Tag: pubmed

Invest Ophthalmol Vis Sci. 2024 May 1;65(5):32. doi: 10.1167/iovs.65.5.32.

ABSTRACT

PURPOSE: To evaluate VEGF-C-induced lymphoproliferation in conjunction with 5-fluorouracil (5-FU) antimetabolite treatment in a rabbit glaucoma filtration surgery (GFS) model.

METHODS: Thirty-two rabbits underwent GFS and were assigned to four groups (n = 8 each) defined by subconjunctival drug treatment: (a) VEGF-C combined with 5-FU, (b) 5-FU, (c) VEGF-C, (d) and control. Bleb survival, bleb measurements, and IOP were evaluated over 30 days. At the end, histology and anterior segment OCT were performed on some eyes. mRNA was isolated from the remaining eyes for RT-PCR evaluation of vessel-specific markers (lymphatics, podoplanin and LYVE-1; and blood vessels, CD31).

RESULTS: Qualitatively and quantitatively, VEGF-C combined with 5-FU resulted in blebs which were posteriorly longer and wider than the other conditions: vs. 5-FU (P = 0.043 for longer, P = 0.046 for wider), vs. VEGF-C (P < 0.001, P < 0.001) and vs. control (P < 0.001, P < 0.001). After 30 days, the VEGF-C combined with 5-FU condition resulted in longer bleb survival compared with 5-FU (P = 0.025), VEGF-C (P < 0.001), and control (P < 0.001). Only the VEGF-C combined with 5-FU condition showed a negative correlation between IOP and time that was statistically significant (r = -0.533; P = 0.034). Anterior segment OCT and histology demonstrated larger blebs for the VEGF-C combined with 5-FU condition. Only conditions including VEGF-C led to increased expression of lymphatic markers (LYVE-1, P < 0.001-0.008 and podoplanin, P = 0.002-0.011). Expression of CD31 was not different between the groups (P = 0.978).

CONCLUSIONS: Adding VEGF-C lymphoproliferation to standard antimetabolite treatment improved rabbit GFS success and may suggest a future strategy to improve human GFSs.

PMID:38771570 | DOI:10.1167/iovs.65.5.32

Nucleosides Nucleotides Nucleic Acids. 2024 May 21:1-9. doi: 10.1080/15257770.2024.2353185. Online ahead of print.

ABSTRACT

INTRODUCTION: Postmenopausal osteoporosis (PMOP) is a common metabolic bone disorder manifested by low bone mineral density and increased fracture risks in postmenopausal women. Vascular endothelial growth factor (VEGF) has been shown to play an important role in bone formation. In this study, we investigated the potential association between the VEGF insertion/deletion (I/D) variant (rs35569394) and PMOP in a cohort of postmenopausal Turkish women.

METHODS: This study included 300 women, including 150 PMOP patients and 150 healthy postmenopausal women. A T score was used in the diagnosis of OP. DNA was extracted from all subjects. The VEGF I/D polymorphism was analyzed by the PCR method. The Hardy-Weinberg equilibrium (HWE) test and odds ratio (OR) were analyzed, considering CI 95% and p ≤ 0.05.

RESULTS: The mean age of patients aged between 40 and 74 was 60.32 ± 8.65. The frequency of the I/I, I/D, and D/D genotypes was 7.34% versus 6.66%; 67.33% versus 65.34%; and 25.33% versus 28%, in patients and the control group, respectively. The allele frequencies were I: 41% (patients) and 39.4% (controls); D: 59% (patients) and 60.66% (controls). There was no statistically significant difference in the VEGF – 2549 I/D allele and genotype distribution between patients with PMOP and control subjects (p = 0.349, p = 0.864, respectively).

CONCLUSION: Our results showed that the VEGF I/D variant was not a significant factor in the development of PMOP in a Turkish population sample. These findings need confirmation in other ethnic populations.

PMID:38771564 | DOI:10.1080/15257770.2024.2353185

Qual Life Res. 2024 May 21. doi: 10.1007/s11136-024-03675-3. Online ahead of print.

ABSTRACT

PURPOSE: Clinical benefits result from electronic patient-reported outcome (ePRO) systems that enable remote symptom monitoring. Although clinically useful, real-time alert notifications for severe or worsening symptoms can overburden nurses. Thus, we aimed to algorithmically identify likely non-urgent alerts that could be suppressed.

METHODS: We evaluated alerts from the PRO-TECT trial (Alliance AFT-39) in which oncology practices implemented remote symptom monitoring. Patients completed weekly at-home ePRO symptom surveys, and nurses received real-time alert notifications for severe or worsening symptoms. During parts of the trial, patients and nurses each indicated whether alerts were urgent or could wait until the next visit. We developed an algorithm for suppressing alerts based on patient assessment of urgency and model-based predictions of nurse assessment of urgency.

RESULTS: 593 patients participated (median age = 64 years, 61% female, 80% white, 10% reported never using computers/tablets/smartphones). Patients completed 91% of expected weekly surveys. 34% of surveys generated an alert, and 59% of alerts prompted immediate nurse actions. Patients considered 10% of alerts urgent. Of the remaining cases, nurses considered alerts urgent more often when patients reported any worsening symptom compared to the prior week (33% of alerts with versus 26% without any worsening symptom, p = 0.009). The algorithm identified 38% of alerts as likely non-urgent that could be suppressed with acceptable discrimination (sensitivity = 80%, 95% CI [76%, 84%]; specificity = 52%, 95% CI [49%, 55%]).

CONCLUSION: An algorithm can identify remote symptom monitoring alerts likely to be considered non-urgent by nurses, and may assist in fostering nurse acceptance and implementation feasibility of ePRO systems.

PMID:38771558 | DOI:10.1007/s11136-024-03675-3

Infect Dis Ther. 2024 May 21. doi: 10.1007/s40121-024-00992-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection.

METHODS: This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value < 30 and symptom onset within 4 days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated.

RESULTS: A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct ≥ 30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p = 0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p = 0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed.

CONCLUSION: Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration.

PMID:38771550 | DOI:10.1007/s40121-024-00992-5

Lasers Med Sci. 2024 May 21;39(1):133. doi: 10.1007/s10103-024-04085-0.

ABSTRACT

BACKGROUND: Tooth discoloration is a common concern in antimicrobial photodynamic therapy (aPDT) using various photosensitizers (PS). Toluidine Blue (TB), Methylene Blue (MB), Phthalocyanine (Pc), and 2-mercaptopyridine-substituted zinc phthalocyanine (TM-ZnPc) are among those studied, but their relative impacts on tooth discoloration remain unclear.

AIM: This study aimed to compare the effects of TB, MB, Pc, and TM-ZnPc in aPDT on tooth discoloration, utilizing a controlled experimental setup.

MATERIALS AND METHODS: The study comprised seventy-five single-rooted incisors with root canals. Following meticulous preparation, a standardized area on the crown surface was designated for examination, and precise measurements of the initial tooth colors were recorded. Samples were randomly divided into five groups: Negative control, MB, TM, Pc, and TM-ZnPc. Photoactivation was performed using LED light, and color measurements were taken at multiple time points up to 90 days. Data were converted to Lab* color values of the CIE Lab* color system (International Commission on Illumination, Vienna, Austria), and ΔE values were calculated. Statistical analysis was performed using Two-way ANOVA and Post-Hoc Tukey tests (p < 0.05).

RESULTS: At day 7 and 30, TM-ZnPc and Pc caused less discoloration compared to MB and TB. TM-ZnPc caused more tooth discoloration compared to Pc (p < 0.05). Compared to baseline, MB and TM-ZnPc caused more tooth discoloration at 30 days and TB caused more tooth discoloration at 90 days (p < 0.05). No significant difference was observed in terms of tooth discoloration at all periods evaluated after Pc application (p > 0.05). All photosensitizers tested in the study caused tooth coloration.

CONCLUSION: All PS induced clinically detectable tooth discoloration, with TB and MB causing more significant discoloration compared to Pc and TM-ZnPc at certain time points. TM-ZnPc and Pc demonstrated more stable coloration levels over time, suggesting their potential reliability in aPDT applications. This study highlights the importance of selecting appropriate PS to minimize tooth discoloration in aPDT, with Pc showing promise in this regard.

PMID:38771549 | DOI:10.1007/s10103-024-04085-0

Endocr Connect. 2024 May 1:EC-24-0170. doi: 10.1530/EC-24-0170. Online ahead of print.

ABSTRACT

OBJECTIVE: The management of thyroid nodules with indeterminate cytology (ITN) is still a challenge. To evaluate the performance of commercial molecular tests for ITN, we performed this comprehensive meta-analysis.

METHODS: We performed an electronic search using PubMed/Medline, Embase and the Cochrane Library. Studies assessing the diagnostic accuracy of Afirma Gene Expression Classifier (GEC), Afirma Gene Sequencing Classifier (GSC), ThyroSeq v2 (TSv2) or ThyroSeq v3 (TSv3) in patients with ITN (only Bethesda category III or IV) were selected; Statistical analyses were performed by using Stata.

RESULTS: 71 samples (GEC, n=38; GSC, n=16; TSv2, n=9; TSv3, n=8) in 53 studies, involving 6,490 fine needle aspirations (FNA) with ITN cytology with molecular diagnostics (GEC, GSC, TSv2 or TSv3) were included in the study. Meta-analysis showed the following pooled estimates: sensitivity 0.95 (95% CI, 0.94-0.97), specificity 0.35 (0.28-0.43), Positive Likelihood Ratio (LR+) 1.5 (1.3-1.6), and Negative Likelihood Ratio (LR-) 0.13 (0.09-0.19), with the best performance for TSv3 (area under the ROC curve 0.95 (0.93-0.96), followed by TSv2 (0.90 (0.87-0.92)), GSC (0.86 (0.82-0.88)) and GEC (0.82 (0.78-0.85)); with the best rule-out property for GSC (LR-, 0.07 (0.02-0.19)), followed by TSv3 (0.11 (0.05-0.24)) and GEC (0.16 (0.10-0.28); with the best rule-in for TSv2 (LR+, 2,9 (1.4-4.6)), followed by GSC (1.9 (1.6-2.4)). Meta-regression analysis revealed that study design, Bethesda category, and type of molecular test were independent factors.

CONCLUSIONS: We showed that in patients with ITN, TSv3 has the best molecular diagnostic performance, followed by TSv2, GSC, and GEC. For rule-out malignancy, GSC, and for rule-in, TSV2 is superior to other tests.

PMID:38771544 | DOI:10.1530/EC-24-0170

Neurol Sci. 2024 May 21. doi: 10.1007/s10072-024-07584-8. Online ahead of print.

ABSTRACT

BACKGROUND: Rett syndrome (RTT) is an uncommon inherited neurodevelopmental disorder that affects brain development, mostly in females. It results from mutation in MECP2 gene in the long arm (q) of the X chromosome.

OBJECTIVE: Trofinetide is a recently developed drug that has a neuroprotective effect on neurons, and it is our aim in this meta-analysis to evaluate its efficacy and safety in treating Rett syndrome patients.

METHODS: We searched 5 databases (PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases) to identify randomized controlled trials (RCTs) comparing Trofinetide and placebo in patients with Rett syndrome until August 13, 2023.Our primary outcomes were the Clinical Global Impression-Improvement (CGI) and the Rett syndrome Behavior Questionnaire (RSBQ). We used Risk of Bias Assessment tool-2 (ROB2) to assess the methodological quality of the included randomized controlled trials.

RESULTS: Three RCTs with a total of 325 patients were included with a follow-up duration ranging from one month to three months. 186 patients received the intervention drug (Trofinetide) and 138 received the placebo. Trofinetide was found to reduce CGI and RSBQ significantly more than placebo (MD = -0.35, 95% CI [-0.52 to -0.18], P 0.0001), (MD = -3.40, 95% CI [-3.69 to -3.12], P 0.00001) respectively. Most adverse events did not show any statistical difference between Trofinetide and the placebo.

CONCLUSION: Trofinetide offers promise as a potential effective and safe therapeutic opportunity for a population without many available treatments, with improvements seen on both CGI and RSBQ assessments and no severe adverse effects reported.

PMID:38771525 | DOI:10.1007/s10072-024-07584-8

Int Urogynecol J. 2024 May 21. doi: 10.1007/s00192-024-05778-4. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome.

METHODS: literature search using Pub Med with the keywords “bladder pain syndrome”, “painful bladder syndrome”, “bladder pain”, “Interstitial cystitis” AND “cytokines” or “inflammation”. This study was except from institutional approval.

RESULTS: Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C-C chemokine group (n = 7).

CONCLUSIONS: CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C-C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients.

PMID:38771505 | DOI:10.1007/s00192-024-05778-4

Clin Exp Med. 2024 May 21;24(1):105. doi: 10.1007/s10238-024-01373-5.

ABSTRACT

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for B cell malignancies. A certain fraction of patients, however, experience post-CAR-T relapse, and due to the difficulty of precise relapse prediction, biomarkers that can predict the strength and duration of CAR-T efficacy are needed before CAR-T infusion. Therefore, we performed a single-center cohort study including 91 diffuse large B cell lymphoma (DLBCL) patients treated with CAR-T in order to identify such a new prognostic biomarker. After confirming that each of the already reported prognostic parameters (disease status at leukapheresis, primary refractoriness, number of treatment lines, CD3⁺ cell counts at leukapheresis) has only limited predictive performance, we established a new composite parameter by integrating these four variables, and found that it predicts progression-free survival (PFS) after CAR-T infusion with statistical significance. Moreover, after comprehensive correlation analyses of this new composite parameter with all individual laboratory variables, we determined that the standard deviation of red blood cell distribution width (RDW-SD) at leukapheresis shows significant correlation with the composite parameter and may be a prognostic biomarker (R² = 0.76, p = 0.02). Validation analysis indicated that a higher RDW-SD is significantly associated with poorer PFS after CAR-T cell therapy (HR, 3.46, P = 0.03). Thus, this study suggests that a single parameter, RDW-SD at leukapheresis, is a novel, useful biomarker that can be obtained early to predict therapeutic effects of CAR-T cell therapy. Post-CAR-T maintenance or re-induction therapies should be adopted for higher risk patients, who may relapse after CAR-T therapy.

PMID:38771501 | DOI:10.1007/s10238-024-01373-5

Arch Womens Ment Health. 2024 May 21. doi: 10.1007/s00737-024-01471-z. Online ahead of print.

ABSTRACT

PURPOSE: Adjuvant endocrine therapy has a vital role in reducing breast cancer mortality. The beliefs in adjuvant endocrine therapy is a very important factor in the medication adherence of breast cancer survivors. Therefore, it is necessary to develop a standardized scale for assessment of adjuvant endocrine therapy. The purpose of this study was to identify the attributes of adjuvant endocrine therapy beliefs, and to evaluate adjuvant endocrine therapy beliefs scale psychometric properties.

METHODS: A hybrid model was applied to identify the concept of adjuvant endocrine therapy beliefs and measurement question were developed by the scale development process. Statistical analysis using validity analysis and Rasch analysis based on item response theory were performed. A total of 228 breast cancer survivors in South Korea participated in the study.

RESULTS: The finally developed adjuvant endocrine therapy beliefs scale consisted of 22 items. The items extracted by 4 factors explained 59.72% of the total variance. The model fit showed an acceptable level. The adjuvant endocrine therapy beliefs scale was excellent in convergent and discriminant validity with reliability.

CONCLUSION: This scale is expected to be practical and useful in identifying adjuvant endocrine therapy beliefs and developing intervention strategies to promote adjuvant endocrine therapy adherence. In addition, continuous education and support should be accompanied so that breast cancer survivors can maintain positive beliefs in adjuvant endocrine therapy adherence.

PMID:38771495 | DOI:10.1007/s00737-024-01471-z