The Significance of Serum Beta-Hydroxybutyrate and Urine Biochemical Markers in Determining the Severity of COVID-19 Infection

Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria

Osteoarthritis (OA) is a complex heterogeneous joint disease affecting more than 35 million people worldwide. The current gold standard diagnostic investigation is the plain radiograph, which lacks sensitivity. Biochemical markers have the potential to act as adjunct markers for imaging in the assessment of knee OA. We undertook this study to determine the association between individual biochemical markers and radiographic features, and to establish whether the association is strengthened when selected biochemical markers are combined into a single factor (a theoretical marker). Twenty serum and urinary biochemical markers were analyzed in 119 patients with predominantly tibiofemoral knee OA. Pearson's correlation was performed, and corresponding coefficients of determination (R(2)) were calculated to determine the association between biochemical markers and a range of imaging features from radiographs and dual x-ray absorptiometry of the knee. Biochemical markers demonstrating a significant association (P < 0.05) with a specific imaging feature were combined by principal components analysis (PCA). Pearson's correlation was repeated to establish whether the combined panel of biochemical markers showed a stronger association with imaging than the best single marker. Fourteen biochemical markers showed significant associations with one or more imaging features. By combining specific panels of biochemical markers to form factors, the association of markers with imaging features (R(2)) increased from 11.9% to 22.7% for the Kellgren/Lawrence (K/L) score, from 5.9% to 9.2% for joint space width (JSW), from 6.6% to 10.8% for sclerosis, from 13.5% to 22.6% for osteophytes, and from 12.0% to 14.2% for bone mineral density (BMD). Biochemical markers identifying patients with osteophytes overlapped with those correlated with a high K/L score, while markers of subchondral BMD formed a completely separate group. Biochemical markers of JSW included markers associated with both osteophytes and BMD. The PCA results suggest that biochemical marker combinations may be more sensitive than individual biochemical markers for reflecting structural damage in patients with knee OA. The differences in biochemical marker profiles associated with osteophytes compared with those associated with subchondral BMD raise the possibility that these 2 processes, commonly seen in bone in knee OA, have underlying biologic differences.

Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in an increased risk of fracture. While the level of bone mass can be estimated by measuring bone mineral density (BMD) using dual X-ray absorptiometry (DXA), its measurement does not capture all the risk factors for fracture. Quantitative changes in skeletal turnover can be assessed easily and non-invasively by the measurement of serum and urinary biochemical markers; the most sensitive markers include serum osteocalcin, bone specific alkaline phosphatase, the N-terminal propeptide of type I collagen for bone formation, and the crosslinked C- (CTX) and N- (NTX) telopeptides of type I collagen for bone resorption. Advances in our knowledge of bone matrix biochemistry, most notably of post-translational modifications in type I collagen, are likely to lead to the development of new biochemical markers that reflect changes in the material property of bone, an important determinant of bone strength. Among those, the measurement of the urinary ratio of native (alpha) to isomerized (beta) CTX - an index of bone matrix maturation - has been shown to be predictive of fracture risk independently of BMD and bone turnover. In postmenopausal osteoporosis, levels of bone resorption markers above the upper limit of the premenopausal range are associated with an increased risk of hip, vertebral, and nonvertebral fracture, independent of BMD. Therefore, the combined use of BMD measurement and biochemical markers is helpful in risk assessment, especially in those women who are not identified as at risk by BMD measurement alone. Levels of bone markers decrease rapidly with antiresorptive therapies, and the levels reached after 3-6 months of therapy have been shown to be more strongly associated with fracture outcome than changes in BMD. Preliminary studies indicate that monitoring changes of bone formation markers could also be useful to monitor anabolic therapies, including intermittent parathyroid hormone administration and, possibly, to improve adherence to treatment. Thus, repeated measurements of bone markers during therapy may help improve the management of osteoporosis in patients.

Preeclampsia (PE) is a disorder which affects 1-10% of pregnant women worldwide. It is characterised by hypertension and proteinuria in the later stages of gestation and can lead to maternal and perinatal morbidity and mortality. Other than the delivery of the foetus and the removal of the placenta, to date there are no therapeutic approaches to treat or prevent PE. It is thus only possible to reduce PE-related mortality through early detection, careful monitoring, and treatment of the symptoms. For these reasons the search for noninvasive, blood-borne, or urinary biochemical markers that could be used for the screening, presymptomatic diagnosis, and prediction of the development of PE is of great urgency. So far, a number of biomarkers have been proposed for predicting PE, based on pathophysiological observations, but these have mostly proven to be unreliable and inconsistent between different studies. The clinical presentation of PE and data gathered for the biochemical markers placental growth factor (PlGF), soluble Feline McDonough Sarcoma- (fms-) like tyrosine kinase-1 (sFlt-1), asymmetric dimethylarginine (ADMA), and methyl-lysine is being reviewed with the aim of providing both a clinical and biochemical understanding of how these biomarkers might assist in the diagnosis of PE or indicate its severity.

To access the effect of repeated extracorporeal shock wave (ESW) on urinary biochemical markers 20 rats were assigned for ESW (Direx Tripter X1(R) - 14 KV) to one of two groups: G1 (n=10) one ESW; G2 (n=10) two ESWs within a 14-day interval. Within the twenty-four hour period before and after the application of shock waves, the animals were placed in metabolic cages for 24 hour urine collection. The ph, creatinine, sodium, potassium, chlorides, calcium, magnesium, phosphorus, oxalates, alkaline phosphatase and citrates were measured. Twenty-four hours after the material was collected for urinary determination, the animals underwent nephrectomy of the kidney submitted to the ESW applications and were, then, sacrificed. The kidneys were processed for histopathological examination. Small variations in the biochemical markers were found in both groups, with no significant differences between the values obtained either prior to or following the ESW applications, except for citrate and alkaline phosphatase. Citraturia decreased significantly in group 2, following the second ESWL application (24.8 +/- 3.0 mg/day after the first ESWL vs. 15.3 +/- 2.2 mg/day after the second ESWL; p < 0.05). Alkaline phosphatase increased significantly following ESWL in group I (0.57 +/- 0.02 vs. 0.79 +/- 0.04 micromol/mg creatinine; p < 0.01) and also in group 2 (0.69 +/- 0.05 vs. 0.83 +/- 0.03 micromol/mg creatinine; p < 0.05). Glomerular, interstitial and sub-capsular hemorrhage with perivascular edema was found in the animals in both groups studied. A significant increase in urinary alkaline phosphatase was found in both groups studied, suggesting a proximal tubule lesion. In the group of rats undergoing more than one ESWL application, a smaller urinary citrate excretion was noticed, which may be a factor contributing for the formation of new calculi.

PL8.2. Use of biochemical markers to monitor therapy in metastatic bone disease

IntroductionAlthough prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis.Materials and methodsDifferences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed.ResultsUrinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test.ConclusionsWe have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.

With the continuous improvement of medical level, the success rate of the treatment for premature infants is increasing, and the incidences of various lung and brain sequelae, as well as endocrine and metabolic system diseases, are going up. The study of lung and brain diseases of premature infants has been very extensive and in-depth. In recent years, the issue of metabolic bone disease in premature infants has received extensive attention and become a hot research topic. The disease lacks typical clinical symptoms in the early stage. When children show clinical symptoms or abnormal X-ray findings, bone mass decalcification has reached 30%-50%, resulting in skeletal malformation and height growth restriction of premature infants. In terms of diagnosis, there is no gold standard, and no specific biochemical markers for metabolic bone disease in premature infants have been found in related studies. This article makes the following review on biochemical markers of bone metabolism, in order to find biochemical markers with high specificity and sensitivity, and help to find early metabolic bone diseases and improve the infants’ quality of life. Key words: Preterm infants; Metabolic bone disease; Serum biochemical markers; Urinebiochemical markers

Urinary Clinical Pathologic Findings and Glomerular Filtration Rate in the Horse

We evaluated the effect of supplementation with vitamin D(3) (excluding the potential effect of calcium supplementation) on the risk of fall and fracture, primarily in postmenopausal women, using a systematic literature review of MEDLINE, EMBASE, BIOSIS and the Cochrane Database of Systematic Reviews for the period January 1985 to June 2005. Studies examining the effect of vitamin D versus placebo on the risk of fall or fracture in postmenopausal females were of particular interest. Studies of vitamin D in combination with calcium were also included where the control group was treated with calcium alone. Studies of men and women where results for men and women were not presented separately were included. Nine studies met the inclusion criteria. Our primary meta-analyses examined the effect of vitamin D(3) on the risk of fall or fracture; additional analyses examined baseline and difference between baseline and final levels of several serum and urinary biochemical markers. The pooled relative risk (RR) for vitamin D(3) preventing falls was 0.88 (95%CI 0.78-1.00). For fractures, the pooled RR for vitamin D(3) preventing non-vertebral fractures was 0.96 (95%CI 0.84-1.09) and the pooled RR for vitamin D(3) preventing vertebral fractures was 1.22 (95%CI 0.64-2.31). In a subgroup analysis of post-menopausal women, the pooled RR for vitamin D(3) preventing falls was 0.92 (95%CI 0.75-1.12) and in preventing non-vertebral fractures the pooled RR was 0.81 (95%CI 0.48-1.34). There is a trend towards a reduction in the risk of fall among patients treated with vitamin D(3) alone compared with placebo, suggesting that vitamin D(3) should be an integral part of effective osteoporosis management.

To date, no shared guidelines have been approved for the diagnosis and management of low bone mineral density (BMD), especially in early infancy. Therefore, there is an increasing demand for new methodologies to allow the assessment of bone health status in this specific cohort, which is exposed to several risk factors (e.g. maternal vitamin D deficiency, pregnancy-associated diseases, preterm birth and comorbidities, low birth weight, intrauterine growth restriction). Currently, the assessment of BMD in newborn and infants relies mainly on serum and urinary biochemical markers, in association with several technologies to measure bone mineral content, such as dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) being traditionally used, despite many limitations. More recently, Radiofrequency Echographic Multi-Spectrometry (REMS) emerged as a promising tool in clinical practice for screening and monitoring BMD. Due to the radiation-free technology, an extremely ease of use, low costs, an excellent degree of sensitivity, specificity, and reproducibility, REMS technology has proven to be the gold standard technique in sensitive populations such as pregnant women, newborns and infants, allowing mass extended screening strategies. However, to date no validate cut-off reference for REMS in paediatric age are available. Future longitudinal studies on REMS methodology are needed to build reference standards and new shared algorithms, combining biochemical and instrumental data, for the diagnosis, management and treatment of decreased BMD before and after birth.

Point-of-care testing (POCT) for urinary tract infection (UTI) holds significant importance in the field of disease prevention and control, as well as the advancement of personalized precision medicine. However, conventional methods for detecting UTIs continue to face challenges such as time-consuming and labor-intensive detection processes, and reliance on specialized equipment and personnel rendering them unsuitable for point-of-care applications, especially in resource-limited areas. Here, we propose a novel flexible programmable manually powered microfluidic (FPM) for rapid point-of-care diagnosis of UTIs. For the first time, the proposed FPMs was achieved through a combined strategy of laser printing, cutting, and laminating, with the entire process completed in under 15 min at a cost of less than $0.5, which effectively circumvent the traditionally time-consuming and labor-intensive soft lithography techniques. By incorporating a modular structure-based design concept, we successfully developed various types of portable FPMs with functionalities including parallel pumping, simultaneous releasing, quantitative dispensing, sequential releasing, cyclic motion of multiple liquids and concentration gradient generating. As a proof-of-concept demonstration, we initially employed a high-throughput parallel dispensing design to analyze six urinary biochemical markers within 1 min, presenting potential applicability for future at-home testing. We then integrated a manually powered concentration gradient generator with spatial confinement signal enhancement to enable rapid phenotypic antimicrobial susceptibility testing (AST) within three to 5 h, while achieving clinical diagnostic accuracy rates of up to 95.56%. Therefore, our proposed FPMs eliminate the need for external pumps or actuators and could serve as an affordable hand-held POCT tool for UTI diagnosis. Moreover, in resource-poor areas, they have potential utility as robust POCT devices addressing diverse rapid detection needs.

Qiangxin bushen decoction attenuates cardiorenal syndrome type II via AMPK/FOXO1-mediated ferroptosis pathway: A multi-omics and experimental study.

Although urinary biochemical markers can be assessed by their ratio to urinary creatinine (U-Cr) concentration, reference values in adults may not be applicable to children because the amount of Cr excreted varies by body size. We therefore measured the relationship between age and the ratios of urinary β-2-microglobulin (U-β2MG), N-acetyl-β-d-glucosaminidase (U-NAG), calcium (U-Ca) and protein (U-Pr) concentration to those of U-Cr in children. Fifty-seven patients aged >1 year with benign familial hematuria (median age, 6.3 years) were divided into three age groups: 1-4, 5-9, and ≥10 years. Urinary biomarkers were assayed using actual values; ratios to actual U-Cr values; and our standardized metric, namely 100-fold the ratio of serum Cr to U-Cr concentration; and the relationship of each of these to age was determined. The ratios of U-β2MG, U-NAG and U-Ca to Cr varied significantly by age, being higher in younger than in older children, but the actual and standardized values of each did not vary by age, nor did any measurement of U-Pr. The ratios of urinary markers of tubular function, including U-β2MG, U-NAG and U-Ca, to Cr vary by age, being higher in younger children. In contrast, the ratios of urinary markers of glomerular filtration (such as U-Pr)to Cr do not vary by age, making them suitable for corrections relative to Cr.

Two recent developments in clinical investigation have led to emergence of interest in so-called “antiestrogens” as potential therapeutic modalities in osteoporosis. The first is the confirmation in numerous well-executed clinical studied that estrogen is, indeed, the most effective therapeutic agent available for the prevention of the bone loss leading to osteoporosis in postmenopausal women. The second is increasing evidence, both basic and clinical, that many agents, rather than being simply “estrogens” or “antiestrogens” are more appropriately characterized as mixed estrogen agonistantagonists, and therefore have the potential of affecting various estrogen-sensitive systems in a highly selective manner. Most of the currently available data on effect of antiestrogens in osteoporosis come from studies with tamoxifen. This agent, widely used in the treatment of bone cancer, has been shown to be bone sparing in a number of retrospective survey investigations, and more recently in prospective, blinded, placebo-controlled studies as well. Data showing apparent estrogen-agonist activity in the skelton, in the face of clear estrogen-antagonist action in other tissues, has led to an intense search for the mechanism of this “selective” action. Animal models have been employed to screen compounds for the desired combinations of selective actions. One of the interesting new compounds in this area is raloxifene. This benzothiophen derivative has been shown in the ovariectomized rat model to have potent estrogen-agonist actions in the skelton, reducing bone turnover and preserving bone mineral density in the face of estrogen deficiency. In addition, its actions on serum lipids appear also to be estrogen agonistic. On the other hand, this compound behaves as a potent estrogen antagonist in the uterus, demonstrating no endometrial stimulatory action, while blocking estrogen action in the same organ. In recently completed Phase 2 clinical trials in postmenopausal women, raloxifene has been shown to reduce born turnover, as measured by a variety of serum and urine biochemical markers. It lowers LDL cholesterol in these women as well, but has no apparent uterine stimulatory activity.