Heterotopic ossification(HO) is a common complication following spinal cord injury(SCI); however, its underlying pathophysiology remains relatively unknown. Although there are options for treating HO, prophylactic treatment is limited. Additionally, evidence supporting the effectiveness of these prophylactic treatments is scarce. Electronic literature search was conducted using four databases. Studies comparing prophylactic medication for HO versus placebo for patients with acute spinal cord injury were included. A meta-analysis comparing the incidence of HO between the two groups was conducted, with a subgroup analysis of non-steroidal anti-inflammatory drugs (NSAIDs) and non-NSAIDs. A total of 5 studies and 815 patients were included. Overall incidence of HO was 9.73 % (n = 25) in the medication group versus 16.5 %(n = 92) in the placebo group. However, the two groups do not statistcally differ(p = 0.21). In the subgroup analysis for NSAIDs, those who received prophylactic treatment with NSAIDs had a lower incidence of HO compared to those who received placebo (RR[95 % CI]:0.32[0.15, 0.68]; p = 0.003). As for studies that used bisphosphonates, a statistically significant difference in incidence of HO was not found (RR[95 % CI]:1.30[0.52, 3.24];p = 0.58) and the overall evidence was inconclusive. In present systematic review and meta-analysis comparing prophylactic medications to placebo for prevention of HO, we found similar incidence rates for both groups. However, subgroup analysis showed a significantly lower incidence rate for those who recevied NSAIDs for HO prophylaxis. Altough this finding is promising for secondary prevention of HO among patients suffering from SCI, further prospective studies with longer follow-ups are required to assess other appropriate medications for HO prevention.

Pharmacologic prophylaxis for heterotopic ossification following spinal cord injury: A systematic review and meta-analysi.

Urinary kidney injury molecule 1 (uKIM-1) is a proximal tubular injury biomarker for predicting acute kidney injury (AKI); its prognostic value varies depending on the clinical and population characteristics. However, the predictive value of uKIM-1 for diagnosis of contrast-induced acute kidney injury (CI-AKI) remains unclear.
Medline, Embase, ClinicalTrials.gov, Cochrane Library database, and the China National Knowledge Infrastructure (CNKI) were used to identify relevant studies from their inception to November 31, 2019. Studies that met the inclusion criteria were included. Relevant data were extracted to obtain pooled sensitivity (SEN) and specificity (SPE), summary receiver operating characteristic curve (ROC), and area under the ROC (AUC or AUROC). A bivariate mixed-effects regression model was used for data analysis.
A total of 946 patients from 8 eligible studies were included. Across all the studies, the diagnostic odds ratio (DOR) for uKIM-1 level to predict CI-AKI was 19 (95% CI 10-39), with SEN and SPE of 0.84 and 0.78, respectively. The AUROC for uKIM-1 in predicting CI-AKI was 0.88 (95% CI 0.85-0.90). There was a substantial heterogeneity across the studies (
Urinary KIM-1 has a high predictive value for diagnosis of CI-AKI in patients who have undergone cardiac catheterization.

The Predictive Value of Urinary Kidney Injury Molecular 1 for the Diagnosis of Contrast-Induced Acute Kidney Injury after Cardiac Catheterization: A Meta-Analysis.

Cardiometabolic parameters are established risk factors for COVID-19 severity. The identification of causal or protective biomarkers for COVID-19 severity may facilitate the development of novel therapies.
To identify protein biomarkers that promote or reduce COVID-19 severity and that mediate the association of cardiometabolic risk factors with COVID-19 severity.
This genetic association study using 2-sample mendelian randomization (MR) was conducted in 2022 to investigate associations among cardiometabolic risk factors, circulating biomarkers, and COVID-19 hospitalization. Inputs for MR included genetic and proteomic data from 4147 participants with dysglycemia and cardiovascular risk factors collected through the Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Genome-wide association study summary statistics were obtained from (1) 3 additional independent plasma proteome studies, (2) genetic consortia for selected cardiometabolic risk factors (including body mass index [BMI], type 2 diabetes, type 1 diabetes, and systolic blood pressure; all n >10 000), and (3) the COVID-19 Host Genetics Initiative (n = 5773 hospitalized and 15 497 nonhospitalized case participants with COVID-19). Data analysis was performed in July 2022.
Genetically determined concentrations of 235 circulating proteins assayed with a multiplex biomarker panel from the ORIGIN trial for the initial analysis.
Hospitalization status of individuals from the COVID-19 Host Genetics Initiative with a positive COVID-19 test result.
Among 235 biomarkers tested in samples totaling 22 101 individuals, MR analysis showed that higher kidney injury molecule-1 (KIM-1) levels reduced the likelihood of COVID-19 hospitalization (odds ratio [OR] per SD increase in KIM-1 levels, 0.86 [95% CI, 0.79-0.93]). A meta-analysis validated the protective association with no observed directional pleiotropy (OR per SD increase in KIM-1 levels, 0.91 [95% CI, 0.88-0.95]). Of the cardiometabolic risk factors studied, only BMI was associated with KIM-1 levels (0.17 SD increase in biomarker level per 1 kg/m2 [95% CI, 0.08-0.26]) and COVID-19 hospitalization (OR per 1-SD biomarker level, 1.33 [95% CI, 1.18-1.50]). Multivariable MR analysis also revealed that KIM-1 partially mitigated the association of BMI with COVID-19 hospitalization, reducing it by 10 percentage points (OR adjusted for KIM-1 level per 1 kg/m2, 1.23 [95% CI, 1.06-1.43]).
In this genetic association study, KIM-1 was identified as a potential mitigator of COVID-19 severity, possibly attenuating the increased risk of COVID-19 hospitalization among individuals with high BMI. Further studies are required to better understand the underlying biological mechanisms.

Biomarkers Associated With Severe COVID-19 Among Populations With High Cardiometabolic Risk: A 2-Sample Mendelian Randomization Study.

With the development of new techniques, blood and other humoral biomarkers have become increasingly important in the diagnosis of sepsis-associated acute kidney injury (AKI). We aimed to review and summarize the biomarkers associated with the diagnosis of sepsis-associated AKI.
We performed a systematic review in PubMed, Embase, Web of Science, Cochrane and CNKI literature databases. Chinese and English articles published before January 30, 2021. We extracted information on the sensitivity and specificity of biomarkers to diagnose sepsis-associated AKI, the sample size of individuals with sepsis-associated AKI, the demographic variables, the diagnostic criteria and the sample acquisition protocol. Revman 5.3 software was used to analyze data. The sources of heterogeneity of included studies main were different diagnostic criteria for sepsis and AKI, time of sample collection and Patients came from different departments. We defined the inclusion of related studies by using PICOs (Patient, Intervention, Comparison and Outcome) criteria, in particular the design of studies to be included. P: Patients of sepsis. I: Patients of sepsis-associated AKI. C: Patients without sepsis-associated AKI. O: Diagnosis of sepsis associated kidney injury.
A total of 1,227 articles, including 42 studies, were identified. Increases in urine and serum neutrophil gelatinase-related lipid carrier protein (NGAL), urinary interleukin-18, urinary Kim-1, urinary Netrin-1, urinary sCD163, serum estradiol levels, and serum soluble thrombolytic regulatory protein were most strongly correlated with the diagnosis of sepsis-associated AKI. The SROC of urinary KIM-1 ranked first, followed by the other biomarkers: urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18. According to the sample size, the SROC values of urinary NGAL, blood NGAL, urinary IL-18 and urinary KIM-1 were 0.907, 0.857, 0.861 and 0.931, respectively. The sequence was still urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18.
According to the SROC curve area, the diagnostic sequence of sepsis-associated AKI biomarkers was urinary Kim-1 > urinary NGAL > blood NGAL > urinary IL-18. This meta-analysis provided diagnostic features of blood and urine biomarkers based on their association with the diagnosis of sepsis-associated AKI.

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