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MicroRNA expression profiling in tears and blood as predictive biomarkers for anti-VEGF treatment response in wet age-related macular degeneration

Graefes Arch Clin Exp Ophthalmol. 2024 Apr 6. doi: 10.1007/s00417-024-06478-x. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to investigate the potential of microRNAs (miRNAs) in tears, blood, and aqueous humor as biomarkers for predicting treatment response in wet age-related macular degeneration (AMD) patients undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy.

METHODS: In a single-center prospective cohort study, treatment-naïve wet AMD patients and age-matched controls were enrolled. Clinical data and miRNA levels (miR-199a-3p, miR-365-3p, miR-200b-3p, miR-195-5p, miR-335-5p, and miR-185-5p) in tears, blood, and aqueous humor were collected. Treatment response was categorized into responders and non-responders based on visual acuity and central subfield thickness. MiRNA levels were quantified using reverse-transcription PCR. Statistical analyses were performed, including ROC analysis, to evaluate predictive accuracy.

RESULTS: Dysregulated miRNA profiles were observed in wet AMD tears and blood compared to controls. Specifically, miR-199a-3p, miR-195-5p, and miR-185-5p were upregulated, while miR-200b-3p was downregulated in tears. All six miRNAs were elevated in wet AMD blood samples. Notably, responders showed higher tear expression of miR-195-5p and miR-185-5p. Combining these miRNAs yielded the highest predictive power (AUC = 0.878, p = 0.006) for anti-VEGF responders.

CONCLUSIONS: Dysregulated miRNA profiles in tears and blood suggest their potential as biomarkers for wet AMD. MiR-195-5p and miR-185-5p in tears demonstrate predictive value for anti-VEGF treatment responders. This study underscores the non-invasive prediction potential of miRNA tear analysis in wet AMD treatment responses.

PMID:38581435 | DOI:10.1007/s00417-024-06478-x

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Lung ultrasound and procalcitonin, improving antibiotic management and avoiding radiation exposure in pediatric critical patients with bacterial pneumonia: a randomized clinical trial

Eur J Med Res. 2024 Apr 6;29(1):222. doi: 10.1186/s40001-024-01712-y.

ABSTRACT

BACKGROUND: Pneumonia is a major public health problem with an impact on morbidity and mortality. Its management still represents a challenge. The aim was to determine whether a new diagnostic algorithm combining lung ultrasound (LUS) and procalcitonin (PCT) improved pneumonia management regarding antibiotic use, radiation exposure, and associated costs, in critically ill pediatric patients with suspected bacterial pneumonia (BP).

METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children < 18y with suspected BP admitted to the PICU from September 2017 to December 2019, were included. PCT was determined at admission. Patients were randomized into the experimental group (EG) and control group (CG) if LUS or chest X-ray (CXR) were done as the first image test, respectively. Patients were classified: 1.LUS/CXR not suggestive of BP and PCT < 1 ng/mL, no antibiotics were recommended; 2.LUS/CXR suggestive of BP, regardless of the PCT value, antibiotics were recommended; 3.LUS/CXR not suggestive of BP and PCT > 1 ng/mL, antibiotics were recommended.

RESULTS: 194 children were enrolled, 113 (58.2%) females, median age of 134 (IQR 39-554) days. 96 randomized into EG and 98 into CG. 1. In 75/194 patients the image test was not suggestive of BP with PCT < 1 ng/ml; 29/52 in the EG and 11/23 in the CG did not receive antibiotics. 2. In 101 patients, the image was suggestive of BP; 34/34 in the EG and 57/67 in the CG received antibiotics. Statistically significant differences between groups were observed when PCT resulted < 1 ng/ml (p = 0.01). 3. In 18 patients the image test was not suggestive of BP but PCT resulted > 1 ng/ml, all of them received antibiotics. A total of 0.035 mSv radiation/patient was eluded. A reduction of 77% CXR/patient was observed. LUS did not significantly increase costs.

CONCLUSIONS: Combination of LUS and PCT showed no risk of mistreating BP, avoided radiation and did not increase costs. The algorithm could be a reliable tool for improving pneumonia management.

CLINICAL TRIAL REGISTRATION: NCT04217980.

PMID:38581075 | DOI:10.1186/s40001-024-01712-y

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Demographic and clinical features of dengue fever infection in Pakistan: a cross-sectional epidemiological study

Trop Dis Travel Med Vaccines. 2024 Apr 5;10(1):11. doi: 10.1186/s40794-024-00221-4.

ABSTRACT

BACKGROUND: Dengue fever caused by dengue virus is a tropical disease and is among the deadliest vector-borne diseases. The humid and hot summers of Pakistan support the probation of the vectors responsible for the transmission of viral and other parasitic diseases.

METHODOLOGY: A retrospective study, from 2012- 2019, of dengue infected individuals from the Punjab province of Pakistan was carried out to analyze epidemiology, clinical and laboratory findings of subjects with dengue virus infection. Data was derived from National Institute of Health (NIH) followed by Dengue control program of Pakistan, covering the incidence rate in 36 districts of Punjab and Islamabad Capital Territory (ICT) respectively. Patients data including the presence of dengue specific antigen or/and antibodies such as NS1 and IgG/IgM were observed. The study also included the analysis of demographic data, geographic data, and the month-wise distribution of dengue cases to examine seasonal trends.

RESULTS: We analyzed 25,682 dengue infected individuals. The statistical analysis revealed a significant association between genders in which male population was more affected by dengue than females. It was also noted that the middle age group was the most affected age group while the highest number of cases were reported in October. Rawalpindi and Lahore were the most affected cities in Punjab province while Islamabad represented the highest number of cases during the recent outbreak in 2019. The IgM and IgG antibodies were highly prevalent among the infected patients.

CONCLUSION: Dengue is endemic in Pakistan, circulating throughout the year. Highest number of cases were observed in the month of October, September and November respectively. Association between climate change and vector-borne diseases need to be investigated in Pakistan as they significantly influence the timing and intensity of dengue and other disease outbreaks. Further exploration of hematological parameters is required to better diagnose and treat the disease. For the effective control of dengue outbreaks, awareness campaigns on sewage management and vector control along with social factors are strongly recommended for better control and eradication of the disease.

PMID:38581059 | DOI:10.1186/s40794-024-00221-4

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Regulatory T cells limit age-associated retinal inflammation and neurodegeneration

Mol Neurodegener. 2024 Apr 5;19(1):32. doi: 10.1186/s13024-024-00724-w.

ABSTRACT

BACKGROUND: Ageing is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown.

METHODS: Regulatory T cells were selectively depleted in both young (2-4 months) and aged (18-23 months) FoxP3-DTR mice. We evaluated neuroretinal degeneration, gliosis, subretinal space phagocyte infiltration, and retinal pigmented epithelium morphology through immunofluorescence analysis. Subsequently, aged Treg depleted animals underwent adoptive transfer of both young and aged regulatory T cells from wild-type mice, and the resulting impact on neurodegeneration was assessed. Statistical analyses employed included the U-Mann Whitney test, and for comparisons involving more than two groups, 1-way ANOVA analysis followed by Bonferroni’s post hoc test.

RESULTS: Our study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes.

CONCLUSION: Our findings demonstrate an essential role for regulatory T cells in maintaining age retinal homeostasis and preventing age-related neurodegeneration. This previously undescribed role of regulatory T cells in limiting retinal inflammation, RPE/choroid epithelium damage and subsequently photoreceptor loss with age, opens novel avenues to explore regulatory T cell neuroprotective and anti-inflammatory properties as potential therapeutic approaches for age-related retinal diseases.

PMID:38581053 | DOI:10.1186/s13024-024-00724-w

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Full endoscopic laminotomy decompression versus anterior cervical discectomy and fusion for the treatment of single-segment cervical spinal stenosis: a retrospective, propensity score-matched study

J Orthop Surg Res. 2024 Apr 5;19(1):227. doi: 10.1186/s13018-024-04710-2.

ABSTRACT

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is the standard procedure for the treatment of cervical spinal stenosis (CSS), but complications such as adjacent segment degeneration can seriously affect the long-term efficacy. Currently, posterior endoscopic surgery has been increasingly used in the clinical treatment of CSS. The aim of this study was to compare the clinical outcomes of single-segment CSS patients who underwent full endoscopic laminotomy decompression or ACDF.

METHODS: 138 CSS patients who met the inclusion criteria from June 2018 to August 2020 were retrospectively analyzed and divided into endoscopic and ACDF groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the groups. Then, perioperative data were recorded and clinical outcomes were compared, including functional scores and imaging data. Functional scores included Visual Analog Scale of Arms (A-VAS) and Neck pain (N-VAS), Japanese Orthopedic Association score (JOA), Neck Disability Index (NDI), and imaging data included Disc Height Index (DHI), Cervical range of motion (ROM), and Ratio of grey scale (RVG).

RESULTS: After PSM, 84 patients were included in the study and followed for 24-30 months. The endoscopic group was significantly superior to the ACDF group in terms of operative time, intraoperative blood loss, incision length, and hospital stay (P < 0.001). Postoperative N-VAS, A-VAS, JOA, and NDI were significantly improved in both groups compared with the preoperative period (P < 0.001), and the endoscopic group showed better improvement at 7 days postoperatively (P < 0.05). The ROM changes of adjacent segments were significantly larger in the ACDF group at 12 months postoperatively and at the last follow-up (P < 0.05). The RVG of adjacent segments showed a decreasing trend, and the decrease was more marked in the ACDF group at last follow-up (P < 0.05). According to the modified MacNab criteria, the excellent and good rates in the endoscopic group and ACDF group were 90.48% and 88.10%, respectively, with no statistically significant difference (P > 0.05).

CONCLUSION: Full endoscopic laminotomy decompression is demonstrated to be an efficacious alternative technique to traditional ACDF for the treatment of single-segment CSS, with the advantages of less trauma, faster recovery, and less impact on cervical spine kinematics and adjacent segmental degeneration.

PMID:38581052 | DOI:10.1186/s13018-024-04710-2

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Trend of using cementless total knee arthroplasty: a nationwide analysis from 2015 to 2021

Arthroplasty. 2024 Apr 6;6(1):24. doi: 10.1186/s42836-024-00241-7.

ABSTRACT

BACKGROUND: Modern cementless total knee arthroplasty (TKA) fixation has shown comparable long-term outcomes to cemented TKA, but the trend of using cementless TKA remains unclear. This study aimed to investigate the trend of using cementless TKA based on a national database.

METHODS: The patients undergoing cementless TKA between 2015 and 2021 were retrospectively extracted from the PearlDiver (Mariner dataset) Database. The annual percentage of cementless TKA was calculated using the following formula: annual number of cementless TKA/annual number of TKA. The trend of the number of patients undergoing cementless TKA was created according to a compounded annual growth rate (CAGR) calculation of annual percentages. Patient age, comorbidity, region, insurance type, etc., were also investigated. Differences were considered statistically significant at P < 0.05.

RESULTS: Of the 574,848 patients who received TKA, 546,731 (95%) underwent cemented fixation and 28,117 (5%) underwent cementless fixation. From 2015 to 2021, the use of cementless TKA significantly increased by 242% from 3 to 9% (compounded annual growth rate (CAGR): + 20%; P < 0.05). From 2015 to 2021, we observed a CAGR greater than 15% for all age groups (< 50, 50-59, 60-69, 70-74, 75 +), insurance types (cash, commercial, government, Medicare, Medicaid), regions (Midwest, Northeast, South, West), sex (male and female), and certain comorbidities (osteoporosis, diabetes mellitus, tobacco use, underweight (BMI < 18.5), rheumatoid arthritis) (P < 0.05 for all). Patients undergoing TKA with chronic kidney disease, prior fragility fractures, and dementia demonstrated a CAGR of + 9%-13% from 2015 to 2021 (P < 0.05).

CONCLUSION: From 2015 to 2021, the use of cementless TKA saw a dramatic increase in all patient populations. However, there is still no consensus on when to cement and in whom. Clinical practice guidelines are needed to ensure safe and effective use of cementless fixation.

PMID:38581037 | DOI:10.1186/s42836-024-00241-7

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Housing debt and depressive symptoms: evidence from the China family panel studies

BMC Psychol. 2024 Apr 5;12(1):186. doi: 10.1186/s40359-024-01667-z.

ABSTRACT

BACKGROUND: There is limited evidence on the association between housing debt and depressive symptoms in China. This study aimed to examine the impact of housing debt on depressive symptoms and explore the heterogeneous impacts arising from two sources of housing debt and two types of housing demands.

METHODS: Using data from the 2016 and 2018 China Family Panel Studies (CFPS), this study included 25,232 Chinese individuals. Depressive symptoms were assessed using the eight-item Center for Epidemiological Studies Depression Scale (CES-D8). Housing debt was measured by dummy variables, indicating whether an individual had housing debt, and continuous variables, which were the logarithm of the total amount of housing debt. The two-way fixed effects model was used to examine the relationship.

RESULTS: Housing debt had a significant positive impact on depressive symptoms in China. Individuals with housing debt had a 0.176-point higher depressive symptom score than those without housing debt. A 10% increase in the total amount of housing debt led to a 0.16-point increase in depressive symptoms. Non-bank housing loans significantly increased the level of depressive symptoms with a larger coefficient (coef = 0.289), while the impact of bank housing loans was small and not statistically significant. In terms of the types of housing demands, a positive impact was observed only among individuals who had only one property meeting their housing consumption demands.

CONCLUSIONS: This study found a significant positive impact of housing debt on depressive symptoms, primarily driven by non-bank housing loans. Furthermore, housing debt increased the depressive symptoms among individuals with consumption demands, while those with investment demands did not show a significant impact. Government interventions should prioritize easing formal financial constraints and providing support for individuals with housing consumption demands.

PMID:38581029 | DOI:10.1186/s40359-024-01667-z

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Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China

Ital J Pediatr. 2024 Apr 5;50(1):62. doi: 10.1186/s13052-024-01630-z.

ABSTRACT

BACKGROUND: Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects.

METHODS: Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis.

RESULTS: The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115-1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003-1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003-1.461) alleles were significantly different between the control group and the case group (P < 0.05). Only the association with the FLT4 polymorphism was statistically significant after adjustment for multiple comparisons.

CONCLUSION: These findings suggest that a possible molecular pathogenesis associated with sporadic ASD is worth exploring in future studies.

PMID:38581027 | DOI:10.1186/s13052-024-01630-z

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Assessing the equivalency of face-to-face and online simulated patient interviews in an educational intervention

Adv Simul (Lond). 2024 Apr 5;9(1):13. doi: 10.1186/s41077-024-00286-3.

ABSTRACT

BACKGROUND: In adapting to COVID-19, many health professional training programs moved abruptly from in-person to online simulated patient interviews for teaching and evaluation without the benefit of evidence regarding the efficacy of this mode of delivery. This paper reports on a multi-methods research project comparing in-person and online simulated patient interviews conducted by allied health professionals as part of an educational intervention offered at a large university teaching hospital.

METHODS: Twenty-three participants conducted two 15-min interviews with simulated patients using previously validated scenarios of patients presenting with suicide risk. In order to assess the equivalency of the two modalities, physiological and psychological stress were measured using heart rate variability parameters and the State-Trait Anxiety Inventory respectively, and then were compared across cohorts using t-tests. Reflective interviews elicited qualitative impressions of the simulations that were subject to thematic qualitative analysis.

RESULTS: There were no statistical differences in measures of psychological stress or physiological arousal of participant health care professionals who engaged with in-person versus online simulated interviews, suggesting they were equally effective in eliciting reactions commonly found in challenging clinical situations. In reflective interviews, participants commented on the realism of both modalities of simulated patient encounters and that simulated interviews provoked emotional and physiological responses consistent with actual patient encounters.

CONCLUSIONS: These findings provide developing evidence that carefully designed online clinical simulations can be a useful tool for the education and assessment of healthcare professionals.

PMID:38581026 | DOI:10.1186/s41077-024-00286-3

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Comparison of laser guidance and freehand hook-wire for CT-guided preoperative localization of pulmonary nodules

J Cardiothorac Surg. 2024 Apr 5;19(1):182. doi: 10.1186/s13019-024-02706-x.

ABSTRACT

PURPOSE: In VATS surgery, precise preoperative localization is particularly crucial when dealing with small-diameter pulmonary nodules located deep within the lung parenchyma. The purpose of this study was to compare the efficacy and safety of laser guidance and freehand hook-wire for CT-guided preoperative localization of pulmonary nodules.

METHODS: This retrospective study was conducted on 164 patients who received either laser guidance or freehand hook-wire localization prior to Uni-port VATS from September 1st, 2022 to September 30th, 2023 at The First Affiliated Hospital of Soochow University. Patients were divided into laser guidance group and freehand group based on which technology was used. Preoperative localization data from all patients were compiled. The localization success and complication rates associated with the two groups were compared. The risk factors for common complications were analyzed.

RESULTS: The average time of the localization duration in the laser guidance group was shorter than the freehand group (p<0.001), and the average CT scan times in the laser guidance group was less than that in the freehand group (p<0.001). The hook-wire was closer to the nodule in the laser guidance group (p<0.001). After the localization of pulmonary nodules, a CT scan showed 14 cases of minor pneumothorax (22.58%) in the laser guidance group and 21 cases (20.59%) in the freehand group, indicating no statistical difference between the two groups (p=0.763). CT scans in the laser guidance group showed pulmonary minor hemorrhage in 8 cases (12.90%) and 6 cases (5.88%) in the freehand group, indicating no statistically significant difference between the two groups (p=0.119). Three patients (4.84%) in the laser guidance group and six patients (5.88%) in the freehand group had hook-wire dislodgement, showing no statistical difference between the two groups (p=0.776).

CONCLUSION: The laser guidance localization method possessed a greater precision and less localization duration and CT scan times compared to the freehand method. However, laser guidance group and freehand group do not differ in the appearance of complications such as pulmonary hemorrhage, pneumothorax and hook-wire dislodgement.

PMID:38581004 | DOI:10.1186/s13019-024-02706-x