Nevin Manimala

Head Neck Pathol. 2025 Feb 7;19(1):20. doi: 10.1007/s12105-025-01753-7.

ABSTRACT

PURPOSE: Extranodal extension (ENE) increases the risk of recurrence and death in head and neck squamous cell carcinoma (HNSCC) patients and is an indication for treatment escalation. Histopathology forms the mainstay of diagnosing ENE. There is substantial variation in the diagnosis of ENE and related terminology. Harmonising the diagnostic criteria for ENE was identified as a priority by the Head and Neck Consensus Language for Ease of Reproducibility (HN CLEAR) Steering Committee and its global stakeholders.

METHODS: An international working group including 16 head and neck pathologists from eight countries across five continents evaluated whole slide images of haematoxylin and eosin-stained sections depicting potential diagnostic problems through nine virtual meetings to develop consensus guidelines.

RESULTS: ENE should be diagnosed only when viable carcinoma extends through the primary lymph node (LN) capsule and directly interacts with the extranodal host environment with or without desmoplastic stromal response. Identifying the original LN capsule and reconstruction of its contour can assist in the detection and assessment of ENE. The term matting is recommended for confluence of two or more nodes due to histologically identifiable tumour extending from one LN to another. Matting constitutes major form of ENE. On the other hand, the terms fusion/adhesion/confluence/conglomeration and other synonyms of adhesion should be limited to confluence due to fibrosis or inflammation without histologically identifiable tumour between involved lymph nodes. Tumour extension along narrow needle tracks or spillage of cyst contents following an FNA do not constitute ENE.

CONCLUSIONS: The consensus recommendations encompassing the definition of ENE, macroscopic and histologic examination of lymph nodes (LN) and practical guidelines for handling challenging cases are provided.

PMID:39918634 | DOI:10.1007/s12105-025-01753-7

Dysphagia. 2025 Feb 7. doi: 10.1007/s00455-025-10804-8. Online ahead of print.

ABSTRACT

Post-stroke dysphagia is a common and debilitating complication affecting millions of people worldwide, often leading to malnutrition, pneumonia, and reduced quality of life. This study, an interim analysis of the Korean Study Cohort for Functional and Rehabilitation, aimed to identify long-term changes and predictive factors associated with post-stroke dysphagia at 3 years after stroke. A total of 4735 patients with acute first-ever stroke, including both ischemic and hemorrhagic subgroups, were followed, and dysphagia was assessed using the ASHA-NOMS scale. All the patients were then followed up for up to 36 months. The results showed significant improvements in dysphagia up to 12 months after stroke in the total and hemorrhagic stroke group, and the decline in swallowing function after 24 months in the total stroke and ischemic stroke groups was a novel finding. The hemorrhagic stroke group showed worsening dysphagia after 30 months. It is unclear whether patients who experienced worsening of swallowing function had other conditions, including new strokes, that might have contributed to this decline. Male gender, age at stroke, K-FAST at 7 days, ASHA-NOMS scale, mRS score at 3 months, and early comprehensive rehabilitation were identified as predictors of a decrease in the ASHA-NOMS score after 24 months. Additionally, the K-MBI score at 3 months post-stroke was found to be a significant factor influencing long-term improvements in swallowing function. These findings suggest that patients should be closely monitored for dysphagia beyond 24 months after stroke onset, as swallowing function may decline over time. During follow-up, it is essential to carefully consider the multiple factors associated with this decline.

PMID:39918632 | DOI:10.1007/s00455-025-10804-8

Eur J Trauma Emerg Surg. 2025 Feb 7;51(1):99. doi: 10.1007/s00068-024-02723-4.

ABSTRACT

BACKGROUND: Epidural hematomas (EDH) are associated with a high rate of mortality and morbidity. Good clinical outcome depends on initial Glasgow Coma Scale (GCS), pupillary abnormalities, hematoma volume, age and time to surgery. The latter is mostly influenced by distance to the next level-1-trauma center.

OBJECTIVE: The aim of this study was to evaluate the surgical care and the influence of a potential interhospital transport of patients with acute EDH.

MATERIAL & METHODS: A retrospective analysis of data from 2009 to 2020 was carried out. All patients who underwent surgical evacuation of an EDH were included. Time and distance to surgery, pupillary abnormalities, initial GCS, age at surgery, direct or indirect transport, outcome (GOS) and comorbidities were collected. The effect on outcome was analyzed by multivariate analysis.

RESULTS: One hundred and thirty-one patients (106 men, 25 women) with EDH were surgical treated at our department. 54% were transported directly to our hospital. Median time to surgery was 4 h (2-336 h) and mean distance was 50 km (road kilometers). There was no difference in surgical treatment between admission patterns. Secondarily transferred patients have been operated at least as fast than primary hospital admissions (median 10 h vs. 11 h, respectively). Direct or indirect transport of patients had no statistically significant influence on outcome (p = 0.72), like sex (p = 0.33) and time to surgery (p = 0.75).

CONCLUSION: Interhospital transport did not cause a significant delay of surgical treatment and outcome was comparable between direct and indirect transport to specialized neurosurgical care. Direct transport was more common on severe TBI and in patients with pupillary abnormalities, but secondary transport also allowed for adequate care.

PMID:39918624 | DOI:10.1007/s00068-024-02723-4

Addiction. 2025 Feb 6. doi: 10.1111/add.16772. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Mechanisms of varenicline preloading in promoting smoking abstinence have not been evaluated. Based on an extinction of reinforcement framework, we tested the hypothesis that pre-quit reductions in smoking rate mediate the effect of extended preloading on abstinence. We also tested alternative indicators of change in smoking reinforcement, as well as smoking aversion, nausea and abstinence self-efficacy as candidate mediators.

DESIGN, PARTICIPANTS AND INTERVENTION: Randomized, double-blind, placebo-controlled trial (NCT03262662) comparing extended (4-week varenicline) to standard (3 weeks of placebo, 1-week varenicline) preloading, preceding 11 weeks of open-label varenicline, in 320 adults (56% female). The primary outcome was self-reported continuous smoking abstinence during the last 4 weeks of treatment, with cotinine bio-verification at end of treatment (EOT).

SETTING: University at Buffalo, State University of New York, USA (part of the trial was conducted at participants’ homes due to the COVID-19 pandemic).

MEASUREMENTS: Candidate mediators, including smoking rate and subjective effects of smoking (reward, satisfaction, aversion), self-reported craving, withdrawal, nausea and abstinence self-efficacy, were assessed daily during the pre-quit period with ecological momentary assessment. At two laboratory visits participants completed a choice task to assess smoking reinforcement.

FINDINGS: There was a statistically significant indirect effect of extended preloading on greater EOT abstinence rates through pre-quit declines in smoking rate [a*b = 0.284, 95% confidence interval (0.072,0.616)] and percent reduction in smoking across the pre-quit period [a*b = 0.225, (0.080,0.437)]. There were also statistically significant indirect effects through reductions in pre-quit craving [a*b = 0.150, (0.01,0.420)] and increases in pre-quit self-efficacy [a*b = 0.157, (0.038,0.375)]. Sex-specific analyses suggested these mediated effects were consistently limited to females. No other candidate mediators yielded statistically significant indirect effects.

CONCLUSIONS: Extended varenicline preloading mediated smoking abstinence through reduced pre-quit smoking and craving among female smokers seeking to quit; increased pre-quit abstinence self-efficacy was also a significant mediator.

PMID:39915904 | DOI:10.1111/add.16772

Stat Med. 2025 Feb 28;44(5):e70001. doi: 10.1002/sim.70001.

ABSTRACT

A surrogate marker is a biological measurement in a clinical trial that aims to replace the primary outcome in evaluating the treatment effect, and can be measured earlier, with less cost, or with less patient burden. In theory, once a surrogate is validated, future studies can evaluate treatment efficacy using only the surrogate. While there are many methods to evaluate a surrogate, these methods rarely account for heterogeneity in surrogacy, that is, when a surrogate is valid for only certain people. We propose a general framework for the assessment of complex heterogeneity in the strength of a surrogate marker, as well as corresponding parametric and semiparametric estimation procedures. Our framework defines the proportion of the treatment effect on the primary outcome that is explained by the treatment effect on the surrogate, as a function of multiple baseline covariates, $\text{W}$ . We additionally propose a formal test of heterogeneity and a method to identify a region of the covariate space where the surrogate is sufficiently strong. We examine the performance of our methods via a simulation study featuring varying levels of heterogeneity and use our methods to examine potential heterogeneity in the strength of a surrogate in an AIDS clinical trial.

PMID:39915898 | DOI:10.1002/sim.70001

Vet Surg. 2025 Feb 6. doi: 10.1111/vsu.14222. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the occurrence, degree, and risk factors associated with arthroscopic stifle joint synovitis in dogs with cranial cruciate ligament (CCL) disease.

STUDY DESIGN: Retrospective, observational study.

SAMPLE POPULATION: Canine CCL disease (n = 163) from 149 dogs and their arthroscopic video recordings.

METHODS: Arthroscopic video recordings were reviewed. A synovitis severity (0-5) and a modified Outerbridge cartilage classification system score were assigned, along with recording the presence or absence of a medial meniscal bucket handle tear. Medical records were reviewed for age, sex, limb, and duration of clinical signs. Univariate analyses were performed via a Fisher’s exact test for categorical independent variables, and ordered logistic regression was used for continuous variables. Multivariable ordered logistic regression considered independent variables with a p-value <.2 on univariate analyses. p-value <.05 was considered statistically significant.

RESULTS: Synovitis was identified in 100% of the stifles examined. The most frequent synovitis severity score was 3/5. Univariate analysis showed a significant association between synovitis severity score and bodyweight (p = .005), median cartilage score (p = .002), and being female (p = .032). On multivariable analysis, the synovitis severity score was significantly associated with median cartilage score (p = .042) and duration of clinical signs (p < .001).

CONCLUSION: Synovitis was arthroscopically always identified in stifles with CCL disease. The severity of synovitis was associated with more progressive damage to the articular cartilage and a longer duration of clinical signs.

CLINICAL SIGNIFICANCE: Earlier intervention in dogs with CCL disease may be warranted to decrease synovitis and progression of osteoarthritis.

PMID:39915894 | DOI:10.1111/vsu.14222

J Health Popul Nutr. 2025 Feb 6;44(1):26. doi: 10.1186/s41043-024-00723-z.

ABSTRACT

BACKGROUND: Caffeine is one of the world’s most frequently consumed central nervous system stimulants. Moderate caffeine intake has beneficial health effects, while increased caffeine intake may have harmful effects in the human body. Existing literature indicated that undergraduates consume caffeine excessively. Till this date, little is known about the consumption pattern of caffeine among Palestinian undergraduates. Therefore, the current study aimed to estimate the percentage of caffeine consumption among Palestinian undergraduates, to assess their caffeine daily intake, and to identify factors associated with unsafe caffeine consumption.

METHODS: A cross-sectional study was conducted in Palestine between March and May 2022. Undergraduates were recruited by random sampling after a personal invitation. Undergraduates aged between 18 and 25 were included in the study, while those who were taking medications, had medical conditions affecting the data collection process, and had incomplete responses were excluded from the study. Caffeine consumption was assessed using a semi-quantitative food frequency questionnaire (FFQ) developed by the research team. The content validity of the FFQ was done by three reviewers. Also, a questionnaire was used to collect data related to sociodemographic characteristics, medical history, lifestyle habits, sleeping quality, physical activity, and psychological status. Data were analyzed through the descriptive statistics and inferential statistics (Chi-square test, Mann-Whitney test, and Kruskal-Wallis H test).

RESULTS: The final analysis included 486 undergraduates with a mean age of 20.1 ± 1.48 years. The majority of the undergraduates were female (65.0%) and single (89.5%). The sample was distributed almost equally between the first (26.3%), second (23.0%), third (22.8%), and fourth (18.7%) academic years, and only 44 undergraduates (9.1%) were in their fifth year. The vast majority of university students (96.5%) consumed caffeinated products, with coffee ranking first place. Nearly half of the participants (32.7%) exceeded the safe levels of caffeine consumption. Males, smokers, poor physical activity, higher Sleep Hygiene Index (SHI) scores, and greater anxiety, stress, and depression scores had significantly higher rates of unsafe caffeine intake than their peers (p < 0.05). The total caffeine consumption was significantly associated with gender, low household income, smoking status, physical activity level, SHI score, as well as anxiety (p < 0.05).

CONCLUSION: Caffeine consumption in the studied sample was significantly high and exceeded the safe levels. The current study revealed that unsafe caffeine consumption was more common among males, smokers, and physically active individuals. Caffeine intake was also linked to poor-quality sleep and higher psychological concerns. Therefore, educational programs are recommended to increase awareness of the adverse effects of high caffeine intake.

PMID:39915865 | DOI:10.1186/s41043-024-00723-z

Alzheimers Res Ther. 2025 Feb 6;17(1):38. doi: 10.1186/s13195-025-01689-8.

ABSTRACT

BACKGROUND: The clinical presentations of early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease are distinct, with EOAD having a more aggressive disease course with greater heterogeneity. Recent publications from the Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) described EOAD as predominantly amnestic, though this phenotypic description was based solely on clinical judgment. To better understand the phenotypic range of EOAD presentation, we applied a neuropsychological data-driven method to subtype the LEADS cohort.

METHODS: Neuropsychological test performance from 169 amyloid-positive EOAD participants were analyzed. Education-corrected normative comparisons were made using a sample of 98 cognitively normal participants. Comparing the relative levels of impairment between each cognitive domain, we applied a cut-off of 1 SD below all other domain scores to indicate a phenotype of “predominant” impairment in a given cognitive domain. Individuals were otherwise considered to have multidomain impairment. Whole-cortex general linear modeling of cortical atrophy was applied as an MRI-based validation of these distinct clinical phenotypes.

RESULTS: We identified 6 phenotypic subtypes of EOAD: Dysexecutive Predominant (22% of sample), Amnestic Predominant (11%), Language Predominant (11%), Visuospatial Predominant (15%), Mixed Amnestic/Dysexecutive Predominant (11%), and Multidomain (30%). These phenotypes did not differ by age, sex, or years of education. The APOE ɛ4 genotype was enriched in the Amnestic Predominant group, who were also rated as least impaired. Cortical thickness analysis validated these clinical phenotypes with dissociations in atrophy patterns observed between the Dysexecutive and Amnestic Predominant groups. In contrast to the heterogeneity observed from our neuropsychological data-driven approach, diagnostic classifications for this same sample based solely on clinical judgment indicated that 82% of individuals were amnestic-predominant, 9% were non-amnestic, 4% met criteria for Posterior Cortical Atrophy, and 5% met criteria for Primary Progressive Aphasia.

CONCLUSION: A neuropsychological data-driven method to phenotype EOAD individuals uncovered a more detailed understanding of the presenting heterogeneity in this atypical AD sample compared to clinical judgment alone. Clinicians and patients may over-report memory dysfunction at the expense of non-memory symptoms. These findings have important implications for diagnostic accuracy and treatment considerations.

PMID:39915859 | DOI:10.1186/s13195-025-01689-8

J Ovarian Res. 2025 Feb 6;18(1):24. doi: 10.1186/s13048-025-01602-9.

ABSTRACT

PURPOSE: To assess whether maternal age influences the pregnancy outcomes after single frozen euploid embryo transfer.

METHODS: This retrospective analysis was conducted on 1037 cycles of single euploid embryo transfer performed at Nanjing Women and Children’s Healthcare Hospital between January 2016 and April 2023. Patients with severe uterine pathologies, immune disorders, or endocrine diseases were excluded. The cycles were categorized into three age groups: <35 years, 35-37 years, and ≥ 38 years. Primary outcomes included live birth rate, clinical pregnancy rate, early pregnancy loss, and miscarriage rate. Data were analyzed using multivariable logistic regression with generalized estimating equations (GEE) to account for confounding factors and restricted cubic splines to visualize the relationship between maternal age and pregnancy outcomes.

RESULTS: Women aged ≥ 38 years demonstrated a significantly diminished live birth rate (41.7%) ,which was lower than that observed in women aged < 35 years (54.5%) and 35-37 years (54.0%), with statistical significance (P < 0.05). Multivariable regression analysis revealed that compared with women aged ≥ 38 years, younger women had reduced risk of miscarriage (aOR = 0.371, 95% CI: 0.139-0.988 for the < 35 years group; aOR = 0.317, 95% CI: 0.106-0.954 for the 35-37 years group) and increased likelihood of live birth (aOR = 2.188, 95% CI: 1.154-4.147 for the < 35 years group; aOR = 2.239, 95% CI: 1.0103-4.548 for the 35-37 years group) after adjusting for relevant confounders. Additionally, the analysis showed that embryos biopsied on day 5 were linked to higher clinical pregnancy rates than those biopsied on day 6, and high-grade blastocysts were associated with superior pregnancy outcomes.

CONCLUSION: Advanced maternal age is associated with a higher miscarriage rate and lower live birth rate following euploid embryo transfer. Despite the exclusion of aneuploidy, age-related factors beyond chromosomal abnormalities appear to impact reproductive outcomes.

PMID:39915851 | DOI:10.1186/s13048-025-01602-9

AIDS Res Ther. 2025 Feb 6;22(1):14. doi: 10.1186/s12981-025-00710-2.

ABSTRACT

AIM: HIV remains one of the major epidemics and public health concerns within low and middle-income countries such as Tanzania. This study aimed to assess the prevalence and the factors associated with HIV testing-seeking behaviors among women of childbearing age in Tanzania.

METHODS: This study used the 2022 Tanzania Demographic and Health Survey dataset. The study utilized individual recodes (IR) files where data was collected using the Women’s Questionnaire to analyze factors influencing HIV testing behavior among women, Descriptive analysis, and bivariate and multivariate logistic regressions were performed and all the data were processed and analyzed using STATA version 17 at 95% CI and significance level P < 0.05.

RESULTS: This study included 2531 women with 90.0% having ever tested for HIV while 7.0% had never tested for HIV. Not employed [AOR:0.35, CI (0.20-0.61)] has lower odds of HIV testing than All-year employed status. Rural residents have reduced odds of HIV testing [AOR:0.43, CI (0.21-0.88)] compared to women living in urban areas. Those able to ask their partner to use a condom are more likely to have been tested with increased odds [AOR: 3.52, CI (2.31-5.37)]. Participants with a history of genital discharge [AOR:4.30, CI (1.28-14.46)] and those who don’t know their genital discharge history have [AOR: 0.20, CI (0.07-0.55)] are significant for HIV testing. Women who have heard about PrEP but are not uncertain about its approval [AOR: 36.07, CI (3.33-390.25)], respondents who have tested before with HIV testing kits [AOR:35.99, CI (4.00-324.13)] and women who are aware of HIV testing kids but never tested with them before [AOR: 2.80, CI (1.19-6.58)] are predictors of HIV testing seeking behaviors.

CONCLUSION: The government and other concerned agencies should introduce mobile or community-based testing units and subsidize testing costs to reach economically disadvantaged or rural populations. Promote Open Communication on Sexual Health: Public health campaigns should encourage open discussions about sexual health within relationships, emphasizing condom negotiation and mutual health checks as preventive measures. Raise Awareness and Accessibility of HIV Prevention Tools: Expand education on PrEP and HIV self-test kits to improve familiarity and acceptance, which may empower individuals to proactively seek testing. Integrate Sexual Health Screening into Routine Healthcare: Health facilities should incorporate HIV testing when individuals present with symptoms like genital discharge to improve early detection and intervention.

PMID:39915844 | DOI:10.1186/s12981-025-00710-2