-
Current Medical Research and Opinion May 2022Examination of postmortem findings can help establish effective therapeutic strategies to reduce mortality. The aim of this study was therefore to review complete... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Examination of postmortem findings can help establish effective therapeutic strategies to reduce mortality. The aim of this study was therefore to review complete autopsy cases and their postmortem findings and comorbidities associated with death caused by COVID-19, in order to establish a profile of the deceased and the likelihood of time to death.
METHODS
A systematic review was carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and meets Cochrane criteria recommendations (PROSPERO registration number CRD 42020209649). An electronic search in the databases Pubmed, Scopus, Web of Science, Wiley Online Library, and Scientific Electronic Library Online (SciELO) was performed.
RESULTS
The search strategy yielded a total of 25 articles where 140 cases of complete autopsies were reported. The most prevalent comorbidity was vascular diseases. Patients with vascular disease, heart disease, and diabetes died significantly in a shorter period of time. Autopsies mainly focused on the lungs. The proliferative phase of Diffuse Alveolar Damage (DAD) was the most reported in the microscopic postmortem findings, and these patients died in a shorter period of time. However, individuals aged over 80 years significantly presented fibrotic phase of DAD at the time of death. The kidney was the second most affected organ with thrombosis and tubular damage, followed by the liver with congestion and necrosis.
CONCLUSION
Given that accurate information of complete autopsies findings is still scarce, it is necessary to perform complete autopsies by examining organs other than the lungs in order to provide information to improve new treatment strategies in patients with a high risk of mortality.
Topics: Aged; Autopsy; COVID-19; Comorbidity; Humans; Lung; SARS-CoV-2; Vascular Diseases
PubMed: 35254193
DOI: 10.1080/03007995.2022.2050110 -
Clinics in Dermatology 2021Immunoglobulin-G4-related disease (IgG4-RD) is an autoimmune-mediated spectrum of diseases, characterized by infiltration of IgG4+ plasma cells into one or multiple...
Immunoglobulin-G4-related disease (IgG4-RD) is an autoimmune-mediated spectrum of diseases, characterized by infiltration of IgG4+ plasma cells into one or multiple organs, with the pancreas being the most commonly affected organ. The disease mostly affects middle-aged to elderly men. Diagnosis requires an integration of clinical, radiologic, pathologic, and serologic studies. Histologically, there is an increased infiltration of IgG4+ plasma cells, elevated ratio of IgG4+/IgG plasma cells of more than 40%, and a storiform pattern of fibrosis. There may be eosinophilia, along with elevated IgG4 levels. IgG4-RD can mimic several diseases and should be differentiated from inflammatory and neoplastic processes. Recently, there has been increased awareness of cutaneous involvement by IgG4-RD either as an isolated lesion or primary involvement or as a secondary involvement from a systemic disease. Clinically, cutaneous IgG4+-related disease presents as papules, plaques, and nodules involving the head and neck areas. We have provided a systematic review of the literature of this new and challenging entity of cutaneous IgG4-RD.
Topics: Aged; Autoimmune Diseases; Fibrosis; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Male; Middle Aged; Skin; Skin Diseases
PubMed: 34272023
DOI: 10.1016/j.clindermatol.2020.10.009 -
American Journal of Transplantation :... Aug 2016Liver transplant outcome has improved considerably as a direct result of optimized surgical and anesthesiological techniques and organ allocation programs. Because there... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Meta-Analysis of the Impact of Computed Tomography-Assessed Skeletal Muscle Mass on Outcome in Patients Awaiting or Undergoing Liver Transplantation.
Liver transplant outcome has improved considerably as a direct result of optimized surgical and anesthesiological techniques and organ allocation programs. Because there remains a shortage of human organs, strict selection of transplant candidates remains of paramount importance. Recently, computed tomography (CT)-assessed low skeletal muscle mass (i.e. sarcopenia) was identified as a novel prognostic parameter to predict outcome in liver transplant candidates. A systematic review and meta-analysis on the impact of CT-assessed skeletal muscle mass on outcome in liver transplant candidates were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Nineteen studies, including 3803 patients in partly overlapping cohorts, fulfilled the inclusion criteria. The prevalence of sarcopenia ranged from 22.2% to 70%. An independent association between low muscle mass and posttransplantation and waiting list mortality was described in 4 of the 6 and 6 of the 11 studies, respectively. The pooled hazard ratios of sarcopenia were 1.84 (95% confidence interval 1.11-3.05, p = 0.02) and 1.72 (95% confidence interval 0.99-3.00, p = 0.05) for posttransplantation and waiting list mortality, respectively, independent of Model for End-stage Liver Disease score. Less-consistent evidence suggested a higher complication rate, particularly infections, in sarcopenic patients. In conclusion, sarcopenia is an independent predictor for outcome in liver transplantation patients and could be used for risk assessment.
Topics: Humans; Liver Diseases; Liver Transplantation; Muscle, Skeletal; Prognosis; Sarcopenia; Tomography, X-Ray Computed
PubMed: 26813115
DOI: 10.1111/ajt.13732 -
European Journal of Cancer (Oxford,... May 2022Local treatment (metastasectomy or stereotactic radiotherapy) for oligometastatic disease (OMD) in patients with esophagogastric cancer may improve overall survival... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Local treatment (metastasectomy or stereotactic radiotherapy) for oligometastatic disease (OMD) in patients with esophagogastric cancer may improve overall survival (OS). The primary aim was to identify definitions of esophagogastric OMD. A secondary aim was to perform a meta-analysis of OS after local treatment versus systemic therapy alone for OMD.
METHODS
Studies and study protocols reporting on definitions or OS after local treatment for esophagogastric OMD were included. The primary outcome was the maximum number of organs/lesions considered OMD and the maximum number of lesions per organ (i.e. 'organ-specific' OMD burden). Agreement was considered to be either absent/poor (< 50%), fair (50%-75%), or consensus (≥ 75%). The secondary outcome was the pooled adjusted hazard ratio (aHR) for OS after local treatment versus systemic therapy alone. The ROBINS tool was used for quality assessment.
RESULTS
A total of 97 studies, including 7 study protocols, and 2 prospective studies, were included. OMD was considered in 1 organ with ≤ 3 metastases (consensus). 'Organ-specific' OMD burden could involve bilobar ≤ 3 liver metastases, unilateral ≤ 2 lung metastases, 1 extra-regional lymph node station, ≤ 2 brain metastases, or bilateral adrenal gland metastases (consensus). Local treatment for OMD was associated with improved OS compared with systemic therapy alone based on 6 non-randomized studies (pooled aHR 0.47, 95% CI: 0.30-0.74) and for liver oligometastases based on 5 non-randomized studies (pooled aHR 0.39, 95% CI: 0.22-0.59). All studies scored serious risk of bias.
CONCLUSIONS
Current literature considers esophagogastric cancer spread limited to 1 organ with ≤ 3 metastases or 1 extra-regional lymph node station to be OMD. Local treatment for OMD appeared associated with improved OS compared with systemic therapy alone. Prospective randomized trials are warranted.
Topics: Esophageal Neoplasms; Humans; Metastasectomy; Neoplasm Metastasis; Prospective Studies; Radiosurgery; Stomach Neoplasms
PubMed: 35339868
DOI: 10.1016/j.ejca.2022.02.018 -
Gels (Basel, Switzerland) Jan 2024Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This... (Review)
Review
Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This technology can set many parameters, like fluid shear stress, chemical concentration gradient, tissue-organ interface, and cell interaction. The use of these devices in medical research permits the investigation of cell patterning, tissue-material interface, and organ-organ interaction, mimicking the complex structures and microenvironment of human and animal bodies. This technology allows us to reconstitute in vitro complex conditions that recapitulate in vivo environments. One of the main advantages of these systems is that they represent a very realistic model that, in many cases, can replace animal experimentation, eliminating costs and related ethical issues. Organ-on-a-chip can also contain bacteria or cancer cells. This technology could be beneficial in dentistry for testing novel antibacterial substances and biomaterials, performing studies on inflammatory disease, or planning preclinical studies. A significant number of publications and reviews have been published on this topic. Still, to our knowledge, they mainly focus on the materials used for fabrication and the different patterns of the chip applied to the experimentations. This review presents the most recent applications of organ-on-a-chip models in dentistry, starting from the reconstituted dental tissues to their clinical applications and future perspectives.
PubMed: 38391432
DOI: 10.3390/gels10020102 -
BMJ Open Jun 2017This review investigates the impact of corticosteroids on donation rates and transplant outcomes in light of findings from randomised controlled trials (RCTs) and to... (Review)
Review
OBJECTIVES
This review investigates the impact of corticosteroids on donation rates and transplant outcomes in light of findings from randomised controlled trials (RCTs) and to highlight the sources of uncertainty in this unresolved donor management issue.
DATA SOURCES
We searched electronic databases, trial registries and conference proceedings for RCTs evaluating corticosteroid therapy in neurologically deceased donors.
STUDY SELECTION AND DATA EXTRACTION
Independent reviewers assessed eligibility, evaluated risk of bias and abstracted data, including donor haemodynamic data, number of organs recovered and transplant outcomes. Where possible, we pooled results. For each outcome, we assessed the overall quality of evidence using The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.
DATA SYNTHESIS
Eleven RCTs with different corticosteroid regimens were included. Most trials assessed a once-daily infusion of methylprednisolone. Aside from one study showing improved liver graft function, no individual study or pooled analysis showed benefit of corticosteroids for any outcome: vasopressor use (three trials; relative risk (RR) 0.96; 95% CI 0.89 to 1.05), multiple organs recovered (two trials; RR 0.82; 95% CI 0.61 to 1.11), acute graft rejection (three trials; RR 0.91; 95% CI 0.60 to 1.39) or graft dysfunction (eight trials; RR 1.01; 95% CI 0.83 to 1.24). Two trials investigated adverse effects and found similar rates between groups. Quality of evidence was moderate or low for all outcomes.
CONCLUSION
Current clinical trials are limited in numbers and size to identify benefits or harms of corticosteroid therapy for deceased organ donors. In the face of these results, administering or withholding steroids both appear reasonable courses of action.
Topics: Adrenal Cortex Hormones; Critical Illness; Graft Rejection; Graft Survival; Humans; Observational Studies as Topic; Organ Transplantation; Randomized Controlled Trials as Topic; Tissue Donors; Transplant Recipients
PubMed: 28667204
DOI: 10.1136/bmjopen-2016-014436 -
World Journal of Emergency Surgery :... 2016Due to the increasing number of solid organs transplantations, emergency abdominal surgery in transplanted patients is becoming a relevant challenge for the general... (Review)
Review
AIMS
Due to the increasing number of solid organs transplantations, emergency abdominal surgery in transplanted patients is becoming a relevant challenge for the general surgeon. The aim of this systematic review of the literature is to analyze morbidity and mortality of emergency abdominal surgery performed in transplanted patients for graft-unrelated surgical problems.
METHODS
The literature search was performed on online databases with the time limit 1990-2015. Studies describing all types of emergency abdominal surgery in solid organ transplanted patients were retrieved for evaluation.
RESULTS
Thirty-nine case series published between 1996 and 2015 met the inclusion criteria and were selected for the systematic review. Overall, they included 71671 transplanted patients, of which 1761 (2.5 %) underwent emergency abdominal surgery. The transplanted organs were the heart in 65.8 % of patients, the lung in 22.1 %, the kidney in 9.5 %, and the liver in 2.6 %. The mean patients' age at the time of the emergency abdominal surgery was 49.4 ± 7.4 years, and the median time from transplantation to emergency surgery was 2.4 years (range 0.1-20). Indications for emergency abdominal surgery were: gallbladder diseases (80.3 %), gastrointestinal perforations (9.2 %), complicated diverticulitis (6.2 %), small bowel obstructions (2 %), and appendicitis (2 %). The overall mortality was 5.5 % (range 0-17.5 %). The morbidity rate varied from 13.6 % for gallbladder diseases to 32.7 % for complicated diverticulitis. Most of the time, the immunosuppressive therapy was maintained unmodified postoperatively.
CONCLUSIONS
Emergency abdominal surgery in transplanted patients is not a rare event. Although associated with relevant mortality and morbidity, a prompt and appropriate surgery can lead to satisfactory results if performed taking into account the patient's immunosuppression therapy and hemodynamic stability.
PubMed: 27582783
DOI: 10.1186/s13017-016-0101-6 -
International Journal of Cancer Mar 2015The prospective evidence for the associations of gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) with risk of cancer in the general population is... (Meta-Analysis)
Meta-Analysis Review
The prospective evidence for the associations of gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) with risk of cancer in the general population is uncertain. We conducted a systematic review and meta-analysis of published prospective observational studies evaluating the associations of baseline levels of GGT and ALT with risk of overall (incidence and/or mortality) and site-specific cancers. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, reference lists of relevant studies to April 2014 and email contact with investigators. Study specific relative risks (RRs) were meta-analyzed using random effects models. Fourteen cohort studies with data on 1.79 million participants and 57,534 cancer outcomes were included. Comparing top versus bottom thirds of baseline circulating GGT levels, pooled RRs (95% confidence intervals) were 1.32 (1.15-1.52) for overall cancer, 1.09 (0.95-1.24) for cancers of the breast and female genital organs, 1.09 (1.02-1.16) for cancers of male genital organs, 1.94 (1.35-2.79) for cancers of digestive organs and 1.33 (0.94-1.89) for cancers of respiratory and intrathoracic organs. For ALT, corresponding RRs for overall cancer were 0.96 (0.94-0.99) and 1.65 (1.52-1.79) in European and Asian populations, respectively. There was an increased risk of cancers of the digestive organs 2.44 (1.23-4.84). The pooled RR for overall cancer per 5 U/L increment in GGT levels was 1.04 (1.03-1.05). Available observational data indicate a positive log-linear association of GGT levels with overall cancer risk. The positive association was generally evident for site-specific cancers. There are geographical variations in the association of ALT and overall cancer.
Topics: Alanine Transaminase; Female; Follow-Up Studies; Humans; Incidence; Male; Neoplasms; Prognosis; Risk Factors; gamma-Glutamyltransferase
PubMed: 25043373
DOI: 10.1002/ijc.29084 -
Journal of Tissue Engineering and... Dec 2022Amniotic membrane (AM) has great potential as a scaffold for tissue regeneration in reconstructive surgery. To date, no systematic review of the literature has been... (Meta-Analysis)
Meta-Analysis Review
Amniotic membrane (AM) has great potential as a scaffold for tissue regeneration in reconstructive surgery. To date, no systematic review of the literature has been performed for the applications of AM in wound closure of internal organs. Therefore, in this systematic review and meta-analysis, we summarize the literature on the safety and efficacy of AM for the closure of internal organs. A systematic search was performed in MEDLINE-PubMed database and OVID Embase to retrieve human and controlled animal studies on wound closure of internal organs. The Cochrane Risk of Bias tool for randomized clinical trials and the SYRCLE risk of bias tool for animal studies were used. Meta-analyses (MAs) were conducted for controlled animal studies to assess efficacy of closure, mortality and complications in subjects who underwent surgical wound closure in internal organs with the application of AM. Sixty references containing 26 human experiments and 36 animal experiments were included. The MAs of the controlled animal studies showed comparable results with regard to closure, mortality and complications, and suggested improved mechanical strength and lower inflammation scores after AM application when compared to standard surgical closure techniques. This systematic review and MAs demonstrate that the application of AM to promote wound healing of internal organs appears to be safe, efficacious, and feasible.
Topics: Humans; Amnion; Wound Healing; Wound Closure Techniques; Plastic Surgery Procedures
PubMed: 36333859
DOI: 10.1002/term.3357 -
The Cochrane Database of Systematic... Sep 2022Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and... (Review)
Review
BACKGROUND
Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and post-transplant recovery, immunosuppressive medications are often accompanied by a high prevalence of gastrointestinal (GI) symptoms and side effects. Apart from GI side effects, long-term exposure to immunosuppressive medications has seen an increase in drug-related morbidities such as diabetes mellitus, hyperlipidaemia, hypertension, and malignancy. Non-adherence to immunosuppression can lead to an increased risk of graft failure. Recent research has indicated that any microbial imbalances (otherwise known as gut dysbiosis or leaky gut) may be associated with cardiometabolic diseases in the long term. Current evidence suggests a link between the gut microbiome and the production of putative uraemic toxins, increased gut permeability, and transmural movement of bacteria and endotoxins and inflammation. Early observational and intervention studies have been investigating food-intake patterns, various synbiotic interventions (antibiotics, prebiotics, or probiotics), and faecal transplants to measure their effects on microbiota in treating cardiometabolic diseases. It is believed high doses of synbiotics, prebiotics and probiotics are able to modify and improve dysbiosis of gut micro-organisms by altering the population of the micro-organisms. With the right balance in the gut flora, a primary benefit is believed to be the suppression of pathogens through immunostimulation and gut barrier enhancement (less permeability of the gut).
OBJECTIVES
To assess the benefits and harms of synbiotics, prebiotics, and probiotics for recipients of solid organ transplantation.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register up to 9 March 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials measuring and reporting the effects of synbiotics, prebiotics, or probiotics, in any combination and any formulation given to solid organ transplant recipients (any age and setting). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.
DATA COLLECTION AND ANALYSIS
Data extraction was independently carried out by two authors using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Five studies (250 participants) were included in this review. Study participants were adults with a kidney (one study) or liver (four studies) transplant. One study compared a synbiotic to placebo, two studies compared a probiotic to placebo, and two studies compared a synbiotic to a prebiotic. Overall, the quality of the evidence is poor. Most studies were judged to have unclear (or high) risk of bias across most domains. Of the available evidence, meta-analyses undertaken were of limited data from small studies. Across all comparisons, GRADE evaluations for all outcomes were judged to be very low certainty evidence. Very low certainty evidence implies that we are very uncertain about results (not estimable due to lack of data or poor quality). Synbiotics had uncertain effects on the change in microbiota composition (total plasma p-cresol), faecal characteristics, adverse events, kidney function or albumin concentration (1 study, 34 participants) compared to placebo. Probiotics had uncertain effects on GI side effects, infection rates immediately post-transplant, liver function, blood pressure, change in fatty liver, and lipids (1 study, 30 participants) compared to placebo. Synbiotics had uncertain effects on graft health (acute liver rejection) (2 studies, 129 participants: RR 0.73, 95% CI 0.43 to 1.25; 2 studies, 129 participants; I² = 0%), the use of immunosuppression, infection (2 studies, 129 participants: RR 0.18, 95% CI 0.03 to 1.17; I² = 66%), GI function (time to first bowel movement), adverse events (2 studies, 129 participants: RR 0.79, 95% CI 0.40 to 1.59; I² = 20%), serious adverse events (2 studies, 129 participants: RR 1.49, 95% CI 0.42 to 5.36; I² = 81%), death (2 studies, 129 participants), and organ function measures (2 studies; 129 participants) compared to prebiotics.
AUTHORS' CONCLUSIONS
This review highlights the severe lack of high-quality RCTs testing the efficacy of synbiotics, prebiotics or probiotics in solid organ transplant recipients. We have identified significant gaps in the evidence. Despite GI symptoms and postoperative infection being the most common reasons for high antibiotic use in this patient population, along with increased morbidity and the growing antimicrobial resistance, we found very few studies that adequately tested these as alternative treatments. There is currently no evidence to support or refute the use of synbiotics, prebiotics, or probiotics in solid organ transplant recipients, and findings should be viewed with caution. We have identified an area of significant uncertainty about the efficacy of synbiotics, prebiotics, or probiotics in solid organ transplant recipients. Future research in this field requires adequately powered RCTs comparing synbiotics, prebiotics, and probiotics separately and with placebo measuring a standard set of core transplant outcomes. Six studies are currently ongoing (822 proposed participants); therefore, it is possible that findings may change with their inclusion in future updates.
Topics: Adult; Albumins; Anti-Bacterial Agents; Cardiovascular Diseases; Dysbiosis; Endotoxins; Humans; Lipids; Organ Transplantation; Prebiotics; Probiotics; Synbiotics
PubMed: 36126902
DOI: 10.1002/14651858.CD014804.pub2