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Annals of Medicine and Surgery (2012) Jun 2023Ventilator-associated pneumonia (VAP) is the most common ICU acquired pneumonia among patients who are invasively intubated for mechanical ventilation. Patients with VAP...
Ventilator-associated pneumonia (VAP) is the most common ICU acquired pneumonia among patients who are invasively intubated for mechanical ventilation. Patients with VAP suffer an increased mortality risk, financial burden, and length of stay in the hospital. The authors aimed to review the literature to describe the incidence, mortality, and microbiological evidence of VAP. We selected 13 peer-reviewed articles published from 1 January 2010 to 15 September 2022 from electronic databases for studies among adult or pediatric patients diagnosed with VAP expressed per thousand days admitted in the ICU. The VAP rates ranged from 7 to 43 per thousand days, varying among different countries of the world. A significant rate of mortality was observed in 13 studies ranging from 6.3 to 66.9%. Gram-negative organisms like Acinetobacter spp., Pseudomonas aeruginosa Gram-positive organisms like Staphylococcus aureus were frequently found. Our findings suggest an alarming situation of VAP among patients admitted to the intensive care units with increasing incidence and mortality. The review also found that VAP is more common in males and that there is a significant variation in the incidence and mortality rates of VAP among different countries. The findings of this review can inform the development of infection control and prevention strategies to reduce the burden of VAP. Thus, there is a crucial need for control and preventive measures like interventional studies and educational programs on staff training, hand-hygiene, and the appropriate use of ventilator bundle approach to curb this preventable threat that is increasing at an alarming rate.
PubMed: 37363470
DOI: 10.1097/MS9.0000000000000836 -
European Urology Open Science Sep 2023Unlike other cancers, the concept of oligometastatic disease (OMD) in bladder cancer (BC) has not been systematically investigated. There is therefore a need to develop... (Review)
Review
CONTEXT
Unlike other cancers, the concept of oligometastatic disease (OMD) in bladder cancer (BC) has not been systematically investigated. There is therefore a need to develop universally accepted definitions and guidelines for the management of oligometastatic BC (OMBC).
OBJECTIVE
To conduct a systematic review to assist a European consensus group in producing a definition of OMBC and to provide recommendations on staging and local therapies.
EVIDENCE ACQUISITION
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Abstracts for articles focused on BC that addressed the issue of OMBC and provided a definition of oligometastatic status were selected. We collected data on the number of metastases, the number of metastases per organ, the number of organs involved, and metastatic sites that were excluded.
EVIDENCE SYNTHESIS
Sixteen eligible articles were retrieved (9 retrospective series involving 330 patients, 4 reviews, 1 consensus statement, 1 guideline paper, and 1 ongoing prospective phase 2 trial). A maximum of three to five metastatic lesions were compatible with the definition of OMBC. The number of organs involved and lesion size were not universally included in the OMBC definitions. OMD categories studied included synchronous OMBC, oligorecurrence, and oligoprogression. F-Fluorodeoxyglucose positron emission tomography combined with computed tomography was used in addition to conventional imaging for OMD detection. Surgery and radiotherapy were both used. Systemic chemotherapy was also used in all studies.
CONCLUSIONS
There is little information on OMBC in the literature. Our systematic review revealed that only three to five metastatic sites amenable to surgery or radiotherapy that respond to systemic therapy is the setting most frequently chosen for a combination of systemic treatment and metastases-directed therapy. This setting could represent a basis for future prospective studies on OMBC.
PATIENT SUMMARY
Oligometastatic bladder cancer is a disease state in which favorable outcomes can be expected after a treatment combination of systemic therapy, plus surgery and/or radiotherapy for sites of bladder cancer metastasis. Our systematic review showed a lack of meaningful evidence to define this disease state. There is an urgent need to develop organized research in this field.
PubMed: 37662704
DOI: 10.1016/j.euros.2023.08.003 -
Frontiers in Medicine 2022Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage...
INTRODUCTION
Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.
METHODS
A systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.
RESULTS
We report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).
CONCLUSION
The results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.
PubMed: 35833101
DOI: 10.3389/fmed.2022.930071 -
Frontiers in Medicine 2021Many putative uremic toxins-like indoxyl sulfate, p-cresol sulfate, kynurenic acid, uric acid, and CMPF-are organic anions. Both inter-organ and inter-organismal...
Many putative uremic toxins-like indoxyl sulfate, p-cresol sulfate, kynurenic acid, uric acid, and CMPF-are organic anions. Both inter-organ and inter-organismal communication are involved. For example, the gut microbiome is the main source of indole, which, after modification by liver drug metabolizing enzymes (DMEs), becomes indoxyl sulfate. Various organic anion transporters (organic anion transporters, OATs; organic anion-transporting polypeptides, OATPs; multidrug resistance-associated proteins, MRPs, and other ABC transporters like ABCG2)-often termed "drug transporters"-mediate movement of uremic toxins through cells and organs. In the kidney proximal tubule, critical roles for OAT1 and OAT3 in regulating levels of protein-bound uremic toxins have been established using knock-out mice. OATs are important in maintaining residual tubular function in chronic kidney disease (CKD); as CKD progresses, intestinal transporters like ABCG2, which extrude urate and other organic anions into the gut lumen, seem to help restore homeostasis. Uremic toxins like indoxyl sulfate also regulate signaling and metabolism, potentially affecting gene expression in extra-renal tissues as well as the kidney. Focusing on the history and evolving story of indoxyl sulfate, we discuss how uremic toxins appear to be part of an extensive "remote sensing and signaling" network-involving so-called drug transporters and drug metabolizing enzymes which modulate metabolism and signaling. This systems biology view of uremic toxins is leading to a new appreciation of uremia as partly due to disordered remote sensing and signaling mechanisms-resulting from, and causing, aberrant inter-organ (e.g., gut-liver- kidney-CNS) and inter-organismal (e.g., gut microbiome-host) communication.
PubMed: 33937275
DOI: 10.3389/fmed.2021.592602 -
Tropical Medicine and Infectious Disease Jan 2021There is increasing evidence that human movement facilitates the global spread of resistant bacteria and antimicrobial resistance (AMR) genes. We systematically reviewed... (Review)
Review
There is increasing evidence that human movement facilitates the global spread of resistant bacteria and antimicrobial resistance (AMR) genes. We systematically reviewed the literature on the impact of travel on the dissemination of AMR. We searched the databases Medline, EMBASE and SCOPUS from database inception until the end of June 2019. Of the 3052 titles identified, 2253 articles passed the initial screening, of which 238 met the inclusion criteria. The studies covered 30,060 drug-resistant isolates from 26 identified bacterial species. Most were enteric, accounting for 65% of the identified species and 92% of all documented isolates. High-income countries were more likely to be recipient nations for AMR originating from middle- and low-income countries. The most common origin of travellers with resistant bacteria was Asia, covering 36% of the total isolates. Beta-lactams and quinolones were the most documented drug-resistant organisms, accounting for 35% and 31% of the overall drug resistance, respectively. Medical tourism was twice as likely to be associated with multidrug-resistant organisms than general travel. International travel is a vehicle for the transmission of antimicrobial resistance globally. Health systems should identify recent travellers to ensure that adequate precautions are taken.
PubMed: 33467065
DOI: 10.3390/tropicalmed6010011 -
SAGE Open Medicine 2023Multifocal fibrosclerosis is a rare disorder causing progressive fibrosis of multiple organ systems. Existing data on the disease show that there are multiple... (Review)
Review
OBJECTIVES
Multifocal fibrosclerosis is a rare disorder causing progressive fibrosis of multiple organ systems. Existing data on the disease show that there are multiple manifestations of the disease, with different outcomes. However, quantitative data are scarce, prompting the need for our investigation.
METHOD
A comprehensive systematic review was performed from inception to November 16, 2022, with the restriction of English language, not including review articles. Article screening and extraction was performed independently, and shortlisted articles were assessed for bias. Analysis was performed using SPSS Version 25 (IBM® SPSS® Statistics; Chicago, IL, USA). Data were presented as frequencies and percentages, with a confidence interval of 95%.
RESULT
This review included 134 patients, with 78 (58.2%) males. Mean age was 53.6 years and included two pediatric patients. The most common comorbidity was diabetes (9.7%). Prevalent presenting symptoms included pain (47.8%) and swelling (35.1%). A mean of 2.51 organs or anatomical sites was affected, retroperitoneum (64.2%) being most affected. The pancreas (30.0%) and digestive system (47.0%) were the organs/organ systems most affected. Patients had favorable outcomes in 79.1% of cases, 87.3% had no relapse, and 91.8% of patients survived the condition.
CONCLUSION
The findings in this study provide a quantitative measurement of the demographics, presentations, organ manifestations, and outcomes of multifocal fibrosclerosis. We found the disease to be prevalent in males in Japan or the United States, with the abdomen and its organs being commonly involved.
PubMed: 37275844
DOI: 10.1177/20503121231178046 -
Diagnostics (Basel, Switzerland) Jan 2022The microbiome is vital for the proper function of the gastrointestinal tract (GIT) and the maintenance of overall wellbeing. Gut ischemia may lead to disruption of the... (Review)
Review
The microbiome is vital for the proper function of the gastrointestinal tract (GIT) and the maintenance of overall wellbeing. Gut ischemia may lead to disruption of the intestinal mucosal barrier, resulting in bacterial translocation. In this systematic review, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines, we constructed a search query using the PICOT (Patient, Intervention, Comparison, Outcome, Time) framework. Eligible studies reported in PubMed, up to April 2021 were selected, from which, 57 publications' data were included. According to these, escape of intraluminal potentially harmful factors into the systemic circulation and their transmission to distant organs and tissues, in utero, at birth, or immediately after, can be caused by reduced blood oxygenation. Various factors are involved in this situation. The GIT is a target organ, with high sensitivity to ischemia-hypoxia, and even short periods of ischemia may cause significant local tissue damage. Fetal hypoxia and perinatal asphyxia reduce bowel motility, especially in preterm neonates. Despite the fact that microbiome arouse the interest of scientists in recent decades, the pathophysiologic patterns which mediate in perinatal hypoxia/asphyxia conditions and gut function have not yet been well understood.
PubMed: 35054381
DOI: 10.3390/diagnostics12010214 -
BMJ (Clinical Research Ed.) Jun 2015To compare the clinical efficacy and bioequivalence of generic immunosuppressive drugs in patients with solid organ transplants. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the clinical efficacy and bioequivalence of generic immunosuppressive drugs in patients with solid organ transplants.
DESIGN
Systematic review and meta-analysis of all studies comparing generic with innovator immunosuppressive drugs.
DATA SOURCES
Medline and Embase from 1980 to September 2014.
REVIEW METHODS
A literature search was performed for all studies comparing a generic to an innovator immunosuppressive drug in solid organ transplantation. Two reviewers independently extracted data and assessed quality of studies. Meta-analyses of prespecified outcomes were performed when deemed appropriate. Outcomes included patient survival, allograft survival, acute rejection, adverse events and bioequivalence.
RESULTS
1679 citations were screened, of which 50 studies met eligibility criteria (17 randomized trials, 15 non-randomized interventional studies, and 18 observational studies). Generics were compared with Neoral (cyclosporine) (32 studies), Prograf (tacrolimus) (12 studies), and Cellcept (mycophenolate mofetil) (six studies). Pooled analysis of randomized controlled trials in patients with kidney transplants that reported bioequivalence criteria showed that Neoral (two studies) and Prograf (three studies) were not bioequivalent with generic preparations according to criteria of the European Medicines Agency. The single Cellcept trial also did not meet bioequivalence. Acute rejection was rare but did not differ between groups. For Neoral, the pooled Peto odds ratio was 1.23 (95% confidence interval 0.64 to 2.36) for kidney randomized controlled trials and 0.66 (0.40 to 1.08) for observational studies. For kidney observational studies, the pooled Peto odds ratios were 0.98 (0.37 to 2.60) for Prograf and 0.49 (0.09 to 2.56) for Cellcept. Meta-analyses for non-renal solid organ transplants were not performed because of a lack of data.There were insufficient data reported on patient or graft survival. Pooling of results was limited by inconsistent study methods and reporting of outcomes. Many studies did not report standard criteria used to determine bioequivalence. While rates of acute rejection seemed similar and were relatively rare, few studies were designed to properly compare clinical outcomes. Most studies had short follow-up times and included stable patients without a history of rejection.
CONCLUSIONS
High quality data showing bioequivalence and clinical efficacy of generic immunosuppressive drugs in patients with transplants are lacking. Given the serious consequences of rejection and allograft failure, well designed studies on bioequivalence and safety of generic immunosuppression in transplant recipients are needed.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Drugs, Generic; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Organ Transplantation; Prognosis; Survival Analysis; Treatment Outcome
PubMed: 26101226
DOI: 10.1136/bmj.h3163 -
Journal of Ovarian Research Jun 2016Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage... (Meta-Analysis)
Meta-Analysis Review
Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage in different organ transplants in animal experiments. Several concentrations and administration pathways have been tested and melatonin has shown encouraging beneficial results in many transplants of organs such as the liver, lungs, heart, pancreas, and kidneys. The objective of the present study was to review the scientific literature regarding the use of melatonin in ovary transplantation. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was carried out using the Cochrane and Pubmed databases and employing the terms 'melatonin' AND 'ovary' AND 'transplantation.' After analysis, 5 articles were extracted addressing melatonin use in ovary transplants and involving 503 animals. Melatonin enhanced various graft aspects like morphology, apoptosis, immunological reaction, revascularization, oxidative stress, and survival rate. Melatonin's antioxidative and antiapoptotic properties seemingly produce positive effects on ovarian graft activity. Despite the promising results, further studies in humans need to be conducted to consolidate its use, as ovary transplantation for fertility preservation is gradually being moved from the experimental stage to a clinical setting.
Topics: Animals; Antioxidants; Apoptosis; Female; Graft Survival; Humans; Melatonin; Neovascularization, Physiologic; Organ Transplantation; Ovary; Oxidative Stress
PubMed: 27287621
DOI: 10.1186/s13048-016-0245-8 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796