KH-741 (KH 741 / KH741)

Missed opportunities: delayed in-hospital palliative care consultations in patients with non-metastatic cancers.

Paschen Christopher C, Pinter Klemens K, Hofbauer Thomas Martin TM, Tschischka Irene I et al.

Cancer is a leading cause of death, often accompanied by significant symptom burden. Palliative care (PC) improves quality of life, clarifies treatment goals, and prevents unnecessary interventions at the end of life. While metastatic disease is considered incurable and routinely leads to PC involvement, the need for PC in patients with non-metastatic cancer is often less clear. This study investigated whether metastatic status affects timing of in-hospital PC consultation and hospitalization length in patients with advanced cancer. We retrospectively analyzed hospitalized patients with cancer who received PC consultations between 2016-2022. Outcomes included time from admission to PC consultation, length of hospitalization, in-hospital mortality, and overall survival, analyzed using Kaplan-Meier estimates and Cox regression models. Among 741 inpatients with cancer, 52.1% had metastatic disease. Patients with non-metastatic cancer received PC involvement later after admission than those with metastatic cancer (median: 9 [95% CI: 7-11] days vs. 7 [95% CI: 6-8] days; p = 0.004), and were less likely transferred to the in-hospital PC unit (24.6% vs. 18.0%, p = 0.03). Early PC (within 72 h) was numerically less frequent in non-metastatic disease (16.9% vs. 22.5%; p = 0.055), and associated with shorter hospital stays (HR: 0.966 [0.961-0.971]; p < 0.001), independent of prevalent metastases (HR: 1.14 [0.99-1.33]; p = 0.08). Inpatients with non-metastatic cancer experienced later PC consultation after admission, while overall rates of early PC consultation remained low. Early PC after admission was associated with shorter hospital stays regardless of metastatic status, highlighting the need for early PC during hospitalization across all cancer stages.

Corrigendum to 'TOX promotes the exhaustion of antitumor CD8+ T cells by preventing PD1 degradation in hepatocellular carcinoma' [J hepatol (2019) 71(4):731-741; doi: 10.1016/j.jhep.2019.05.015].

Wang Xiaochen X, He Qifeng Q, Shen Haiyuan H, Xia Anliang A et al.

Cumulative Atopic Disease Burden and Keratoconus: Cross-Sectional and Longitudinal Associations in the All of Us Research Program.

Butt Fahad R FR, Dhivagaran Thanansayan T, Miller Tasha T, Muayad Jawad J et al.

To evaluate the association between cumulative atopic disease burden and keratoconus (KC) in a large, diverse United States cohort. Longitudinal and cross-sectional cohort study. A total of 283,040 keratoconus-free adults from the All of Us Research Program contributing 498 incident KC events over a median of 9.0 years (longitudinal cohort), and 508,527 adults including 741 with KC (cross-sectional cohort). A cumulative atopic burden score (0-3) was defined by the presence of asthma, atopic dermatitis, and allergic rhinitis. Cox proportional hazards and multivariable logistic regression estimated associations with incident and prevalent KC, adjusted for demographics, socioeconomic variables, and healthcare utilization, with a prespecified analysis restricted to participants aged 18-40 years at baseline and a matched case-control analysis in the age-appropriate window. Allergic conjunctivitis was evaluated as an independent covariate and, exploratorily, as a mediator. Incident keratoconus (longitudinal) and prevalent keratoconus (cross-sectional). Baseline atopic burden was associated with incident KC in a dose-dependent manner (per-condition trend HR 1.59; 95% CI, 1.30-1.94). Among participants aged 18-40 years at baseline, the association was stronger (trend HR 1.74; 95% CI, 1.31-2.32) and incident cases were diagnosed at a median age of 38 years. Cross-sectionally, the dose-response persisted after full adjustment (per-condition trend OR 1.33; 95% CI, 1.21-1.47). Adjustment for healthcare utilization attenuated the crude association, and a matched case-control analysis equalizing administrative presence further attenuated the gradient (OR 1.03; 95% CI, 0.77-1.38); this matched analysis was underpowered (105 cases) and did not exclude a residual effect. Allergic conjunctivitis was independently associated with KC (OR 2.81; 95% CI, 2.15-3.62). Atopy preceded KC coding in most co-affected patients. Cumulative atopic burden was associated with incident keratoconus in a reproducible, dose-dependent manner, with atopy coding preceding keratoconus in a majority of co-affected patients. Differential healthcare ascertainment likely contributes to this association, although the matched analysis quantifying it was underpowered and did not exclude a true residual effect. These hypothesis-generating findings identify multi-condition atopy as a candidate marker warranting prospective, imaging-based evaluation.

Exclusive human milk diet and mortality before discharge in premature and very low birthweight infants: a systematic review and meta-analysis.

Reyes Sarah M SM, Paul Tristen L TL, Ferry Jenelle J

Survival to hospital discharge remains a critical outcome for premature and very low birthweight infants (VLBW), who often require fortification of human milk to meet nutritional needs within tolerated feeding volumes. Although exclusive human milk diets (EHMD) that include human milk-derived fortifiers have been proposed as an alternative to cow milk-derived fortification or formula supplementation, evidence for their association with improved survival remains inconsistent across studies. To evaluate the association between an EHMD and survival to hospital discharge among premature and low birthweight infants, synthesizing evidence from randomized and non-randomized studies. PubMed, Scopus, and Web of Science were searched through July 2025 for studies comparing an EHMD (human milk fortified with human milk-derived fortifier) with diets containing cow milk-derived products. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Pooled odds ratios (OR) were calculated using random-effects meta-analysis, with subgroup analyses by study design. Five randomized and 9 non-randomized studies were included, encompassing 4,713 infants born between 2004 and 2021. Mean birthweights ranged from 741 to 1,361 g, and mean gestational ages ranged from 25.5 to 29.7 weeks. In pooled analyses, EHMD was associated with lower odds of death before discharge (pooled OR 0.80, 95% CI 0.65-0.98; I 2 = 0%, tau2 = 0.00, p = 0.03). Directionally similar associations were observed in randomized (OR 0.62, 95% CI 0.28-1.38) and non-randomized studies (OR 0.82, 95% CI 0.66-1.03), although no significant differences emerged within either subgroup. In the two randomized trials directly comparing human milk-derived and cow milk-derived fortifiers, mortality estimates were directionally similar but no significant difference was observed between groups. EHMD was associated with lower odds of death before discharge in pooled analyses. Although no significant differences emerged in the subgroup analyses, the consistency in effect direction across study designs supports the possibility of a clinically meaningful association. Adequately powered randomized and pragmatic trials are needed to confirm this association. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251059764, PROSPERO: CRD420251059764.