Trends for opioid prescribing and the impact of the COVID-19 pandemic in patients with rheumatic and musculoskeletal diseases between 2006 and 2021.

OBJECTIVE: To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs). METHODS: Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. RESULTS: The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic. CONCLUSION: The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.

Lower product of magnesium × potassium is associated with higher mortality in chronic hemodialysis patients: a cohort study.

This study aimed to investigate the Mg × K product on the mortality risk of hemodialysis patients with concomitant hypokalemia and lower magnesium levels. This was a prospective observational study of patients in a HD center in southern Taiwan. A total of 444 HD patients were divided into 5 groups by the Mg × K product: group 1, bottom quintile, median Mg × K: 7.87, IQR: 7.03-8.12 (n = 89, age: 64 ± 13 years old); group 2, median Mg × K: 9.37, IQR: 8.97-9.86 (n = 89, age:62 ± 13 years old); group 3, median Mg × K: 10.95, IQR: 10.50-11.26 (n = 89, age:64 ± 13 years old); group 4, median Mg × K: 12.30, IQR: 11.87-12.82 (n = 89, 61 ± 12 years old); and group 5, top quintile, median Mg × K: 14.92, IQR:14.07-16.23 (n = 88, 62 ± 11 years old). The patients were followed up for 2 years to determine the risk of all-cause mortality. Patients with a lower Mg × K product had more comorbidities, malnutrition-inflammation status, and a higher mortality risk. Using multivariable Cox regression analysis, a higher Mg × K [HR, 0.89; 95%CI (0.81-0.98)] was found to be an independent predictor of better survival. HD patients with a lower Mg × K product had more comorbidities, a marked malnutrition-inflammation status, and were associated with long-term mortality. A higher Mg × K value is a favorable survival factor.

Single-nucleus transcriptome inventory of giant panda reveals cellular basis for fitness optimization under low metabolism.

BACKGROUND: Energy homeostasis is essential for the adaptation of animals to their environment and some wild animals keep low metabolism adaptive to their low-nutrient dietary supply. Giant panda is such a typical low-metabolic mammal exhibiting species specialization of extremely low daily energy expenditure. It has low levels of basal metabolic rate, thyroid hormone, and physical activities, whereas the cellular bases of its low metabolic adaptation remain rarely explored. RESULTS: In this study, we generate a single-nucleus transcriptome atlas of 21 organs/tissues from a female giant panda. We focused on the central metabolic organ (liver) and dissected cellular metabolic status by cross-species comparison. Adaptive expression mode (i.e., AMPK related) was prominently displayed in the hepatocyte of giant panda. In the highest energy-consuming organ, the heart, we found a possibly optimized utilization of fatty acid. Detailed cell subtype annotation of endothelial cells showed the uterine-specific deficiency of blood vascular subclasses, indicating a potential adaptation for a low reproductive energy expenditure. CONCLUSIONS: Our findings shed light on the possible cellular basis and transcriptomic regulatory clues for the low metabolism in giant pandas and helped to understand physiological adaptation response to nutrient stress.

Association between soluble α-klotho and mortality risk in middle-aged and older adults.

Introduction: Studies on association of α-klotho levels with mortality risk in general population are relatively scarce and inconclusive. Therefore, we conducted a population-based cohort study to investigate the relationship between soluble α-klotho and all-cause mortality in a nationally representative sample of middle-aged and older adults in the United States (U.S.). Methods: The study population was 2007-2016 National Health and Nutrition Examination Survey (NHANES) participants, totaling 13,583 adults aged 40-79 years. Participants were divided into 7 groups by septile of α-klotho levels. We linked the NHANES data to the National Death Index to determine participants' survival status. End of follow-up was participants' death date or December 31, 2019. Results: We observed that males, current smokers, older age, higher body mass index, and lower estimated glomerular filtration rate correlated to lower α-klotho levels, while hepatitis C virus infection correlated to higher α-klotho. The population mortality rate was 11.8 per 10,000 person-months (1,490 deaths); group 1 (the first septile) had higher mortality risk compared with group 2 through group 7. By weighted Cox regression with adjustment for potential confounders, we found that group 2 through group 6, but not group 7, were associated with 25% to 35% lower risk of all-cause mortality compared with group 1. When compared with group 4, we observed that both group 1 (HR: 1.46, 95% CI 1.13-1.88) and group 7 (HR: 1.38, 95% CI 1.09-1.74) were associated with higher mortality risk. Conclusion: In summary, among middle-aged and older U.S. adults, we observed a non-linear association between soluble α-klotho and all-cause mortality, with individuals at the two extremes at increased risk of death.

The Impact of Long-Term Conditions and Comorbidity Patterns on COVID-19 Infection and Hospitalisation: A Cohort Study.

INTRODUCTION: Older adults are more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher risk of COVID-19 infection. This study investigated the role of long-term conditions or comorbidity patterns on COVID-19 infection and related hospitalisations. METHODS: This study included 4,428 individuals from Waves 8 (2016-2017) and 9 (2018-2019) of the English Longitudinal Study of Ageing (ELSA) who also participated in the ELSA COVID-19 Substudy in 2020. Comorbidity patterns were identified using an agglomerative hierarchical clustering method. The relationships between comorbidity patterns or long-term conditions and COVID-19-related outcomes were examined using multivariable logistic regression. RESULTS: Among a representative sample of community-dwelling older adults in England, those with cardiovascular disease (CVD) and complex comorbidities had an almost double risk of COVID-19 infection (OR = 1.87, 95% CI = 1.42-2.46) but not of COVID-19-related hospitalisation. A similar pattern was observed for the heterogeneous comorbidities cluster (OR = 1.56, 95% CI = 1.24-1.96). The individual investigations of long-term conditions with COVID-19 infection highlighted primary associations with CVD (OR = 1.46, 95% CI = 1.23-1.74), lung diseases (OR = 1.40, 95% CI = 1.17-1.69), psychiatric conditions (OR = 1.40, 95% CI = 1.16-1.68), retinopathy/eye diseases (OR = 1.39, 95% CI = 1.18-1.64), and arthritis (OR = 1.27, 95% CI = 1.09-1.48). In contrast, metabolic disorders and diagnosed diabetes were not associated with any COVID-19 outcomes. CONCLUSION: This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and hospitalisations, highlighting the vulnerability of those with CVD and other complex comorbidities. These findings facilitate crucial new evidence that should be considered for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak.

Remimazolam versus propofol for procedural sedation: a meta-analysis of randomized controlled trials.

Background: To improve patient tolerability and satisfaction as well as minimize complications, procedural sedation has been widely used. Propofol is the most widely used agent for induction of anesthesia and sedation by anesthesiologists. With a different mechanism compared to propofol, remimazolam is a new short-acting GABA-A receptor agonist. It is an ester-based benzodiazepine. This meta-analysis aims to clarify the efficacy and safety of remimazolam versus propofol for procedure sedation. Methods: Electronic databases were searched for randomized controlled trials (RCTs) comparing efficacy or safety of remimazolam versus propofol. Meta-analysis were conducted using RStudio with "metafor" package with random-effects model. Results: A total of twelve RCTs were included in the meta-analysis. The pooled results demonstrated that patients with remimazolam for procedural sedation had lower risk of bradycardia (OR 0.28, 95% CI [0.14-0.57]), hypotension (OR 0.26, 95% CI [0.22-0.32]), and respiratory depression (OR 0.22, 95% CI [0.14-0.36]). There was no difference in the risk of developing postoperative nausea and vomiting (PONV) (OR 0.65, 95% CI [0.15-2.79]) and dizziness (OR 0.93, 95% CI [0.53-1.61]) between the remimazolam and propofol groups. Using remimazolam for procedural sedation is significantly associated with less injection pain compared to propofol (OR 0.06, 95% CI [0.03-0.13]). Regarding the sedation efficacy, there was no difference in sedation success rate or time to loss of consciousness, recover and discharge between the remimazolam and the propofol groups. Conclusions: Based on our meta-analysis, patients receiving procedural sedation with remimazolam had lower risk of bradycardia, hypotension, respiratory depression and injection pain compared with propofol. On the other hand, there was no difference in sedation success rate, risk of PONV, dizziness, time to LOC, recovery and discharge between these two sedatives. PROSPERO registration number: CRD42022362950.

The impact of long-term conditions and comorbidity patterns on COVID-19 infection and hospitalisation: a cohort study.

Introduction: Older adults are usually more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher probability of COVID-19 infection. This study investigated the role of long-term conditions or comorbidity patterns on COVID-19 infection and related hospitalisations. Methods: This study included 4,428 individuals from Waves 8 (2016-2017) and 9 (2018-2019) of the English Longitudinal Study of Ageing (ELSA), who also participated in the ELSA COVID-19 Substudy in 2020. Comorbidity patterns of chronic conditions were identified using an agglomerative hierarchical clustering method. The relationships between comorbidity patterns or long-term conditions and COVID-19 related outcomes were examined using multivariable logistic regression. Results: Among a representative sample of community-dwelling older adults in England, those with cardiovascular disease (CVD) and complex comorbidities had an almost double risk of COVID-19 infection (OR=1.87, 95% CI=1.42-2.46) but not of COVID-19 related hospitalisation. A similar pattern was observed for the heterogeneous comorbidities cluster (OR=1.56, 95% CI=1.24-1.96). The individual investigations of long-term conditions with COVID-19 infection highlighted primary associations with CVD (OR=1.46, 95% CI=1.23-1.74), lung diseases (OR=1.40, 95% CI=1.17-1.69), psychiatric conditions (OR=1.40, 95% CI=1.16-1.68), retinopathy/eye diseases (OR=1.39, 95% CI=1.18-1.64), and arthritis (OR=1.27, 95% CI=1.09-1.48). In contrast, metabolic disorders and diagnosed diabetes were not associated with any COVID-19 outcomes. Discussion/Conclusion: This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and highlights the importance of CVD and complex comorbidities.These findings facilitate crucial new evidence for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak.

Impact of perioperative α1-antagonists on postoperative urinary retention in orthopaedic surgery: meta-analysis.

BACKGROUND: Postoperative urinary retention (POUR) is a common complication following orthopaedic surgery. Previous studies attempted to establish the preventative role of α1-antagonist in POUR in the general surgical population; however, there is still no consensus regarding its use in orthopaedic surgery due to limited evidence. METHODS: Electronic databases of Cochrane Library, Embase, MEDLINE, and ClinicalTrials.gov were searched by two independent investigators from inception to 1 March 2022 to identify relevant randomized clinical trials. Two reviewers independently completed a critical appraisal of included trials by using the Cochrane Risk of Bias tool version 2.0 and extracted data from included articles. Risk of POUR was summarized as risk ratio (RR) with 95 per cent confidence intervals (c.i.). Mean difference (MD) was used for meta-analysis of continuous outcomes. RESULTS: Five randomized clinical trials involving 878 patients (α1-antagonist, 434; placebo, 444) undergoing hip/knee arthroplasty and spine surgeries were included. One study was assessed as high risk of bias from the randomization process and was excluded from the final meta-analysis. There was no difference in the risk of POUR between patients taking α1-antagonist and the placebo in arthroplasty (RR, 0.64; 95 per cent c.i., 0.36 to 1.14) and in spine surgeries (RR, 1.03; 95 per cent c.i., 0.69 to 1.55). There was no difference in length of stay (MD, -0.14 days; 95 per cent c.i., -0.33 to 0.05). Use of α1-antagonist was associated with a higher risk of adverse events (RR, 1.97; 95 per cent c.i., 1.27 to 3.06), with a composite of dizziness, light-headedness, fatigue, altered mental status, and syncope being the most commonly reported symptoms. CONCLUSION: In patients undergoing spinal surgery and joint arthroplasty, routine administration of perioperative α1-antagonist does not decrease risk of POUR but does increase perioperative dizziness, light-headedness, and syncope.

Immune response and homeostasis mechanism following administration of BBIBP-CorV SARS-CoV-2 inactivated vaccine.

The BBIBP-CorV severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccine has been authorized for emergency use and widely distributed. We used single-cell transcriptome sequencing to characterize the dynamics of immune responses to the BBIBP-CorV inactivated vaccine. In addition to the expected induction of humoral immunity, we found that the inactivated vaccine induced multiple, comprehensive immune responses, including significantly increased proportions of CD16+ monocytes and activation of monocyte antigen presentation pathways; T cell activation pathway upregulation in CD8+ T cells, along with increased activation of CD4+ T cells; significant enhancement of cell-cell communications between innate and adaptive immunity; and the induction of regulatory CD4+ T cells and co-inhibitory interactions to maintain immune homeostasis after vaccination. Additionally, comparative analysis revealed higher neutralizing antibody levels, distinct expansion of naive T cells, a shared increased proportion of regulatory CD4+ T cells, and upregulated expression of functional genes in booster dose recipients with a longer interval after the second vaccination. Our research will support a comprehensive understanding of the systemic immune responses elicited by the BBIBP-CorV inactivated vaccine, which will facilitate the formulation of better vaccination strategies and the design of new vaccines.

Chromosome-scale genomes reveal genomic consequences of inbreeding in the South China tiger: A comparative study with the Amur tiger.

The South China tiger (Panthera tigris amoyensis, SCT) is the most critically endangered subspecies of tiger due to functional extinction in the wild. Inbreeding depression is observed among the captive population descended from six wild ancestors, resulting in high juvenile mortality and low reproduction. We assembled and characterized the first SCT genome and an improved Amur tiger (P. t. altaica, AT) genome named AmyTig1.0 and PanTig2.0. The two genomes are the most continuous and comprehensive among any tiger genomes yet reported at the chromosomal level. By using the two genomes and resequencing data of 15 SCT and 13 AT individuals, we investigated the genomic signature of inbreeding depression of the SCT. The results indicated that the effective population size of SCT experienced three phases of decline, ~5.0-1.0 thousand years ago, 100 years ago, and since captive breeding in 1963. We found 43 long runs of homozygosity fragments that were shared by all individuals in the SCT population and covered a total length of 20.63% in the SCT genome. We also detected a large proportion of identical-by-descent segments across the genome in the SCT population, especially on ChrB4. Deleterious nonsynonymous single nucleotide polymorphic sites and loss-of-function mutations were found across genomes with extensive potential influences, despite a proportion of these loads having been purged by inbreeding depression. Our research provides an invaluable resource for the formulation of genetic management policies for the South China tiger such as developing genome-based breeding and genetic rescue strategy.

Association of dietary magnesium intake and glycohemoglobin with mortality risk in diabetic patients.

BACKGROUND: Dietary magnesium intake inversely correlated to risk of death in general population. However, it is relatively unknown whether the beneficial effect remains significant in individuals with diabetes. Our study purpose is to evaluate the association of dietary magnesium intake with mortality risk in diabetic population. METHODS: The study population is recruited from 2003-2014 National Health and Nutrition Examination Survey, totaling 2,045 adults with diabetes being included. Participants were divided based on glycohemoglobin (HbA1c < 7% and ≥ 7%) and daily dietary magnesium intake (≤ and > 250mg/day) ascertained by 24-hour dietary recall interviews. RESULTS: The average age of the study population was 52.9±10.1 years, with 49.1% being male. During a median follow-up of 77.0 months (interquartile range: 45.0-107.0 months), a total of 223 participants died (1.5 per 1000 person-months). Our results showed that individuals with lower dietary magnesium intake (≤250mg/day) had higher risk of all-cause (HR: 1.56, 95% CI: 1.13-2.16) and other-cause (non-cardiovascular and non-cancer) mortality (HR: 1.68, 95% CI: 1.09-2.60), while cardiovascular and cancer-related mortality were similar compared with individuals with magnesium intake > 250mg/day. We also showed that the risk of all-cause (HR: 1.86, 95% CI: 1.33-2.60) and other-cause mortality (HR: 2.03, 95% CI: 1.29-3.19) were higher in individuals with poorly controlled diabetes (HbA1c ≥7.0%) compared with HbA1c <7.0%; however, the association attenuated in the subgroup of higher magnesium intake (>250mg/day). When combining HbA1c and dietary magnesium intake, we showed that individuals with HbA1c ≥ 7% and dietary magnesium intake ≤ 250 mg/day had higher all-cause and other-cause (non-cardiovascular and non-cancer) mortality risk compared with those with HbA1c < 7% and/or dietary magnesium intake > 250 mg/day. CONCLUSION: Higher magnesium intake may help reduce mortality risk in individuals with diabetes and attenuate mortality risk of poor diabetic control.

Albumin to prealbumin ratio in peritoneal dialysis patients: Clinical implication and outcome prediction.

BACKGROUND: Serum prealbumin level is slightly higher, whereas albumin is lower in peritoneal dialysis (PD) than hemodialysis (HD) patients. It is unknown whether albumin to prealbumin ratio (APR) is associated with mortality risk among PD patients. This study aimed to evaluate the clinical implications of APR and its prediction value on long-term outcomes of PD patients. METHODS: The study population were prevalent PD patients at a tertiary hospital. Based on APR, a total of 220 PD patients were divided into 3 groups: group 1: top tertile, median APR: 121.1; IQR:109.5-131.9 (n = 73, male: 37%; age: 59±13); group 2: middle tertile, median APR: 97.1; IQR 93.5-100.0 (n = 73, male:37%; age: 54±14), and group3: bottom tertile, median APR: 81.3; IQR:76.8-85.0 (n = 74, male:38%; 54±11). Patients were followed up for a maximum of 5 years. Outcome of interest was all-cause mortality. RESULTS: Group 1 was characterized by older age, higher prevalence of diabetes, lower nPCR, higher Davies score and hs-CRP level. APR positively correlated to hs-CRP (ß = 0.149, p = 0.045), but negatively correlated to nPCR (ß = -0.161, p = 0.034). Hyperprealbuminemia, accounting for 0%, 23.3%, and 82.4% in groups 1,2, and 3, was associated with a lower risk for mortality (HR:0.41, 95%CI = 0.23-0.73). The cumulative survival is significantly lower in group 1 than the other two groups. By multivariable Cox regression, APR (HR:1.02; 95%CI:1.01-1.03) was found to be an independent predictor of long-term mortality. CONCLUSION: PD patients with high APR are characterized by having more comorbidities and marked malnutrition-inflammation status, and are associated with long-term mortality, whereas hyperprealbuminemia and lower APR are favorable prognostic factors.

Association between hypomagnesemia and mortality among dialysis patients: a systematic review and meta-analysis.

Background: Malnutrition-inflammation-atherosclerosis (MIA) syndrome is caused by the inflammatory cytokines in end stage renal disease (ESRD) patients, and MIA complex-related factors may be associated with hypomagnesemia and mortality. However, the association between serum magnesium level and mortality for dialysis patients is still not clear. Additionally, no meta-analysis has investigated the impact of serum magnesium on peritoneal dialysis and hemodialysis, separately. Methods: We searched published studies in PubMed, Embase, Cochrane, Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews through April 2022. Studies associated with serum magnesium and all-cause mortality or cardiovascular (CV) mortality in ESRD on kidney replacement therapy (KRT) patients were included. A hazard ratio (HR) with 95% confidence intervals (CI) was used to report the outcomes. Results: Twenty-one studies involving 55,232 patients were included. Overall, there was a significant association between hypomagnesemia and all-cause mortality for dialysis patients (HR: 1.67, 95% CI [1.412-2.00], p < 0.001; certainty of evidence: moderate) using a mixed unadjusted and adjusted HR for analysis. There was also a significantly increased risk of CV mortality for individuals with hypomagnesemia compared with the non-hypomagnesemia group (HR 1.56, 95% CI [1.08-2.25], p < 0.001; certainty of evidence: moderate). In addition, a subgroup analysis demonstrated that hypomagnesemia was associated with a high risk of both all-cause mortality and CV mortality (all-cause mortality, HR:1.80, 95% CI [1.48-2.19]; CV mortality, HR:1.84, 95% CI [1.10-3.07]) in hemodialysis (HD) patients, but not in participants receiving peritoneal dialysis (PD; all-cause mortality, HR:1.26, 95% CI [0.84-1.91]; CV mortality, HR:0.66, 95% CI [0.22-2.00]). The systematic review protocol was prespecified and registered in PROSPERO [CRD42021256187]. Conclusions: Hypomagnesemia may be a significant risk factor for all-cause mortality and CV mortality in KRT patients, especially in those receiving hemodialysis. However, because of the limited certainty of evidence, more studies are required to investigate this association.

Assessment of recombinant antigens Tp0100 and Tp1016 of Treponema pallidum for serological diagnosis of syphilis.

OBJECTIVE: To discover novel serodiagnostic candidates for the serological diagnosis of syphilis. METHODS: Two recombinant Treponema pallidum proteins Tp0100 and Tp1016 were expressed, purified, and identified by Western Blotting. A total of 600 clinical serum samples were tested with the Tp0100-based ELISA, the Tp1016-based ELISA, and the commercial LICA Syphilis TP kit (ChIVD, Beijing, China). The sensitivities were determined by testing 340 samples from individuals with clinically diagnosed primary, secondary, latent, and tertiary syphilis. The specificities were determined by screening 260 samples from healthy controls and individuals with potentially cross-reactive infections, including leptospirosis, Lyme disease, hepatitis B, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus. Kappa (κ) values were applied to compare the agreement between clinical syphilis diagnosis and the Tp0100-based ELISA, the Tp1016-based ELISA, or the LICA Syphilis TP test. RESULTS: Using clinical syphilis diagnosis as the gold standard, Tp0100 exhibited an overall sensitivity of 95.6% and specificity of 98.1% for testing IgG antibody while Tp1016 demonstrated only an overall sensitivity of 75.0% and specificity of 79.6%. In contrast, the LICA Syphilis TP test revealed an overall sensitivity of 97.6% and specificity of 96.2%. In addition, the overall percent agreement and corresponding κ values were 96.7% (95% CI 95.6%-97.8%) and 0.93 for the Tp0100-based ELISA, 77.0% (95% CI 74.3%-79.7%) and 0.54 for the Tp1016-based ELISA, and 97.0% (95% CI 96.0%-98.0%) and 0.94 for the LICA Syphilis TP test, respectively. CONCLUSION: The recombinant T. pallidum protein Tp0100 shows promise as a novel diagnostic antigen in the serological tests for syphilis.

Association of hepatitis C virus infection status and genotype with kidney disease risk: A population-based cross-sectional study.

BACKGROUND: Whether there is difference in kidney disease risk between chronic hepatitis C virus (HCV) infection and resolved HCV infection remains inconclusive. Additionally, the impact of different HCV genotypes on kidney disease risk is relatively unknown. Accordingly, we conducted a population-based cross-sectional study to investigate the association of HCV infection status and genotype on kidney disease risk. METHODS: The study population were adult participants of 1999-2018 National Health and Nutrition Examination Survey in the United States. Chronic and resolved infection were defined as HCV seropositivity with and without detectable HCV RNA, respectively. HCV genotypes were classified into genotype 1, genotype 2, and other genotypes. Prevalent estimated glomerular filtration rate < 60 ml/min/1.73 m2 or urinary albumin creatinine ratio ≥ 30 mg/g was defined as kidney disease. RESULTS: The average age of study population (n = 44,998) was 46.7±17.0 years with 49.8% being males. Compared with individuals without HCV infection (n = 44,157), those with resolved (n = 255) or chronic HCV infection (n = 586) had higher prevalence of kidney disease: 14.8%, 23.5%, and 20.1%, respectively (p<0.001). After adjusting for potential confounders, we found that both resolved (adjusted OR: 1.40, 95% CI: 1.02-1.93) and chronic HCV infection (adjusted OR: 1.26, 95% CI: 1.01-1.57) correlated to increased kidney disease risk compared with no HCV infection. Additionally, individuals with HCV genotype 1 (adjusted OR: 1.41, 95% CI: 1.09-1.82) but not genotype 2 or other genotypes had greater kidney disease risk compared with no HCV infection. Furthermore, we observed that genotype 1 had 2-fold higher kidney disease risk (adjusted OR: 2.20, 95% CI: 1.07-4.53) compared with non-genotype 1 HCV infection. CONCLUSION: Both resolved and chronic HCV infection, particularly genotype 1, were associated with higher kidney disease risk.

Accelerated versus watchful waiting strategy of kidney replacement therapy for acute kidney injury: a systematic review and meta-analysis of randomized clinical trials.

Background: Critically ill patients with severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) have a grim prognosis. Recently, multiple studies focused on the impact of KRT initiation time [i.e., accelerated versus watchful waiting KRT initiation (WWS-KRT)] on patient outcomes. We aim to review the results of all related clinical trials. Methods: In this systematic review, we searched all relevant randomized clinical trials from January 2000 to April 2021. We assessed the impacts of accelerated versus WWS-KRT on KRT dependence, KRT-free days, mortality and adverse events, including hypotension, infection, arrhythmia and bleeding. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. Results: A total of 4932 critically ill patients with AKI from 10 randomized clinical trials were included in this analysis. The overall 28-day mortality rate was 38.5%. The 28-day KRT-dependence rate was 13.0%. The overall incident of KRT in the accelerated group was 97.4% and 62.8% in the WWS-KRT group. KRT in the accelerated group started 36.7 h earlier than the WWS-KRT group. The two groups had similar risks of 28-day [pooled log odds ratio (OR) 1.001, P = 0.982] and 90-day (OR 0.999, P = 0.991) mortality rates. The accelerated group had a significantly higher risk of 90-day KRT dependence (OR 1.589, P = 0.007), hypotension (OR 1.687, P < 0.001) and infection (OR 1.38, P = 0.04) compared with the WWS-KRT group. Conclusions: This meta-analysis revealed that accelerated KRT leads to a higher probability of 90-day KRT dependence and dialysis-related complications without any impact on mortality rate when compared with WWS-KRT. Therefore, we suggest the WWS-KRT strategy for critically ill patients.

Correction to: Accelerated versus watchful waiting strategy of kidney replacement therapy for acute kidney injury: a systematic review and meta-analysis of randomized clinical trials.

[This corrects the article DOI: 10.1093/ckj/sfac011.].

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.