Coral adaptive capacity insufficient to halt global transition of coral reefs into net erosion under climate change.

Projecting the effects of climate change on net reef calcium carbonate production is critical to understanding the future impacts on ecosystem function, but prior estimates have not included corals' natural adaptive capacity to such change. Here we estimate how the ability of symbionts to evolve tolerance to heat stress, or for coral hosts to shuffle to favourable symbionts, and their combination, may influence responses to the combined impacts of ocean warming and acidification under three representative concentration pathway (RCP) emissions scenarios (RCP2.6, RCP4.5 and RCP8.5). We show that symbiont evolution and shuffling, both individually and when combined, favours persistent positive net reef calcium carbonate production. However, our projections of future net calcium carbonate production (NCCP) under climate change vary both spatially and by RCP. For example, 19%-35% of modelled coral reefs are still projected to have net positive NCCP by 2050 if symbionts can evolve increased thermal tolerance, depending on the RCP. Without symbiont adaptive capacity, the number of coral reefs with positive NCCP drops to 9%-13% by 2050. Accounting for both symbiont evolution and shuffling, we project median positive NCPP of coral reefs will still occur under low greenhouse emissions (RCP2.6) in the Indian Ocean, and even under moderate emissions (RCP4.5) in the Pacific Ocean. However, adaptive capacity will be insufficient to halt the transition of coral reefs globally into erosion by 2050 under severe emissions scenarios (RCP8.5).

Reversal of proliferation deficits caused by chromosome 16p13.11 microduplication through targeting NFκB signaling: an integrated study of patient-derived neuronal precursor cells, cerebral organoids and in vivo brain imaging.

The molecular basis of how chromosome 16p13.11 microduplication leads to major psychiatric disorders is unknown. Here we have undertaken brain imaging of patients carrying microduplications in chromosome 16p13.11 and unaffected family controls, in parallel with iPS cell-derived cerebral organoid studies of the same patients. Patient MRI revealed reduced cortical volume, and corresponding iPSC studies showed neural precursor cell (NPC) proliferation abnormalities and reduced organoid size, with the NPCs therein displaying altered planes of cell division. Transcriptomic analyses of NPCs uncovered a deficit in the NFκB p65 pathway, confirmed by proteomics. Moreover, both pharmacological and genetic correction of this deficit rescued the proliferation abnormality. Thus, chromosome 16p13.11 microduplication disturbs the normal programme of NPC proliferation to reduce cortical thickness due to a correctable deficit in the NFκB signalling pathway. This is the first study demonstrating a biologically relevant, potentially ameliorable, signalling pathway underlying chromosome 16p13.11 microduplication syndrome in patient-derived neuronal precursor cells.

Four-year outcomes from a multiparametric magnetic resonance imaging (MRI)-based active surveillance programme: PSA dynamics and serial MRI scans allow omission of protocol biopsies.

OBJECTIVES: To report outcomes from a multiparametric (mp) magnetic resonance imaging (MRI)-based active surveillance programme that did not include performing protocol biopsies after the first confirmatory biopsy. PATIENTS AND METHODS: All patients diagnosed with Gleason 3 + 3 prostate cancer because of a raised PSA level who underwent mpMRI after diagnosis were included. Patients were recorded in a prospective clinical database and followed up with PSA monitoring and repeat MRI. In patients who remained on active surveillance after the first MRI (with or without confirmatory biopsy), we investigated PSA dynamics for association with subsequent progression. Comparison between first and second MRI scans was undertaken. Outcomes assessed were: progression to radical therapy at first MRI/confirmatory biopsy and progression to radical therapy in those who remained on active surveillance after first MRI. RESULTS: A total of 211 patients were included, with a median of 4.2 years of follow-up. The rate of progression to radical therapy was significantly greater at all stages among patients with visible lesions than in those with initially negative MRI (47/125 (37.6%) vs 11/86 (12.8%); odds ratio 4.1 (95% CI 2.0-8.5), P < 0.001). Only 1/56 patients (1.8%) with negative initial MRI scans who underwent a confirmatory systematic biopsy had upgrading to Gleason 3 + 4 disease. PSA velocity was significantly associated with subsequent progression in patients with negative initial MRI (area under the curve 0.85 [95% CI 0.75-0.94]; P <0.001). Patients with high-risk visible lesions on first MRI who remained on active surveillance had a high risk of subsequent progression 19/76 (25.0%) vs 9/84 (10.7%) for patients with no visible lesions, despite reassuring targeted and systematic confirmatory biopsies and regardless of PSA dynamics. CONCLUSION: Men with low-risk Gleason 3 + 3 prostate cancer on active surveillance can forgo protocol biopsies in favour of MRI and PSA monitoring with selective re-biopsy.

Outcomes following surgery in subgroups of comatose and very elderly patients with chronic subdural hematoma.

Increasing age and lower pre-operative Glasgow coma score (GCS) are associated with worse outcome after surgery for chronic subdural haematoma (CSDH). Only few studies have quantified outcomes specific to the very elderly or comatose patients. We aim to examine surgical outcomes in these patient groups. We analysed data from a prospective multicentre cohort study, assessing the risk of recurrence, death, and unfavourable functional outcome of very elderly (≥ 90 years) patients and comatose (pre-operative GCS ≤ 8) patients following surgical treatment of CSDH. Seven hundred eighty-five patients were included in the study. Thirty-two (4.1%) patients had pre-operative GCS ≤ 8 and 70 (8.9%) patients were aged ≥ 90 years. A higher proportion of comatose patients had an unfavourable functional outcome (38.7 vs 21.7%; p = 0.03), although similar proportion of comatose (64.5%) and non-comatose patients (61.8%) functionally improved after surgery (p = 0.96). Compared to patients aged < 90 years, a higher proportion of patients aged ≥ 90 years had unfavourable functional outcome (41.2 vs 20.5%; p < 0.01), although approximately half had functional improvement following surgery. Mortality risk was higher in both comatose (6.3 vs 1.9%; p = 0.05) and very elderly (8.8 vs 1.1%; p < 0.01) groups. There was a trend towards a higher recurrence risk in the comatose group (19.4 vs 9.5%; p = 0.07). Surgery can still provide considerable benefit to very elderly and comatose patients despite their higher risk of morbidity and mortality. Further research would be needed to better identify those most likely to benefit from surgery in these groups.

Tibial slope in total ankle arthroplasty: Anterior or lateral approach.

BACKGROUND: A new total ankle arthroplasty (TAA) system performed through a lateral approach provides direct visualization of the centre of rotation, allowing for accurate reconstruction of the joint alignment and less bone resection. Radiographic references are needed to describe deformities and plan the surgical procedures. The tibial slope is an important factor when treating malalignment. The aim of this study is to show if there is any difference regarding the post-operative tibial slope (ß angle) measurement comparing a fixed-bearing TAA through a lateral approach and a mobile-bearing TAA through an anterior approach. METHODS: The study included 217 ankles. Between May 2011 and April 2015, 77 patients underwent a TAA with a mobile-bearing implant through an anterior approach and 45 with a fixed-bearing implant through a lateral approach: in these patients the ß angle was measured 2 and 12 months postoperatively. 95 subjects with unilateral post-traumatic ankle arthritis composed the control group: in these patients we measured the anterior distal tibial angle (ADTA) of the controlateral, non arthritic tibiotalar joint. RESULTS: In the mobile-bearing group, the mean ß angle at 2 and 12 months postoperatively was 86.4±3.1 and 86.8±3.1 (p-value=0.12). In the fixed-bearing group, the mean ß angle at 2 and 12 months postoperatively was 83.1±5.4 and 83.9±6.5 (p-value=0.26). A statistically significant difference was found between the ß angle of the two groups. In the control group the mean ADTA was 84.9±2.5. A non-statistically significant difference was observed only between ß angle of the fixed-bearing group and the ADTA of the control group. CONCLUSIONS: Regarding the tibial slope, fixed-bearing TAA through a lateral approach showed a more anatomic placement. In contrast, ß angle in mobile-bearing group appeared more reproducible than fixed-bearing group.

No evidence for altered intracellular calcium-handling in airway smooth muscle cells from human subjects with asthma.

BACKGROUND: Asthma is characterized by airway hyper-responsiveness and variable airflow obstruction, in part as a consequence of hyper-contractile airway smooth muscle, which persists in primary cell culture. One potential mechanism for this hyper-contractility is abnormal intracellular Ca(2+) handling. METHODS: We sought to compare intracellular Ca(2+) handling in airway smooth muscle cells from subjects with asthma compared to non-asthmatic controls by measuring: i) bradykinin-stimulated changes in inositol 1,4,5-trisphosphate (IP3) accumulation and intracellular Ca(2+) concentration, ii) sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) expression, iii) mechanisms of cytoplasmic Ca(2+) clearance assessed following instantaneous flash photolytic release of Ca(2+) into the cytoplasm. RESULTS: We found no differences in airway smooth muscle cell basal intracellular Ca(2+) concentrations, bradykinin-stimulated IP3 accumulation or intracellular Ca(2+) responses. Quantification of SERCA2 mRNA or protein expression levels revealed no differences in ASM cells obtained from subjects with asthma compared to non-asthmatic controls. We did not identify differences in intracellular calcium kinetics assessed by flash photolysis and calcium uncaging independent of agonist-activation with or without SERCA inhibition. However, we did observe some correlations in subjects with asthma between lung function and the different cellular measurements of intracellular Ca(2+) handling, with poorer lung function related to increased rate of recovery following flash photolytic elevation of cytoplasmic Ca(2+) concentration. CONCLUSIONS: Taken together, the experimental results reported in this study do not demonstrate major fundamental differences in Ca(2+) handling between airway smooth muscle cells from non-asthmatic and asthmatic subjects. Therefore, increased contraction of airway smooth muscle cells derived from asthmatic subjects cannot be fully explained by altered Ca(2+) homeostasis.

Is intramedullary nailing more effective than non-operative treatment in adults with displaced middle-third clavicle fractures?

BACKGROUND: Clavicle fractures are common, accounting for 5-12 % of all fractures. Traditionally, displaced middle-third clavicle fractures have been managed non-operatively but the associated displacement often leads to mal-union with shortening, cosmetic deformity and occasionally non-union, with clinicians looking towards alternative operative methods such as intramedullary nailing (IMN). However, such methods have their own complications. In order to ascertain the effectiveness of IMN in the management of middle-third clavicle fractures compared with non-operative treatment, analysis of recent evidence is required and this review aims to achieve that, focusing on relevant, contemporary randomised-control trials. MATERIALS AND METHODS: Essential search-terms identified from the research question were used to formulate a search strategy. A systematic search of multiple databases was then performed from 1966 until present and appropriate papers for appraisal identified. RESULTS: Thirteen papers were identified, with 10 excluded using appropriate eligibility criteria. The remaining papers were then critically appraised. With regards shoulder function, all papers demonstrated an association between IMN and a significantly (P < 0.05) superior shoulder function score, but no consensus with regards to complication rates. However, all have identified limitations; therefore, their overall findings must be considered conservatively. CONCLUSIONS: Further, high-quality research, ideally in the form of well-designed, multi-centre RCTs is required to allow acceptable implementation of IMN of middle-third clavicle fractures into widespread practice. However, early results demonstrate that in young patients with displaced middle-third clavicle fractures, who are motivated to return to work, IMN provides superior functional results and should be considered. However, the importance of considering each patient individually as to their suitability for each management option, before coming to an informed decision with the patient rather than having a blanket approach to MTCF is essential. LEVEL OF EVIDENCE: Level 1.

Fresh Osteochondral Allograft for Large Talar Osteochondral Lesions.

Osteochondral lesions of the talus are being recognized as an increasingly common injury. Large osteochondral lesions have significant biomechanical consequences and often require resurfacing with both boney and cartilaginous graft. The current treatment options include osteochondral autograft transfer, mosaicplasty, autologous chondrocyte implantation, or osteochondral allograft transplantation. Allograft procedures have the advantage of no donor site morbidity and ability to match the defect line to line. Careful transportation, storage, and handling of the allograft are critical to success. The failure of nonoperative management, failure of arthroscopic treatment, or large defects are an indication for resurfacing.

Comparison of clinical and radiological outcomes for the anterior and medial approaches to open reduction in the treatment of bilateral developmental dysplasia of the hip: a systematic review protocol.

BACKGROUND: Developmental dysplasia of the hip (DDH) affects 1-3% of newborns and 20% of cases are bilateral. The optimal surgical management strategy for patients with bilateral DDH who fail bracing, closed reduction or present too late for these methods to be used is unclear. There are proponents of both medial approach open reduction (MAOR) and anterior approach open reduction (AOR); however, there is little evidence to inform this debate. METHODS: We will perform a systematic review designed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search the medical and scientific databases including the grey and difficult to locate literature. The Medical Subject Headings "developmental dysplasia of the hip", "congenital dysplasia of the hip", "congenital hip dislocation", "developmental hip dislocation", and their abbreviations, "DDH" and "CDH" will be used, along with the qualifier "bilateral". Reviewers will independently screen records for inclusion and then independently extract data on study design, population characteristics, details of operative intervention and outcomes from the selected records. Data will be synthesised and a meta-analysis performed if possible. If not possible we will analyse data according to Systematic Review without Meta-Analysis guidance. All studies will be assessed for risk of bias. For each outcome measure a summary of findings will be presented in a table with the overall quality of the recommendation assessed using the Grading of Recommendations Assessment Development and Evaluation approach. DISCUSSION: The decision to perform MAOR or AOR in patients with bilateral DDH who have failed conservative management is not well informed by the current literature. High-quality, comparative studies are exceptionally challenging to perform for this patient population and likely to be extremely uncommon. A systematic review provides the best opportunity to deliver the highest possible quality of evidence for bilateral DDH surgical management. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO ID CRD42022362325).

Functional Status Associations With Treatment Receipt and Outcomes Among Older Adults Newly Diagnosed With Multiple Myeloma.

PURPOSE: Multiple myeloma (MM) is a prevalent hematologic malignancy in older adults, who often experience physical disability, increased health care usage, and reduced treatment tolerance. Home health (HH) services are frequently used by this group, but the relationship between disability, HH use, and MM treatment receipt is unclear. This study examines the connections between disability, treatment receipt, and survival outcomes in older adults with newly diagnosed MM using a nationwide data set. METHODS: The SEER-Medicare data set was used to identify adults aged 66 years and older diagnosed with MM from 2010 to 2017, who used HH services the year before diagnosis. Disability was assessed with the Outcome and Assessment Information Set, using a composite score derived from items related to ability to complete activities of daily living. Mortality, therapy receipt, and health care utilization patterns were evaluated. RESULTS: Of 37,280 older adults with MM, 6,850 (18.2%) used HH services before diagnosis. Moderate disability at HH assessment resulted in similar MM-directed therapy receipt as mild disability, with comparable health care usage after diagnosis to severe disability. HH users had a higher comorbidity burden and higher mortality (adjusted risk ratio for 3-year mortality: 1.59 [95% CI, 1.55 to 1.64]). Severe functional disability before diagnosis was strongly related to postdiagnosis mortality. CONCLUSION: Among older adults with MM receiving HH services, disability is a predictor of early mortality. Moderately disabled individuals undergo similar therapy intensity as the mildly disabled but experience increased acute care utilization. Previous HH use could identify patients with MM requiring intensive support during therapy initiation.

Reporting of PPI and the MCID in phase III/IV randomised controlled trials-a systematic review.

BACKGROUND: Patient and public involvement (PPI) in clinical trial design contributes to ensuring the research objectives and outcome measures are relevant to patients. The minimal clinically important difference (MCID) in the primary outcome influences trial design and feasibility and should be predicated on PPI. We aimed to determine current practice of reporting PPI and the MCID in phase III/IV randomised controlled trials (RCTs). METHODS: Following a search of Medline, Embase, and the Cochrane Central Register of Controlled Trials, we included primary publications of phase III/IV RCTs, in English, inclusive of any medical specialty or type of intervention, that reported a health-related outcome. We excluded protocols and secondary publications of RCTs. We extracted RCT characteristics, the use of PPI, and use of the MCID. RESULTS: Between 1 July 2019 and 13 January 2020, 123 phase III/IV RCTs matched our eligibility criteria. Ninety percent evaluated a medical rather than surgical intervention. Oncology accounted for 21% of all included RCTs. Only 2.4% (n = 3) and 1.6% (n = 2) RCTs described PPI and the MCID respectively. CONCLUSIONS: PPI and the MCID are poorly reported, so it is uncertain how these contributed to trial design. Improvement in the reporting of these items would increase confidence that results are relevant and clinically significant to patients, contributing to improving the overall trial design. TRIAL REGISTRATION: Not registered.

Systems to model the personalized aspects of microbiome health and gut dysbiosis.

The human gut microbiome is a complex and dynamic microbial entity that interacts with the environment and other parts of the body including the brain, heart, liver, and immune system. These multisystem interactions are highly conserved from invertebrates to humans, however the complexity and diversity of human microbiota compositions often yield a context that is unique to each individual. Yet commonalities remain across species, where a healthy gut microbiome will be rich in symbiotic commensal biota while an unhealthy gut microbiota will be experiencing abnormal blooms of pathobiont bacteria. In this review we discuss how omics technologies can be applied in a personalized approach to understand the microbial crosstalk and microbial-host interactions that affect the delicate balance between eubiosis and dysbiosis in an individual gut microbiome. We further highlight the strengths of model organisms in identifying and characterizing these conserved synergistic and/or pathogenic host-microbe interactions. And finally, we touch upon the growing area of personalized therapeutic interventions targeting gut microbiome.

Parenthood in people with kidney failure: evolution and evaluation of completeness of ANZDATA registry parenthood data.

BACKGROUND: Parenthood data has been collected by the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) since its inception in 1968, with a specific parenthood survey since 2001 of core maternal and fetal outcomes, which was further expanded in 2017 to collect additional obstetric and clinical data. We evaluated the parenthood dataset completeness over the evolution of the surveys. METHODS: Descriptive statistics were used to quantify the completeness of data reported for male and female patients receiving KRT between 1963 and 2021 and compare parenthood surveys over time. RESULTS: Core data items consistently had more than 85% completeness rates for all survey iterations. Most data items introduced in 2018 had less than 85% completeness. Of these, drug therapy during pregnancy, common medical complications, and labour and delivery data items had the highest completeness (70-85%), whereas dialysis-related items had a wide range of completeness, ranging from 44 to 80%. CONCLUSION: Our findings underpin the robustness of the ANZDATA parenthood dataset but also highlight that more detailed clinical data can be difficult to capture, despite enabling better understanding of drivers of outcomes and risk stratification in this high-risk cohort. To overcome current limitations, strategies must be implemented to augment data completeness.

Analytic approaches to clinical validation of results from preclinical models of glioblastoma: A systematic review.

INTRODUCTION: Analytic approaches to clinical validation of results from preclinical models are important in assessment of their relevance to human disease. This systematic review examined consistency in reporting of glioblastoma cohorts from The Cancer Genome Atlas (TCGA) or Chinese Glioma Genome Atlas (CGGA) and assessed whether studies included patient characteristics in their survival analyses. METHODS: We searched Embase and Medline on 02Feb21 for studies using preclinical models of glioblastoma published after Jan2008 that used data from TCGA or CGGA to validate the association between at least one molecular marker and overall survival in adult patients with glioblastoma. Main data items included cohort characteristics, statistical significance of the survival analysis, and model covariates. RESULTS: There were 58 eligible studies from 1,751 non-duplicate records investigating 126 individual molecular markers. In 14 studies published between 2017 and 2020 using TCGA RNA microarray data that should have the same cohort, the median number of patients was 464.5 (interquartile range 220.5-525). Of the 15 molecular markers that underwent more than one univariable or multivariable survival analyses, five had discrepancies between studies. Covariates used in the 17 studies that used multivariable survival analyses were age (76.5%), pre-operative functional status (35.3%), sex (29.4%) MGMT promoter methylation (29.4%), radiotherapy (23.5%), chemotherapy (17.6%), IDH mutation (17.6%) and extent of resection (5.9%). CONCLUSION: Preclinical glioblastoma studies that used TCGA for validation did not provide sufficient information about their cohort selection and there were inconsistent results. Transparency in reporting and the use of analytic approaches that adjust for clinical variables can improve the reproducibility between studies.

Nrf2 activation in the human brain after stroke due to supratentorial intracerebral haemorrhage: a case-control study.

Aims: Pharmacological activation of the antioxidative transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) improves outcomes in experimental models of intracerebral haemorrhage (ICH). However, the Nrf2 pathway has not been previously studied in humans after ICH. Our study aims to address this gap. Methods: We selected cases with fatal ICH from a prospective community-based inception cohort study and age-matched and sex-matched controls who died suddenly of non-neurological disease. We used immunohistochemistry to quantify Nrf2 (% total area stained overall and % of nuclei stained) and CD68 expression in controls and perihaematomal, ipsilateral and contralateral brain tissue from cases. We measured downstream haem oxygenase-1 (HMOX1) and NAD(P)H dehydrogenase quinone 1 [NQO1] expression using RNA in situ hybridisation. Results: 26 ICH cases (median age: 82 (IQR 76-86); 13 (50%) male) and eight controls (median age: 79 (IQR 77-80); 3 (37.5%) male) were included. We found no significant differences in overall % of Nrf2 staining between ICH cases and controls. However, the mean % of nuclei staining for Nrf2 seemed higher in perihaematomal compared with contralateral regions, although this was only statistically significant >60 days after ICH (25% (95% CI 17% to 33%) vs 14% (95% CI 11% to 17%), p=0.029). The percentage of perihaematomal tissue staining for CD68 was higher >60 days after ICH (6.75%, 95% CI 2.78% to 10.73%) compared with contralateral tissue (1.45%, 95% CI 0.93% to 1.96%, p=0.027) and controls (1.08%, 95% CI 0.20% to 1.97%, p=0.0008). RNA in situ hybridisation suggested increased abundance of HMOX1 and NQO1 transcripts in perihaematomal versus distant ipsilateral brain tissue obtained <7 days from onset of ICH. Conclusions: We found evidence of Nrf2 activation in human brain tissue after ICH. Pharmacological augmentation of Nrf2 activation after ICH might be a promising therapeutic approach.

The effectiveness of PTSD treatment for adolescents in the juvenile justice system: A systematic review.

OBJECTIVE: The objective of this study was to systematically review existing empirical evidence on the effectiveness of trauma-specific treatment for justice-involved adolescents and evaluate the impact of the interventions on the reduction of posttraumatic stress disorder (PTSD) symptoms, co-occurring mental health symptoms, and juvenile justice-related outcomes. METHOD: A systematic literature search was conducted using a four-step process. Studies were included if they used a manualized, trauma-specific treatment with at least one control or comparison group and a sample comprised exclusively of justice-involved adolescents. RESULTS: In total, 1,699 unique records were identified, and 56 full-text articles were reviewed, of which 7 met the criteria for inclusion. Trauma-specific interventions led to a decrease in PTSD symptoms compared with a control group in four of seven studies, and two studies also demonstrated a reduction in trauma-related depressive symptoms. Finally, juvenile justice-related outcomes were measured in only four studies, with one study finding moderately reduced rates of delinquent behavior and recidivism following trauma-specific treatment. CONCLUSIONS: The results from this systematic review suggest that trauma-specific treatment interventions have promising effects for justice-involved adolescents. However, the results reveal a dearth of quality intervention research for treating youths with histories of trauma in the justice system. Significant gaps in the literature are highlighted, and suggestions for future directions are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effect of Probiotic, Prebiotic, and Synbiotic Supplementation on Cardiometabolic and Oxidative Stress Parameters in Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis.

PURPOSE: Chronic kidney disease (CKD) is a major health problem worldwide. Evidence supporting the use of probiotic, prebiotic, and synbiotic supplementation in the management of CKD is mixed, although some studies suggest they may be useful. A systematic review and meta-analysis was performed to evaluate the effectiveness of probiotic, prebiotic, and synbiotic supplementation for improving cardiometabolic and oxidative stress parameters in patients with CKD. METHODS: A comprehensive key word search was performed in EMBASE, Medline, Scopus, Cochrane Central, and Web of Science until April 2020. Randomized controlled trials investigating the effectiveness of probiotic, synbiotic, and prebiotic supplementation for the management of adults with CKD were included. Primary outcomes were measures of cardiometabolic parameters such as cholesterol and fasting blood glucose. Secondary outcomes were measures of oxidative stress (eg, malondialdehyde levels) and body mass index. Random effects meta-analyses were used to estimate mean treatment effects. Results are reported as standardized mean differences (SMDs) and 95% CIs. FINDINGS: Fourteen articles were included. In patients with CKD, probiotic, prebiotic, and synbiotic supplementation significantly reduced total cholesterol (SMD, -0.25; 95% CI, -0.46 to -0.04; I2 = 00.0%), fasting blood glucose (SMD, -0.41; 95% CI, -0.65 to -0.17; I2 = 00.0%), homeostatic model assessment of insulin resistance (SMD, -0.63; 95% CI, -0.95 to -0.30; I2 = 43.3%), insulin levels (SMD, -0.49; 95% CI, -0.90 to -0.08; I2 = 65.2%), high-sensitivity C-reactive protein levels (SMD, -0.52; 95% CI, -0.81 to -0.22; I2 = 52.7%), and malondialdehyde levels (SMD, -0.79; 95% CI, -1.22 to -0.37; I2 = 69.8%) compared with control interventions. Supplementation significantly increased the quantitative insulin sensitivity check index (SMD, 0.78; 95% CI, 0.51 to 1.05; I2 = 00.0%), total antioxidant capacity (SMD, 0.42; 95% CI, 0.18 to 0.66; I2 = 00.0%), and glutathione levels (SMD, 0.52; 95% CI, 0.19 to 0.86; I2 = 37.0%). IMPLICATIONS: Probiotic, prebiotic, and synbiotic supplementation seems to be a promising intervention for improving cardiometabolic and oxidative stress parameters in patients with CKD.