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Computers in Biology and Medicine Jun 2022Recent research on artificial intelligence indicates that machine learning algorithms can auto-generate novel drug-like molecules. Generative models have revolutionized... (Review)
Review
Recent research on artificial intelligence indicates that machine learning algorithms can auto-generate novel drug-like molecules. Generative models have revolutionized de novo drug discovery, rendering the explorative process more efficient. Several model frameworks and input formats have been proposed to enhance the performance of intelligent algorithms in generative molecular design. In this systematic literature review of experimental articles and reviews over the last five years, machine learning models, challenges associated with computational molecule design along with proposed solutions, and molecular encoding methods are discussed. A query-based search of the PubMed, ScienceDirect, Springer, Wiley Online Library, arXiv, MDPI, bioRxiv, and IEEE Xplore databases yielded 87 studies. Twelve additional studies were identified via citation searching. Of the articles in which machine learning was implemented, six prominent algorithms were identified: long short-term memory recurrent neural networks (LSTM-RNNs), variational autoencoders (VAEs), generative adversarial networks (GANs), adversarial autoencoders (AAEs), evolutionary algorithms, and gated recurrent unit (GRU-RNNs). Furthermore, eight central challenges were designated: homogeneity of generated molecular libraries, deficient synthesizability, limited assay data, model interpretability, incapacity for multi-property optimization, incomparability, restricted molecule size, and uncertainty in model evaluation. Molecules were encoded either as strings, which were occasionally augmented using randomization, as 2D graphs, or as 3D graphs. Statistical analysis and visualization are performed to illustrate how approaches to machine learning in de novo drug design have evolved over the past five years. Finally, future opportunities and reservations are discussed.
Topics: Artificial Intelligence; Drug Design; Drug Discovery; Machine Learning; Neural Networks, Computer
PubMed: 35339849
DOI: 10.1016/j.compbiomed.2022.105403 -
Breast (Edinburgh, Scotland) Aug 2021Locoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Locoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).
METHODS
RCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.
RESULTS
Analyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72-1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14-0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65-1.43), triple negative (HR 1.4, 95% CI 0.50-3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68-1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58-1.62) and in visceral disease (HR = 1.02, 95% CI 0.77-1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.
CONCLUSIONS
LRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.
Topics: Breast Neoplasms; Female; Humans; Proportional Hazards Models; Radiotherapy, Adjuvant; Survival Rate
PubMed: 34158167
DOI: 10.1016/j.breast.2021.05.003 -
Frontiers in Pediatrics 2022Liver transplant (LT) recipients, particularly children, have an increased risk of developing food allergies (FAs) after transplantation both compared to all the other...
BACKGROUND
Liver transplant (LT) recipients, particularly children, have an increased risk of developing food allergies (FAs) after transplantation both compared to all the other transplant groups and to the general population. Little is known about the pathogenesis underlying this phenomenon and comprehensive recommendations or clinical practice guidelines are still lacking, mainly due to the scarcity of high-quality evidence.
AIM
We aimed to prepare a systematic review on FA in pediatric LT recipients to assess epidemiology and risk factors, evaluate the correlation to specific food groups, describe clinical manifestations, investigate the rate of tolerance acquisition over time and report available therapeutic strategies.
METHODS
We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). MEDLINE, Scopus, Web of Science, Wiley online library, Cochrane Library, and ClinicalTrials.gov databases were systematically searched for studies published from January 1980 to September 2021. All the articles were checked independently by two reviewers in two steps. A total of 323 articles were screened, and 40 were included for data extraction.
RESULTS AND CONCLUSIONS
We found that FAs develop in the 15% of pediatric LT recipients, especially in the first 2 years after surgery, with higher risk related to younger age at transplantation (especially <2 years of age) and tacrolimus immunosuppression. Subjects are often allergic to multiple foods, and 15% of them suffer from anaphylaxis. The majority of patients do not spontaneously outgrow their symptoms during follow-up. The discontinuation of tacrolimus in favor of cyclosporine or the association of tacrolimus with mycophenolate have been associated with the resolution or the improvement of FA in small retrospective case series and could be considered in case of severe or multiple, difficult to manage FAs. Prospective multicenter studies are needed to confirm these findings, guide the risk-based stratification of pediatric LT recipients, and provide for high-evidence therapeutic strategies for children with FA.
PubMed: 35633971
DOI: 10.3389/fped.2022.885942 -
Journal of the European Academy of... Sep 2023The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review... (Meta-Analysis)
Meta-Analysis Review
The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood.
Topics: Child; Humans; Melanoma; Nevus; Nevus, Epithelioid and Spindle Cell; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 37210654
DOI: 10.1111/jdv.19220 -
World Journal of Clinical Cases Dec 2022As operative techniques and mortality rates of pancreatectomy have improved, there has been a shift in focus to maintaining and improving the nutritional status of these...
BACKGROUND
As operative techniques and mortality rates of pancreatectomy have improved, there has been a shift in focus to maintaining and improving the nutritional status of these patients as we continue to learn more about post-operative complications. Although pancreatic endocrine and exocrine insufficiencies are known complications of pancreatectomy, increased longevity of these patients has also led to a higher incidence of fatty liver disease which differs from traditional fatty liver disease given the lack of metabolic syndrome.
AIM
To identify and summarize patterns and risk factors of post-pancreatectomy fatty liver disease to guide future management.
METHODS
We performed a database search on PubMed selecting papers published between 2001 and 2022 in the English language. PubMed was last accessed 1 June 2022.
RESULTS
Various factors influence the development of fatty liver including indication for surgery (benign malignant), type of pancreatectomy, amount of pancreas remnant, and peri-operative nutritional status. With an incidence rate up to 75%, non-alcoholic fatty liver disease (NAFLD) can develop within 12 mo after pancreatectomy and various risk factors have been established including pancreatic resection line and remnant pancreas volume, peri-operative malnutrition and weight loss, pancreatic exocrine insufficiency (EPI), malignancy as the indication for surgery, and postmenopausal status.
CONCLUSION
Since majority of risk factors leads to EPI and malnutrition, peri-operative focus on nutrition and enzymes replacement is key in preventing and treating NAFLD after pancreatectomy.
PubMed: 36569000
DOI: 10.12998/wjcc.v10.i35.12946 -
Diabetes Therapy : Research, Treatment... Sep 2020Unhealthy behaviors, such as energy-dense food choices and a sedentary lifestyle, both of which are established risk factors for diabetes, are common and increasing... (Review)
Review
BACKGROUND
Unhealthy behaviors, such as energy-dense food choices and a sedentary lifestyle, both of which are established risk factors for diabetes, are common and increasing among Nepalese adults. Previous studies have reported a wide variation in the prevalence of prediabetes and diabetes in Nepal, and thus a more reliable pooled estimate is needed. Furthermore, Nepal underwent federalization in 2015, and the province-specific prevalence, which is necessary for the de novo provincial government to formulate local health policies, is lacking. This study aims to provide a comprehensive summary of the current literature on various aspects of diabetes in Nepal, i.e., the prevalence of prediabetes and diabetes as well as of the awareness, treatment, and control of diabetes in Nepal.
METHODS
This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched three electronic databases-PubMed, Scopus, and Web of Science-using a comprehensive search strategy to identify eligible studies published up to April 2, 2020. Data on prevalence estimates of prediabetes and diabetes were extracted and pooled in a meta-analysis using a random effect model. Subgroup analyses and meta-regression were conducted to assess heterogeneity across the studies. The quality of included studies was assessed using the New Castle-Ottawa scale.
RESULTS
We included 14 eligible studies that comprised a total of 44,129 participants and 3517 diabetes cases. Half of the included studies had good quality. Overall, the prevalence of prediabetes and diabetes was 9.2% (95% CI 6.6-12.6%) and 8.5% (95% CI 6.9-10.4%), respectively. Among the participants with diabetes, only 52.7% (95% CI 41.7-63.4%) were aware of their diabetes status, and 45.3% (95% CI 31.6-59.8%) were taking antidiabetic medications. Nearly one-third of those under antidiabetic treatment (36.7%; 95% CI 21.3-53.3%) had their blood glucose under control. The prevalence of prediabetes and diabetes gradually increased with increasing age and was more prevalent among males and urban residents. There was a wide variation in diabetes prevalence across the provinces in Nepal, the lowest 2% in Province 6 to the highest 10% in Province 3 and Province 4.
CONCLUSIONS
The prevalence of prediabetes and diabetes was high in Nepal, while its awareness, treatment, and control were low. Our findings call for urgent nationwide public health action in Nepal.
PubMed: 32712902
DOI: 10.1007/s13300-020-00884-0 -
Children (Basel, Switzerland) Dec 2021The available endoscopic techniques for ureterocele decompression include laser puncture (LP), electrosurgical incision (ES), and cold-knife incision. This systematic... (Review)
Review
De Novo Vesicoureteral Reflux Following Ureterocele Decompression in Children: A Systematic Review and Meta-Analysis Comparing Laser Puncture versus Electrosurgical Incision Techniques.
BACKGROUND
The available endoscopic techniques for ureterocele decompression include laser puncture (LP), electrosurgical incision (ES), and cold-knife incision. This systematic review was performed to compare the efficacy of LP versus ES techniques with special emphasis on de novo VUR.
METHODS
Four databases were systematically searched by the authors. The inclusion criteria were all comparative studies in which ureterocele decompression was performed by either LP or ES endoscopic techniques. Outcomes including the incidence of de novo VUR, the need for endoscopic retreatment of the ureterocele, and the need for secondary surgical procedures were studied. Risk ratios (RR) were calculated for all outcomes and the Mantel-Haenszel method was utilized for the estimation of pooled RR. The methodological quality was assessed by the Downs and Black scale.
RESULTS
Five studies were considered for systematic review, while four of them were included in the meta-analysis. Out of 202 children, 67 developed de novo VUR. Significantly lower rates of reflux were observed in the LP group vis-a-vis ES group (RR = 0.17, 95% CI 0.09 to 0.32, 0.00001). Endoscopic retreatment rates ( = 20) demonstrated no significant difference among the two patient groups (RR = 0.66, 95% CI 0.26-1.68, = 0.38). A total of 46 secondary procedures were performed in 170 children, mostly ureteral re-implantations, with a significantly lower need of secondary surgeries following LP versus ES (RR = 0.26, 95% CI 0.13-0.49, 0.0001). The risk of bias in the included studies was low-to-moderate.
CONCLUSIONS
When compared to the ES technique, the LP technique is associated with a significantly low incidence of de novo VUR and requirement for secondary surgeries (particularly anti-reflux surgeries). Endoscopic retreatment rates showed no significant difference between the two techniques. However, due to the moderate risk of bias in two out of four included studies, randomized controlled trials are needed in the future.
PubMed: 35053634
DOI: 10.3390/children9010010 -
Surgical Endoscopy Jan 2024Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open,... (Review)
Review
BACKGROUND
Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open, and image-guided techniques have evolved as the most popular techniques. The aim of this guideline was to develop evidence-based guidelines that support surgeons, patients, and other physicians in decisions on minimally invasive peritoneal dialysis access and the salvage of malfunctioning catheters in both adults and children.
METHODS
A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons reviewed the literature since the prior guideline was published in 2014 and developed seven key questions in adults and four in children. After a systematic review of the literature, by the panel, evidence-based recommendations were formulated using the Grading of Recommendations Assessment, Development and Evaluation approach. Recommendations for future research were also proposed.
RESULTS
After systematic review, data extraction, and evidence to decision meetings, the panel agreed on twelve recommendations for the peri-operative performance of laparoscopic peritoneal dialysis access surgery and management of catheter dysfunction.
CONCLUSIONS
In the adult population, conditional recommendations were made in favor of: staged hernia repair followed by PD catheter insertion over simultaneous and traditional start over urgent start of PD when medically possible. Furthermore, the panel suggested advanced laparoscopic insertion techniques rather than basic laparoscopic techniques or open insertion. Conditional recommendations were made for either advanced laparoscopic or image-guided percutaneous insertion and for either nonoperative or operative salvage. A recommendation could not be made regarding concomitant clean-contaminated surgery in adults. In the pediatric population, conditional recommendations were made for either traditional or urgent start of PD, concomitant clean or clean-contaminated surgery and PD catheter placement rather than staged, and advanced laparoscopic placement rather than basic or open insertion.
Topics: Adult; Child; Humans; Catheterization; Catheters, Indwelling; Kidney Failure, Chronic; Laparoscopy; Peritoneal Dialysis; Peritoneum
PubMed: 37989887
DOI: 10.1007/s00464-023-10550-8 -
European Urology Focus May 2023De Novo nephrolithiasis in renal transplant can have severe consequences since renal transplantation involves a single functioning kidney with medical and anatomical... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
De Novo nephrolithiasis in renal transplant can have severe consequences since renal transplantation involves a single functioning kidney with medical and anatomical specificities (heterotopic transplantation on iliac vessels, immunosuppressive treatments, and comorbidities).
OBJECTIVE
To systematically review all available evidence on the prevalence of de novo nephrolithiasis in renal transplant, presentation, and stone characteristics, and to report in a meta-analysis the efficacy of stone treatments (extracorporeal shock wave lithotripsy [ESWL], medical treatment, percutaneous nephrolithotomy [PCNL], open surgery, and ureteroscopy).
EVIDENCE ACQUISITION
Medline, Embase, and the Cochrane Library were searched up to November 2021 for all relevant publications reporting the management of de novo nephrolithiasis in renal allografts. The primary outcome was stone-free rate (SFR) at 3 mo. Secondary outcomes included prevalence, stone characteristics (size, density, and composition), symptoms on presentation, need for drainage, complications, and recurrence. Data were narratively synthesized in light of methodological and clinical heterogeneity, and a meta-analysis was performed for SFR. The risk of bias of each included study was assessed.
EVIDENCE SYNTHESIS
We included 37 retrospective studies with 553 patients and 612 procedures; of the 612 procedures 20 were antegrade ureteroscopy, 154 retrograde ureteroscopy, 118 PCNL, 25 open surgery, 155 ESWL, and 140 surveillance/medical treatment. The prevalence of nephrolithiasis in renal transplant was 1.0%. The mean stone size on diagnosis was 11 mm (2-50). The overall SFR at 3 mo was 82%: 96% with open surgery, 95% with antegrade ureteroscopy, 86% with PCNL, 81% with retrograde ureteroscopy, and 75% with ESWL.
CONCLUSIONS
De novo nephrolithiasis in renal transplant is an infrequent condition. A high SFR were obtained with an antegrade approach (ureteroscopy, PCNL, and open approach) that should be considered in renal transplant patients owing to the heterotopic position of the renal graft. The choice of technique was correlated with stone size: generally ureteroscopy and ESWL for stones 11-12 mm (mean stone size) versus PCNL and open surgery for 17-25 mm stones.
PATIENT SUMMARY
De novo nephrolithiasis in renal transplants is an infrequent situation that can have severe consequences on the function of the renal graft. We evaluated the efficacy of each treatment and noted that antegrade approaches (open surgery, percutaneous nephrolithotomy, and antegrade ureteroscopy) were associated with the highest stone-free rate. As opposed to the management of nephrolithiasis in native kidney, an antegrade approach should be considered more in renal transplant patients.
Topics: Humans; Kidney; Kidney Calculi; Nephrolithotomy, Percutaneous; Retrospective Studies; Ureteroscopy
PubMed: 36567234
DOI: 10.1016/j.euf.2022.11.019 -
Health Technology Assessment... May 2021Early diagnosis of acute myocardial infarction is important, but only 20% of emergency admissions for chest pain will actually have an acute myocardial infarction....
BACKGROUND
Early diagnosis of acute myocardial infarction is important, but only 20% of emergency admissions for chest pain will actually have an acute myocardial infarction. High-sensitivity cardiac troponin assays may allow rapid rule out of myocardial infarction and avoid unnecessary hospital admissions.
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of high-sensitivity cardiac troponin assays for the management of adults presenting with acute chest pain, in particular for the early rule-out of acute myocardial infarction.
METHODS
Sixteen databases were searched up to September 2019. Review methods followed published guidelines. Studies were assessed for quality using appropriate risk-of-bias tools. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies; otherwise, random-effects logistic regression was used. The health economic analysis considered the long-term costs and quality-adjusted life-years associated with different troponin testing methods. The de novo model consisted of a decision tree and a state-transition cohort model. A lifetime time horizon (of 60 years) was used.
RESULTS
Thirty-seven studies (123 publications) were included in the review. The high-sensitivity cardiac troponin test strategies evaluated are defined by the combination of four factors (i.e. assay, number and timing of tests, and threshold concentration), resulting in a large number of possible combinations. Clinical opinion indicated a minimum clinically acceptable sensitivity of 97%. When considering single test strategies, only those using a threshold at or near to the limit of detection for the assay, in a sample taken at presentation, met the minimum clinically acceptable sensitivity criterion. The majority of the multiple test strategies that met this criterion comprised an initial rule-out step, based on high-sensitivity cardiac troponin levels in a sample taken on presentation and a minimum symptom duration, and a second stage for patients not meeting the initial rule-out criteria, based on presentation levels of high-sensitivity cardiac troponin and absolute change after 1, 2 or 3 hours. Two large cluster randomised controlled trials found that implementation of an early rule-out pathway for myocardial infarction reduced length of stay and rate of hospital admission without increasing cardiac events. In the base-case analysis, standard troponin testing was both the most effective and the most costly. Other testing strategies with a sensitivity of 100% (subject to uncertainty) were almost equally effective, resulting in the same life-year and quality-adjusted life-year gain at up to four decimal places. Comparisons based on the next best alternative showed that for willingness-to-pay values below £8455 per quality-adjusted life-year, the Access High Sensitivity Troponin I (Beckman Coulter, Brea, CA, USA) [(symptoms > 3 hours AND < 4 ng/l at 0 hours) OR (< 5 ng/l AND Δ < 5 ng/l at 0 to 2 hours)] would be cost-effective. For thresholds between £8455 and £20,190 per quality-adjusted life-year, the Elecsys Troponin-T high sensitive (Roche, Basel, Switzerland) (< 12 ng/l at 0 hours AND Δ < 3 ng/l at 0 to 1 hours) would be cost-effective. For a threshold > £20,190 per quality-adjusted life-year, the Dimension Vista High-Sensitivity Troponin I (Siemens Healthcare, Erlangen, Germany) (< 5 ng/l at 0 hours AND Δ < 2 ng/l at 0 to 1 hours) would be cost-effective.
CONCLUSIONS
High-sensitivity cardiac troponin testing may be cost-effective compared with standard troponin testing.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42019154716.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in ; Vol. 25, No. 33. See the NIHR Journals Library website for further project information.
Topics: Chest Pain; Cost-Benefit Analysis; Humans; Myocardial Infarction; Quality-Adjusted Life Years; Troponin
PubMed: 34061019
DOI: 10.3310/hta25330