Category: Nevin Manimala

Clin Transplant. 2024 Dec;38(12):e70048. doi: 10.1111/ctr.70048.

ABSTRACT

Kidney transplant ultrasonography is an important diagnostic tool in the care of transplant recipients. This modality of nonradiation-based imaging allows for precise and expedient reporting of allograft architecture, which can inform clinical decision-making. However, as with any diagnostic tool, overuse may lead to unnecessary interventions and costs on the healthcare system. To better understand the use of ultrasonography in hospitalized kidney transplant recipients and outcomes of subsequent interventions, we conducted a single-center retrospective study at a large transplant program in Ontario, Canada. We noted that over 30% of admissions resulted in a ultrasonographic survey within the first 24 h of presentation; however, most of these did not change clinical management or lead to a subsequent procedural intervention. Using multivariable logistic regression, we identified predictors for receiving an ultrasound, including time from transplantation, elevated serum creatinine and infectious diagnosis. Procedural interventions (e.g., drain or biopsy) resulted from less than 20% of all ultrasound investigations, with patients closer to the time of index transplant or with elevated serum creatinine values more likely to receive an intervention. In conducting a cost analysis, we estimated that approximately $80 000 CAD per year could be saved with more selective decisions on ultrasound requisitions. Overall, our results indicate that despite being an informative tool, the broad use of ultrasonography in the kidney transplant population may not yield significant changes to transplant care.

PMID:39624933 | DOI:10.1111/ctr.70048

Clin Transplant. 2024 Dec;38(12):e70026. doi: 10.1111/ctr.70026.

ABSTRACT

BACKGROUND: Living kidney donor (LKD) candidates of African ancestry are increasingly asked to undergo Apolipoprotein L1 (APOL1) genetic testing during the donor evaluation process to better understand their risk of kidney disease. LKD candidates’ attitudes about using a clinical chatbot on APOL1 remain unknown. This study builds on prior work to culturally adapt the Gia (Genetic Information Assistant) chatbot on APOL1 by assessing donor, recipient, and community member attitudes about the Gia chatbot for enhancing the integration of APOL1 testing into the LKD clinical evaluation workflow.

METHODS: This study involved focus groups and a post-focus group survey in two US cities about the APOL1 Gia chatbot. Qualitative data were analyzed via thematic analysis, and descriptive statistics were used for demographic data.

RESULTS: We conducted 10 focus groups including 54 participants (25 LKDs, 23 community members, and 6 living donor kidney transplant recipients of African ancestry). Five themes emerged: (1) participants supported LKD candidates using the Gia chatbot before the nephrologist clinic visit, (2) participants were interested in undergoing APOL1 testing after using Gia, (3) APOL1 testing costs may influence LKD candidates’ willingness to get tested, (4) patients of African ancestry may hold varying preferences for using chatbots in the healthcare setting, and (5) individual-level barriers may limit the use of Gia in the healthcare setting.

CONCLUSIONS: Individuals of African ancestry were highly receptive to integrating the APOL1 chatbot into LKD candidate clinical evaluation, which bodes well for integrating chatbots into the APOL1 clinical genetic testing process.

PMID:39624929 | DOI:10.1111/ctr.70026

Otolaryngol Head Neck Surg. 2024 Dec 3. doi: 10.1002/ohn.1073. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyse the clinical, radiological, and surgical management of temporal bone aneurysmal bone cysts (ABCs) and identify factors affecting outcomes.

STUDY DESIGN: Ambispective study.

SETTING: A single tertiary care institution.

METHODS: This study reviewed 6 cases of temporal bone ABCs treated between 2017 and 2024. Patient demographics, clinical presentation, imaging characteristics, surgical details, and outcomes were collected. A systematic review of the literature was conducted, adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, to compare institutional cases with published data. Statistical analyses were performed to identify predictors of treatment success and recurrence.

RESULTS: The cohort had a mean age of 27.5 years. Presenting symptoms included scalp swelling, aural fullness, tinnitus, and hearing impairment. Imaging showed expansile lesions with fluid-fluid levels and bone erosion. All patients underwent gross total excision, with a mean intraoperative blood loss of 230.6 ml. One patient experienced temporary grade III facial palsy, which resolved within 3 months. No recurrences were observed during a mean follow-up of 35 months. A pooled analysis of 45 cases from the literature revealed that swelling in the temporal region was the most common presenting feature, and gross total resection was the most frequently employed treatment. Recurrences were rare and typically associated with subtotal resections or advanced-stage tumors.

CONCLUSION: Surgical excision, particularly gross total resection, is the treatment of choice for temporal bone ABCs, with a low recurrence rate. Stage and extent of resection are critical factors in predicting outcomes. This study enhances understanding of the diagnostic and therapeutic approaches for this rare condition.

PMID:39624923 | DOI:10.1002/ohn.1073

Otolaryngol Head Neck Surg. 2024 Dec 3. doi: 10.1002/ohn.1072. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop and validate a patient-reported outcome measure (PROM) to evaluate the quality of life (QoL) among patients with obstructive sleep apnea (OSA).

STUDY DESIGN: A prospective cohort study.

SETTINGS: Tertiary referral center.

METHODS: We developed a 15-item English questionnaire that was administered to 176 adults with OSA and 22 adult controls without symptoms of OSA in a tertiary sleep surgery clinic between June 2021 and December 2021. The internal consistency and test-retest reliability were measured using the Cronbach’s α and the intraclass correlation coefficient, respectively. The 2-sample Wilcoxon rank-sum (Mann-Whitney) test was applied to compare the 2 groups. Convergent validity of the test scores of the questionnaire was compared to previously validated outcome measures and objective sleep study outcomes using the Spearman correlation coefficient.

RESULTS: Of the 198 respondents (176 cases and 22 controls); 71% were men and 29% were women. The internal consistency was excellent with the α of .92 (lower 95% confidence limit of 0.90). All the test-retest correlations were positive, significant, and strong ranging from 0.50 to 0.90. The differences between cases and controls were statistically significant for all the items and for the total score. The total score of the questionnaire with the Epworth Sleepiness Scale and objective OSA measures was moderate to strong.

CONCLUSIONS AND RELEVANCE: The new tool provides a validated PROM to evaluate the QoL among OSA patients specifically, with excellent internal consistency, reasonable test-retest reliability, discriminant validity, and construct validity.

LEVEL OF EVIDENCE: Level 4.

PMID:39624914 | DOI:10.1002/ohn.1072

Otolaryngol Head Neck Surg. 2024 Dec 3. doi: 10.1002/ohn.1056. Online ahead of print.

ABSTRACT

OBJECTIVE: We aim to compare the diagnostic accuracy of the different methodologies used in the detection of cell-free human papillomavirus (HPV) DNA in HPV-associated head and neck squamous cell carcinoma detection using bivariate analysis methods.

DATA SOURCES: Pubmed, Embase, and Scopus were queried using a broad search strategy to search for relevant studies.

REVIEW METHODS: Test characteristics were extracted from 33 studies following literature screening, and underwent analyses utilizing a bivariate approach. Summary statistics were identified for each type of methodology, and forest plots and summary receiver operating characteristic curves were constructed. Bias was estimated using Deek’s Funnel Plot and the QUADAS-2 tool.

RESULTS: In terms of diagnostic accuracy, digital droplet polymerase chain reaction (ddPCR) based testing exhibited the highest diagnostics odds ratio at 138 (59.5, 318), followed closely by next-generation sequencing (NGS) at 120 (39.7, 362), then by polymerase chain reaction (PCR) at 31.4 (14.4, 68.6), and quantitative PCR at 8.74 (4.63, 16.5).

CONCLUSION: NGS and ddPCR are comparable in overall diagnostic accuracy, bringing into question their relative roles in diagnosis and screening. Cost-effective ddPCR assays may serve as useful diagnostic and screening tests in the clinic with their low false positive rates and high sensitivity. However, NGS assays also offer high sensitivity and companion metrics, suggesting they may have a more precise role in disease monitoring. Importantly, assay development and benchmarking need further standardization to improve comparison between assays. Finally, saliva-based testing needs to be further investigated using NGS and ddPCR to further understand its limitations in disease detection and monitoring.

PMID:39624913 | DOI:10.1002/ohn.1056

Iran J Immunol. 2024 Dec 3;21(4). doi: 10.22034/iji.2024.100817.2710. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical features of SARS-CoV-2 infection vary, ranging from asymptomatic cases to pneumonia, and other serious complications. Some populations have been observed to be at higher risk for severe disease and death compared to other ethnical groups.

OBJECTIVE: To evaluate two parameters of the innate immune system, that play a significant role in viral immunity.

METHODS: In samples of peripheral blood from sixteen patients with severe COVID-19, ten with asymptomatic to mild illness, and fifteen healthy subjects, the percentage of NK and NKT cells, the expression of different NK cell receptors and the blood levels of pro-inflammatory cytokines were tested.

RESULTS: We observed that patients with severe COVID-19 showed significantly lower frequencies of both CD56dim and CD56bright NK cells compared to patients with mild illness or healthy controls. Furthermore, patients with severe manifestation of COVID-19 exhibited an aberrant expression of the natural cytotoxicity receptors NKp30, NKp44 and NKp46. Similarly, NK cells from these patients showed statistically significant differences in the expression of various killer immunoglobulin-like receptors (KIRs) in the two main cell subsets (CD56bright, CD56dim) compared to controls or patients with mild disease. Moreover, patients with severe illness displayed decreased frequency of NKT cells (defined as CD3+CD56+) and elevated blood levels of the cytokines IL-6 and IL-8.

CONCLUSION: This study suggests that the abnormal features of NK and NKT cells observed in patients with severe SARS-CoV-2 infection may play an important role in the outcome of this infectious disease in various population groups.

PMID:39624905 | DOI:10.22034/iji.2024.100817.2710

Hip Int. 2024 Dec 3:11207000241302471. doi: 10.1177/11207000241302471. Online ahead of print.

ABSTRACT

INTRODUCTION: Various techniques have been described for restoring leg length and offset during total hip arthroplasty (THA). We herein describe a novel “Quartered Head Technique” (QHT) involving a series of femoral osteotomies.

METHODS: 124 hips were included in the analysis. An anterolateral approach was used in all cases. Leg length, and offset were assessed intraoperatively and reproduced using the QHT. A leg-length discrepancy (LLD) of <6 mm was chosen as acceptable based on previously published literature. Postoperative pelvic radiographs were assessed by two independent observers to ensure inter-observer reliability.

RESULTS: The mean absolute postoperative difference in leg length from the contralateral leg was +3.58 mm. 84% of patients had LLD within ±6 mm of the contralateral limb. Mean absolute postoperative difference in offset from the contralateral leg was +3.88 mm. 90% of patients were within ±6 mm offset of the contralateral limb. There was no statistical difference noted between observer measurement.

CONCLUSIONS: The QHT provides a simple, inexpensive, yet effective method of maintaining femoral leg length and offset during total hip arthroplasty.

PMID:39624855 | DOI:10.1177/11207000241302471

Front Pharmacol. 2024 Nov 18;15:1505926. doi: 10.3389/fphar.2024.1505926. eCollection 2024.

ABSTRACT

BACKGROUND: Epimedium total flavonoids (EF) have been recommended to be one of the effective components in Traditional Chinese Medicine (TCM) for the treatment of primary osteoporosis (POP) in China. Due to the lack of evidence-based medical evidence on the efficacy and safety of EF for the treatment of POP, the current systematic review and meta-analysis was carried out aimed at evaluating the curative effects and safety profile of EF treatment for POP in order to provide decision making references for clinical research.

METHODS: The PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang, and VIP databases were searched from the date of inception to 11 August 2024. The outcomes of effectiveness and safety of included studies were collected to conduct meta-analysis or systematic review.

RESULTS: A total of 6 RCTs were included in this study, involving 838 participants. Overall, our results revealed that the experimental group (EG) had comparable results of efficacy to the control group (CG). The lumbar vertebra bone mineral density (BMD) was statistically different compared to the CG (MD = 0.03; 95% CI: 0.01, 0.04; p = 0.0003), but the clinical significance deserved consideration because the 95% CI nearly crossed the invalid line. The femoral neck BMD was neither statistically different nor clinically different between two groups (MD = 0.00; 95% CI: 0.01, 0.02; p = 0.67). The total complication rates were comparable among the two groups (RR = 0.68; 95% CI: 0.39, 1,19; p = 0.18). The quality of the evidence of the present study was judged as moderate and low based on the GRADE analysis.

CONCLUSION: EF treatment exhibited good curative effects and safety. The result was comparable to the CG, including other Chinese patent medicines and calcium and vitamin D supplements. The EF treatment was proved to be a reliable alternative option for POP.

PMID:39624844 | PMC:PMC11608984 | DOI:10.3389/fphar.2024.1505926

Front Pharmacol. 2024 Nov 18;15:1488367. doi: 10.3389/fphar.2024.1488367. eCollection 2024.

ABSTRACT

INTRODUCTION: Arylamine N-acetyltransferase 2 (NAT2) expresses a well-defined genetic polymorphism in humans that modifies drug and xenobiotic metabolism. Recent studies and genome wide association studies have reported that genetic variants of NAT2 are associated with differential risks of developing dyslipidemia and cardiometabolic disorders, suggesting a previously unrecognized role of NAT2 in pathophysiology of metabolic disorders. In support of this notion, we recently showed that human NAT2 expression is differentially regulated by glucose and insulin. Moreover, our in silico analysis showed that NAT2 is co-expressed with nuclear receptors enriched in the liver, e.g., NR1H4 (FXR) and NR1I2 (PXR), that have been previously implicated in regulation of hepatic glucose and lipid homeostasis. Identification of transcriptional regulator(s) of human NAT2 would aid in understanding novel functions that it may play in the liver. Thus, the present study was designed to investigate if NAT2 is transcriptionally regulated by hepatic nuclear receptors.

METHODS: To test this, we treated cryopreserved human hepatocytes with agonists towards four different hepatic transcription factors/nuclear hormone receptors, namely FXR (NR1H4), PXR (NR1I2), LXR (NR1H3), and PPARα (PPARA), and measured their effects on the level of NAT2 mRNA.

RESULTS: While the treatment with a FXR, PXR, or LXR agonist (i.e., GW-4064, SR-12813, or GW-3965) significantly induced their respective target genes, treatment with these agonists did not significantly alter the transcript level of NAT2 in human hepatocytes. PPARα agonist, GW-7647, treatment resulted in a statistically significant decrease in the NAT2 transcript level. However, its magnitude was marginal.

CONCLUSION: In summary, hepatic nuclear receptors we examined in the present study (FXR, PXR, LXR, and PPARα) did not significantly alter NAT2 expression in cryopreserved human hepatocytes. Additional studies are needed to identify transcriptional regulators of hepatic NAT2 expression.

PMID:39624836 | PMC:PMC11608957 | DOI:10.3389/fphar.2024.1488367

Front Endocrinol (Lausanne). 2024 Nov 18;15:1333881. doi: 10.3389/fendo.2024.1333881. eCollection 2024.

ABSTRACT

OBJECTIVE: The aim of this study was to assess the predictive capabilities of a radiomics signature obtained from arterial spin labeling (ASL) imaging in forecasting and detecting stages of kidney damage in patients with diabetes mellitus (DM), as well as to analyze the correlation between texture feature parameters and biological clinical indicators. Additionally, this study seeks to identify the imaging risk factors associated with early renal injury in diabetic patients, with the ultimate goal of offering novel insights for predicting and diagnosing early renal injury and its progression in patients with DM.

MATERIALS AND METHODS: In total, 42 healthy volunteers (Group A); 68 individuals with diabetes (Group B) who exhibited microalbuminuria, defined by a urinary albumin-to-creatinine ratio (ACR)< 30 mg/g and an estimated glomerular filtration rate (eGFR) within the range of 60-120 mL/min/1.73m²; and 53 patients with diabetic nephropathy (Group C) were included in the study. ASL using magnetic resonance imaging (MRI) at 3.0T was conducted. The radiologist manually delineated regions of interest (ROIs) on the ASL maps of both the right and left kidney cortex. Texture features from the ROIs were extracted utilizing MaZda software. Feature selection was performed utilizing a range of methods, such as the Fisher coefficient, mutual information (MI), probability of classification error, and average correlation coefficient (POE + ACC). A radiomics model was developed to detect early diabetic renal injury, extract imaging risk factors associated with early diabetic renal injury, and examine the relationship between significant texture feature parameters and biological clinical indicators. Patients with DM and kidney injury were followed prospectively. The study utilized seven machine learning algorithms to develop a detective radiomics model and a comprehensive predictive model for assessing the progression of kidney damage in patients with DM. The diagnostic efficacy of the models in detecting variations in diabetic kidney damage over time was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Empower (R) was used to establish a correlation between clinical biological indicators and texture feature metrics. Statistical analysis was conducted using R, Python, MedCalc 15.8, and GraphPad Prism 8.

RESULTS: A total of 367 texture features were extracted from the ROIs in the kidneys and refined based on selection criteria using MaZda software across groups A, B, and C. The renal blood flow (RBF) values of the renal cortex in groups A, B, and C exhibited a decreasing trend, with values of 256.458 ± 54.256 mL/100g/min, 213.846 ± 52.109 mL/100g/min, and 170.204 ± 34.992 mL/100g/min, respectively. There was a positive correlation between kidney RBF and eGFR (r = 0.439, P<0.001). The negative correlation between RBF and various clinical parameters including urinary albumin-to-creatinine ratio (UACR), body mass index (BMI), diastolic blood pressure (DBP), blood urea nitrogen (BUN), and serum creatinine (SCr) was investigated. Through the use of a least absolute shrinkage and selection operator (LASSO) regression model, the study identified the eight most significant texture features and biological indicators, namely GeoY, GeoRf, GeoRff, GeoRh, GeoW8, GeoW12, S (0, 4) Entropy, and S (5, -5) Entropy. Spearman correlation analysis revealed associations between imaging markers in early diabetic patients with kidney damage and factors such as age, systolic blood pressure (SBP), Alanine Transaminase (ALT), Aspartate Amino Transferase (AST) albumin, uric acid (UA), microalbuminuria (UMA), UACR, 24h urinary protein, fasting blood glucose (FBG), two hours postprandial blood glucose (P2BG), and HbA1c. The study utilized ASL imaging as a detection model to identify renal injury in patients with DM across different stages, achieving a sensitivity of 85.1%, specificity of 65.5%, and an AUC of 0.865. Additionally, a comprehensive prediction model combining imaging labels and biological indicators, with the naive Bayes machine learning algorithm as the best model, demonstrated an AUC of 0.734, accuracy of 0.74, and precision of 0.43.

CONCLUSION: ASL imaging sequences demonstrated the ability to accurately detect alterations in kidney function and blood flow in patients with DM. Strong associations were observed between renal blood flow values in ASL imaging and established clinical biomarkers. These values show promise in detecting early microstructural changes in the kidneys of diabetic patients. Utilizing image markers in conjunction with clinical indicators was effective in identifying early renal dysfunction and its progression in individuals with DM. Furthermore, the integration of imaging texture feature parameters with clinical biomarkers holds significant potential for predicting early renal damage and its progression in patients with diabetes.

PMID:39624821 | PMC:PMC11608948 | DOI:10.3389/fendo.2024.1333881