Nevin Manimala

Metabolomics. 2023 Mar 29;19(4):29. doi: 10.1007/s11306-023-01989-w.

ABSTRACT

INTRODUCTION: Pompe disease is a rare, lysosomal disorder, characterized by intra-lysosomal glycogen accumulation due to an impaired function of α-glucosidase enzyme. The laboratory testing for Pompe is usually performed by enzyme activity, genetic test, or urine glucose tetrasaccharide (Glc4) screening by HPLC. Despite being a good preliminary marker, the Glc4 is not specific for Pompe.

OBJECTIVE: The purpose of the present study was to develop a simple methodology using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for targeted quantitative analysis of Glc₄ combined with untargeted metabolic profiling in a single analytical run to search for complementary biomarkers in Pompe disease.

METHODS: We collected 21 urine specimens from 13 Pompe disease patients and compared their metabolic signatures with 21 control specimens.

RESULTS: Multivariate statistical analyses on the untargeted profiling data revealed Glc₄, creatine, sorbitol/mannitol, L-phenylalanine, N-acetyl-4-aminobutanal, N-acetyl-L-aspartic acid, and 2-aminobenzoic acid as significantly altered in Pompe disease. This panel of metabolites increased sample class prediction (Pompe disease versus control) compared with a single biomarker.

CONCLUSION: This study has demonstrated the potential of combined acquisition methods in LC-HRMS for Pompe disease investigation, allowing for routine determination of an established biomarker and discovery of complementary candidate biomarkers that may increase diagnostic accuracy, or improve the risk stratification of patients with disparate clinical phenotypes.

PMID:36988742 | DOI:10.1007/s11306-023-01989-w

Arch Orthop Trauma Surg. 2023 Mar 29. doi: 10.1007/s00402-023-04848-4. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study was to evaluate the management of orthopaedic device-related infections (ODRIs) due to Enterococcus spp.

MATERIALS AND METHODS: We performed a retrospective cohort study in a French tertiary university hospital. Patients with prosthetic joint- or osteosynthesis-associated infections caused by enterococci from 2013 to 2020 were included. Patients who died within 5 days after surgery; who were in palliative care; or who had osteosynthesis of the hand, foot or vertebra were excluded.

RESULTS: Thirty-six patients were included, with 24 in the arthroplasty group and 12 in the osteosynthesis material group. Most infections were polymicrobial (63.9%, n = 23). Debridement, antibiotics and implant retention (DAIR) was performed in 30.6% (n = 11), withdrawal of material in 16.7% (n = 6), one-stage exchange in 30.6% (n = 11) and two-stage exchange in 22.2% of cases (n = 8). The antibiotic regimen was amoxicillin in 41.6% (n = 15), rifampicin in 27.8% (n = 10), linezolid in 25% (n = 9) and/or fluoroquinolones in 30.6% (n = 11). Clinical success at 1 year was 67% (18/27). The only variable statistically associated with a decreased risk of clinical failure was a duration of antibiotic therapy of 12 weeks (p = 0.04). Patients with a lower body mass index and age tended to decrease the risk of clinical failure (p = 0.05 and 0.06 respectively).

CONCLUSIONS: The management of enterococcal ODRIs is complex, and ODRI patients are at high risk for relapse. In our small study, a better outcome was not demonstrated for patients with combination therapy and rifampicin use. Further studies are needed to improve the medico-surgical strategy for treating these infections.

PMID:36988713 | DOI:10.1007/s00402-023-04848-4

Arch Virol. 2023 Mar 29;168(4):125. doi: 10.1007/s00705-023-05747-0.

ABSTRACT

Human endogenous retroviruses (HERVs) are LTR retrotransposons that are present in the human genome. Among them, members of the HERV-K (HML-2) group are suspected to play a role in the development of different types of cancer, including lung, ovarian, and prostate cancer, as well as leukemia. Acute myeloid leukemia (AML) is an important disease that causes 1% of cancer deaths in the United States and has a survival rate of 28.7%. Here, we describe a method for assessing the statistical association between HERV-K (HML-2) transposable element insertion polymorphisms (or TIPs) and AML, using whole-genome sequencing and read mapping using TIP_finder software. Our results suggest that 101 polymorphisms involving HERV-K (HML-2) elements were correlated with AML, with a percentage between 44.4 to 56.6%, most of which (70) were located in the region from 8q24.13 to 8q24.21. Moreover, it was found that the TRIB1, LRATD2, POU5F1B, MYC, PCAT1, PVT1, and CCDC26 genes could be displaced or fragmented by TIPs. Furthermore, a general method was devised to facilitate analysis of the correlation between transposable element insertions and specific diseases. Finally, although the relationship between HERV-K (HML-2) TIPs and AML remains unclear, the data reported in this study indicate a statistical correlation, as supported by the χ² test with p-values < 0.05.

PMID:36988711 | DOI:10.1007/s00705-023-05747-0

J Cancer Res Clin Oncol. 2023 Mar 29. doi: 10.1007/s00432-023-04700-7. Online ahead of print.

ABSTRACT

PURPOSE: Renal cell carcinoma belongs among the deadliest malignancies despite great progress in therapy and accessibility of primary care. One of the main unmet medical needs remains the possibility of early diagnosis before the tumor dissemination and prediction of early relapse and disease progression after a successful nephrectomy. In our study, we aimed to identify novel diagnostic and prognostic biomarkers using next-generation sequencing on a novel cohort of RCC patients.

METHODS: Global expression profiles have been obtained using next-generation sequencing of paired tumor and non-tumor tissue of 48 RCC patients. Twenty candidate lncRNA have been selected for further validation on an independent cohort of paired tumor and non-tumor tissue of 198 RCC patients.

RESULTS: Sequencing data analysis showed significant dysregulation of more than 2800 lncRNAs. Out of 20 candidate lncRNAs selected for validation, we confirmed that 14 of them are statistically significantly dysregulated. In order to yield better discriminatory results, we combined several best performing lncRNAs into diagnostic and prognostic models. A diagnostic model consisting of AZGP1P1, CDKN2B-AS1, COL18A1, and RMST achieved AUC 0.9808, sensitivity 95.96%, and specificity 90.4%. The model for prediction of early relapse after nephrectomy consists of COLCA1, RMST, SNHG3, and ZNF667-AS1 and achieved AUC 0.9241 with sensitivity 93.75% and specificity 71.07%. Notably, no combination has outperformed COLCA1 alone. Lastly, a model for stage consists of ZNF667-AS1, PVT1, RMST, LINC00955, and TCL6 and achieves AUC 0.812, sensitivity 85.71%, and specificity 69.41%.

CONCLUSION: In our work, we identified several lncRNAs as potential biomarkers and developed models for diagnosis and prognostication in relation to stage and early relapse after nephrectomy.

PMID:36988708 | DOI:10.1007/s00432-023-04700-7

Pediatr Nephrol. 2023 Mar 29. doi: 10.1007/s00467-023-05947-5. Online ahead of print.

ABSTRACT

BACKGROUND: Uromodulin is the most abundant protein in the urine of healthy adults, and higher urine concentrations mark better tubular health. Greater kidney size and function are predictors of higher uromodulin levels in adults. Urine uromodulin has not yet been studied in children with chronic kidney disease (CKD). Thus, we sought to determine the relationship between age and kidney function with urine uromodulin levels in children with CKD.

METHODS: In the CKD in Children (CKiD) cohort, we utilized multivariable linear regression to evaluate the relationship of age and eGFR with urine uromodulin levels. The primary outcome was uromodulin indexed to urine creatinine (Umod/Cr, mg/g), which was log₂-transformed given its skewed distribution.

RESULTS: Among 677 CKiD participants, the median age was 11.8 years (8.2-15.3), the median eGFR was 49 ml/min/1.73 m² (37-63), the etiology of CKD was glomerular disease in 31%, and the median Umod/Cr level was 0.114 mg/g (0.045-0.226). In the multivariable models, each one-year older age was associated with 0.18 (12%) lower log₂(Umod/Cr) and 0.20 (13%) lower log₂(Umod/Cr) among those with non-glomerular and glomerular disease, respectively (p < 0.001). However, we did not find a statistically significant association between eGFR and Umod/Cr in either participants with non-glomerular or glomerular disease (p = 0.13 and p = 0.58, respectively).

CONCLUSIONS: Among children with CKD, older age is significantly associated with lower Umod/Cr, independent of eGFR. Further studies are needed to comprehensively evaluate age-specific reference ranges for urine uromodulin and to evaluate the longitudinal relationship of uromodulin with both age and eGFR in children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

PMID:36988691 | DOI:10.1007/s00467-023-05947-5

Eur J Pediatr. 2023 Mar 29. doi: 10.1007/s00431-023-04947-9. Online ahead of print.

ABSTRACT

Congenital cryptorchidism is a well-established risk factor of testicular malignancies. However, there is still remarkable variability in the measures of associations between of these two clinical entities. The current meta-analysis investigates the up-to-date risk of testicular cancer in adults with a history of surgically corrected congenital cryptorchidism until adolescence. The meta-analysis was conducted with strict criteria for the identification of the congenital cryptorchidism cases that underwent surgery before adulthood. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the PubMed and the Scopus databases was conducted, using a defined strategy, from inception to February 2023. Two independent authors screened the literature and extracted the data, using inclusion and exclusion criteria. Of the 2176 articles identified, 93 articles were fully retrieved, and 6 articles met all the inclusion criteria. The Newcastle-Ottawa scale was applied for the studies’ quality assessment. The random-effects model in RevMan 5.4 program was used for the meta-analysis. Three case-control studies and three cohort studies were selected. They included 371,681 patients and 1786 incidents of testicular cancer. The pooled odds ratio (OR) was 3.99 (95% confidence intervals (CI): 2.80-5.71). The heterogeneity was moderate and estimated at 51% with the I-squared statistic. A forest plot and a funnel plot were produced to evaluate the ORs and the probable publication bias, respectively. The mean Newcastle-Ottawa score was 8/9 for all the included reports. Conclusion: This systematic review and meta-analysis verifies, with an updated estimate, the increased risk of testicular cancer in adults with an orchidopexy history. New evidence on the maldescent laterality supports that the cancer risk remains increased and for the contralateral, unaffected testicle, although to a lesser extent. The orchidopexy in the first year of life prevents the testicular damage and decreases the overall cancer risk. What is Known: • Congenital cryptorchidism is the commonest genitourinary abnormality and a risk factor for testicular cancer. • The most recent meta-analysis reporting this association was in 2013. What is New: • After reviewing literature until February 2023, the association of congenital cryptorchidism with testicular cancer risk in adulthood was verified: odds ratio=3.99 [2.80-5.71], 95% CI. • The meta-analysis highlights the protective role of early orchidopexy and the controversial data about maldescent and testicular cancer laterality.

PMID:36988678 | DOI:10.1007/s00431-023-04947-9

Rheumatol Int. 2023 Mar 29. doi: 10.1007/s00296-023-05311-8. Online ahead of print.

ABSTRACT

This study provides insight in behavior and perspective of rheumatic patients during the first COVID-19 wave. Especially, we analyzed the patients’ fear of COVID-19 and unauthorized change of immunosuppressive medication in consequence of their fear. We hereby provide data from 877 patients with valuable insights into the patients’ point of view. We retrospectively interviewed patients of our rheumatic university outpatient clinic. This way, we collected information about the patients’ personal point of view. Data like the rheumatic diagnosis and immunosuppressive medication was extracted from the health records. Statistical analysis was conducted using IBM® SPSS® Statistics (version 26). A total of 877 patients were included into our study. We could show that fear of COVID-19 was clearly present in rheumatic patients. Higher fear levels seem to be associated with comorbidity burden. Unauthorized change of immunosuppressive medication was rare in our study (5%). In our study we provide novel insight into patients’ point of view and behavior of rheumatic patients. Unauthorized change of immunosuppressive medication was rare (5%) as seen in other studies. The low rate of unauthorized change and high rate of compliance is reassuring since good disease control appears to be prognostically important in the progression of COVID-19 disease. Therefore, as the pandemic continues, treatment decisions should be made in close consultation between patient and practitioner to improve adherence and reduce morbidity and mortality.

PMID:36988675 | DOI:10.1007/s00296-023-05311-8

Diagn Interv Radiol. 2023 Mar 29;29(2):367-372. doi: 10.4274/dir.2023.222003. Epub 2023 Mar 8.

ABSTRACT

PURPOSE: To investigate the safety and efficacy of percutaneous cholecystoduodenal stent (CDS) placement to prevent recurrence of acute cholecystitis in patients who were unfit for cholecystectomy.

METHODS: Between April 2016 and January 2022, 46 patients [median age (range) = 81 (37-99) years; men = 15] with acute cholecystitis who were unfit for surgery underwent percutaneous cholecystostomy followed by a CDS placement in two institutions. Plastic stents of three different materials were used [polyethylene, polyurethane (PU), and polycarbonate (PCB)-based PU]. Clinical outcomes, including technical and clinical success rates and early (<30 days) and delayed adverse events, were retrospectively assessed by stent type.

RESULTS: CDS placement was technically successful in 39 patients. Clinical success, defined as cholecystostomy catheter removal, was achieved in 35 of 39 patients. Immediate complications, such as acute pancreatitis and peritonitis, occurred in two patients. Two patients experienced recurrent cholecystitis during a 113-day follow-up (range, 3-1,723). Three-stent groups had significantly different delayed complications on Fisher’s exact test (P = 0.021). The Bonferroni post-hoc analysis showed the PCB-PU group tended to have fewer complications than the PU group (P = 0.060).

CONCLUSION: CDS placement is applicable in treating acute cholecystitis patients who were initially unfit for surgery, but further investigation is needed. Although it was not statistically significant, a PCB-PU stent can be suitable for this use because it tends to have fewer delayed complications and is equipped with a drawstring and side holes.

PMID:36988025 | DOI:10.4274/dir.2023.222003

Nurs Ethics. 2023 Mar 29:9697330221142079. doi: 10.1177/09697330221142079. Online ahead of print.

ABSTRACT

BACKGROUND: The increasing prevalence of moral distress in the stressful environment of the intensive care unit (ICU) provides grounds for nursing error and endangers patients’ health, safety, and even life. One of the most important reasons for this distress is the treatment team’s second victim syndrome (SVS), especially nurses, following errors in the treatment system.

OBJECTIVES: The present study aimed to determine the relationship between moral distress and SVS in ICUs.

RESEARCH DESIGN: This cross-sectional study involved a sample size of 96 ICU nurses working in hospitals affiliated with Tehran University of Medical Sciences, Iran, in the 2021-2022 period, who were selected via a simple random sampling method. Data were collected using the Demographic Questionnaire, the second victim experience and support tool (SVEST) and Moral Distress Scale-Revised (MDS-R). Descriptive statistics (percentage, frequency, mean, and SD) and analytical tests (Spearman correlation coefficient test, independent t-test, and ANOVA) were employed for data analysis.

PARTICIPANTS AND RESEARCH CONTEXT: This study used a sample size of 96 intensive care unit nurses working in hospitals affiliated to Tehran University of Medical Sciences selected by simple random sampling.

ETHICAL CONSIDERATIONS: The study obtained research ethics approval, and all participants were informed of the voluntary and anonymous nature of their participation.

FINDINGS: The results showed that 59.4% of nurses suffered a low level of moral distress, and 40.6% suffered from a moderate level of moral distress. The SVS score of 86.5% of the nurses was moderate. There was no significant and direct correlation between moral distress and SVS in nurses; however, there was a significant and inverse correlation between the moral distress intensity and SVS (p = 0.011).

CONCLUSION: Despite no significant correlation between moral distress and SVS, these variables were at moderate levels. Accordingly, it is suggested to provide a proper ground for expressing morally stressful situations, counseling and training strategies to deal with moral distress, creating support resources for those suffering from SVS, and implementing empowerment programs.

PMID:36988002 | DOI:10.1177/09697330221142079

Diagn Interv Radiol. 2023 Mar 29;29(2):331-341. doi: 10.4274/dir.2022.22352. Epub 2023 Feb 21.

ABSTRACT

PURPOSE: To evaluate the technical, radiological, and clinical outcomes after type 2 endoleak (T2EL) embolization in patients with a growing aneurysm sac after endovascular aortic aneurysm repair (EVAR). Additionally, to determine clinical and imaging-based factors for outcome prediction after embolization of a T2EL.

METHODS: A single-institution, retrospective analysis was performed of 60 patients who underwent a T2EL embolization procedure between September 2005 and August 2016 to treat a growing aneurysm sac diameter following EVAR. The patients’ electronic medical records and all available pre- and post-embolization imaging were reviewed. Statistical analysis methods included logistic regression models for binary outcomes, proportional odds models for ordinal outcomes, and linear regression models for continuous outcomes. The Kaplan-Meier method was used to estimate the overall survival probability.

RESULTS: Technical, radiological, and clinical success rates after T2EL embolization were 95% (n = 57), 26.7% (n = 16), and 76.7% (n = 46), respectively. Persistent aneurysm sac expansion was found in 31 patients (51.7%). Unsharp or blurred T2EL delineation on pre-interventional computed tomography (CT) was a predictive factor for a post-embolization persistent visible endoleak and persistent growth of the aneurysm sac (P = 0.025). Median survival after T2EL embolization was 5.35 years, with no difference observed between patients with persistent sac expansion compared with patients with stable or decreased sac diameter.

CONCLUSION: Progression of the aneurysm sac diameter was observed in half the study patients, despite technically successful T2EL embolization. Unsharp or blurred T2EL delineation on pre-interventional CT seemed to be an imaging-based predictor for a persistent T2EL and progressive aneurysm sac growth after embolization.

PMID:36987998 | DOI:10.4274/dir.2022.22352