Tag: pubmed

JAMA Dermatol. 2024 May 29. doi: 10.1001/jamadermatol.2024.1315. Online ahead of print.

ABSTRACT

IMPORTANCE: Frontal fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, causing irreversible hair loss predominantly in postmenopausal individuals. An earlier genome-wide meta-analysis of female FFA identified risk loci in genes implicated in self-antigen presentation and T-cell homeostasis, including HLA-B*07:02, ST3GAL1, and SEMA4B. However, CYP1B1, which is important for hormone metabolism, was also implicated with the substitution of serine for asparagine at position 453 (c.1358A>G, p.Asn453Ser) exhibiting a protective effect against FFA. Increasing understanding of genetic and environmental variables and their interactions will improve understanding of disease pathogenesis and has the potential to inform risk mitigation strategies.

OBJECTIVE: To investigate whether oral contraceptive pill (OCP) use modulates the protective effect of the common missense variant in CYP1B1 (c.1358A>G, p.Asn453Ser) on FFA risk.

DESIGN, SETTING, AND PARTICIPANTS: This gene-environment interaction study using a case-control design enrolled female patients with FFA from UK-based dermatology clinics. The patients were matched with unrelated age- and ancestry-matched female control individuals derived from UK Biobank in a 1:66 ratio, determined by the first 4 principal components from genome-wide genotypes. Data were collected from July 2015 to September 2017, and analyzed from October 2022 to December 2023.

MAIN OUTCOME AND MEASURE: The main outcomes were the modulatory effect of OCP use on the contribution of the CYP1B1 missense variant to female FFA risk and a formal gene-environment interaction test evaluated by a logistic regression model with a multiplicative interaction term, under the assumptions of an additive genetic model interaction term, under the assumptions of an additive genetic model.

RESULTS: Of the 489 female patients with FFA, the mean (SD) age was 65.8 (9.7) years, and 370 (75.7%) had a history of OCP use. Of the 34 254 age- and ancestry-matched control individuals, the mean (SD) age was 65.0 (8.4) years, and previous OCP use was reported in 31 177 (91.0%). An association between female FFA and the CYP1B1 risk allele was observed in individuals who reported OCP use (odds ratio, 1.90 [95% CI, 1.50-2.40]; P = 8.41 × 10-8) but not in those with no documented exposure to OCPs (odds ratio, 1.16 [95% CI, 0.82-1.64]; P = .39). A full gene-environment interaction model demonstrated a significant additive statistical interaction between c.1358A, p.453Asn, and history of OCP use on FFA risk (OR for interaction, 1.63 [95% CI, 1.07-2.46]; P = .02).

CONCLUSIONS AND RELEVANCE: This gene-environment interaction analysis suggests that the protective effect of the CYP1B1 missense variant on FFA risk might be mediated by exposure to OCPs. The allele that encodes an asparagine at position 453 of CYP1B1 was associated with increased odds of FFA only in participants with OCP history.

PMID:38809548 | DOI:10.1001/jamadermatol.2024.1315

Cancer. 2024 May 29. doi: 10.1002/cncr.35383. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) surveillance is recommended for some individuals with a pathogenic or likely pathogenic variant (PV/LPV) in a PDAC susceptibility gene; the recommendation is often dependent on family history of PDAC. This study aimed to describe PDAC family history in individuals with PDAC who underwent genetic testing to determine the appropriateness of including a family history requirement in these recommendations.

METHODS: Individuals with PDAC with a germline heterozygous PV/LPV in ATM, BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PALB2, or PMS2 (PV/LPV carriers) were assessed for family history of PDAC in first-degree relatives (FDRs) or second-degree relatives (SDRs) from nine institutions. A control group of individuals with PDAC without a germline PV/LPV was also assessed.

RESULTS: The study included 196 PV/LPV carriers and 1184 controls. In the PV/LPV carriers, 25.5% had an affected FDR and/or SDR compared to 16.9% in the control group (p = .004). PV/LPV carriers were more likely to have an affected FDR compared to the controls (p = .003) but there was no statistical difference when assessing only affected SDRs (p = .344).

CONCLUSIONS: Most PV/LPV carriers who developed PDAC did not have a close family history of PDAC and would not have met most current professional societies’ recommendations for consideration of PDAC surveillance before diagnosis. However, PV/LPV carriers were significantly more likely to have a family history of PDAC, particularly an affected FDR. These findings support family history as a risk modifier in PV/LPV carriers, and highlight the need to identify other risk factors.

PMID:38809542 | DOI:10.1002/cncr.35383

Transl Vis Sci Technol. 2024 May 1;13(5):23. doi: 10.1167/tvst.13.5.23.

ABSTRACT

PURPOSE: To develop convolutional neural network (CNN)-based models for predicting the axial length (AL) using color fundus photography (CFP) and explore associated clinical and structural characteristics.

METHODS: This study enrolled 1105 fundus images from 467 participants with ALs ranging from 19.91 to 32.59 mm, obtained at National Taiwan University Hospital between 2020 and 2021. The AL measurements obtained from a scanning laser interferometer served as the gold standard. The accuracy of prediction was compared among CNN-based models with different inputs, including CFP, age, and/or sex. Heatmaps were interpreted by integrated gradients.

RESULTS: Using age, sex, and CFP as input, the mean ± standard deviation absolute error (MAE) for AL prediction by the model was 0.771 ± 0.128 mm, outperforming models that used age and sex alone (1.263 ± 0.115 mm; P < 0.001) and CFP alone (0.831 ± 0.216 mm; P = 0.016) by 39.0% and 7.31%, respectively. The removal of relatively poor-quality CFPs resulted in a slight MAE reduction to 0.759 ± 0.120 mm without statistical significance (P = 0.24). The inclusion of age and CFP improved prediction accuracy by 5.59% (P = 0.043), while adding sex had no significant improvement (P = 0.41). The optic disc and temporal peripapillary area were highlighted as the focused areas on the heatmaps.

CONCLUSIONS: Deep learning-based prediction of AL using CFP was fairly accurate and enhanced by age inclusion. The optic disc and temporal peripapillary area may contain crucial structural information for AL prediction in CFP.

TRANSLATIONAL RELEVANCE: This study might aid AL assessments and the understanding of the morphologic characteristics of the fundus related to AL.

PMID:38809531 | DOI:10.1167/tvst.13.5.23

JAMA. 2024 May 29. doi: 10.1001/jama.2024.4970. Online ahead of print.

NO ABSTRACT

PMID:38809526 | DOI:10.1001/jama.2024.4970

Vet Res Commun. 2024 May 29. doi: 10.1007/s11259-024-10426-9. Online ahead of print.

ABSTRACT

The aim of the study was to investigate the effect of the immunostimulant Mycobacterium Cell Wall Fraction (MCWF) on the treatment of S. aureus SCM by intravenous application. The study included 45 HF dairy cows in 2nd and 3rd month after parturition divided into three groups (n = 15 per group): the MC + group – cows with S. aureus SCM treated with MCWF; the MC- group – cows with S. aureus SCM, with no treatment; and the C group – the control group of healthy cow with no treatment. Samples were collected 0th (I sample), 7th (II), and 14th day (III) from the day of SCM diagnosis and on day 21st (IV). A greater influx of leukocytes was confirmed into milk after 7 days after MCWF treatment in MC + group, which was followed by increase of WBC and LYM in blood. These results support the hypothesis of effective action of MCWF, and in quarters with lower-grade infection, bacteriological cure was achieved. The MC- group had a statistically higher concentration of TBARS and CAT activity in milk, while MC + group had lower blood serum LDH activity, which indicates a positive effect of the MCWF application and a lower exposure of the tissue to lipide peroxidation and inflammation caused by S. aureus. The application of MCWF would give new possibilities in the prevention and therapy of mammary gland diseases without fear of the presence of residues and the emergence of bacterial resistance. In future studies, the effects of local and systemic application of MCWF in the treatment of S. aureus SCM should be compared.

PMID:38809504 | DOI:10.1007/s11259-024-10426-9

Vet Res Commun. 2024 May 29. doi: 10.1007/s11259-024-10416-x. Online ahead of print.

ABSTRACT

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3 mg/dL within 48 h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice.

PMID:38809503 | DOI:10.1007/s11259-024-10416-x

Eur Geriatr Med. 2024 May 29. doi: 10.1007/s41999-024-00992-1. Online ahead of print.

ABSTRACT

PURPOSE: Fear of falling (FOF) may result in activity restriction and deconditioning. The aim of the study was to identify factors associated with FOF in older patients and to investigate if FOF influenced long-term outcomes.

METHODS: Multicentric, observational, prospective study including patients 65 years or older attending the emergency department (ED) after a fall. Demographical, patient- and fall-related features were recorded at the ED. FOF was assessed using a single question. The primary outcome was all-cause death. Secondary outcomes included new fall-related visit, fall-related hospitalisation, and admission to residential care. Logistic regression and Cox regression models were used for statistical analyses.

RESULTS: Overall, 1464 patients were included (47.1% with FOF), followed for a median of 6.2 years (2.2-7.9). Seven variables (age, female sex, living alone, previous falls, sedative medications, urinary incontinence, and intrinsic cause of the fall) were directly associated with FOF whereas use of walking aids and living in residential care were inversely associated. After the index episode, 748 patients (51%) died (median 3.2 years), 677 (46.2%) had a new fall-related ED visit (median 1.7 years), 251 (17.1%) were hospitalised (median 2.8 years), and 197 (19.4%) were admitted to care (median 2.1 years). FOF was associated with death (HR 1.239, 95% CI 1.073-1.431), hospitalisation (HR 1.407, 95% CI 1.097-1.806) and institutionalisation (HR 1.578, 95% CI 1.192-2.088), but significance was lost after adjustment.

CONCLUSION: FOF is a prevalent condition in older patients presenting to the ED after a fall. However, it was not associated with long-term outcomes. Future research is needed to understand the influence of FOF in maintenance of functional capacity or quality of life.

PMID:38809489 | DOI:10.1007/s41999-024-00992-1

Radiat Environ Biophys. 2024 May 29. doi: 10.1007/s00411-024-01075-2. Online ahead of print.

ABSTRACT

This study aimed to evaluate the modulated arc therapy (mARC) technique as a planning and treatment option for hippocampal sparing whole brain radiotherapy (HS-WBRT) following the Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) were selected retrospectively for 15 patients. Two types of plans were created for each patient, namely an intensity-modulated radiation therapy (IMRT) and a mARC plan. IMRT and mARC plans were compared in terms of plan quality indices, absorbed dose to organs at risk (OARs), number of monitor units (MUs), and treatment time. All plans in both techniques were considered clinically acceptable for treatment. However, IMRT plans presented a higher conformity (p = 0.01) as well as a higher homogeneity as compared to mARC plans, but this difference was not statistically significant (p > 0.05). In terms of the preservation of the hippocampus, it was observed that the IMRT plans achieved significantly lower doses for both 100% of its volume and for its maximum dose (p < 0.001). The evaluation of the remaining OARs showed that the IMRT technique resulted in lower doses, and significant differences were observed for the following organs: left cochlea (p < 0.001), left eye (p < 0.001), right eye (p = 0.03), both lenses of the eye (p < 0.001), and right optic nerve (p = 0.02). Despite these differences, the absolute differences in all dosimetric parameters were low enough to bear any clinical relevance. A drastic (close to 65%) and significant (p < 0.001) decrease was observed in the number of MUs for the mARC plans. This resulted in a substantial decrease in treatment time (60.45%, p < 0.001). It is concluded that the mARC technique is a feasible planning and treatment solution for HS-WBRT that meets the RTOG 0933 criteria. The main advantage of using mARC over IMRT for HS-WBRT is the considerable reduction in MUs and treatment time.

PMID:38809486 | DOI:10.1007/s00411-024-01075-2

EJNMMI Res. 2024 May 29;14(1):52. doi: 10.1186/s13550-024-01110-9.

ABSTRACT

BACKGROUND: F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population.

METHODS: 191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmax_CLN), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmax_CLN was estimated using linear regression models.

RESULTS: Increased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmax_CLN was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmax_CLN. However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmax_CLN was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years.

CONCLUSION: SUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients.

TRIAL WAS REGISTERED: In the internal hospital registry under TRN 0209-22-HMO on date 23.04.2022.

PMID:38809472 | DOI:10.1186/s13550-024-01110-9

Zhonghua Wai Ke Za Zhi. 2024 May 29;62(7):671-676. doi: 10.3760/cma.j.cn112139-20240317-00130. Online ahead of print.

ABSTRACT

Objective: To compare the perioperative outcomes of laparoscopic duodenal-preserving pancreatic head resection(LDPPHR) with laparoscopic pancreaticoduodenectomy(LPD) in the treatment of borderline and benign diseases of the pancreatic head. Methods: This is a retrospective cohort study. Perioperative data from 87 patients with non-malignant pancreatic head diseases who underwent LDPPHR or LPD were retrospectively collected in the Department of Biliary-Pancreatic Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2020 to December 2022. There were 49 male and 38 female patients with an age of 57.0(16.5) years (range: 20 to 75 years). Forty patients underwent LDPPHR and 47 patients underwent LPD. Quantitative data following a normal distribution were compared using Student’s t-test, while quantitative data not following a normal distribution were compared using the Mann-Whitney U test. Comparisons of categorical or ordinal variables were made using χ² test or Fisher’s exact test. Logistic regression analysis was used to estimate the risk factors associated with the rate of complications. Results: There were no statistically significant differences between the LDPPHR group and the LPD group in terms of reoperation rate,total hospital stay duration,postoperative hospital stay duration,90-day mortality rate,30-day and 90-day readmission rates,and 2-year tumor recurrence rate (all P>0.05). The complication rate was higher in the LDPPHR group compared to the LPD group(32 cases (80.0%) vs. 24 cases (51.1%),χ²=7.89,P=0.005),but there was no difference in the rate of Clavien-Dindo classification of surgical complications≥Ⅲ between the two groups(4 cases (10.0%) vs. 6 cases (12.8%), χ²<0.01, P=0.947). Additionally,the rate of delayed gastric emptying (DGE) was higher in the LDPPHR group compared to the LPD group (χ²=10.79,P=0.001),but there was no statistically significant difference in the rate of B,C grade DGE between the two groups (χ²=0.48, P=0.487). There were no statistically significant differences in the rates of postoperative pancreatic fistula,bile leakage,post-pancreatectomy hemorrhage,intra-abdominal infection,and pulmonary infection between the two groups (all P>0.05). The results of the univariate logistic regression analysis showed that LDPPHR (compared to LPD, OR=3.83, 95%CI: 1.46 to 10.04, Z=2.73,P=0.006) and preoperative biliary stent placement (compared to non-use of biliary stent, OR=5.30, 95%CI: 1.13 to 25.00, Z=2.11, P=0.035) were risk factors for the complication rate,but neither was an independent risk factor for complication rate (all P>0.05). Conclusion: The preliminary results suggest that LDPPHR can achieve perioperative safety and effectiveness comparable to LPD.

PMID:38808434 | DOI:10.3760/cma.j.cn112139-20240317-00130