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Immunohistochemical Expression of Hypoxia-Inducible Factor-1 Alpha in Oral Squamous Cell Carcinoma

Cureus. 2025 May 22;17(5):e84597. doi: 10.7759/cureus.84597. eCollection 2025 May.

ABSTRACT

Oral squamous cell carcinoma (OSCC), a malignant neoplasm of the oral cavity, is commonly observed in the northeastern region of India, likely due to dietary habits, the prevalence of infections, and possibly genetic predisposition. Hypoxia plays a crucial role in regulating tumor proliferation and survival. In the absence of sufficient oxygen, several mechanisms and factors become instrumental in driving tumorigenesis. One such factor is hypoxia-inducible factor-1 alpha (HIF-1α), a key transcription factor from the inducible factor family that regulates gene expression in response to reduced cellular oxygen levels. Despite its significance, studies investigating HIF-1α overexpression in OSCC remain limited, and only a few have explored its correlation with clinical and pathological parameters. This study involved a retrospective analysis of histopathologically confirmed OSCC cases from resected oral specimens collected over a four-year period (2020-2024). HIF-1α overexpression was evaluated in relation to clinical variables such as age and sex and pathological features including histological grade, stage, depth of invasion (DOI), tumor size, lymphovascular invasion, perineural invasion, and worst pattern of invasion. A statistically significant association was observed between HIF-1α overexpression and both higher tumor stage and greater DOI, supporting its link to more aggressive disease behavior. Given the complexity of OSCC, identifying markers that may serve as therapeutic targets is of critical importance. HIF-1α emerges as one such marker – its presence not only indicates a more aggressive tumor phenotype but also suggests potential for future targeted therapies.

PMID:40546546 | PMC:PMC12181812 | DOI:10.7759/cureus.84597

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Area deprivation index and breast cancer outcomes among patients in Western New York

Breast Cancer Res Treat. 2025 Jun 22. doi: 10.1007/s10549-025-07733-3. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies have shown that residing in regions with high area deprivation index (ADI) is associated with worse outcomes. We evaluated associations between ADI and breast cancer (BC) outcomes among patients in Western New York (WNY), a region that includes multiple underserved areas.

METHODS: This retrospective, single-institution study analyzed data from 404 BC patients diagnosed between 2014 and 2018. Demographic and clinicopathological data were abstracted. Data were compared between high (≥ 60) and low (< 60) ADI groups, reflective of high and low levels of socioeconomic disadvantage, respectively. The primary objective was overall survival (OS) by ADI. Secondary objectives included assessment of recurrence free survival (RFS) or time to next treatment (TNT) by ADI and frequency of germline and somatic testing.

RESULTS: Over half of the patients (59%) resided in ADI ≥ 60. 77% of patients had stage I-III BC and 23% had de novo metastatic BC. Patients in ADI ≥ 60 had a lower 5-year OS rate (73%) than those in ADI < 60 (84%) (95%CI: 67.5-79.7, P = 0.05). In multivariable analysis, similar trend was observed but was not statistically significant (HR 1.56, 95%CI: 0.98-2.46, P = 0.058). There were no differences in TNT or RFS by ADI. Germline testing was performed less frequently (33%) in ADI ≥ 60 than ADI < 60 group (45%) (P = 0.04) for patients with stage I-III BC, while no difference observed for stage IV patients. Finally, prevalence of somatic mutations in TP53, PIK3CA, and ESR1 were higher in ADI ≥ 60.

CONCLUSIONS: We observed a trend towards worse OS in areas with high ADI, though not statistically significant. The incidence of germline testing was lower in high ADI compared to low ADI regions.

PMID:40544410 | DOI:10.1007/s10549-025-07733-3

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Effect of thrombus composition on first pass recanalization and bleeding in acute ischemic stroke patients : Association between thrombus composition and first-pass effect

J Thromb Thrombolysis. 2025 Jun 22. doi: 10.1007/s11239-025-03133-y. Online ahead of print.

ABSTRACT

In acute ischemic stroke, the first-pass effect, the occurrence of complete reperfusion after a single pass during endovascular therapy (EVT), is linked to favorable clinical outcomes. This study aimed to investigate the association between thrombus composition and first-pass recanalization (FPR), as well as symptomatic intracranial hemorrhage (sICH), in AIS patients undergoing mechanical thrombectomy (MT). We retrospectively analyzed thrombi retrieved from 172 patients treated with MT. Clots were classified as RBC-rich or platelet-rich. FPR was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b or 3 after a single device pass. Associations with FPR and hemorrhagic outcomes were assessed. A total of 172 patients (91 women, 81 men; mean age 71 years) who were treated with mechanical thrombectomy were included in the study. First-pass recanalization (FPR) was achieved in 55.2% of the patients (95/172). There was no statistically significant relationship between clot composition and FPR (p = 0.991). The rate of intracranial hemorrhage (ICH) was 15.8% in the RBC-dominant group and 1.7% in the fibrin/platelet-dominant group. A statistically significant association was found between clot composition and ICH (p = 0.005), whereas no significant relationship was observed between clot composition and symptomatic intracranial hemorrhage (sICH) (p = 0.975). Successful FPR was associated with a lower rate of sICH (p = 0.003). The percentage of RBCs in clot composition was positively correlated with the presence of the dense artery sign. Gender was not significantly associated with clot composition (p = 0.455), and neither gender nor age showed a significant relationship with FPR (p = 0.316 and p = 0.470, respectively). These findings indicate that while clot composition does not significantly affect the success of FPR, it is significantly associated with the risk of intracranial hemorrhage. This underscores the potential clinical relevance of clot histology in predicting post-thrombectomy outcomes, beyond the well-established importance of FPR itself. Future studies with larger and more diverse patient cohorts are warranted to further elucidate these associations and optimize treatment strategies.

PMID:40544390 | DOI:10.1007/s11239-025-03133-y

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Eptifibatide as an adjuvant therapy to thrombolysis versus thrombolysis alone in stroke management: a systematic review and meta-analysis of randomized controlled trials

J Thromb Thrombolysis. 2025 Jun 22. doi: 10.1007/s11239-025-03131-0. Online ahead of print.

ABSTRACT

Stroke is a leading cause of death and disability. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the primary treatment for acute ischemic stroke (AIS), but outcomes remain suboptimal. Eptifibatide, a glycoprotein IIb/IIIa inhibitor, has been explored as an adjunct to enhance reperfusion. This systematic review and meta-analysis assesses its effectiveness and safety compared to rt-PA alone. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). Primary outcomes included 90-day functional independence (modified Rankin Scale, mRS 0-1), mortality, and symptomatic intracranial hemorrhage (sICH). Meta-analyses used random-effects models to calculate Odds Ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed with I². We included 988 patients from four RCTs. Eptifibatide was administered to 566 patients (57.3%). Adjuvant therapy did not significantly improved mRS 0-1 rates at 90 days (OR 1.12, 95% CI 0.60-2.09, p = 0.72, I²=74%) and did not reduce mortality (OR 1.55, 95% CI 0.92-2.61, p = 0.099, I²=0%). sICH was not statistically significantly different between the groups (OR 0.38, 95% CI 0.09-1.65, p = 0.196, I²=56%). Eptifibatide as an adjunct to rt-PA does not significantly impact functional independence, mortality, or sICH risk in AIS. Larger studies are needed to clarify its potential benefits and risks.

PMID:40544389 | DOI:10.1007/s11239-025-03131-0

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Safety and efficacy of routine anticoagulation after primary PCI in STEMI: a systematic review and meta-analysis

J Thromb Thrombolysis. 2025 Jun 22. doi: 10.1007/s11239-025-03130-1. Online ahead of print.

ABSTRACT

Percutaneous Coronary Intervention (PCI) is a widely used minimally invasive procedure that restores blood flow to the coronary artery, improving survival in STEMI patients. Despite its widespread application in clinical settings, the necessity and efficacy of postprocedural anticoagulation (PPAC) remain contentious. Our study aims to assess the outcomes of PPAC in STEMI patients who have undergone PCI. A comprehensive search of Embase, PubMed, and Clinicaltrials was conducted to identify randomized controlled trials (RCTs) comparing the clinical outcomes between PPAC and control (placebo or no PPAC) for STEMI after primary PCI. Statistical analyses were performed using RevMan version 5.4.1, employing a random-effects model to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Risk of Bias Assessment of the articles was assessed using RoB 2.0 software by the Cochrane Collaboration. A total of 5 RCTs comprising 13,586 patients were included, of which 6,829 patients (50.26%) received PPAC. Compared to the non-PPAC group, PPAC did not significantly reduce all-cause mortality (OR 1.08; 95% CI 0.84-1.39; P = 0.54, I2 = 0%), cardiovascular mortality (OR 1.08; 95% CI 0.83-1.39; P = 0.57, I2 = 0%), and MACE (major adverse cardiovascular events) (OR 1.13; 95% CI 0.92-1.37; P = 0.25, I2 = 22%). Additionally, the odds of stent thrombosis (OR 1.07; 95% CI 0.77-1.47; P = 0.69, I2 = 0%) and stroke (OR 1.50; 95% CI 0.49-4.57; P = 0.48, I2 = 58%) did not differ significantly between the groups. However, PPAC was associated with higher odds of bleeding (OR 1.78; 95% CI 1.07-2.97; P = 0.03, I2 = 94%). This meta-analysis reveals no significant differences in the odds of all-cause mortality, cardiovascular mortality, stent thrombosis, and stroke between PPAC and control following PCI for the management of STEMI. However, PPAC was associated with higher odds of bleeding. Further randomized controlled trials are warranted to corroborate these findings.

PMID:40544386 | DOI:10.1007/s11239-025-03130-1

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Recurrence rate and risk factors of recurrent anaphylaxis: A ten-year retrospective cohort study

Asian Pac J Allergy Immunol. 2025 Jun 22. doi: 10.12932/AP-130325-2047. Online ahead of print.

ABSTRACT

BACKGROUND: Few studies have investigated the risk factors for recurrent anaphylaxis. Identifying these factors may help patients implement preventive measures.

OBJECTIVE: To determine the rate and risk factors for recurrent anaphylaxis, assess the time to recurrence, and compare the characteristics, triggers, and clinical manifestations between recurrent and non-recurrent cases.

METHODS: A retrospective cohort study was conducted at Naresuan University Hospital from March 2011 to February 2021, using medical records of patients with ICD-10-confirmed anaphylaxis. Risk factors for recurrence were analyzed using Cox proportional hazards regression model.

RESULTS: A total of 439 anaphylactic episodes were identified in 381 patients (49 children, 332 adults). Of these, 42 patients (11.2%) experienced 58 recurrent episodes (7/49 [14.3%] children, 35/332 [10.6%] adults). Food and medications were the most and second most common triggers. The median time to recurrence was 9.9 months (IQR: 3.1-18.8), while the median follow-up duration for non-recurrent cases was 41.8 months (IQR: 23.8-61.8). The recurrent anaphylaxis rate was 4.1 events per 100 person-years. Statistically significant risk factors included a history of food, a history of insect, a history of drug allergies, chest discomfort, and severe anaphylaxis (HR [95%CI]: 3.31 [1.50-7.29], p = 0.003; 4.96 [1.47-16.82], p = 0.010; 5.87 [2.64-13.07], p < 0.001; 2.43 [1.19-4.99], p = 0.015; and 2.29 [1.07-4.88], p = 0.033, respectively). Conversely, palpitations were associated with a lower risk of recurrence (HR 0.11 [0.01-0.86], p = 0.036).

CONCLUSIONS: Identifying risk factors in anaphylaxis patients enhances medical care and aids in preventing recurrence.

PMID:40544373 | DOI:10.12932/AP-130325-2047

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Ultrasonographic diagnosis of caudoproximal humeral stress fracture in thoroughbred racehorses

Equine Vet J. 2025 Jun 22. doi: 10.1111/evj.14546. Online ahead of print.

ABSTRACT

BACKGROUND: Humeral stress fractures in racehorses can progress to catastrophic fracture if unrecognised. Scintigraphy is the gold standard diagnostic technique but is limited by accessibility and cost. It was hypothesised that ultrasonography could be used to visualise caudoproximal humeral stress fractures.

OBJECTIVES: To determine the utility of ultrasonography to identify caudoproximal humeral stress fractures in racehorses.

STUDY DESIGN: Clinical case series.

METHODS: Seven racehorses that had a clinical history consistent with the presence of a humeral stress fracture were examined using humeral ultrasonography and radiography with or without scintigraphy from June 2013 to June 2021. Clinical and imaging findings, outcomes and descriptive statistics are reported.

RESULTS: Seven Thoroughbred racehorses aged 2-4 years had a history of acute onset of a severe lameness, with four returning to training 3-12 months after layup for an unrelated reason. Nine of 10 humeral stress fractures (2 bilateral, 3 left, 2 right) were identified with ultrasonography. Ultrasonographic abnormalities included a step defect (5 humeri, 5 horses), periosteal callus/roughening (7 humeri, 4 horses) and/or an abnormally convex contour of the caudal aspect of the humeral neck (6 humeri, 5 horses). Radiographs revealed periosteal (8 humeri, 6 horses) and/or endosteal (6 humeri, 4 horses) proliferation adjacent to the caudoproximal aspect of the humeral cortex. Scintigraphy of five horses identified increased radiopharmaceutical uptake in the caudoproximal aspect of seven humeri. Serial recheck radiography and ultrasonography (5 horses) revealed bone remodelling. Horses were returned to intended use as racehorses (4) riding horses (2) or were retired (1).

MAIN LIMITATIONS: Small case series in only Thoroughbred racehorses with a clinical indication of possible humeral stress fracture. Ultrasonographic examination was limited to the caudoproximal aspect of the humerus. Not all cases underwent all imaging modalities.

CONCLUSIONS: Ultrasonography is useful for caudoproximal humeral stress fracture detection and can be used to monitor healing.

PMID:40544361 | DOI:10.1111/evj.14546

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Risk factors for mortality and re-admission of children with hematological malignancies to the intensive care unit due to sepsis

Leuk Lymphoma. 2025 Jun 22:1-11. doi: 10.1080/10428194.2025.2521650. Online ahead of print.

ABSTRACT

Children with hematological malignancies, are often hospitalized in pediatric intensive care units (PICU) for sepsis with high mortality and re-admission rates. Risk factors for both are inconsistent. We reviewed data of 190 admissions of children with hematological malignancies to PICU for sepsis. Survival rate (SR) was 85%. Mortality risk factors were: non-complete remission (p < 0.01) and status post-stem cell transplantation (p = 0.02), and best predictors were inotropic drugs (p < 0.01), and Pediatric logistic organ dysfunction-2 (p < 0.01) scores. Patients with viremia had the lowest SR (50%, 0.001). One-quarter of the children were re-admitted due to sepsis, and risk factors were: High-risk (HR) hematological malignancy (p < 0.01) and lack of central venous line (CVL) removal (p < 0.01). Sepsis remains a major cause of death in children with hematological malignancies, and re-admissions are common. Our findings support the recommendation of removing CVL during sepsis and highlight those at the highest risk for sepsis to consider individualized anti-infectious prophylaxis.

PMID:40544355 | DOI:10.1080/10428194.2025.2521650

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Pathogenic Features, Experimental Models, and Molecular Tools of Human Fungal Pathogens: Who’s on WHO’s Radar?

ACS Infect Dis. 2025 Jun 22. doi: 10.1021/acsinfecdis.5c00081. Online ahead of print.

ABSTRACT

With the prevalence of immunocompromising infections, the emergence of new pathogenic species, rising multidrug resistance, hospital outbreaks, and high mortality rates, once neglected fungal pathogens are now taking over the global healthcare arena, necessitating breakthroughs in diagnostics and therapeutics. The World Health Organization (WHO) recently published a list of critical and high-priority fungal pathogens, underlining the need and significance of broadening the focus to include fungal infections, among other life-threatening infectious diseases. This is also a wake-up call to the scientific community to facilitate a better understanding of the emergence, life cycle, spread, virulence, and drug resistance mechanisms in fungal pathogens. The strategies that fungal pathogens adopt to escape the immune system, establish an infection, and combat antifungal drugs are diverse. In this review, we focus on the pathogenic lifestyles of WHO critical and high priority fungal pathogens, with a brief introduction to the epidemiology and infection statistics.

PMID:40544349 | DOI:10.1021/acsinfecdis.5c00081

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Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer’s disease

Alzheimers Dement. 2025 Jun;21(6):e70224. doi: 10.1002/alz.70224.

ABSTRACT

INTRODUCTION: In EMERGE (NCT02484547), participants receiving aducanumab had significantly less progression versus placebo on all prespecified clinical endpoints at week 78. Here, we explicate the clinical meaningfulness of these treatment effects by analyzing item-level data and the persistence of treatment benefit.

METHODS: Participants with early Alzheimer’s disease (AD) were stratified by apolipoprotein E (APOE) ε4 status and randomized (1:1:1) to receive low- or high-dose aducanumab, or placebo. Prespecified principal component analyses (PCAs) per the Statistical Analysis Plan were followed by post hoc examination of individual domains/items across all five clinical endpoints. Progression analysis assessed reduction in clinical decline.

RESULTS: High-dose aducanumab demonstrated clinically meaningful slowing of progression across clinical endpoints measuring cognition, daily function, and behavioral symptoms. Delay of progression over 18 months was consistent across measures; treatment effects increased over time.

DISCUSSION: Across multiple analyses aducanumab slowed cognitive decline, prolonged functional independence, and attenuated behavioral symptoms in participants with early AD. These outcomes comprise the elements of a clinically meaningful response to treatment.

HIGHLIGHTS: Endpoints in EMERGE assessed different aspects of cognition, daily function, and behavioral symptoms. Treatment benefits were observed across subdomains on all five clinical endpoints. Aducanumab meaningfully slowed disease progression in participants with early AD.

PMID:40545559 | DOI:10.1002/alz.70224