Tag: pubmed

Cancer Metastasis Rev. 2026 Jan 30;45(1):7. doi: 10.1007/s10555-026-10314-5.

ABSTRACT

Efforts to translate advances in immunology into anti-cancer immunotherapies have progressed rapidly in recent years. Six antibodies acting on programmed death ligand 1 or programmed death 1 pathways were approved in 75 cancer indications between 2015 and 2021. Several of these therapies were granted accelerated approval for specific cancer indications based on evidence from single-arm phase II clinical trials. In the absence of randomization, however, patient prognosis for progression-free and overall survival may not have been studied under standard chemotherapies for PD-1 and PD-L1 biomarker subpopulations. In 2021, two immunotherapies were withdrawn from accelerated approval applications for treatment of metastatic urothelial carcinoma after randomized phase III trials failed to demonstrate evidence for survival advantage over standard of care. This re-analysis uses digitized data to quantify PD-L1 heterogeneity in chemotherapy response, extending prior meta-analyses by incorporating digitized data and design simulation. The findings of the IMvigor210 (NCT02108652) and IMvigor211 (NCT02302807) trials of atezolizumab are reviewed to elucidate the statistical implications of PD-L1 subpopulation heterogeneity. To place the findings into the context of external evidence, digitization software is used to combine results from journal articles of eleven trials that assigned metastatic urothelial carcinoma patients to the same chemotherapy agents administered in the IMvigor211 control arm. This article defines the extent to which PD-L1 IC2/3 subpopulations appeared to outperform historical expectations in the IMvigor211 study based on external evidence from digitized data. Given the extent of PD-L1 heterogeneity suggested by this analysis, trial simulation is applied to define the probability that IMvigor211 would have resulted in a positive trial based on its actual design and alternative designs that enrolled more IC2/3 patients or had longer durations.

PMID:41615520 | DOI:10.1007/s10555-026-10314-5

Int Ophthalmol. 2026 Jan 30;46(1):89. doi: 10.1007/s10792-026-03948-5.

ABSTRACT

PURPOSE: Prospective randomized single-blinded study of 261 cataract patients to investigate the influence of different instruments and techniques in continuous curvilinear capsulorhexis (CCC) on the stability of the anterior chamber using intraoperative rebound tonometry.

METHODS: The study included 261 eyes allocated to six groups according to three ophthalmic viscoelastic device (OVD) conditions-hyaluronic acid (HA), hydroxypropylmethylcellulose (HPMC), and their combination via the soft-shell technique (SST)-and two instruments (Utrata forceps UF and a 26-G cystotome RN). Intraocular pressure (IOP) was measured before and after CCC using rebound tonometry with sterilized probes.

RESULTS: IOP reached 78.6 mmHg in the RN group and 76.5 mmHg in the UF group after OVD instillation and after the creation of the CCC. The mean IOP drop during capsulorhexis was significantly greater with UF (67.1 ± 12.3 mmHg; n = 117) compared to RN (56.5 ± 11.6 mmHg; n = 144) (P < 0.001).

CONCLUSION: The results of this study showed a statistically significant difference in the stability of the anterior chamber depending on the instrument used. The use of different OVDs had no statistically significant influence on anterior chamber stability. Maintaining a more stable IOP with a 26-gauge cystotome may be advantageous in complex cases, such as increased posterior vitreous pressure, zonular weakness or heightened intracapsular pressure.

PMID:41615516 | DOI:10.1007/s10792-026-03948-5

World J Urol. 2026 Jan 30;44(1):139. doi: 10.1007/s00345-025-05923-8.

ABSTRACT

OBJECTIVE: To describe the demographic profile and risk factors for kidney stone formation in patients with sarcoidosis.

MATERIAL AND METHODS: 158 sarcoidosis patients were analyzed, comparing groups with and without kidney stones evaluating clinical and metabolic factors and medication use. Statistical analysis was carried out using R software (p < 0.05).

RESULTS: The sample consisted of 138 patients (87.34%), with a majority of females (67.4%) and a median age of 54. Frequent comorbidities included hypertension (38.4%), diabetes (18.1%), and dyslipidemia (6.5%). Nephrolithiasis was reported by 11.9% of patients. Laboratory tests showed hypercalcemia in 9.4% and hypercalciuria in 17.4%. Kidney stones were found in 15.9% of patients, three of whom were bilateral. The comparative analysis revealed a significant association with a previous history of nephrolithiasis (40% vs. 6.6%). There was no statistical correlation with laboratory tests, except for uric acid, which was lower in the group with stones. Hydroxychloroquine was more frequent in the group with stones but without statistical significance. Logistic regression did not identify any significant associations.

CONCLUSION: Nephrolithiasis occurred in 16% of sarcoidosis patients and was more prevalent in women and adults. Calcium disturbances persist, requiring continuous monitoring. A history of renal lithiasis should be valued in diagnosis and follow-up.

PMID:41615515 | DOI:10.1007/s00345-025-05923-8

Histochem Cell Biol. 2026 Jan 30;164(1):7. doi: 10.1007/s00418-026-02457-x.

ABSTRACT

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a lipid-metabolizing enzyme implicated in ferroptosis regulation and tumor aggressiveness. Although ACSL4 overexpression has been reported in various malignancies, its immunohistochemical profile in primary cutaneous melanoma has not been fully characterized. This study aimed to evaluate ACSL4 expression in melanoma compared with normal skin using quantitative digital image analysis. A total of 80 formalin-fixed paraffin-embedded samples were analyzed, including 50 primary cutaneous melanoma specimens and 30 control skin samples obtained from benign dermatologic excisions. Hematoxylin-eosin staining was used to assess histopathologic features, and ACSL4 immunostaining was performed using a standardized protocol. Quantitative evaluation was conducted with QuPath software by calculating the percentage of positive cells, mean intensity scores (0-3), and H-scores (0-300) in epidermal and dermal compartments. Group comparisons were performed using the independent t test, with p < 0.05 considered statistically significant. Control tissues exhibited minimal ACSL4 expression (epidermal H-score 12; dermal H-score 9), whereas melanoma specimens demonstrated markedly increased ACSL4 immunoreactivity. Dermal atypical melanocytic tumor cells showed the highest expression levels (mean intensity 2.10 ± 0.35; H-score 168; p < 0.001), while epidermal layers also exhibited moderately elevated staining (H-score 58; p < 0.001). Histopathologic evaluation revealed characteristic features of invasive melanoma, including atypical melanocytic nests, pagetoid spread, cytologic atypia, and architectural disorder. Overall, ACSL4 expression was significantly upregulated in primary cutaneous melanoma compared with normal skin, particularly within dermal atypical melanocytic tumor cells, suggesting that ACSL4 may contribute to melanoma biology through lipid metabolic pathways and may represent a potential biomarker of tumor aggressiveness, warranting further investigation into its diagnostic and prognostic relevance.

PMID:41615507 | DOI:10.1007/s00418-026-02457-x

Breast Cancer Res Treat. 2026 Jan 30;215(3):67. doi: 10.1007/s10549-026-07897-6.

ABSTRACT

PURPOSE: The study aims to develop and validate a predictive tool for assessing the risk of in-breast tumor recurrence (IBTR) in breast cancer patients considered candidates for intraoperative radiotherapy using electrons (IOERT).

METHODS: This study included 3397 breast cancer patients treated with IOERT at a single institution between 2000 and 2016. The primary endpoint was IBTR, with or without nodal or distant metastasis. Fine and Gray regression models were used to identify predictors of IBTR. A nomogram predicting the 5- and 10-year probability of IBTR was developed based on the multivariable model and was validated both internally and externally using data from the IOERT arm of the ELIOT phase III trial (585 patients).

RESULTS: With a median follow-up of 6.1 years (interquartile range 4.3-8.0), 265 IBTRs (7.8%) were observed, resulting in an IBTR cumulative incidence of 4.4% (95% CI 3.7-5.2) at 5 years and 13.5% (95% CI 11.7-15.5) at 10 years. Multivariable analysis revealed that age under 60, certain histologic subtypes, positive axillary nodes, and intermediate/high tumor grade were key risk factors for IBTR. The overall Harrell’s concordance statistic was 0.69 (95% CI 0.66-0.73) in the internal and 0.64 (95% CI 0.57-0.71) in the external validation.

CONCLUSION: The nomogram has demonstrated moderate discriminative ability in predicting IBTR in the internal validation set and may be a useful tool to support treatment decision-making in breast cancer patients eligible for IOERT.

PMID:41615490 | DOI:10.1007/s10549-026-07897-6

Eur Radiol. 2026 Jan 30. doi: 10.1007/s00330-026-12349-2. Online ahead of print.

NO ABSTRACT

PMID:41615471 | DOI:10.1007/s00330-026-12349-2

Eur Radiol. 2026 Jan 30. doi: 10.1007/s00330-026-12334-9. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the safety and diagnostic performance of CT-guided core needle biopsy (CNB) of focal pulmonary lesions with coexisting interstitial lung abnormalities (ILAs).

MATERIALS AND METHODS: This retrospective 1:1 matched case-control study included patients with ILAs and controls who underwent CT-guided CNB of a focal pulmonary lesion from February 2010 to December 2023. Complications, nondiagnostic specimens, and CNB diagnostic performance for malignancy were compared. Logistic regression was used to identify predictors of complications and nondiagnostic specimens. Resected cases were reviewed for histopathological changes in the nonneoplastic lung.

RESULTS: Seventy-three patients with ILAs and matched controls were included (both groups: median age, 73.0 years; 13 women). No significant difference was found in complications (overall: 21/73 [29%] vs 24/73 [33%], p = 0.72; major: 2/73 [3%] vs 3/73 [4%], p = 1.00; minor: 19/73 [26%] vs 21/73 [29%], p = 0.85), nondiagnostic specimens (12/73 [16%] vs 9/73 [12%], p = 0.20), or diagnostic performance (accuracy: 89% [65/73] vs 96% [70/73], p = 0.11; sensitivity: 88% [61/69] vs 95% [62/65], p = 0.13; specificity: 100% [4/4] vs 100% [8/8], p = 1.00). Needle traversal of ILAs (OR, 7.04; 95% CI: 2.07-26.28; p = 0.008) and multiple pleural passes (OR, 8.06; 95% CI: 1.26-70.46; p = 0.03) were associated with complications. Nonneoplastic lung in ILAs revealed more complex histology and increased fibrotic features than controls.

CONCLUSION: CT-guided CNB of focal pulmonary lesions with coexisting ILAs was as safe and accurate as in patients without ILAs. However, traversing ILAs and multiple pleural passes increased complication risk.

KEY POINTS: Question Whether CT-guided CNB of focal pulmonary lesions with coexisting ILAs is as safe and accurate as in those without ILAs. Findings CNB in patients with ILAs showed similar safety and diagnostic performance to controls; however, complications were more frequent when ILAs were traversed or multiple pleural passes were performed. Clinical relevance CNB is a safe and effective diagnostic tool in patients with ILAs. Avoiding ILA traversal and multiple pleural passes may help minimize the risk of complications.

PMID:41615470 | DOI:10.1007/s00330-026-12334-9

Anaesthesiologie. 2026 Jan 30. doi: 10.1007/s00101-026-01648-4. Online ahead of print.

ABSTRACT

BACKGROUND: A regression model to estimate the duration from the onset of resuscitation efforts to the return of spontaneous circulation (ROSC) could help improving both resuscitation care and the quality control of registries. This study aims to evaluate the prediction accuracy and to identify challenges for future model development.

METHOD: Regression models based on M5P, random forest (RF) algorithms and a linear regression (LR) modified using M5P were retrospectively developed using a Belgian cohort of 84 individuals in whom ROSC was achieved. Model performance was assessed using quality metrics, such as the correlation coefficient (CC), coefficient of determination (R²), and root mean square error (RMSE) in a cross-validation approach.

RESULTS: In the cohort 61.9% were male with a mean age of 65.7 years. A shockable rhythm was present in 27.7% of cases and the bystander cardiopulmonary resuscitation (CPR) rate was 48.2%. The no-flow time averaged 5.13 min. The mean time from CPR onset to first defibrillation was 7.81 min and to first medication administration 11.31 min. The ROSC occurred after an average of 16.8 min, the LR showed the highest correlation (0.73, 95% confidence interval, CI 0.72-0.74) and R² (0.53 [0.52-0.55]) along with the lowest RMSE (6.76 min [6.63-6.90]). The M5P yielded similar not significantly different values (CC 0.72 [0.70-0.73], R² 0.52 [0.50-0.53], RMSE 6.84 min [6.69-6.99]). In contrast, RF performed significantly worse (CC 0.62 [0.61-0.63], R² 0.38 [0.37-0.40], RMSE 7.89 min [7.82-7.96], all p < 0.01). Only LR showed no significant difference between predicted and actual values in terms of mean (p = 0.75) and variance (p = 0.15). The proportion of potentially prematurely terminated resuscitation attempts, defined as cases with actual ROSC occurring later than predicted ROSC plus RMSE, ranged from 13% (M5P) to 18% (LR).

CONCLUSION: The duration from the start of CPR to ROSC appears to be a process that is suitable for modelling with machine learning algorithms. At this early stage of development, the individual regression models did not demonstrate sufficient validity possibly due to low sample size and simplified data structure; however, the findings indicated potential for an application as a quality assurance tool to compare actual vs. predicted time to ROSC. Therefore, to increase the robustness the results require further evaluation in a larger cohort with additional variables and improved data quality based on the Utstein criteria.

PMID:41615433 | DOI:10.1007/s00101-026-01648-4

J Gerontol A Biol Sci Med Sci. 2026 Jan 30:glag019. doi: 10.1093/gerona/glag019. Online ahead of print.

ABSTRACT

BACKGROUND: Visual impairment is a potential risk factor for depression and other outcomes in older adults. In population-based studies, vision can be measured using self-report or performance-based visual acuity, but epidemiologic associations often depend on which measure is used.

METHODS: In this Research Practice article, we illustrate the use of propensity scores to harmonize analyses of self-reported and performance-based vision in older adults. Using 2021 data from the National Health and Aging Trends Study (NHATS; n = 2,447), we measured associations between self-reported visual difficulty, distance visual impairment (logMAR >0.3), and depression. To harmonize self-reported and performance-based measures of vision, we modeled distance visual impairment as a function of self-reported vision and covariates and calculated exposure misclassification overlap weights. External validation was conducted using the Canadian Longitudinal Study on Aging (CLSA) and the Longitudinal Aging Study in India (LASI).

RESULTS: Self-reported visual difficulty was associated with depression (adjusted OR 2.32, 95% CI: 1.46-3.69), but distance visual impairment was not (OR 1.41, 95% CI: 0.99-2.01). After exposure misclassification overlap weighting, self-reported vision was no longer associated with depression, and results mirrored the association between distance visual impairment and depression (OR 1.49, 95% CI: 0.93-2.36). Similar findings were observed in CLSA and LASI.

CONCLUSIONS: Associations between vision and depression in older adults differ according to how vision is measured. In studies that measure self-reported vision but not visual acuity, propensity score methods that leverage known relationships between the two can be used to approximate associations between reduced visual acuity and health outcomes.

PMID:41615430 | DOI:10.1093/gerona/glag019

Pharmacoepidemiol Drug Saf. 2026 Feb;35(2):e70323. doi: 10.1002/pds.70323.

ABSTRACT

PURPOSE: This nationwide cohort study examined the effects of discontinuation versus continuation of renin-angiotensin system inhibitors (RASis) on major renal and cardiovascular outcomes after the estimated glomerular filtration rate (eGFR) decreased to below 45 mL/min/1.73 m² in patients with type 2 diabetes and treated with RASis.

METHODS: Using linked Taiwanese databases with claims and clinical data, we identified patients with type 2 diabetes who used RASis during 2016-2020, and either discontinued or continued RASis within 180 days when their eGFR fell below 45 mL/min/1.73 m². The outcomes of interest included end-stage renal disease (ESRD), myocardial infarction, stroke, heart failure, and all-cause mortality. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for RASi discontinuation versus RASi continuation using on-treatment and intention-to-treat analyses and inverse probability weighting to adjust for baseline and time-varying covariates.

RESULTS: We identified 251 853 eligible patients, of whom 37 108 (15%) discontinued RASis and 214 745 (85%) continued RASis. The on-treatment HR associated with RASi discontinuation was 2.52 (95% CI, 2.33-2.73) for ESRD, 1.18 (1.08-1.30) for myocardial infarction, 1.28 (1.19-1.37) for stroke, 1.18 (1.13-1.24) for heart failure, and 1.77 (1.70-1.84) for all-cause mortality. Results from the intention-to-treat analysis were similar, albeit more conservative. Findings remained consistent across eGFR strata (≥ 30 to < 45 and < 30 mL/min/1.73 m²), urine albumin-creatinine ratio categories (≥ 300 and < 300 mg/g), and patient subgroups with various baseline characteristics.

CONCLUSION: Our results support continuing RASi treatment even when the eGFR declines to below 45 mL/min/1.73 m² based on potential renal, cardiovascular, and survival benefits.

PMID:41614370 | DOI:10.1002/pds.70323