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The Application of Transbronchial Cryo-biopsy in the Diagnosis of Pulmonary Alveolar Proteinosis

J Bronchology Interv Pulmonol. 2025 May 21;32(3):e01013. doi: 10.1097/LBR.0000000000001013. eCollection 2025 Jul 1.

ABSTRACT

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by abnormal alveolar surfactant accumulation. In recent years, transbronchial cryo-biopsy (TBCB) has gradually been applied as it can obtain larger and better-quality specimens. This study aims to assess the diagnostic yield and safety of TBCB in PAP.

METHODS: This study included 78 PAP patients who underwent lung biopsy. Thirty-six of them underwent transbronchial lung biopsy (TBLB) with forceps and the other 42 underwent TBCB. Clinical data, biopsy specimen number and size, the pathologic lesion proportion of biopsied specimens, complications, and pathologic diagnosis of patients from both groups were recorded.

RESULTS: Our data show that the diagnostic yield of TBCB is significantly superior to that of TBLB (78.6% vs. 50%, P<0.05). The TBCB group exhibited a greater number and size of biopsy specimens than the TBLB group (P<0.05). As for pathologic diagnosis, the specimen size in the PAP-positive group was notably larger than in the PAP-negative group (P<0.05). According to the receiver operating characteristic curve, the specimen size of at least 2 mm2 was identified as the cut-off with a higher positive predictive value (area under the curve = 0.676, P=0.007). For complications of TBLB and TBCB, there was no statistically significant difference in the incidence of pneumothorax and bleeding.

CONCLUSION: TBCB emerges as a minimally invasive, effective, and safe technique with a higher diagnostic yield than TBLB in PAP. Augmenting the specimen size can effectively improve the diagnostic yield.

PMID:40396301 | DOI:10.1097/LBR.0000000000001013

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Ferroptosis and Dysfunction of CD3+CD4-CD8- T Cells are Associated with Poor Immune Reconstitution in HIV Patients

Curr HIV Res. 2025 May 20. doi: 10.2174/011570162X366300250509112302. Online ahead of print.

ABSTRACT

INTRODUCTION: Some HIV patients stay in an immune unresponsive state after antiretroviral therapy (ART), with a notably higher risk of AIDS-related and non-AIDS-related complications. Double-negative T cells (DNT) can compensate for immunity and prevent immune overactivation in HIV patients. Also, immune non-responders (INRs) have fewer DNT cells than immune responders (IRs). HIV infection and ART can change the dynamic function of cell mitochondria, which are crucial in ferroptosis. Ferroptosis is a form of cell death marked by the accumulation of reactive oxygen species (ROS) and iron-dependent lipid peroxidation. Yet, the changes in DNT cell function in INRs and the impact of ferroptosis on immune reconstitution remain unclear.

AIMS: Our study focused on the expression level of DNT cells in HIV immune non-responders. Then, we detected markers of ferroptosis, cell activation, proliferation, killing function, and inflammatory states of DNT cells in INRs.

METHODS: The study involved 88 PLHIVs who had received antiretroviral therapy for over 4 years and tested virus-negative. These patients were classified into two groups: 28 INRs (CD4 < 350/μl) and 60 IRs (CD4 ≥350/μl). Additionally, 25 sex- and age-matched HCs were included. Flow cytometry was used to detect ferroptosis markers (JC-1, Lipid ROS, lipid peroxidation), cell proliferation, and cell activation. Transmission electron microscopy (TEM) was applied to observe mitochondrial morphology. Finally, statistical analysis was performed on the detection results.

RESULTS: After long-term antiretroviral therapy, we found that INRs had a lower DNT cell count than IRs. Regarding proliferation and activation, our results showed higher CD38/HLA-DR co-expression and Ki67 expression in INRs’ DNT cells than in IRs’, indicating over-activation of DNT cells in INRs. In terms of killing function, the perforin and granzyme B levels in INRs’ DNT cells were lower than those in IRs’, suggesting impaired killing function of DNT cells in INRs. For ferroptosis, the proportion of DNT cells with decreased MMP in INRs was higher than in IRs and HCs. INRs’ DNT cells also had higher levels of lipid ROS and lipid peroxidation compared to those in IRs and HCs. TEM revealed that the mitochondria of INRs’ DNT cells had typical morphological features. Moreover, INRs’ DNT cells had a greater degree of inflammation.

CONCLUSION: Our study centered on the proliferation, activation, ferroptosis, killing function, and inflammatory status of DNT cells in INRs. We found that DNT cells in INRs had more active proliferation and activation, weakened killing function, mitochondrial function with typical ferroptosis features, and increased TNF-αlevels. Correlation analysis indicated that DNT cell overactivation (Ki-67+, CD38+HLA-DR+), MMP reduction ratio, and TNF-αexpression were negatively related to immune reconstitution in PLHIVs. In contrast, the killing function (perforin+) of DNT cells was positively related to it. These findings provide a theoretical basis for targeting the functional remodeling of DNT cells. In the future, therapeutic strategies can be explored, such as regulating the mitochondrial metabolic pathway or enhancing the immunoregulatory activity of DNT cells. These strategies can thus offer innovative solutions to the dilemma of immune reconstitution in HIV-infected individuals.

PMID:40396294 | DOI:10.2174/011570162X366300250509112302

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Enhancing Ergonomics in Paediatric Dentistry: A Longitudinal Study on the Role of Photography in Undergraduate Student Training

Eur J Dent Educ. 2025 May 21. doi: 10.1111/eje.13111. Online ahead of print.

ABSTRACT

PURPOSE: Dental surgeons are particularly exposed to musculoskeletal disorders. Ergonomics can help prevent them. Third-party ergonomic assessment is beneficial in the short term. However, self-assessment of one’s working posture is even more valuable, as it fosters lifelong awareness.

METHODS: Fifth year odontology students were randomly assigned to one of two groups (control and training) to evaluate whether a protocol for ergonomic self-assessment by paediatric odontology students, using photography, led to an improvement in their working position. The Modified-Dental Operator Posture Assessment Instrument was used.

RESULTS: The study included 82 fifth-year odontology students who performed paediatric care between September 2022 and June 2023. A statistically significant difference was found between the control and training groups for both self-assessments (p < 0.001) and evaluator analyses (p < 0.001).

CONCLUSIONS: The longitudinal follow-up approach appears to be unique in the field of ergonomics education in dentistry. The results demonstrated a significant reduction in ergonomics scores for the group that received ergonomic advice and visual feedback compared to the control group. This improvement was confirmed both by evaluator-assigned scores and by students’ self-assessments.

PMID:40396283 | DOI:10.1111/eje.13111

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Improving Diversity in Recruitment: Lessons Learned During the REACH Pregnancy Circles Pilot Trial

Health Expect. 2025 Jun;28(3):e70300. doi: 10.1111/hex.70300.

ABSTRACT

INTRODUCTION: Our ability to address inequities in health outcomes is hampered by the under-representation of underserved groups in research. Research exploring this topic has focused on observational studies in the American context. This is a pivotal concern for maternity research in the UK as perinatal outcome variables vary by ethnicity, socioeconomic and linguistic background. This paper reports the findings of an analysis of the diversity achieved by different recruitment strategies used within a feasibility study and pilot trial of group antenatal care (Pregnancy Circles).

METHOD: A pilot randomised controlled trial involved implementation of Pregnancy Circles across three maternity services in an area of high ethnic, socioeconomic and linguistic diversity. Following findings of high ethnic diversity but low levels of educational and linguistic diversity amongst participants recruited in our prior feasibility study, equity-informed strategies were put into place to attempt to increase recruitment diversity in the pilot trial, addressing organisational barriers (additional language support); attitudinal barriers (staff training to counteract recruitment bias) and practical barriers (extending the recruitment period to reach women accessing care late). Women who declined participation were invited to complete a short anonymous questionnaire covering demographic details and reasons for declining. The demographic characteristics of participants in the feasibility and pilot studies, and the pilot study decliners, were compared using descriptive statistics and free-text reasons for declining were analysed thematically.

RESULTS: The targeted recruitment processes were successful in widening the diversity of participants in this study, in particular for women with limited English proficiency and low educational achievement. Nevertheless, comparison of participants to those who declined showed some barriers persisted. The most common reason to decline was lack of time, most commonly due to caring responsibilities, and this was more likely to be cited by ethnically minoritized women.

CONCLUSION: Recruitment plans focused on widening diversity can be effective but are likely to require additional resources such as funding longer recruitment periods or interpreting services. The gendered nature of maternity research poses particular challenges, and our study suggests that addressing barriers such as those around childcare would enhance the recruitment of socio-economically deprived and minoritized women.

PATIENT OR PUBLIC CONTRIBUTION: Our study team included two service user representatives as co-investigators, feeding into all aspects of the study. The focus of the work reported here was to increase the participation of underserved communities in the pilot trial and to inform the Pregnancy Circles RCT, to enable them to contribute their data and lived experience to the findings and evaluation of this intervention.

TRIAL REGISTRATION: Due to an administrative oversight, trial registration for this pilot trial was applied for during the 6-week recruitment period, rather than before recruitment commencing (ISRCTN66925258. Retrospectively registered 3 April 2017). Registration occurred before programme intervention, outcomes and process data collection and all data analysis.

PMID:40396261 | DOI:10.1111/hex.70300

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Impact of Hypovolemic Phlebotomy with Low Central Venous Pressure on Intraoperative Blood Loss in Open Liver Resection: A Double-Blind Randomized Controlled Trial

Ann Surg. 2025 May 21. doi: 10.1097/SLA.0000000000006760. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of hypovolemic phlebotomy (HP) versus conventional management (control group) in achieving low central venous pressure (CVP) to reduce blood loss during open liver resections.

BACKGROUND: Excessive blood loss increases perioperative complications and worsen patient outcomes. HP is used to reduce blood loss and the need for allogenic transfusions. This study compares intraoperative blood loss between HP and conventional techniques in liver resection.

METHODS: This prospective, randomized controlled trial, conducted between 2020 and 2024, evaluated intraoperative blood loss as the primary endpoint, with secondary endpoints of allogenic transfusion and postoperative outcomes.

RESULTS: One hundred participants were randomized to either HP or control groups, with similar baseline characteristics. The HP group had significantly lower blood loss during parenchymal transection (300 (250-500) vs. 500 (300-750) mL, difference = 150, 95% CI [50, 275]; P = 0.02), shorter time to achieve low CVP (50 (30-100) vs. 107.5 (45-150) minutes, difference = -75.0, 95% CI [-95.0, -56.0]; P = 0.01), and a lower surgical bleeding score (2 (1-3) vs. 2 (2-4), difference = -1.0, 95% CI [-1.0, -0.5]; P = 0.01). Transfusion rates and postoperative complications were similar. HP was an independent protective against blood loss > 500 mL (AOR = 0.19, 95% CI [0.04-0.80]; P = 0.02).

CONCLUSIONS: HP significantly reduces intraoperative blood loss and enhances bleeding control by achieving low CVP more quickly. It is an effective technique for minimizing blood loss and improving outcomes in open liver resections.

PMID:40396243 | DOI:10.1097/SLA.0000000000006760

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Characterization and correlation analysis of oral NET markers and inflammatory factor levels in patients after orthodontic treatment: a pilot study

Front Immunol. 2025 May 6;16:1490637. doi: 10.3389/fimmu.2025.1490637. eCollection 2025.

ABSTRACT

INTRODUCTION: Changes in oral neutrophil number and function may occur in patients after orthodontic treatment, affecting the oral immune microenvironment. However, the specific mechanisms are unclear. In this study, we describe the changes in the levels of neutrophil extracellular traps (NET) markers and inflammatory factors in the gingival crevicular fluid (GCF) and saliva of patients after orthodontic treatment and further explore the correlation between them.

METHODS: 68 patients underwent fixed orthodontic treatment in the Department of Orthodontics from January 2021 to June 2023 were selected. GCF and saliva samples were collected from the patients 1 day before orthodontic treatment and 2 h, 24 h, and 1 week after orthodontic treatment to evaluate changes in NET marker and inflammatory factors. The differences in and associations between NET markers and inflammatory cytokine levels in the GCF and saliva of patients were evaluated.

RESULTS: After fixed orthodontic treatment, the neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone 3 (CitH3), and MPO-DNA in the GCF and saliva of the patients increased gradually, the interleukin (IL)-1β and IL-8 in the GCF increased gradually, and there were significant differences among the different time points (P<0.05). There was a positive correlation between the NE, MPO, CitH3, MPO-DNA, IL-1β and IL-8 in the GCF of patients at 2 hours and 24 hours after orthodontic treatment (P<0.05). There was a significant positive correlation between the GCF and saliva levels of NE, MPO, CitH3, MPO-DNA, IL-1β and IL-8 (P<0.05); however, there was no statistically sex- or age-dependent differences in the NE, MPO, CitH3, MPO-DNA, IL-1β and IL-8 levels in the GCF of orthodontic patients (P>0.05).

CONCLUSION: This study significantly reveals that NET marker levels in the GCF and saliva rapidly change following the initial orthodontic arch wire stress. The inflammation in periodontal tissues induced by orthodontic stress has the potential to trigger oral inflammation via the GCF. These findings are crucial for understanding the oral immune microenvironment changes during orthodontic treatment, providing a theoretical basis for preventing and treating orthodontic – related periodontal complications, thus having important implications for improving orthodontic treatment outcomes.

PMID:40396177 | PMC:PMC12089083 | DOI:10.3389/fimmu.2025.1490637

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Comparative effectiveness of a multimodal intervention package on surface cleaning and disinfection in Brazilian neonatal intensive care units

Front Public Health. 2025 May 6;13:1557538. doi: 10.3389/fpubh.2025.1557538. eCollection 2025.

ABSTRACT

OBJECTIVE: To compare the impact of a package of interventions on surface cleaning and disinfection in two public and private neonatal intensive care units (NICUs).

METHOD: This is a quasi-experimental, quantitative study. The study consisted of three phases: baseline (phase I), implementation of the intervention package without feedback to the team (phase II), and, finally, short-term monitoring with feedback to the team (phase III). A total of 864 evaluations were carried out according to the monitoring methods: adenosine triphosphate, visual inspection, microbial load counting, and detection of Staphylococcus aureus and testing for its methicillin resistance (MRSA) in each unit over 4 months, evaluating six high-frequency touch surfaces, before and after cleaning and disinfection carried out by nursing and sanitizing professionals.

RESULTS: When comparing the effect of the package in the two units (public and private), no significant differences were found in the proportions of MRSA-positive surfaces in all the phases evaluated. The same occurred concerning the ATP method, which showed no significant differences between the hospitals in all study phases. Concerning the microbial count, in phase II of the study, only on one surface (scales) was a significantly lower difference found in the private hospital compared to the public one. Visual inspection indicated that the private NICU had a substantially higher proportion of surfaces with adequate hygiene in phase I: the infusion pump and the armchair; in phase II, the counter and in phase III again the counter surface. Concerning human factors, when comparing the two institutions, there were no statistically significant associations or correlations with job satisfaction. However, the public institution had higher work performance scores than the private one.

CONCLUSION: The study highlights that the rigorous implementation of intervention packages for cleaning in NICUs, even though they are different, still showed similar results in terms of effectiveness for all the methods used, except visual inspection. This study showed that even though the employees had various levels of work performance, there was still a similar effect on the outcome of the intervention package.

PMID:40396167 | PMC:PMC12088969 | DOI:10.3389/fpubh.2025.1557538

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Twelve-Month Outcomes of Faricimab for Patients with Sub-Optimally Responsive Diabetic Macular Oedema: A Retrospective Single-Centre Study

Clin Ophthalmol. 2025 May 16;19:1583-1591. doi: 10.2147/OPTH.S513009. eCollection 2025.

ABSTRACT

PURPOSE: To evaluate the visual and anatomical outcomes of switching diabetic macular oedema (DMO) patients with suboptimal response to aflibercept 2mg to faricimab over a 12-month period.

PATIENTS AND METHODS: This retrospective single centre study enrolled 62 eyes from 50 patients with diabetic macular oedema (DMO) who demonstrated a sub-optimal response to aflibercept 2mg. Sub-optimal response was defined by a central subfield thickness (CST) exceeding 325µm or greater than 20% increase from the best CST despite receiving aflibercept 2mg at intervals of 8 weeks or less. Patients had received at least six 4-weekly doses of aflibercept 2mg. Faricimab was administered as four intravitreal loading injections at 4-weekly intervals, followed by a treat-and-extend approach. Outcome measures, including best-recorded visual acuity (BRVA), CST, and treatment intervals, were assessed at baseline, post-loading (6.5 ± 1.9 weeks) and at the latest clinic review (57.1 ± 19.7 weeks). Statistical analysis included paired t-tests (normal distribution) and Wilcoxon signed-rank tests (non-normal distribution), with p < 0.05 considered statistically significant.

RESULTS: Mean age was 63.9 (±11.4) years, 56% participants were male. At baseline, the mean BRVA was 67.6 (±11.8) letters, and CST measured 406.4 (±105.9) µm. The initial mean treatment interval was 6.5 (±1.8) weeks. BRVA increased to 70.4 (±12.7) letters (p=0.008), while CST reduced to 372.8 (±132.0) µm (p=0.002). The mean injection interval extended to 7.4 (±2.6) weeks (p=0.03). At the latest follow-up BRVA was maintained at 68.7 (±14.6) letters (p=0.572), and CST reduced further to 343.1 (±117.5) µm (p=0.020). At the final follow-up 53.2% were on ≥8-weekly intervals. The mean injection interval increased to 9.2 (±3.2) weeks (p < 0.001), and a mean of 7.92 (±2.53) faricimab injections was administered.

CONCLUSION: DMO patients with sub-optimal response to aflibercept 2mg experienced improved anatomical outcomes and extended treatment intervals while maintaining vision on faricimab, with no new safety concerns.

PMID:40396158 | PMC:PMC12091065 | DOI:10.2147/OPTH.S513009

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Transfer Learning and Multi-Feature Fusion-Based Deep Learning Model for Idiopathic Macular Hole Diagnosis and Grading from Optical Coherence Tomography Images

Clin Ophthalmol. 2025 May 16;19:1593-1607. doi: 10.2147/OPTH.S521558. eCollection 2025.

ABSTRACT

BACKGROUND: Idiopathic macular hole is an ophthalmic disease that seriously affects vision, and its early diagnosis and treatment have important clinical significance to reduce the occurrence of blindness. At present, OCT is the gold standard for diagnosing this disease, but its application is limited due to the need for professional ophthalmologist to diagnose it. The introduction of artificial intelligence will break this situation and make its diagnosis efficient, and how to build an effective predictive model is the key to the problem, and more clinical trials are still needed to verify it.

OBJECTIVE: This study aims to evaluate the role of deep learning systems in Idiopathic Macular Hole diagnosis, grading, and prediction.

METHODS: A single-center, retrospective study used binocular OCT images from IMH patients at the First Affiliated Hospital of Nanchang University (November 2019 – January 2023). A deep learning algorithm, including traditional omics, Resnet101, and fusion models incorporating multi-feature fusion and transfer learning, was developed. Model performance was evaluated using accuracy and AUC. Logistic regression analyzed clinical factors, and a nomogram predicted surgical risk. Analysis was conducted with SPSS 22.0 and R 3.6.3. P < 0.05 was statistically significant.

RESULTS: Among 229 OCT images, the traditional omics, Resnet101, and fusion models achieved accuracies of 93%, 94%, and 95%, respectively, in the training set. In the test set, the fusion model and Resnet101 correctly identified 39 images, while the traditional omics model identified 35. The nomogram had a C-index of 0.996, with macular hole diameter most strongly associated with surgical risk.

CONCLUSION: The deep learning system with transfer learning and multi-feature fusion effectively diagnoses and grades IMH from OCT images.

PMID:40396157 | PMC:PMC12091069 | DOI:10.2147/OPTH.S521558

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Efficacy of Acotiamide in Pediatric Patients with Functional Dyspepsia

Pediatr Gastroenterol Hepatol Nutr. 2025 May;28(3):176-184. doi: 10.5223/pghn.2025.28.3.176. Epub 2025 May 8.

ABSTRACT

PURPOSE: Functional dyspepsia (FD) is a chronic disorder characterized by upper abdominal symptoms in the absence of an identifiable organic cause. Although the efficacy of acotiamide has been demonstrated in adults with FD, its effectiveness in pediatric patients remains unclear. This study aimed to evaluate the efficacy of acotiamide in pediatric patients with FD.

METHODS: We conducted a retrospective analysis of 33 patients with FD, aged <16 years, who received acotiamide at a single children’s hospital between August 2013 and March 2022.

RESULTS: Symptomatic improvement was observed in 57.6% (19/33) of patients one month after acotiamide administration. The improvement rates were 63.6%, 20.0%, and 66.7% among patients with epigastric pain syndrome (EPS), postprandial distress syndrome (PDS), and overlap PDS-EPS, respectively. No statistically significant differences in symptomatic improvement rates were noted among the subtypes (p=0.213). Two patients discontinued acotiamide because of abdominal pain, but no serious adverse events were reported.

CONCLUSION: Acotiamide demonstrated efficacy in pediatric FD, which is consistent with previously reported outcomes in adults. Acotiamide may be a beneficial treatment option for pediatric FD across all subtypes.

PMID:40396150 | PMC:PMC12088856 | DOI:10.5223/pghn.2025.28.3.176