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Exercise Immunology Review 2022There is a knowledge gap regarding the consequences of exercise during acute infections in humans and contradictory findings in animal studies, compromising public... (Meta-Analysis)
Meta-Analysis
There is a knowledge gap regarding the consequences of exercise during acute infections in humans and contradictory findings in animal studies, compromising public health advice on the potential benefits of physical activity for immunity. Here, we carried out a meta-analysis of studies of the effects of moderate exercise (ME) and exercise until fatigue (EF) on symptom severity, morbidity and mortality during viral infection in animal models. The systematic review on PubMed, Scopus, Embase, Web of Science, Cochrane and EBSCOhost (CINAHL and SPORT Discus) identified 8 controlled studies, with 15 subgroups within them. The studies exposed the animals (mice [7 studies] and monkeys [1 study]) to exercise immediately before or after viral inoculation (HSV-1, H1N1 influenza and B.K. virus) with follow-up for 21 days. ME significantly reduced morbidity (OR 0.43 [0.19; 0.98], P = 0.04) with no change for symptom severity (SMD -3.37 [-9.01; 2.28], P = 0.24) or mortality (OR 0.48 [0.08;3.03], P = 0.43). In contrast, EF gave a trend towards increased symptom severity (SMD 0.96 [-0.06; 1.98], P = 0.07) and mortality (OR 1.47 [0.96;2.28], P =0.08) with no change in morbidity (OR 1.22 [0.60;2.5], P = 0.58). We conclude that in animals moderate exercise during infection is advantageous, whilst exercise until fatigue should be avoided. Further research is required to determine if moderate exercise may also be beneficial in humans during infection.
Topics: Animals; Exercise Therapy; Fatigue; Humans; Influenza A Virus, H1N1 Subtype; Mice; Morbidity; Virus Diseases
PubMed: 35913495
DOI: No ID Found -
Transplant Infectious Disease : An... Aug 2019There is a growing base of literature describing BK nephropathy (BKVN) in patients outside of the setting of kidney transplant. Previous systematic reviews of the...
BACKGROUND
There is a growing base of literature describing BK nephropathy (BKVN) in patients outside of the setting of kidney transplant. Previous systematic reviews of the literature have been limited by methodology or by the scope of patients included.
STUDY DESIGN AND METHODS
Systematic Review (Prospero # CRD42018088524).
SETTING & POPULATION
Patients without kidney transplant who had biopsy-proven BKVN.
SELECTION CRITERIA FOR STUDIES
Full-text articles that describe native BKVN patient cases.
ANALYTICAL APPROACH
Descriptive synthesis.
RESULTS
The search identified 630 unique articles of which 51 were included in the final review. Sixty-five cases (including two new cases presented in this review) were identified, all but one occurred in the setting of known immunosuppression.
LIMITATIONS
The primary limitation was the exclusion of studies that did not fulfill the stringent review criteria. We excluded reports with only a clinical diagnosis of BKVN, such as those with viruria and/or viremia without biopsy.
CONCLUSIONS
As of May 2018, there are 65 reported cases of BKVN in native kidneys. This represents the most comprehensive description of biopsy-proven BKVN in native kidneys to date. Evaluation for BK nephropathy should be considered in immunocompromised patients who exhibit unexplained renal failure.
Topics: Adult; Aged; BK Virus; Biopsy; Humans; Immunocompromised Host; Immunosuppression Therapy; Kidney; Kidney Diseases; Kidney Transplantation; Male; Polyomavirus Infections; Tumor Virus Infections; Viremia
PubMed: 30907978
DOI: 10.1111/tid.13083 -
Expert Opinion on Biological Therapy Sep 2021This systematic review and meta-analysis were performed to explore the association between rabbit thymoglobulin (rATG) doses and transplant-related efficacy and safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis were performed to explore the association between rabbit thymoglobulin (rATG) doses and transplant-related efficacy and safety outcomes.
METHODS
We searched PubMed and Scopus databases from inception up to June 2020. The primary efficacy and safety endpoints in kidney transplant recipients were evaluated.
RESULTS
Data of 23 cohort studies (3457 patients) and three RCTs (154 patients) were extracted and analyzed. rATG doses of ≤4.5 m/kg was associated with lower rates of biopsy proven acute rejection, cytomegalovirus infection, BK virus infection, and malignancy with a comparable rate of delayed graft function, patients' mortality, and death-censored graft loss compared to rATG total doses of 4.5-6 mg/kg or more than 6 mg/kg. The rATG doses of 3-4.5 mg/kg was associated with better outcomes in dose-response analysis.
EXPERT OPINION
Cumulative rATG induction doses as much as 3-4.5 mg/kg is as effective as higher doses regarding to allograft and patient outcomes while minimizing potential adverse effects in kidney transplant recipients.
Topics: Antilymphocyte Serum; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Retrospective Studies
PubMed: 34304664
DOI: 10.1080/14712598.2021.1960978 -
JHEP Reports : Innovation in Hepatology Jan 2023The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This...
BACKGROUND & AIMS
The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This systematic review and meta-analysis aimed to evaluate current literature on this issue.
METHODS
We searched PubMed, Embase, and Web of Science for NUC stop studies that noted clinical outcomes published between January 1, 2006 and August 18, 2022. We performed meta-research analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with non-overlapping populations to provide risk estimates for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flare-related death or liver transplantation.
RESULTS
The meta-research analysis included 50 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only ten studies prespecified safety events as the study outcome, and only four had an outcome definition to include hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 15 studies with 4,525 individuals and estimated that severe hepatitis flares or decompensation would occur in 1.21% (95% CI 0.70-2.08%), with significant heterogeneity ( = 54%, <0.01), while hepatitis flare-related death or liver transplantation would occur in 0.37% (95% CI 0.20-0.67%), without significant heterogeneity ( = 0.00%, = 1.00).
CONCLUSIONS
Current literature on the risk of serious clinical outcomes following NUC cessation is very limited and highly heterogeneous. Pooled analyses of available data found approximately 1% of patients who stopped NUCs developed severe flares or hepatic decompensation.
IMPACT AND IMPLICATIONS
Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.
PubMed: 36466989
DOI: 10.1016/j.jhepr.2022.100617 -
Journal of Clinical Virology : the... Jul 2021BK virus (BKV) infection after kidney transplantation can cause BKV nephropathy (BKVAN) resulting in graft dysfunction and allograft loss. The treatment for BKVAN is... (Meta-Analysis)
Meta-Analysis
BK virus (BKV) infection after kidney transplantation can cause BKV nephropathy (BKVAN) resulting in graft dysfunction and allograft loss. The treatment for BKVAN is reduction of the immunosuppressive load which increases the risk of kidney transplant rejection. There is no biomarker to monitor BKV activity besides BK viral load. The value of the Enzyme-Linked Immunosorbent Spot (ELISPOT) assay as a tool to monitor the recipient's anti-BKV immune response after transplantation was investigated systematically. Electronic databases, including MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched for studies of ELISPOT evaluating the immune response against BKV. BKV status was categorized as "active BKV infection" and as "resolving BKV infection". Random-effects model meta-analysis was performed to determine the diagnostic performance of the ELISPOT assay, after stratifying patients into groups based on positive and negative ELISPOT results. One-hundred twenty-seven articles were identified of which nine were included. Patients with negative ELISPOT had an increased risk of having active BKV replication (odds ratio of 71.9 (95%-CI 31.0-167.1). Pooled sensitivity was 0.95 (95%-CI 0.89-0.98) and specificity was 0.88 (95%-CI 0.78-0.94). The standardized mean difference of the number of IFN-γ producing cells between patients with active BKV infection compared with patients who had resolving BKV infection was -2.09 (95%-CI -2.50, -1.68). The ELISPOT assay is a useful tool for BKV risk assessment and in combination with BKV load may support clinicians in guiding immunosuppressive therapy in patients with BKV replication.
Topics: BK Virus; Enzyme-Linked Immunospot Assay; Humans; Immunity; Immunosorbents; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections
PubMed: 33979739
DOI: 10.1016/j.jcv.2021.104848 -
Hepatology Communications Jul 2022Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have... (Meta-Analysis)
Meta-Analysis
Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p = 0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p = 0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.
Topics: Adult; Carcinoma, Hepatocellular; Hepatectomy; Hepatitis B; Hepatitis C; Humans; Liver Neoplasms; Survival Analysis
PubMed: 35234371
DOI: 10.1002/hep4.1923 -
Journal of Viral Hepatitis Jul 2021Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). HIV/HDV co-infection is associated with a high rate of hepatic decompensation events and... (Meta-Analysis)
Meta-Analysis
Epidemiology estimates of hepatitis D in individuals co-infected with human immunodeficiency virus and hepatitis B virus, 2002-2018: A systematic review and meta-analysis.
Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). HIV/HDV co-infection is associated with a high rate of hepatic decompensation events and death. We aimed to characterize the epidemiology of HDV infection in HIV/HBV co-infected individuals. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, CINAHL and Scopus for studies published from 1 Jan 2002 to 7 May 2018 measuring prevalence of HDV among the HIV population. Pooled seroprevalence was calculated with the DerSimonian-Laird random-effects model. Our search returned 4624 records, 38 of which met the inclusion and exclusion criteria. These studies included data for 63 cohorts from 18 countries and regions. The overall HDV seroprevalence of HIV-infected individuals was 1.03% (95% CI 0.43-1.85) in 2002-2018 globally. Moreover, the estimated pooled HDV seroprevalence among the general population was 1.07% (95% CI 0.65-1.59) in 2002-2018, which was not significantly different from the HDV seroprevalence of individuals living with HIV (p = 0.951). The overall HDV seroprevalence of the HBsAg positive population was 12.15% (95% CI 10.22-14.20), p = 0.434 when compared with the corresponding data of HIV/HBV co-infected individuals. This meta-analysis suggested that there was no difference between the HDV seroprevalence in HIV-infected individuals and the general population.
Topics: Coinfection; HIV; HIV Infections; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; Prevalence; Seroepidemiologic Studies
PubMed: 33877742
DOI: 10.1111/jvh.13512 -
Progres En Urologie : Journal de... Jan 2021To propose surgical recommendations for urothelial carcinoma management in kidney transplant recipients and candidates.
OBJECTIVE
To propose surgical recommendations for urothelial carcinoma management in kidney transplant recipients and candidates.
METHOD
A review of the literature (Medline) following a systematic approcah was conducted by the CTAFU regarding the epidemiology, screening, diagnosis and treatment of urothelial carcinoma in kidney transplant recipients and candidates for renal transplantation. References were assessed according to a predefined process to propose recommendations with levels of evidence.
RESULTS
Urothelial carcinomas occur in the renal transplant recipient population with a 3-fold increased incidence as compared with general population. While major risk factors for urothelial carcinomas are similar to those in the general population, aristolochic acid nephropathy and BK virus infection are more frequent risk factors in renal transplant recipients. As compared with general population, NMIBC in the renal transplant recipients are associated with earlier and higher recurrence rate. The safety and efficacy of adjuvant intravesical therapies have been reported in retrospective series. Treatment for localized MIBC in renal transplant recipients is based on radical cystectomy. In the candidate for a kidney transplant with a history of urothelial tumor, it is imperative to perform follow-up cystoscopies according to the recommended frequency, depending on the risk of recurrence and progression of NMIBC and to maintain this follow-up at least every six months up to transplantation whatever the level of risk of recurrence and progression. Based on current data, the present recommendations propose guidelines for waiting period before active wait-listing renal transplant candidates with a history of urothelial carcinoma.
CONCLUSION
The french recommendations from CTAFU should contribute to improve the management of urothelial carcinoma in renal transplant patients and renal transplant candidates by integrating both oncologic objectives and access to transplantation.
Topics: Carcinoma, Transitional Cell; Humans; Kidney Failure, Chronic; Kidney Transplantation; Postoperative Complications; Urologic Neoplasms
PubMed: 33423744
DOI: 10.1016/j.purol.2020.04.028 -
Transplantation Reviews (Orlando, Fla.) Oct 2020BK polyomavirus (BKPyV) associated nephropathy (BKVAN) is seen in about 5% of renal transplant patients and can lead to chronic graft failure or graft loss. No effective...
BK polyomavirus (BKPyV) associated nephropathy (BKVAN) is seen in about 5% of renal transplant patients and can lead to chronic graft failure or graft loss. No effective therapy is available. Leflunomide has shown promising results in BKVAN. We performed a systematic review about the use of leflunomide for the treatment of BKVAN. The recommendations of the Cochrane Handbook of systematic Reviews were followed. Due to different study designs and endpoints no meta-analysis was performed. The literature search for primary studies yielded 274 results. Finally, twelve studies were included with a total of 267 patients. Clearance of BKPyV viremia was reported in 33.3% to 92.3% of cases and 27 graft losses (10.1%). The included studies were very heterogeneous, especially in terms of leflunomide dosing. Pharmacokinetics seem to have an important impact on the efficacy of leflunomide in BKVAN. There was no correlation between leflunomide serum levels and virus reduction. New adverse events of leflunomide have been described, e.g. haemolytic anaemia and thrombotic microangiopathy. Overall, the risk of bias in the studies was assessed as high and the quality of evidence was rated low. The role of leflunomide in BKVAN remains unclear, but further studies seem reasonable and should address pharmacokinetic aspects.
Topics: Humans; BK Virus; Kidney; Kidney Diseases; Leflunomide; Polyomavirus Infections; Tumor Virus Infections
PubMed: 32611496
DOI: 10.1016/j.trre.2020.100565 -
International Journal of Molecular... Sep 2021Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes...
Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes such as infection and rejection after kidney transplantation. This, and the unmet need for biomarkers diagnosing kidney transplant dysfunction, has led to the current high level of interest in uEV. uEV provide non-intrusive access to local protein, DNA, and RNA analytics without invasive biopsy. To determine the added value of uEV measurements for detecting allograft dysfunction after kidney transplantation, we systematically included all related literature containing directly relevant information, with the addition of indirect evidence regarding urine or kidney injury without transplantation. According to their varying characteristics, uEV markers after transplantation could be categorized into kidney-specific, donor-specific, and immune response-related (IR-) markers. A few convincing studies have shown that kidney-specific markers (PODXL, ion cotransporters, SYT17, NGAL, and CD133) and IR-markers (CD3, multi-mRNA signatures, and viral miRNA) could diagnose rejection, BK virus-associated nephropathy, and calcineurin inhibitor nephrotoxicity after kidney transplantation. In addition, some indirect proof regarding donor-specific markers (donor-derived cell-free DNA) in urine has been demonstrated. Together, this literature review provides directions for exploring novel uEV markers' profiling complications after kidney transplantation.
Topics: Allografts; Biomarkers; Extracellular Vesicles; Graft Rejection; Humans; Kidney; Kidney Transplantation
PubMed: 34638835
DOI: 10.3390/ijms221910499