Endovascular Surgery, European Society for Trauma and Emergency Surgery 2016, and World Society of Emergency Surgery 2017 guidelines also had heterogeneous low quality data for use in the diagnosis of AMI. CONCLUSION: This systematic review demonstrates high heterogeneity and low quality of the available evidence on biomarkers for arterial occlusive AMI. No clinical conclusions can be drawn on a biomarker or combination of biomarkers for patients suspected of arterial occlusive AMI. Restraint is advised when rejecting or determining AMI solely based on biomarkers.

Surgical margins after partial nephrectomy as prognostic factor for the risk of local recurrence in pT1 RCC: a systematic review and narrative synthesis.

PURPOSE: To systematically review the published literature on surgical margins as a risk factor for local recurrence (LR) in patients undergoing partial nephrectomy (PN) for pT1 renal cell carcinomas (RCC). EVIDENCE ACQUISITION: A systematic literature search of relevant databases (MEDLINE, Embase and the Cochrane Library) was performed according to the PRISMA criteria up to February 2022. The hypothesis was developed using the PPO method (Patients = patients with pT1 RCC undergoing PN, Prognostic factor = positive surgical margins (PSM) detected on final pathology versus negative surgical margins (NSM) and Outcome = LR diagnosed on follow-up imaging). The primary outcome was the rate of PSM and LR. The risk of bias was assessed by the QUIPS tool. EVIDENCE SYNTHESIS: After assessing 1525 abstracts and 409 full-text articles, eight studies met the inclusion criteria. The percentage of PSM ranged between 0 and 34.3%. In these patients with PSM, LR varied between 0 and 9.1%, whereas only 0-1.5% of LR were found in the NSM-group. The calculated odds ratio (95% confident intervals) varied between 0.04 [0.00-0.79] and 0.27 [0.01-4.76] and was statistically significant in two studies (0.14 [0.02-0.80] and 0.04 [0.00-0.79]). The quality analysis of the included studies resulted in an overall intermediate to high risk of bias and the level of evidence was overall very low. A meta-analysis was considered unsuitable due to the high heterogeneity between the included studies. CONCLUSION: PSM after PN in patients with pT1 RCC is associated with a higher risk of LR. However, the evidence has significant limitations and caution should be taken with the interpretation of this data.

Consensus Statement on Mandatory Measurements for Pancreatic Cancer Trials for Patients With Resectable or Borderline Resectable Disease (COMM-PACT-RB): A Systematic Review and Delphi Consensus Statement.

Importance: Pancreatic cancer is the third most common cause of cancer death; however, randomized clinical trials (RCTs) of survival in patients with resectable pancreatic cancer lack mandatory measures for reporting baseline and prognostic factors, which hampers comparisons between outcome measures. Objective: To develop a consensus on baseline and prognostic factors to be used as mandatory measurements in RCTs of resectable and borderline resectable pancreatic cancer. Evidence Review: We performed a systematic literature search of the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Embase for RCTs on resectable and borderline resectable pancreatic cancer with overall survival as the primary outcome. We produced a systematic summary of all baseline and prognostic factors identified in the RCTs. A Delphi panel that included 13 experts was surveyed to reach a consensus on mandatory and recommended baseline and prognostic factors. Findings: The 42 RCTs that met inclusion criteria reported a total of 60 baseline and 19 prognostic factors. After 2 Delphi rounds, agreement was reached on 50 mandatory baseline and 20 mandatory prognostic factors for future RCTs, with a distinction between studies of neoadjuvant vs adjuvant treatment. Conclusion and Relevance: This findings of this systematic review and international expert consensus have produced this Consensus Statement on Mandatory Measurements in Pancreatic Cancer Trials for Resectable and Borderline Resectable Disease (COMM-PACT-RB). The baseline and prognostic factors comprising the mandatory measures will facilitate better comparison across RCTs and eventually will enable improved clinical practice among patients with resectable and borderline resectable pancreatic cancer.

How to evaluate a flexible ureterorenoscope? Systematic mapping of existing evaluation methods.

OBJECTIVES: The objective of this study was to identify, map and review scope-related and user-related parameters used to evaluate the quality of flexible ureterorenoscopes. Thereby identifying key items and variability in grading systems. METHODS: A literature search of four databases (MEDLINE [Ovid], EMBASE [Ovid], Web of Science, Google scholar and the Cochrane Library) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines encompassing articles published up to August 2020. A total of 2386 articles were screened. RESULTS: A total of 48 articles were included in this systematic scoping review. All studies had a prospective design. Five key items in the assessment of flexible ureterorenoscopy were distinguished: 'Manoeuvrability' (87.5%), 'Optics' (64.6%), 'Irrigation' (56.3%), 'Handling' (39.6%) and 'Durability' (35.4%). After regrouping, every key item could be divided into specific subcategories. However, the quality assessment showed a wide variation in denomination, method of measurement, circumstances of measurement, tools used during measurements, number of measurements performed, number of observers, and units of outcomes. CONCLUSION: The research field regarding quality assessment of ureterorenoscopes is heterogeneous. In this systematic scoping review we identified five key parameters: Manoeuvrability, Optics, Irrigation, Handling and Durability, used to grade flexible ureterorenoscopes. However, within these categories we found a wide variety in terms of method of measurements. A standardised, uniform grading tool is required to assess and compare the quality of flexible ureterorenoscopes in the future.

Diagnostic accuracy of fibrosis tests in children with non-alcoholic fatty liver disease: A systematic review.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. Even at young age, it can progress to liver fibrosis. Given the drawbacks of liver biopsy, there is a need for non-invasive methods to accurately stage liver fibrosis in this age group. In this systematic review, we evaluate the diagnostic accuracy of non-invasive methods for staging liver fibrosis in children with NAFLD. METHODS: We searched MEDLINE, Embase, Web of Science and the Cochrane Library, for studies that evaluated the performance of a blood-based biomarker, prediction score or imaging technique in staging liver fibrosis in children with NAFLD, using liver biopsy as the reference standard. RESULTS: Twenty studies with a total of 1787 NAFLD subjects were included, which evaluated three prediction scores, five simple biomarkers, two combined biomarkers and six imaging techniques. Most studies lacked validation. Substantial heterogeneity of studies and limited available study data precluded a meta-analysis of the few fibrosis tests evaluated in more than one study. The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis. CONCLUSION: Due to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.

Health-related quality of life in curatively-treated patients with esophageal or gastric cancer: A systematic review and meta-analysis.

Surgery and chemoradiotherapy can potentially cure esophageal and gastric cancer patients, although they may impact health-related quality of life (HRQoL). We aim to systemically review and meta-analyze literature to determine the effect of curative treatments on HRQoL in esophageal and gastric cancer.- A systematic search was performed identifying studies assessing HRQoL. Meta-analyses were performed on baseline and subsequent time-points.- From the 6067 articles retrieved, 49 studies were included (61 % low quality). Meta-analyses showed short-term HRQoL differences between esophageal cancer patients receiving definitive chemoradiotherapy (dCRT), neoadjuvant chemo(radio)therapy (nC(R)T), or surgery alone (p < 0.001), with better HRQoL with nC(R)T and surgery compared to dCRT. Over the course of 12 months, no HRQoL difference was identified between treatments in esophageal cancer (p = 0.633). Esophagectomy, but not gastrectomy, resulted in a clinically relevant decline in HRQoL. No long-term HRQoL differences were identified between curative treatments in esophageal and gastric cancer. More high-quality HRQoL studies are warranted.

Priming the tumor immune microenvironment with chemo(radio)therapy: A systematic review across tumor types.

BACKGROUND: Chemotherapy (CT), radiotherapy (RT), and chemoradiotherapy (CRT) are able to alter the composition of the tumor immune microenvironment (TIME). Understanding the effect of these modalities on the TIME could aid in the development of improved treatment strategies. Our aim was to systematically review studies investigating the influence of CT, RT or CRT on different TIME markers. METHODS: The EMBASE (Ovid) and PubMed databases were searched until January 2019 for prospective or retrospective studies investigating the dynamics of the local TIME in cancer patients (pts) treated with CT, RT or CRT, with or without targeted agents. Studies could either compare baseline and follow-up specimens - before and after treatment - or a treated versus an untreated cohort. Studies were included if they used immunohistochemistry and/or flow cytometry to assess the TIME. RESULTS: In total we included 110 studies (n = 8850 pts), of which n = 89 (n = 6295 pts) compared pre-treatment to post-treatment specimens and n = 25 (n = 2555 pts) a treated versus an untreated cohort (4 studies conducted both comparisons). For several tumor types (among others; breast, cervical, esophageal, ovarian, rectal, lung mesothelioma and pancreatic cancer) remodeling of the TIME was observed, leading to a potentially more immunologically active microenvironment, including one or more of the following: an increase in CD3 or CD8 lymphocytes, a decrease in FOXP3 Tregs and increased PD-L1 expression. Both CT and CRT were able to immunologically alter the TIME. CONCLUSION: The TIME of several tumor types is significantly altered after conventional therapy creating opportunities for concurrent or sequential immunotherapy.

The effect of additional drug therapy as metaphylaxis in patients with cystinuria: a systematic review.

INTRODUCTION: To systematically review the effect of additional drug therapy as metaphylaxis in patients with cystinuria. EVIDENCE ACQUISITION: A literature search of three databases (MEDLINE, Embase and the Cochrane Library) was performed according to the PRISMA-guidelines enclosing articles published up to May 2019. A total of 1117 articles were screened. Thirty-four publications met the inclusion criteria for this review. EVIDENCE SYNTHESIS: Male-female ratio in the studied cohorts was 49.9% - 50.1%. The majority of studies showed a positive effect in reducing stone events and/or urinary cystine excretion. D-Penicillamine showed success in 13/14 (92%) studies, whereas Tiopronin-treatment showed a reduction in all (8/8; 100%) studies. All studies on Captopril (4/4) showed a decrease, however not all significant. The same is true for studies on Thiols in combination with Captopril (2/2). Furthermore, Tiopronin showed less side effects compared to D-penicillamine, respectively 30% and 37%. Captopril showed the least adverse events, with one event in nine patients. CONCLUSIONS: The evidence on benefit of additional drug therapy in patients with cystinuria is scarce. All studied medications showed an effect on stone event and urinary cystine excretion, when used in addition to hyperhydration, alkalization and a diet low on methionine. Based on this systematic review, no drug can be preferred over another. An important aspect in the choice of drug is the risk of side effects. Therefore, the choice of additional drug should be personalized for every patient where the risk of side effects should be taken into consideration.

Diagnostic Accuracy of Transabdominal Ultrasound in Detecting Intestinal Inflammation in Paediatric IBD Patients-a Systematic Review.

BACKGROUND AND AIMS: Currently used non-invasive tools for monitoring children with inflammatory bowel disease [IBD], such as faecal calprotectin, do not accurately reflect the degree of intestinal inflammation and do not provide information on disease location. Ultrasound [US] might be of added value. This systematic review aimed to assess the diagnostic test accuracy of transabdominal US in detecting intestinal inflammation in children with IBD in both diagnostic and follow-up settings. METHODS: We systematically searched PubMed, Embase [Ovid], Cochrane Library, and CINAHL [EBSCO] databases for studies assessing diagnostic accuracy of transabdominal US for detection of intestinal inflammation in patients diagnosed or suspected of IBD, aged 0-18 years, with ileo-colonoscopy and/or magnetic resonance enterography [MRE] as reference standards. Studies using US contrast were excluded. Risk of bias was assessed with QUADAS-2. RESULTS: The search yielded 276 records of which 14 were included. No meta-analysis was performed, because of heterogeneity in study design and methodological quality. Only four studies gave a clear description of their definition for an abnormal US result. The sensitivity and specificity of US ranged from 39-93% and 90-100% for diagnosing de novo IBD, and 48-93% and 83-93% for detecting active disease during follow-up, respectively. CONCLUSIONS: The diagnostic accuracy of US in detecting intestinal inflammation as seen on MRE and/or ileo-colonoscopy in paediatric IBD patients remains inconclusive, and there is currently no consensus on defining an US result as abnormal. Prospective studies with adequate sample size and methodology are needed before US can be used in the diagnostics and monitoring of paediatric IBD.

The negative effect of joint line elevation after total knee arthroplasty on outcome.

PURPOSE: Total knee arthroplasty (TKA) is widely used as a treatment for knee osteoarthritis. However, still up to 20% of the patients are dissatisfied. Joint line elevation after TKA might be a contributing factor as it alters knee kinematics. The aim of this study was to investigate the effect of joint line elevation on outcome. METHODS: A systematic review of the literature was performed to select studies that reported on joint line alterations after primary or revision TKA and outcome. Studies with comparable outcome parameters were included in a correlation analysis. RESULTS: In total, 396 studies were identified, of which 27 met the inclusion criteria. 8 studies could be included in the correlation analysis. Mean joint line elevation after primary TKA was 3.0 mm and after revision TKA this was 3.6 mm. A statistically significant negative correlation was found between joint line elevation and the postoperative Knee Society Score (KSS) function score (ρ = - 0.496, p < 0.001). In a pooled analysis, the maintained joint line revision TKA group had statistically significant better postoperative KSS total scores compared to an elevated joint line group (p < 0.001). CONCLUSION: In this systematic review, a negative correlation between joint line elevation and outcome was found. Furthermore, revision TKAs with a maintained joint line have statistically significant better postoperative KSS scores compared to an elevated joint line group. To achieve optimal outcome after TKA, restoration of the joint line is one of the parameters that should be pursued and introduced elevation should not exceed 4 mm. LEVEL OF EVIDENCE: IV.

Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review.

INTRODUCTION: Chronic idiopathic nausea (CIN) and functional dyspepsia (FD) cause considerable strain on many children's lives and their families. Areas covered: This study aims to systematically assess the evidence on efficacy and safety of pharmacological treatments for CIN or FD in children. CENTRAL, EMBASE, and Medline were searched for Randomized Controlled Trials (RCTs) investigating pharmacological treatments of CIN and FD in children (4-18 years). Cochrane risk of bias tool was used to assess methodological quality of the included articles. Expert commentary: Three RCTs (256 children with FD, 2-16 years) were included. No studies were found for CIN. All studies showed considerable risk of bias, therefore results should be interpreted with caution. Compared with baseline, successful relief of dyspeptic symptoms was found for omeprazole (53.8%), famotidine (44.4%), ranitidine (43.2%) and cimetidine (21.6%) (p = 0.024). Compared with placebo, famotidine showed benefit in global symptom improvement (OR 11.0; 95% CI 1.6-75.5; p = 0.02). Compared with baseline, mosapride versus pantoprazole reduced global symptoms (p = 0.011; p = 0.009). One study reported no occurrence of adverse events. This systematic review found no evidence to support the use of pharmacological drugs to treat CIN or FD in children. More high-quality clinical trials are needed. ABBREVIATIONS: AP-FGID: Abdominal Pain Related Functional Gastrointestinal Disorders; BART: Biofeedback-Assisted Relaxation Training; CIN: Chronic Idiopathic Nausea; COS: Core Outcomes Sets; EPS: Epigastric Pain Syndrome; ESPGHAN: European Society for Pediatric Gastroenterology Hepatology and Nutrition; FAP: Functional Abdominal Pain; FD: Functional Dyspepsia; GERD: Gastroesophageal Reflux Disease; GES: Gastric Electrical Stimulation; H2RAs: H2 Receptor Antagonists; IBS: irritable bowel syndrome; NASPGHAN: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; PDS: Postprandial Distress Syndrome; PPIs: Proton Pump Inhibitor; PROMs: Patient Reported Outcome Measures; RCTs: Randomized Controlled Trials; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants.

A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas.

Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic biomarkers in resectable EAC treated with curative intent. The Medline, Cochrane and EMBASE databases were systematically searched, focusing on overall survival (OS). The quality of the studies was assessed using a scoring system ranging from 0-7 points based on modified REMARK criteria. To evaluate all identified prognostic biomarkers, the hallmarks of cancer were adapted to fit all biomarkers based on their biological function in EAC, resulting in the features angiogenesis, cell adhesion and extra-cellular matrix remodeling, cell cycle, immune, invasion and metastasis, proliferation, and self-renewal. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were derived by random effects meta-analyses performed on each hallmarks of cancer feature. Of the 3298 unique articles identified, 84 were included, with a mean quality of 5.9 points (range 3.5-7). The hallmarks of cancer feature 'immune' was most significantly associated with worse OS (HR 1.88, (95%CI 1.20-2.93)). Of the 82 unique prognostic biomarkers identified, meta-analyses showed prominent biomarkers, including COX-2, PAK-1, p14ARF, PD-L1, MET, LC3B, IGFBP7 and LGR5, associated to each hallmark of cancer.

The role of the general practitioner in return to work after cancer-a systematic review.

Background: The number of cancer patients and survivors of working age is increasing. General Practitioners (GPs) may have a significant role in psychosocial cancer care, including work-related concerns. Therefore, we performed a systematic literature review to identify the role of the GP in work-related concerns and integration/reintegration into work of cancer patients and/or survivors. Methods: We searched PubMed, Embase, Cinahl, PsycINFO and Cochrane Library, irrespective of study design. We found 4863 articles and, after removing duplicates, we screened 3388 articles by title and abstract and reviewed 66 of these in full text. The Critical Appraisal Skills Programme tool was used to assess the methodological quality of included articles. We used narrative synthesis to describe the role of the GP. Results: We included four qualitative studies from three countries. Two of these studies focused on the health care professionals' perspectives and two studies focused on patients' perspectives regarding the role of the GP. Lack of communication between health care professionals, lack of knowledge about work-related concerns and limited resources were recurring themes in these papers. Fully establishing the role of the GP is difficult given the small number of studies on work-related concerns in cancer patients in primary care. Conclusion: There is little evidence regarding the role of the general practitioner in cancer care and work guidance. Therefore, further research should focus on the role that is desired for GPs and on interventions to study the feasibility of GP involvement in the return to work of cancer patients and/or survivors.

Variations in Definitions and Outcome Measures in Gastroesophageal Reflux Disease: A Systematic Review.

CONTEXT: Gastroesophageal reflux (GER) is defined as GER disease (GERD) when it leads to troublesome symptoms and/or complications. We hypothesized that definitions and outcome measures in randomized controlled trials (RCTs) on pediatric GERD would be heterogeneous. OBJECTIVES: Systematically assess definitions and outcome measures in RCTs in this population. DATA SOURCES: Data were obtained through Cochrane, Embase, Medline, and Pubmed databases. STUDY SELECTION: We selected English-written therapeutic RCTs concerning GERD in children 0 to 18 years old. DATA EXTRACTION: Data were tabulated and presented descriptively. Each individual parameter or set of parameters with unique criteria for interpretation was considered a single definition for GER(D). Quality was assessed by using the Delphi score. RESULTS: A total of 2410 unique articles were found; 46 articles were included. Twenty-six (57%) studies defined GER by using 25 different definitions and investigated 25 different interventions. GERD was defined in 21 (46%) studies, all using a unique definition and investigating a total of 23 interventions. Respectively 87 and 61 different primary outcome measures were reported by the studies in GER and GERD. Eight (17%) studies did not report on side effects. Of the remaining 38 (83%) studies that did report on side effects, 18 (47%) included this as predefined outcome measure of which 4 (22%) as a primary outcome measure. Sixteen studies (35%) were of good methodological quality. LIMITATIONS: Only English-written studies were included. CONCLUSIONS: Inconsistency and heterogeneity exist in definitions and outcome measures used in RCTs on pediatric GER and GERD; therefore, we recommend the development of a core outcome set.