Urinary biomarkers in pediatric appendicitis

Purpose

The diagnosis of pediatric appendicitis is still a challenge, resulting in perforation and negative appendectomies. The aim of this study was to evaluate novel biomarkers in urine and to use the most promising biomarkers in conjunction with the Pediatric Appendicitis Score (PAS), to see whether this could improve the accuracy of diagnosing appendicitis.

Methods

A prospective study of children with suspected appendicitis was conducted with assessment of PAS, routine blood tests, and measurements of four novel urinary biomarkers: leucine-rich α-2-glycoprotein (LRG), calprotectin, interleukin 6 (IL-6), and substance P. The biomarkers were blindly determined with commercial ELISAs. Urine creatinine was used to adjust for dehydration. The diagnosis of appendicitis was based on histopathological analysis.

Results

Forty-four children with suspected appendicitis were included, of which twenty-two (50 %) had confirmed appendicitis. LRG in urine was elevated in children with appendicitis compared to children without (p < 0.001), and was higher in children with gangrenous and perforated appendicitis compared to those with phlegmonous appendicitis (p = 0.003). No statistical significances between groups were found for calprotectin, IL-6 or substance P. LRG had a receiver operating characteristic area under the curve of 0.86 (95 % CI 0.79–0.99), and a better diagnostic performance than all routine blood tests. LRG in conjunction with PAS showed 95 % sensitivity, 90 % specificity, 91 % positive predictive value, and 95 % negative predictive value.

Conclusion

LRG, adjusted for dehydration, is a promising novel urinary biomarker for appendicitis in children. LRG in combination with PAS has a high diagnostic performance.

     

The efficacy of problem solving therapy in reducing mental and physical health problems: a meta-analysis

This paper describes a meta-analysis of 31 studies that examined the efficacy of problem solving therapy (PST). The meta-analysis, encompassing 2895 participants, showed that PST is significantly more effective than no treatment (d=1.37), treatment as usual (d=0.54), and attention placebo (d=0.54), but not significantly more effective than other bona fide treatments offered as part of a study (d=0.22). Significant moderators included whether the PST included problem-orientation training, whether homework was assigned, and whether a developer of PST helped conduct the study.     

Efficacy of high-level microwave disinfection of dental gypsum casts: the effects of number and weight of casts

The aim of this study was to determine if the bactericidal effect of microwaving gypsum casts is maintained at maximum capacity of the oven (16 casts). Batches of 8 and 16 gypsum casts made from in vivo impressions were divided in half. One half of each cast was microwaved at 900 W for 5 minutes. The remaining halves were left untreated. When assessed for bacteriological growth, the median cfu/mL of the untreated casts was between 10(5) and 10(6) [corrected] while the microwaved casts showed a cfu/mL of 0, indicating that microwaving as described will disinfect gypsum casts even at maximum capacity of the oven.     

Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture,Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

We investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight-bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T-score > −1.0) to osteoporotic (T-score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR-484, miR-328-3p, miR-27a-5p, miR-28-3p, and miR-409-3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM-receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross-validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty-eight iliac ncRNAs were associated with risk of fracture (FDR < 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis-eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel-BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Individual Variation in Adaptive Immune Responses and Risk of Hip Fracture—A NOREPOS Population-Based Cohort Study

Immune-mediated bone loss significantly impacts fracture risk in patients with autoimmune disease, but to what extent individual variations in immune responses affect fracture risk on a population level is unknown. To examine how immune responses relate to risk of hip fracture, we looked at the individual variation in a post-vaccination skin test response that involves some of the immune pathways that also drive bone loss. From 1963 to 1975, the vast majority of the Norwegian adult population was examined as part of the compulsory nationwide Norwegian mass tuberculosis screening. These examinations included standardized tuberculin skin tests (TSTs). Our study population included young individuals (born 1940 to 1960 and aged 14 to 30 years at examination) who had all received Bacille Calmette-Guerin (BCG) vaccination after a negative TST at least 1 year prior and had no signs of tuberculosis upon clinical examination. The study population ultimately included 244,607 individuals, whose data were linked with a national database of all hospitalized hip fractures in Norway from 1994 to 2013. There were 3517 incident hip fractures during follow-up. Using a predefined Cox model, we found that men with a positive or a strong positive TST result had a 20% (hazard ratio [HR] = 1.20, 95% confidence interval [CI] 1.01–1.44) and 24% (HR = 1.24, 95% CI 1.03–1.49) increased risk of hip fracture, respectively, compared with men with a negative TST. This association was strengthened in sensitivity analyses. Total hip bone mineral density (BMD) was available for a limited subsample and similarly revealed a non-significantly reduced BMD among men with a positive TST. Interestingly, no such clear association was observed in women. An increased immune response after vaccination is associated with an increased risk of hip fracture decades later among men, possibly because of increased immune-mediated bone loss. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Acetabular Wall Augmentation in Selected Patients With Recurrent Dislocation After THA

We reviewed 42 patients operated with PMMA augmentation of the acetabular wall for recurrent posterior dislocation of cemented total hip arthroplasties with a cemented all-poly acetabular component. 38 patients never experienced subsequent dislocations after the procedure. 4 patients had recurrent dislocations, and two additional patients underwent a revision procedure due to aseptic loosening of the acetabular component. 1, 5 and 10 years survival of the prosthesis free of dislocation were 95%, 95% and 64% respectively. 90% of the patients were satisfied, four patients experienced pain and 3 patients sustained an infection. The procedure is simple, effective, takes less time and results in less blood loss compared to full revision surgery. It should be considered in cases of recurrent posterior dislocation in elderly patients.     

Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection

ObjectiveTo identify predictors of recurrence-free survival (RFS) based on the clinicopathological features of patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU) with bladder cuff resection.Materials and methodsWe retrospectively reviewed the records of patients from October 1998 to July 2012 at our tertiary institution and identified 120 patients with sufficient data who underwent RNU for UTUC. We recorded various clinical and histopathological parameters as potential predictors of outcome. Recurrence was defined as any occurrence of urothelial carcinoma after RNU either intravesically, local/regionally, or at distant sites. Univariate, multivariate, and RFS analyses were conducted using the Cox regression and Kaplan-Meier methods.ResultsThe median age of our cohort was 71 years (interquartile range: 64–78). Median RNU-specimen tumor size was 3.0 cm (interquartile range: 2.0–5.0 cm). Fifty-four patients (45%) had a tumor<3.0 cm and 66 (55%) had a tumor≥3.0 cm. Eighty patients (66.7%) had organ-confined UTUC (≤pT2) and 40 (33.3%) had non–organ-confined UTUC (≥pT3). Sixty-five patients (54.2%) experienced at least 1 recurrence. Forty-three patients (35.8%) had at least 1 episode of intravesical recurrence and 28 (23.3%) had distant recurrence. A multivariate analysis revealed non–organ-confined disease (hazard ratio [HR] = 3.62, P<0.001), tumor diameter≥3 cm (HR = 1.97, P = 0.011), and male gender (HR = 1.81, P = 0.047) to be significant independent predictors of disease recurrence. The 5-year RFS rate was 46.9% and 25.8% for patients with tumor size<3 and≥3 cm, respectively.ConclusionsFollowing RNU, the incidence of recurrence remains high among patients with UTUC. In our cohort of patients, tumor diameter≥3.0 cm, non–organ-confined UTUC, and male gender constitute important risk factors for poor RFS outcomes following RNU. These patients require diligent postoperative surveillance and may potentially benefit from perioperative systemic therapy.     

Expression of CD18 (integrin β2 chain) correlates with prognosis in malignant B cell lymphomas

Summary. Several studies have shown that cell cycle related parameters including DNA synthesis and activation antigen expression can predict patient survival in lymphoma patients. In this study of 69 malignant B cell lymphomas we have examined the cell surface expression of several cell interaction and activation molecules by flow cytometry. Expression of CD18 (integrin β₂ chain) was found to correlate strongly with patient survival (median follow up 50 months) even when adjusting for other important prognostic factors ( P = 0.0001). The percentage of cells positive for CDw75 proved important both as a single parameter and in the multivariate analysis. Histology, classified as low versus high grade malignancy, bulky versus not bulky disease and high versus low thymidine incorporation, was also found to correlate with prognosis in this study.     

Head impact exposure in youth football—Are current interventions hitting the target?

Restrictions on heading in youth football have been implemented in some countries to limit head impact exposure. However, current interventions remain poorly guided by evidence. Our objective was to quantify heading exposure in youth football, assessing the effects of sex and age. Football matches played during an international youth football tournament with no heading restrictions were directly observed, including players from both sexes (11-19 years). The elite senior level was included for comparison, using video analysis. All heading events were registered, classified, and assigned to individual players. Heading rates were calculated for each sex and age group. We observed a total of 267 matches, corresponding to 4011 player hours (1927 player hours for females, 2083 player hours for males). Males headed more frequently than females (2.7 vs 1.8 headers/player hour; P < .001). Heading rates increased with age (ANOVA, P < .001), approaching the elite senior level for players 16 years and older. There was substantial variation within teams for all age and sex groups, with the widest range (1-18 headers) observed for girls aged 19. Girls younger than 12 years had the lowest exposure, with an average of <2 players per team heading the ball, each with 1-2 headers. In conclusion, age and sex influence head impact exposure in youth football, and warrants careful consideration when introducing injury prevention measures. Males are more frequently exposed than females, heading rates increase with age, and there is substantial variation between players. Heading is a rare event in the youngest age groups, especially among females.     

The Hypotonic Environmental Changes Affect Liposomal Formulations for Nose-to-Brain Targeted Drug Delivery

Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within minutes. However, the nasal mucosa properties (e.g., tonicity, pH) are not constant because of physiological and environmental factors, and this might limit the therapeutic outcome of nanocarrier-based formulations. To shine light on the impact of environmental ionic strength on nanocarrier-based formulations, we have studied how liposomal formulations respond to the change of tonicity of the external environment. Large unilamellar vesicles loaded with 6 different drugs were exposed to different hypotonic environments, creating an osmotic gradient within the inner core and external environment of the liposomes up to 650 mOsm/kg. Both size and polydispersity of liposomes were significantly affected by tonicity changes. Moreover, the release kinetics of hydrophilic and lipophilic drugs were largely enhanced by hypotonic environments. These results clearly demonstrate that the environmental ionic strength has an impact on liposomal formulation stability and drug release kinetics and it should be considered when liposomal formulations for nose-to-brain targeted drug delivery are designed.