scholarly journals Prognostic factors for the outcome of nonfunctioning pancreatic neuroendocrine tumors in MEN1: a systematic review of literature

2020 ◽  
Vol 27 (6) ◽  
pp. R145-R161 ◽  
Author(s):  
S M Sadowski ◽  
C R C Pieterman ◽  
N D Perrier ◽  
F Triponez ◽  
G D Valk

Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Nonfunctioning pNETs (NF-pNETs) are highly prevalent in MEN1 and clinically heterogeneous. Therefore, management is controversial. Data on prognostic factors for risk stratification are limited. This systematic review aims to establish the current state of evidence regarding prognostic factors in MEN1-related NF-pNETs. We systematically searched four databases for studies assessing prognostic value of any factor on NF-pNET progression, development of distant metastases, and/or overall survival. In- and exclusion, critical appraisal and data-extraction were performed independently by two authors according to pre-defined criteria. Thirteen studies (370 unique patients) were included. Prognostic factors investigated were tumor size, timing of surgical resection, WHO grade, methylation, p27/p18 expression by immunohistochemistry (IHC), ARX/PDX1 IHC and alternative lengthening of telomeres. Results were complemented with evidence from studies in MEN1-related pNET for which data could not be separately extracted for NF-pNET and data from sporadic NF-pNET. We found that the most important prognostic factors used in clinical decision making in MEN1-related NF-pNETs are tumor size and grade. NF-pNETs <2 cm may be managed with watchful waiting, while surgical resection is advised for NF-pNETs ≥2 cm. Grade 2 NF-pNETs should be considered high risk. The most promising and MEN1-relevant avenues of prognostic research are multi-analyte circulating biomarkers, tissue-based molecular factors and imaging-based prognostication. Multi-institutional collaboration between clinical, translation and basic scientists with uniform data and biospecimen collection in prospective cohorts should advance the field.

CJEM ◽  
2010 ◽  
Vol 12 (05) ◽  
pp. 435-442 ◽  
Author(s):  
Brian E. Grunau ◽  
Matthew O. Wiens ◽  
Jeffrey R. Brubacher

ABSTRACTObjective:The use of dantrolene in the treatment of hyperpyrexia related to MDMA (3,4-methylenedioxymethamphetamine) is controversial, with little data available to guide clinical decision-making. Although the treatment is recommended by several poison control centres, published data are primarily in the form of case reports and animal and in vitro experiments. We conducted a systematic review to investigate the published evidence regarding the safety and benefits of dantrolene for MDMA-related hyperpyrexia in humans.Data sources:A systematic search of Embase and MEDLINE was conducted from the earliest possible date to November 2008.Study selection:All human trials and case reports of MDMA-related hyperpyrexia were considered.Data extraction:Data were abstracted systematically and characteristics including use of dantrolene, adverse reactions attributed to dantrolene, peak temperature, complications from MDMA-related hyperpyrexia and survival were recorded.Data synthesis:Our search yielded 668 articles of which 53, reporting 71 cases of MDMA-induced hyperpyrexia, met our inclusion criteria. No clinical trials, randomized controlled trials, observational studies or meta-analyses were identified. Dantrolene was used in 26 cases. Patient characteristics were similar in the dantrolene and no dantrolene groups. The proportion of survivors was higher in the dantrolene group (21/26) than in the no dantrolene group (25/45). This difference was especially pronounced in those with extreme (≥ 42°C) and severe (≥ 40°C) fever, with a survival rate of 8 of 13 and 10 of 10, respectively, in the dantrolene group compared with 0 of 4 and 15 of 27 in the no dantrolene group. There were no reports of adverse events attributable to dantrolene with the exception of a possible association with an episode of transient hypoglycemia.Conclusion:Our systematic review suggests that dantrolene is safe for patients with MDMA-related hyperpyrexia. Dantrolene may also be associated with improved survival and reduced complications, especially in patients with extreme (≥ 42°C) or severe (≥ 40°C) hyperpyrexia, although this conclusion must be interpreted with caution given the risk of reporting or publication bias.


2021 ◽  
Vol 29 (Supplement_1) ◽  
pp. i18-i18
Author(s):  
N Hassan ◽  
R Slight ◽  
D Weiand ◽  
A Vellinga ◽  
G Morgan ◽  
...  

Abstract Introduction Sepsis is a life-threatening condition that is associated with increased mortality. Artificial intelligence tools can inform clinical decision making by flagging patients who may be at risk of developing infection and subsequent sepsis and assist clinicians with their care management. Aim To identify the optimal set of predictors used to train machine learning algorithms to predict the likelihood of an infection and subsequent sepsis and inform clinical decision making. Methods This systematic review was registered in PROSPERO database (CRD42020158685). We searched 3 large databases: Medline, Cumulative Index of Nursing and Allied Health Literature, and Embase, using appropriate search terms. We included quantitative primary research studies that focused on sepsis prediction associated with bacterial infection in adult population (&gt;18 years) in all care settings, which included data on predictors to develop machine learning algorithms. The timeframe of the search was 1st January 2000 till the 25th November 2019. Data extraction was performed using a data extraction sheet, and a narrative synthesis of eligible studies was undertaken. Narrative analysis was used to arrange the data into key areas, and compare and contrast between the content of included studies. Quality assessment was performed using Newcastle-Ottawa Quality Assessment scale, which was used to evaluate the quality of non-randomized studies. Bias was not assessed due to the non-randomised nature of the included studies. Results Fifteen articles met our inclusion criteria (Figure 1). We identified 194 predictors that were used to train machine learning algorithms to predict infection and subsequent sepsis, with 13 predictors used on average across all included studies. The most significant predictors included age, gender, smoking, alcohol intake, heart rate, blood pressure, lactate level, cardiovascular disease, endocrine disease, cancer, chronic kidney disease (eGFR&lt;60ml/min), white blood cell count, liver dysfunction, surgical approach (open or minimally invasive), and pre-operative haematocrit &lt; 30%. These predictors were used for the development of all the algorithms in the fifteen articles. All included studies used artificial intelligence techniques to predict the likelihood of sepsis, with average sensitivity 77.5±19.27, and average specificity 69.45±21.25. Conclusion The type of predictors used were found to influence the predictive power and predictive timeframe of the developed machine learning algorithm. Two strengths of our review were that we included studies published since the first definition of sepsis was published in 2001, and identified factors that can improve the predictive ability of algorithms. However, we note that the included studies had some limitations, with three studies not validating the models that they developed, and many tools limited by either their reduced specificity or sensitivity or both. This work has important implications for practice, as predicting the likelihood of sepsis can help inform the management of patients and concentrate finite resources to those patients who are most at risk. Producing a set of predictors can also guide future studies in developing more sensitive and specific algorithms with increased predictive time window to allow for preventive clinical measures.


Digestion ◽  
2021 ◽  
pp. 1-8
Author(s):  
Haruna Miyashita ◽  
Takuji Yamasaki ◽  
Yoshihiro Akita ◽  
Yoshitaka Ando ◽  
Yuki Maruyama ◽  
...  

<b><i>Background and Aims:</i></b> In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. <b><i>Methods:</i></b> We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. <b><i>Results:</i></b> Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases &#x3c;5 mm, with a lymphovascular invasion rate of 8.7% for those 5–10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion. <b><i>Conclusions:</i></b> GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.


2021 ◽  
Author(s):  
Julien Déry ◽  
Béatrice Ouellet ◽  
Élaine de Guise ◽  
Ève-Line Bussières ◽  
Marie-Eve Lamontagne

Abstract Background: Mild traumatic brain injury (mTBI) is an increasing public health problem, because of its persistent symptoms and several functional consequences. Understanding the prognosis of a condition is an important component of clinical decision-making and can help to guide prevention of persistent symptoms following mTBI. Prognosis of mTBI has stimulated several empirical primary research papers and many systematic reviews leading to the identification of a wide range of factors. We aim to synthesize these factors to get a better understanding of their breadth and scope.Methods: We conducted an overview of systematic reviews. We searched in databases systematic reviews synthesizing evidence about prognosis of persistent symptoms after mTBI in the adult population. Two reviewers independently screened all references and selected eligible reviews based on eligibility criteria. They extracted relevant information using an extraction grid. They also rated independently the risk of bias using the ROBIS tool. We synthesized evidence into a comprehensive conceptual map to facilitate the understanding of prognostic factors that have an impact on persistent post-concussion symptoms.Results: From the 3857 references retrieved in database search, we included 25 systematic reviews integrating the results of 312 primary articles published between 1957 and 2019. We examined 35 prognostic factors from the systematics reviews. No single prognostic factor demonstrated convincing and conclusive results. However, age, sex and multiple concussions showed an affirmatory association with persistent post-concussion outcomes in systematic reviews.Conclusion: We highlighted the need of a comprehensive picture of prognostic factors related to persistent post-concussion symptoms. We believe that these prognostic factors would guide clinical decision and research related to prevention and intervention regarding persistent post-concussion symptoms.Systematic review registration: PROSPERO CRD42020176676


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi123-vi124
Author(s):  
Sybren Maas ◽  
Damian Stichel ◽  
Thomas Hielscher ◽  
Philipp Sievers ◽  
Anna Berghoff ◽  
...  

Abstract PURPOSE Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from cases with benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for the individual patient is of pivotal importance in clinical management. However, only biomarkers for highly aggressive tumors are established at present (CDKN2A/B and TERT), while no molecularly-based stratification exists for the broad spectrum of low- and intermediate-risk meningioma patients. PATIENTS AND METHODS DNA methylation data and copy-number information were generated for 3,031 meningiomas of 2,868 individual patients, with mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNV), mutations and WHO grading were comparatively analyzed. Prediction power for outcome of these parameters was assessed in an initial retrospective cohort of 514 patients, and validated on a retrospective cohort of 184, and on a prospective cohort of 287 multi-center cases, respectively. RESULTS Both CNV and methylation family- (MF)-based subgrouping independently resulted in an increase in prediction accuracy of risk of recurrence compared to the WHO classification (c-indexes WHO 2016, CNV, and MF 0.699, 0.706 and 0.721, respectively). Merging all independently powerful risk stratification approaches into an integrated molecular-morphological score resulted in a further, substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference p=0.005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (HR 4.56 [2.97;7.00], 4.34 [2.48;7.57] and 3.34 [1.28; 8.72] for discovery, retrospective, and prospective validation cohort, respectively). CONCLUSIONS Merging these layers of histological and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision-making for meningioma patients on the basis of robust outcome prediction.


2018 ◽  
Vol 11 (5) ◽  
pp. 321-331
Author(s):  
Cody Davis ◽  
Jenna Immormino ◽  
Brendan M Higgins ◽  
Kyle Clark ◽  
Samuel Engebose ◽  
...  

Background The Active Compression Test has been proposed to have high diagnostic accuracy for superior labrum anterior to posterior tears. The aim of this systematic review was to compile the available evidence for this test and evaluate its diagnostic accuracy. Methods The databases PubMed, Embase, Cochrane, CINAHL, and SCOPUS were searched for case control, diagnostic studies that evaluated the Active Compression Test between 1999 (date of test introduction) and February 2018. Two independent review authors screened the search results, assessed the risk of bias using QUADAS-2, and extracted the data. Results Eighteen studies (pooled sample = 3091) were included in this review. Twelve out of 18 studies either had high or unclear risk of bias (66.6%). Results from the pooled analysis of all 18 studies provided that the Active Compression Test is more sensitive (71.5: 95% CI = 68.8, 74.0) than specific (51.9: 95% CI = 50.7, 53.1) and only marginally influenced posttest probability from a pretest probability of 31.7–40.72% with a positive finding and a pretest probability of 31.7–20.33% with a negative finding. Discussion The Active Compression Test has both limited screening and confirmation ability; therefore, we do not advocate for its use in clinical decision making.


2020 ◽  
Author(s):  
Vignesh Chidambaram ◽  
Nyan Lynn Tun ◽  
Waqas Haque ◽  
Marie Gilbert Majella ◽  
Ranjith Kumar Sivakumar ◽  
...  

Background: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Results: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45; 95%CI 1.23,1.71), dyspnea (RR 2.55; 95%CI 1.88,2.46), diabetes (RR 1.59; 95%CI 1.41,1.78), hypertension (RR 1.90; 95%CI 1.69,2.15). Congestive heart failure (OR 4.76; 95%CI 1.34,16.97), hilar lymphadenopathy (OR 8.34; 95%CI 2.57,27.08), bilateral lung involvement (OR 4.86; 95%CI 3.19,7.39) and reticular pattern (OR 5.54; 95%CI 1.24,24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. Conclusion: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.


2020 ◽  
Author(s):  
Clinton J Daniels ◽  
Zachary A. Cupler ◽  
Jordan A Gliedt ◽  
Sheryl Walters ◽  
Alec L Schielke ◽  
...  

Abstract BackgroundThe purpose was to identify, summarize, and rate scholarly literature that describes manipulative and manual therapy following lumbar surgery.MethodsThe review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered with PROSPERO. PubMed, Cochrane Database of Systematic Reviews, ICL, CINAHL, and PEDro were searched through July 2019. Articles were screened independently by at least two reviewers for inclusion. Articles included described the practice, utilization, and/or clinical decision making to post surgical intervention with manipulative and/or manual therapies. Data extraction consisted of principal findings, pain and function/disability, patient satisfaction, opioid/medication consumption, and adverse events. Scottish Intercollegiate Guidelines Network critical appraisal checklists were utilized to assess study quality.ResultsLiterature search yielded 1916 articles, 348 duplicates were removed, 109 full-text articles were screened and 50 citations met inclusion criteria. There were 37 case reports/case series, 3 randomized controlled trials, 3 pilot studies, 5 systematic/scoping/narrative reviews, and 2 commentaries. ConclusionThe findings of this review may help inform practitioners who utilize manipulative and/or manual therapies regarding levels of evidence for patients with prior lumbar surgery. Following lumbar surgery, the evidence indicated inpatient neural mobilization does not improve outcomes. There is inconclusive evidence to recommend for or against most manual therapies after most surgical interventions.Trial registrationProspectively registered with PROSPERO (#CRD42020137314). Registered 24 January 2020.


Author(s):  
Hideya Yamazaki ◽  
Gen Suzuki ◽  
Norihiro Aibe ◽  
Satoaki Nakamura ◽  
Ken Yoshida ◽  
...  

Abstract The aim of this study was to survey the present status and patterns of reirradiation (Re-RT) practice using external beam radiotherapy in Japan. We distributed an e-mail questionnaire to the Japanese Society for Radiation Oncology partner institutions, which consisted of part 1 (number of Re-RT cases in 2008–2012 and 2013–2018) and part 2 (indications and treatment planning for Re-RT and eight case scenarios). Of the 85 institutions that replied to part 1, 75 (88%) performed Re-RTs. However, 59 of these 75 institutions (79%) reported difficulty in obtaining Re-RT case information from their databases. The responses from 37 institutions included the number of Re-RT cases, which totaled 508 in the period from 2009 to 2013 (institution median 3; 0–235), and an increase to 762 cases in the period from 2014 to 2018 (12.5; 0–295). A total of 47 physicians responded to part 2 of the survey. Important indications for Re-RT that were considered were age, performance status, life expectancy, absence of distant metastases and time interval since previous radiotherapy. In addition to clinical decision-making factors, previous total radiation dose, volume of irradiated tissue and the biologically equivalent dose were considered during Re-RT planning. From the eight site-specific scenarios presented to the respondents, &gt;60% of radiation oncologists agreed to perform Re-RT. Re-RT cases have increased in number, and interest in Re-RT among radiation oncologists has increased recently due to advances in technology. However, several problems exist that emphasize the need for consensus building and the establishment of guidelines for practice and prospective evaluation.


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