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Nevin Manimala Statistics

α2-Macroglobulin Concentrations in Canine and Equine Serum Donors

Vet Ophthalmol. 2025 Aug 4. doi: 10.1111/vop.70057. Online ahead of print.

ABSTRACT

PURPOSE: To determine if serum α2-macroglobulin (A2M) concentration varies based on donor species-canine or equine-and signalment.

METHODS: Serum A2M concentration ([A2M]) was measured in healthy dogs (n = 30) and horses (n = 31) using species-specific ELISAs.

RESULTS: Canine and equine [A2M] median (IQR; range) were 98.70 ng/mL (92.79 ng/mL; 34.33-696.18 ng/mL) and 557 000 ng/mL (437 900 ng/mL; 62 600-3 042 900 ng/mL), respectively. Equine [A2M] was significantly higher than canine [A2M]. Depending on the statistical analysis performed, sex had either no statistical (p = 0.17) or medium practical (η2 = 0.07) effect on canine serum [A2M], with male dogs having higher [A2M] practically. There was no association between serum [A2M] and duration of serum storage at -80°C.

CONCLUSIONS: Equine serum [A2M] was exponentially higher than that of dogs. Sex may affect [A2M] in dogs. Further study is needed to evaluate how this difference affects antiprotease activity.

PMID:40755436 | DOI:10.1111/vop.70057

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Nevin Manimala Statistics

Atrial fibrillation and female sex: use of oral anticoagulants in a large European cohort and residual risk of thromboembolism and stroke

Eur Heart J Qual Care Clin Outcomes. 2025 Aug 4:qcaf075. doi: 10.1093/ehjqcco/qcaf075. Online ahead of print.

ABSTRACT

BACKGROUND: The role of female sex in stroke risk and oral anticoagulant (OAC) use in atrial fibrillation (AF) remains controversial. This study evaluates sex-specific differences in OAC prescription, residual risk of stroke/TIA and thromboembolism (STE), and the predictive performance of CHA₂DS₂-VASc vs. CHA₂DS₂-VA scores.

METHODS: We analyzed data from a European prospective cohort. The association between female sex and OAC prescription was assessed in patients with CHA₂DS₂-VA score ≥1. We analyzed the residual STE risk in OAC-treated patients and compared the predictive performance of CHA₂DS₂-VASc and CHA₂DS₂-VA scores.

RESULTS: Among 10,080 patients (41.8% women; mean age 69.7 [SD 10.7] years) with CHA₂DS₂-VA ≥1, women had higher burden of comorbidities and less likely to receive OACs than men (OR 0.79, 95% CI: 0.69-0.90). In OAC-treated patients, STE rates were higher in women (IR 1.33 vs. 0.94 per 100 person-years). After adjusting for confounders and the competing risk of death, female sex was not statistically significantly associated with an increased risk of STE (sHR 1.24, 95% CI 0.89-1.74, P=0.210). CHA₂DS₂-VA and CHA₂DS₂-VASc scores had similar predictive performance (AUC 0.603 vs. 0.605, P=0.665). CHA₂DS₂-VA showed worse (ie. negative) reclassification compared to CHA₂DS₂-VASc (net reclassification index -0.088, 95% CI -0.164 to -0.001), with no significant differences in discrimination or net benefit.

CONCLUSIONS: In AF patients treated with OAC, the increased residual risk of STE associated with female sex was non-significant after adjusting for confounders and the competing risk of death. Both scores had similar predictive performance but CHA₂DS₂-VA showed worse reclassification compared to CHA₂DS₂-VASc.

PMID:40755396 | DOI:10.1093/ehjqcco/qcaf075

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Kidney Machine Perfusion Is Associated With Improved Long-Term Graft Survival Mediated by Reduced Delayed Graft Function: A Mate-Kidney Analysis

Artif Organs. 2025 Aug 4. doi: 10.1111/aor.15066. Online ahead of print.

ABSTRACT

BACKGROUND: Kidney machine perfusion (MP) prevents delayed graft function (DGF). Whether this benefit translates into improved long-term graft survival (LGS) remains uncertain. We evaluated the association between MP and LGS and its potential mediation by DGF.

METHODS: UNOS analysis of adult deceased donor kidney transplant recipients (KTRs) from January 2010 to June 2019. We selected KTRs with cold ischemia time (CIT) > 12 h and on tacrolimus maintenance. We included KTRs from dual-kidney donors and compared outcomes where one mate kidney received MP and the other did not. The primary endpoint was all-cause graft failure (GF) analyzed using a stratified multivariable Cox proportional hazards model. We assessed the association of MP and DGF with conditional logistic regression. We evaluated the mediation effect of DGF by combining the predictor and outcome models and bootstrapping with 1000 iterations to calculate 95% confidence intervals (CI).

RESULTS: We included 2355 mate-kidney pairs with 5.8 years (IQR 4-8) median follow-up. MP was associated with lower GF risk (aHR 0.86, 95% CI 0.75-0.98) and DGF odds (aOR 0.41, 95% CI 0.34-0.51) than no MP. DGF fully mediated the association between MP and GF, as the effect was no longer statistically significant after adjusting for DGF (aHR 0.89, 95% CI 0.78-1.03). DGF explained 76.8% of the association between MP and GF.

CONCLUSIONS: In mate-kidney pairs with discordant MP use and CIT > 12 h, MP was associated with decreased GF risk, mediated by decreased DGF likelihood. MP both mate kidneys with CIT > 12 h should be considered to potentially improve LGS.

PMID:40755387 | DOI:10.1111/aor.15066

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The role of gip in carbohydrate metabolism: Implications in the development of therapies for T2DM, a narrative review

Histol Histopathol. 2025 Jul 15:18967. doi: 10.14670/HH-18-967. Online ahead of print.

ABSTRACT

INTRODUCTION: For the last three decades, bariatric/metabolic surgeries have highlighted the relevance of certain gastrointestinal hormones in controlling and regulating glucose metabolism. The incretins have been a significant focus in developing therapies against Type 2 Diabetes Mellitus (T2DM). Glucagon-like peptide-1 (GLP-1) has been a primary focus in this field, leading to the development of analogues with high therapeutic potential and efficiency, such as semaglutide. However, recently another incretin, glucose-dependent insulinotropic polypeptide (GIP), has become a key target in T2DM drug development due to its complex pleiotropic effects, which include modulating insulin/glucagon secretion, acting on adipose tissue, and regulating appetite. The description of GIP properties as dual can be ambiguous, as this may refer either to its capacity to regulate both insulin and glucagon or to its distinct actions at the central versus peripheral level. Connecting this multifaceted activity was the rationale for developing combined GIP/GLP-1 analogues, like tirzepatide, and has culminated in triple-receptor agonists such as retratutide, which also engages the glucagon receptor (LY3437943). These multi-agonists potentially enhance the therapeutic potential of GLP-1 analogues.

COMMENTARIES: This review covers GIP physiology, its role within the context of T2DM, and the properties of GIP analogues, which represent a new line of drugs against T2DM. This field includes not only GIP analogues, since some are dual or triple agonists that also target GLP-1. We aim to elucidate the future perspectives offered by the use of these drugs.

PMID:40755350 | DOI:10.14670/HH-18-967

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Nevin Manimala Statistics

Assessment of the status of DNA mismatch repair proteins by immunohistochemistry. Proposal for evaluation with two antibodies

Pol J Pathol. 2025;76(1):54-58. doi: 10.5114/pjp.2025.148390.

ABSTRACT

Determining the status of DNA mismatch repair (MMR) proteins is crucial for patients because they may respond differently to specific treatments and have a better prognosis. We proposed a panel with only 2 antibodies to determine the status of the MMR proteins, improving costs, workload, and delivery of results. Patients with adenocarcinoma and MMR determination were reclassified using only the evaluation of PMS2 and MSH6. The diagnostic performance of the 2-antibody test (proposed panel) and 4-antibody (traditional panel) test was compared against the polymerase chain reaction study (reference standard). A total of 202 cases were identified. The predominant histological type was adenocarcinoma not otherwise specified, the predominant histological grade was 2, and 60.9% of the cases were found in clinical stage II. When comparing the diagnostic performance of the traditional panel of 4 antibodies against a panel of 2 antibodies, no statistically significant differences were found (sensitivity 95.35% vs. 90.7%; specificity 98.74% vs. 98.11%; positive predictive value 95.35% vs. 92.86%; negative predictive value 98.74% vs. 97.50%; area under the curve 0.970 vs. 0.944; p = 0.419).Analysis of MMR status determination with only 2 antibodies demonstrates that it is as effective as using 4 antibodies.

PMID:40755331 | DOI:10.5114/pjp.2025.148390

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Immunohistochemical expression and association of hypoxia-inducible factor 1a and carbonic anhydrase IX in colorectal cancer

Pol J Pathol. 2025;76(1):16-24. doi: 10.5114/pjp.2025.149408.

ABSTRACT

The presented work focuses on hypoxia-inducible factor 1a (HIF-1a) and carbonic anhydrase IX (CA IX) in colorectal cancer (CRC). The HIF-1a protein shows increased expression due to hypoxia, resulting in up-regulation of CA IX, which is involved in the survival of hypoxic cancer cells in the tumour microenvironment, with overexpression in various types of carcinomas. HIF-1a and CA IX immunohistochemical analysis was performed on 111 CRC samples. The primary goal was to determine the correlation of expression of proteins with clinical-morphological parameters and mutual correlation of the proteins in question. The HIF-1a expression was detected in 72.1% of CRC samples with exclusive nuclear localisation. The immunoreaction intensity was predominantly strong. Carbonic anhydrase IX protein was expressed in 75.7% of cases. The membrane positivity and strong immunoreaction intensity were mainly noticed. No statistically significant correlation between the expression of studied proteins and clinical-morphological parameters was confirmed. However, the results proved a statistically significant correlation in mutual co-localisation of given proteins. Despite contradictory scientific data, our findings suggest a mutual correlation between HIF-1a and CA IX in CRC. The presented hypothesis that their overexpression may represent a potential new therapeutic target in colorectal carcinogenesis might unveil novel strategies in disease development.

PMID:40755327 | DOI:10.5114/pjp.2025.149408

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Expression of C-terminal tensin-like in breast carcinoma and its correlation with known prognostic factors

Pol J Pathol. 2025;76(1):10-15. doi: 10.5114/pjp.2025.149282.

ABSTRACT

C-terminal tensin-like (Cten) is a marker for poorly differentiated breast cancer. We evaluated the immunohistochemical expression of Cten in invasive breast carcinoma in our population and correlated it with known histopathologic prognostic variables. Fifty-seven specimens of modified radical mastectomy diagnosed as invasive ductal carcinoma were collected. The histopathologic findings were noted independent of the result of Cten. According to the results of Cten immunohistochemistry, the tumors were categorized as negative/mild, moderate, or high expression and were statistically corelated with histologic findings. In our study, 47 (82.5%) cases showed negative/mild expression, 2 (3.5%) cases showed moderate staining, and 8 (14%) cases showed strong expression of Cten. Positive Cten was present in pT4 stage tumors. Similarly, grade III tumor showed moderate expression in 2 (3.5%) cases and strong staining in 8 (14%) cases. Posi-tive expression of Cten was observed in cases with lymphovascular invasion (LVI) and high axillary lymph nodal involvement (N3). All these poor prognostic factors were significantly associated with moderate to high expression of Cten. We found that tumor size and extent, histologic grade, LVI, and lymph node status were significantly associated with Cten expression. C-terminal tensin-like can be used as marker of poor prognosis in breast carcinoma.

PMID:40755326 | DOI:10.5114/pjp.2025.149282

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Does SOX-2 expression have a prognostic value in triple-negative breast cancer?

Pol J Pathol. 2025;76(1):1-9. doi: 10.5114/pjp.2025.149426.

ABSTRACT

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. At the cell of origin level, cancer stem cells (CSC) are the tumour initiators in breast cancer. SRY-box transcription factor 2 (SOX-2) is a CSC marker that plays a role in tumourigenesis. The objective of this study was to evaluate the association of SOX-2 expression with histopathological parameters and clinical outcomes in TNBC patients. The study included 95 TNBC cases. An in vitro diagnostic SOX-2 antibody was applied to the tumoural slides in a validated automated stainer. The expression of SOX-2 was defined as a SOX-2 H-score ≥ 1. The expression of SOX-2 was observed in 29 cases (30.5%). At a median follow-up of 76 months, SOX-2 expression was not associated with overall or disease-free survival. R-based statistical analysis determined a SOX-2 H-score cut-off of 2. Although the overall and disease-free survival rates of cases with an H-score ≥ 3 were lower than the others, the differences were not statistically significant. The percentage of SOX-2 staining is typically low, as only 1% of tumour cells exhibit CSC characteristics. In conclusion, the prognostic significance of SOX-2 could become clear in a larger group of TNBC patients using standardized methodologies.

PMID:40755325 | DOI:10.5114/pjp.2025.149426

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Examining the Correlation Between Out-On-Pass Privileges and Post-Discharge Urine Drug Test Outcomes in an Addiction Rehabilitation Center in Qatar

Subst Use Addctn J. 2025 Aug 4:29767342251357089. doi: 10.1177/29767342251357089. Online ahead of print.

ABSTRACT

BACKGROUND: Substance use disorder (SUD) is a chronic and recurrent condition posing a significant health burden. The integration of out-on-pass (OOP) or day leave privileges during inpatient rehabilitation has been theorized to support recovery by enhancing social reintegration and preparing patients for discharge. However, evidence on the impact of inpatient OOP on post-discharge relapse rates is scant. This study investigates the effect of OOP during inpatient treatment and relapse outcomes.

METHODS: A retrospective cohort design was used to analyze data from 72 patients discharged from the Umm Salal Treatment and Rehabilitation Center in 2023, focusing on OOP during rehabilitation and urine drug test results during aftercare. Key variables included OOP frequency, comorbid personality disorders, forensic history, and relapse indicators. Statistical evaluation utilized logistic regression, chi-squared tests (Fisher’s exact test where appropriate), and survival analysis to identify predictors of relapse, adjusted for potential confounders.

RESULTS: Of the participants, 28 (38.9%) were granted OOP during inpatient treatment, while 44 (61.1%) were not. Relapse, defined by a positive urine drug screening post-discharge, occurred in 29 patients (40.3%). The median time-to-relapse was 28 days, with a longer duration observed among those granted OOP. Specifically, during the 26-week study period, 25% of patients with OOP relapsed compared to 50% of those without OOP (statistically significant difference; P = .04892). Survival analysis revealed that time-to-relapse was substantially longer for patients who were granted OOP compared to those who were not (P = .034). Furthermore, the granting of OOP during inpatient treatment of SUD was associated with a 73.2% reduction in relapse hazards ratio (P = .00876).

CONCLUSION: This study highlights the potential of OOP as a therapeutic strategy and tool to support sustained recovery in patients with SUD. While relapse remains a significant challenge, OOP may contribute to extended abstinence periods and reduced relapse rates.

PMID:40755318 | DOI:10.1177/29767342251357089

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Prophylactic Effect of Prefrontal Alternating Current Stimulation on Postoperative Sleep Disturbance in Patients Undergoing Gynecological Laparoscope: A Randomized, Double-Blind, Sham-Controlled Trial

CNS Neurosci Ther. 2025 Aug;31(8):e70529. doi: 10.1111/cns.70529.

ABSTRACT

AIMS: Postoperative sleep disturbance (PSD) is a common complication following surgical procedures. We aimed to evaluate the effect of prefrontal transcranial alternating current stimulation (tACS) in preventing PSD among patients undergoing gynecological laparoscopic surgery.

METHODS: A total of 176 eligible patients, aged 18-65 years, with ASA Class I to III, and scheduled for gynecological laparoscopic surgery, were randomly allocated to receive either a single 20-min session of prefrontal tACS (2 mA, 7 Hz) or sham stimulation immediately after extubation. The primary outcome was the occurrence of PSD on postoperative day (POD) 1.

RESULTS: The intention-to-treat analysis showed a statistically significant reduction in PSD incidence on POD 1 in the active tACS group (23.9%) compared to the sham group (43.2%), with an odds ratio of 0.41 (95% CI, 0.22-0.79; p = 0.007). Additionally, patients in the active tACS group reported significantly lower anxiety scores on POD 1 (p < 0.001), while depression scores were comparable between the groups. The active tACS group also reported significantly lower pain scores, both on PODs 1 (movement: p = 0.002; rest: p < 0.001) and 3 (movement: p = 0.028; rest: p < 0.001).

CONCLUSIONS: A single session of prefrontal tACS significantly reduces the incidence of PSD on POD 1 and may offer additional benefits in reducing early postoperative anxiety and pain, with a favorable safety and tolerability profile.

TRIAL REGISTRATION: China Clinical Trial Registration Center: ChiCTR2300078658.

PMID:40755300 | DOI:10.1111/cns.70529