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Scientific Reports Jul 2022Differential gene expression normalised to a single housekeeping (HK) is used to identify disease mechanisms and therapeutic targets. HK gene selection is often...
Differential gene expression normalised to a single housekeeping (HK) is used to identify disease mechanisms and therapeutic targets. HK gene selection is often arbitrary, potentially introducing systematic error and discordant results. Here we examine these risks in a disease model of brain hypoxia. We first identified the eight most frequently used HK genes through a systematic review. However, we observe that in both ex-vivo and in vivo, their expression levels varied considerably between conditions. When applying these genes to normalise expression levels of the validated stroke target gene, inducible Nox4, we obtained opposing results. As an alternative tool for unbiased HK gene selection, software tools exist but are limited to individual datasets lacking genome-wide search capability and user-friendly interfaces. We, therefore, developed the HouseKeepR algorithm to rapidly analyse multiple gene expression datasets in a disease-specific manner and rank HK gene candidates according to stability in an unbiased manner. Using a panel of de novo top-ranked HK genes for brain hypoxia, but not single genes, Nox4 induction was consistently reproduced. Thus, differential gene expression analysis is best normalised against a HK gene panel selected in an unbiased manner. HouseKeepR is the first user-friendly, bias-free, and broadly applicable tool to automatically propose suitable HK genes in a tissue- and disease-dependent manner.
Topics: Algorithms; Gene Expression; Gene Expression Profiling; Genes, Essential; Humans; Hypoxia, Brain
PubMed: 35853974
DOI: 10.1038/s41598-022-15989-8 -
Medicine Apr 2023Laparoscopic banded sleeve gastrectomy (LBSG) has been compared to laparoscopic sleeve gastrectomy (LSG) in terms of anthropometric results and postoperative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Laparoscopic banded sleeve gastrectomy (LBSG) has been compared to laparoscopic sleeve gastrectomy (LSG) in terms of anthropometric results and postoperative complications, which are controversial. This systematic review and meta-analysis aimed to compare the safety and efficacy of LBSG and LSG.
METHODS
We performed a systematic review with meta-analysis according to preferred reporting items for systematic review and meta-analysis 2020 and assessing the methodological quality of systematic review 2 guidelines. We included studies that systematically searched electronic databases and compared LBSG with LSG conducted until August 10, 2021.
RESULTS
The literature search yielded 8 comparative studies. Seven hundred forty-three patients were included: 352 in the LBSG group and 391 in the LSG group. LBSG group allowed greater anthropometric parameters (body mass index [BMI] after 1 year (mean difference [MD] = -3.18; 95% CI [-5.45, -0.92], P = .006), %EWL after 1 year (MD = 8.02; 95% CI [1.22, 14.81], P = .02), and %EWL after 3 years (MD = 10.60; 95% CI [5.60, 15.69], P < .001) and similar results with LSG group in terms of operative time (MD = 1.23; 95% CI [-4.71, 7.17], P = .69), food intolerance (OR = 1.72; 95% CI [0.84, 3.49], P = .14), postoperative vomiting (OR = 2.10; 95% CI [0.69, 6.35], P = .19), and De novo GERD (OR = 0.65; 95% CI [0.34, 1.26], P = .2). Nevertheless, major postoperative complications did not differ between the 2 groups.
CONCLUSIONS
This systematic review and meta-analysis comparing LBSG and LSG concluded that banding sleeve gastrectomy (SG) may ensure a lower BMI and %EWL after 1 year of follow-up, and a significant reduction in %EWL after 3 years of follow-up. There is no evidence to support LBSG in vomiting, de novo GERD, food intolerance, or operative time.
Topics: Humans; Food Intolerance; Gastroplasty; Postoperative Complications; Gastrectomy; Postoperative Nausea and Vomiting; Gastroesophageal Reflux; Laparoscopy; Obesity, Morbid; Treatment Outcome; Retrospective Studies
PubMed: 37058050
DOI: 10.1097/MD.0000000000032982 -
Vaccines Apr 2022As the coronavirus disease 2019 (COVID-19) pandemic is ongoing, and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging,... (Review)
Review
As the coronavirus disease 2019 (COVID-19) pandemic is ongoing, and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, vaccines are needed to protect individuals at high risk of complications and to potentially control disease outbreaks by herd immunity. After SARS-CoV-2 vaccination, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presenting with a pulmonary hemorrhage has been described. Previous studies suggested that monocytes upregulate major histocompatibility complex (MHC) II cell surface receptor human leukocyte antigen receptor (HLA-DR) molecules in granulomatosis with polyangiitis (GPA) patients with proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA seropositivity. Here, we present a case of new-onset AAV after booster vaccination with the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine. Moreover, we provide evidence that the majority of monocytes express HLA-DR in AAV after SARS-CoV-2 booster vaccination. It is possible that the enhanced immune response after booster vaccination and presence of HLA-DR monocytes could be responsible for triggering the production of the observed MPO- and PR3-ANCA autoantibodies. Additionally, we conducted a systematic review of de novo AAV after SARS-CoV-2 vaccination describing their clinical manifestations in temporal association with SARS-CoV-2 vaccination, ANCA subtype, and treatment regimens. In light of a hundred million individuals being booster vaccinated for SARS-CoV-2 worldwide, a potential causal association with AAV may result in a considerable subset of cases with potential severe complications.
PubMed: 35632410
DOI: 10.3390/vaccines10050653 -
Journal of Gastrointestinal Surgery :... Feb 2023The frequency and management of gallstone disease (GD) in bariatric patients, including the role of routine prophylactic concomitant cholecystectomy (CCY), are still a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The frequency and management of gallstone disease (GD) in bariatric patients, including the role of routine prophylactic concomitant cholecystectomy (CCY), are still a matter of debate. This study aims to assess the risk of de novo GD in patients undergoing bariatric surgery (BS) and their predictive factors, as well as mortality and morbidity in prophylactic CCY compared to BS alone.
METHODS
We performed a systematic review, searching PubMed, EMBASE, and Web of Science until April 2021. We performed a Bayesian meta-analysis to estimate the risk of GD development after BS and the morbidity and mortality associated with BS alone versus BS + prophylactic CCY. Sources of heterogeneity were explored by meta-regression analysis.
RESULTS
The risk of de novo post bariatric GD was 20.7% (95% credible interval [95% CrI] = 13.0-29.7%; I = 75.4%), and that of symptomatic GD was 8.2% ([95% CrI] = 5.9-11.1%; I = 66.9%). Pre-operative average BMI (OR = 1.04; 95% CrI = 0.92-1.17) and female patients' proportion (OR = 1.00; 95% CrI = 0.98-1.04) were not associated with increased risk of symptomatic GD. BS + prophylactic CCY was associated with a 97% probability of a higher number of postoperative major complications compared to BS alone (OR = 1.74, 95% CrI = 0.97-3.55; I = 56.5%). Mortality was not substantially different between the two approaches (OR = 0.79; 95% CrI = 0.03-3.02; I = 20.7%).
CONCLUSION
The risk of de novo symptomatic GD after BS is not substantially high. Although mortality is similar between groups, odds of major postoperative complications were higher in patients submitted to BS + prophylactic CCY. It is still arguable if prophylactic CCY is a fitting approach for patients with a preoperative lithiasic gallbladder.
Topics: Female; Humans; Bariatric Surgery; Bayes Theorem; Cholecystectomy; Cholelithiasis; Obesity, Morbid; Postoperative Complications
PubMed: 36627465
DOI: 10.1007/s11605-022-05567-8 -
Cancers Nov 2022In the case of synchronous metastatic disease, the local treatment of primary tumors by radiotherapy has long been reserved for palliative indications. The emergence of... (Review)
Review
In the case of synchronous metastatic disease, the local treatment of primary tumors by radiotherapy has long been reserved for palliative indications. The emergence of the concept of oligometastatic and oligopersistent diseases, the advent of new systemic therapies enabling longer overall survival with an enhanced quality of life, a better understanding of the biologic history of metastatic spread, and technical advances in radiation therapy are revolutionizing the management of patients with de novo metastatic cancer. The prognosis of these patients has been markedly improved and many studies have investigated the survival benefits from the local treatment of various primary tumors in cases of advanced disease at the time of diagnosis or in the case of oligopersistence. This article provides an update on the place of irradiation of the primary tumor in cancer with synchronous metastases, and discusses its interest through published or ongoing trials.
PubMed: 36497410
DOI: 10.3390/cancers14235929 -
European Journal of Vascular and... Jul 2021The efficacy and cost effectiveness of atherectomy for femoropopliteal (FP) arterial diseases have not been determined yet. A systematic review and meta-analysis were... (Comparative Study)
Comparative Study Meta-Analysis
Atherectomy Combined with Balloon Angioplasty versus Balloon Angioplasty Alone for de Novo Femoropopliteal Arterial Diseases: A Systematic Review and Meta-analysis of Randomised Controlled Trials.
OBJECTIVE
The efficacy and cost effectiveness of atherectomy for femoropopliteal (FP) arterial diseases have not been determined yet. A systematic review and meta-analysis were performed to compare the efficacy and safety between atherectomy combined with balloon angioplasty (BA) and BA alone for patients with de novo FP steno-occlusive lesions.
METHODS
The Cochrane Library, Medline, and Embase were used to search for studies evaluating outcomes of atherectomy combined with BA compared with BA alone in FP arterial diseases from inception to July 2020. The methodological quality of the included studies was evaluated with the Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was used to assess the level of evidence for each outcome. The fixed effects model was chosen to combine the data when I < 50%; otherwise, the random effects model was used. Subgroup and sensitivity analyses were performed to further analyse the results.
RESULTS
Four RCTs were included. The meta-analysis showed that atherectomy combined with BA was associated with improved technical success rate (risk ratio [RR] 0.22, 95% confidence interval [CI] 0.13-0.38, p < .001; I = 0; high quality), reduced bailout stenting (RR 0.15, 95% CI 0.07-0.32, p < .001; I = 16%; high quality), and flow limiting dissection (RR 0.24, 95% CI 0.13-0.47, p < .001; I = 0; high quality). No statistically significant difference was found in target lesion revascularisation (TLR), primary patency, mortality, major adverse event (MAE), or ankle brachial index (ABI) after one year follow up.
CONCLUSION
Compared with BA alone, atherectomy combined with BA may not improve primary patency, TLR, mortality rate, or ABI, but may reduce the need for bailout stenting and the incidence of flow limiting dissection and increase the technical success rate in FP arterial diseases. More studies are warranted to further confirm the conclusion.
Topics: Aortic Dissection; Angioplasty, Balloon; Ankle Brachial Index; Atherectomy; Combined Modality Therapy; Femoral Artery; Follow-Up Studies; Humans; Peripheral Arterial Disease; Postoperative Complications; Randomized Controlled Trials as Topic; Stents; Treatment Outcome; Vascular Patency
PubMed: 34112574
DOI: 10.1016/j.ejvs.2021.02.012 -
Frontiers in Pharmacology 2023The work aimed to compare the pharmacokinetic (PK) profiles and other outcomes reported in observational studies in kidney transplant recipients (KTRs) receiving novel...
The work aimed to compare the pharmacokinetic (PK) profiles and other outcomes reported in observational studies in kidney transplant recipients (KTRs) receiving novel once-daily extended-release tablet tacrolimus (LCPT; LCP-tacrolimus; Envarsus XR) or receiving standard-of-care capsule tacrolimus (PR-Tac; prolonged-release tacrolimus; Advagraf/IR-Tac; immediate-release tacrolimus; Prograf). A systematic review was conducted for all randomized controlled trials (RCTs) and cohort studies investigating the outcomes in KTRs receiving LCPT or PR-Tac/IR-Tac. We systematically searched PubMed, Web of Science, and EMBASE, with no language restriction. The registered trials and references listed in relevant studies were also searched. Data were extracted for the PK profile, tacrolimus trough level (TTL), and changes in the estimated glomerular filtration rate (eGFR) and serum creatinine (Scr), biopsy-proven acute rejection (BPAR) rate, delayed graft function (DGF) rate, post-transplant diabetes mellitus (PTDM) rate, tremor rate (TR), death rate (DR), and rate of infection by cytomegalovirus (CMV). This study was registered with PROSPERO (registration number: CRD42023403787). A total of seven eligible articles including 1,428 patients with 712 in the LCPT group versus 716 in the PR-Tac/IR-Tac group were included in this study for evidence synthesis. The baseline characteristics of the LCPT, PR-Tac, and IR-Tac groups were similar. The pooled analysis showed a higher PK profile in the LCPT group, and this result was consistent with those of all the included studies. In addition, no significant difference was observed for other outcomes. Considering heterogeneity between studies and potential bias, care providers should select agents based on patient-specific factors and their clinical experience for the immunosuppressive treatment of KTRs.
PubMed: 38143499
DOI: 10.3389/fphar.2023.1310339 -
The Oncologist Jan 2024Breast surgery in cases of de novo metastatic breast cancer (MBC) is associated with improved outcomes in retrospective studies, although the results of randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Breast surgery in cases of de novo metastatic breast cancer (MBC) is associated with improved outcomes in retrospective studies, although the results of randomized controlled trials (RCTs) are conflicting. We aimed to investigate whether surgery in this context prolongs patient survival.
METHODS
We performed a systematic review of the literature to identify RCTs comparing surgery of primary breast cancer to no surgery in patients with de novo MBC. Cochrane Library, Embase, Medline (OVID), and Web of Science were searched with latest update in July 2023, while conference proceedings were manually searched. Data concerning patient and tumor characteristics, as well as outcomes, were extracted. A meta-analysis with random effects models was performed considering heterogeneity between trials.
RESULTS
Overall, 3255 entries were identified and 5 RCTs fulfilled all inclusion criteria, which had enrolled 1381 patients. The overall estimation in the intention-to-treat population showed no benefit for patients who had surgical excision of the primary breast tumor (HR = 0.93; 95% CI, 0.76-1.14). No subgroups in terms of receptor status or patterns of metastasis seemed to benefit from surgery, except for younger/premenopausal patients (HR = 0.74, 95% CI, 0.58-0.94). Breast surgery was associated with improved local progression-free survival (HR = 0.37, 95% CI, 0.19-0.74).
CONCLUSION
Surgery of the primary tumor in patients with de novo MBC does not prolong survival, except possibly in younger/premenopausal patients. Breast surgery should be offered within the context of well-designed clinical trials examining the issue.
Topics: Humans; Female; Breast Neoplasms; Mastectomy; Breast; Retrospective Studies
PubMed: 37700450
DOI: 10.1093/oncolo/oyad266 -
Clinical Microbiology and Infection :... Sep 2021Coronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease.
BACKGROUND
Coronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease.
OBJECTIVES
To assess the range of cardiac sequelae after COVID-19 recovery.
DATA SOURCES
PubMed, Embase, Scopus (inception through 17 February 2021) and Google scholar (2019 through 17 February 2021).
STUDY ELIGIBILITY CRITERIA
Prospective and retrospective studies, case reports and case series.
PARTICIPANTS
Adult patients assessed for cardiac manifestations after COVID-19 recovery.
EXPOSURE
Severe acute respiratory syndrome coronavirus 2 infection diagnosed by PCR.
METHODS
Systematic review.
RESULTS
Thirty-five studies (fifteen prospective cohort, seven case reports, five cross-sectional, four case series, three retrospective cohort and one ambidirectional cohort) evaluating cardiac sequelae in 52 609 patients were included. Twenty-nine studies used objective cardiac assessments, mostly cardiac magnetic resonance imaging (CMR) in 16 studies, echocardiography in 15, electrocardiography (ECG) in 16 and cardiac biomarkers in 18. Most studies had a fair risk of bias. The median time from diagnosis/recovery to cardiac assessment was 48 days (1-180 days). Common short-term cardiac abnormalities (<3 months) included increased T1 (proportion: 30%), T2 (16%), pericardial effusion (15%) and late gadolinium enhancement (11%) on CMR, with symptoms such as chest pain (25%) and dyspnoea (36%). In the medium term (3-6 months), common changes included reduced left ventricular global longitudinal strain (30%) and late gadolinium enhancement (10%) on CMR, diastolic dysfunction (40%) on echocardiography and elevated N-terminal proB-type natriuretic peptide (18%). In addition, COVID-19 survivors had higher risk (risk ratio 3; 95% CI 2.7-3.2) of developing heart failure, arrythmias and myocardial infarction.
CONCLUSIONS
COVID-19 appears to be associated with persistent/de novo cardiac injury after recovery, particularly subclinical myocardial injury in the earlier phase and diastolic dysfunction later. Larger well-designed and controlled studies with baseline assessments are needed to better measure the extent of cardiac injury and its clinical impact.
Topics: Adult; COVID-19; COVID-19 Nucleic Acid Testing; Echocardiography; Electrocardiography; Heart Diseases; Humans; Magnetic Resonance Imaging, Cine; SARS-CoV-2
PubMed: 34171458
DOI: 10.1016/j.cmi.2021.06.015 -
Frontiers in Oncology 2022Immunotherapies represented by immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. A large part of the population has both cancer and psoriasis but...
BACKGROUND
Immunotherapies represented by immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. A large part of the population has both cancer and psoriasis but is usually excluded from ICI clinical trials because of the dysregulated activation of the immune system. This is the first study to evaluate the safety and efficacy of ICI therapy in patients with cancer and preexisting psoriasis.
METHODS
PubMed, EMBASE, Cochrane, and MEDLINE databases were searched from inception through February 2022. Observational studies on patients with cancer and confirmed psoriasis before ICI initiation were included. Outcomes included the incidence of psoriasis flares, immune-related adverse events (irAEs), discontinuation rate due to flare/ irAEs, and efficacy of ICI therapy. Clinical manifestations, management, and outcomes for adverse events (AEs) were systematically reviewed. All pooled analyses were based on a random-effects model using Stata software. Meta-regression and subgroup analyses were performed to identify sources of heterogeneity.
RESULTS
Twelve studies involving 191 patients were included. The pooled incidence of psoriasis flares was 45.0% (95% CI: 31.1%-58.9%, I = 71.7%) and 44.9% (95% CI: 29.0%-60.7%, I = 71.8%) for irAEs. The tumor type, psoriasis subtype, ICI class, and country were the main sources of heterogeneity. Grade 3-4 flares occurred in 10.8% (95% CI: 5.3%-16.3%) of patients, and about 16.6% (95% CI: 10.7%-22.5%) of patients experienced grade 3-4 irAEs. The estimated incidence of ICI discontinuation due to AE was 18.5% (95% CI: 6.1%-30.8%, I = 68.7%). The median times to develop flare and irAEs were 44 and 63 days, respectively. Endocrinopathies and colitis were the most common irAEs. Conventional therapy is effective for most AEs. The estimated objective response rate (ORR) of ICIs was 38.1% (95% CI: 11.8%-64.3%, I = 81.7%), and the disease control rate (DCR) was 64.5% (95% CI: 55.3%-73.8%, I = 0).
CONCLUSIONS
The flare of patients with cancer and preexisting psoriasis treated with ICI therapy is frequent, but the incidence of irAEs and the efficacy of ICI therapy are comparable to those of the general population. Most AEs are mild and manageable with conventional therapy, which required discontinuation of ICI therapy in 18.5%.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022320646.
PubMed: 35912183
DOI: 10.3389/fonc.2022.934093