Background: Data on the clinical patterns and histopathology of SARS-CoV-2 related skin lesions, as well as on their relationship with the severity of COVID-19 are limited. Methods and Materials: Retrospective analysis of a prospectively collected cohort of patients with SARS-CoV-2 infection in a teaching hospital in Barcelona, Spain, from 1 April to 1 May 2020. Clinical, microbiological and therapeutic characteristics, clinicopathological patterns of skin lesions, and direct immunofluorescence and immunohistochemical findings in skin biopsies were analyzed. Results: Fifty-eight out of the 2761 patients (2.1%) either consulting to the emergency room or admitted to the hospital for COVID-19 suspicion during the study period presented COVID-19 related skin lesions. Cutaneous lesions could be categorized into six patterns represented by the acronym “GROUCH”: Generalized maculo-papular (20.7%), Grover’s disease and other papulo-vesicular eruptions (13.8%), livedo Reticularis (6.9%), Other eruptions (22.4%), Urticarial (6.9%), and CHilblain-like (29.3%). Skin biopsies were performed in 72.4%, including direct immunofluorescence in 71.4% and immunohistochemistry in 28.6%. Patients with chilblain-like lesions exhibited a characteristic histology and were significantly younger and presented lower rates of systemic symptoms, radiological lung infiltrates and analytical abnormalities, and hospital and ICU admission compared to the rest of patients. Conclusion: Cutaneous lesions in patients with COVID-19 appear to be relatively rare and varied. Patients with chilblain-like lesions have a characteristic clinicopathological pattern and a less severe presentation of COVID-19.

Pembrolizumab is standard adjuvant therapy for high-risk clear cell renal cell carcinoma, but serositis is an uncommon immune-related adverse event that may mimic recurrence or infection. We report a 55-year-old man who achieved no evidence of disease after nephrectomy and metastasectomy and developed anasarca, large bilateral pleural effusions, mild ascites, peripheral eosinophilia, and a small pericardial effusion after six cycles of adjuvant pembrolizumab. Pleural fluid was exudative and contained 20% eosinophils. Cytology showed inflammatory cells without evidence of malignancy; bacterial, mycobacterial, and fungal studies were negative; and mildly elevated adenosine deaminase did not support tuberculosis. Cardiac function and natriuretic peptides were preserved. Pembrolizumab was discontinued, thoracentesis and corticosteroids were administered, and symptoms, eosinophilia, renal function, and albumin improved rapidly. Follow-up through March 2026 showed no oncologic progression, although some residual pleural and abdominal fluid persisted alongside imaging findings suggestive of portal-hypertension physiology, which may have contributed to residual fluid but did not explain the eosinophilic pleural syndrome. In a targeted literature review, effusion eosinophil data were infrequently reported. This case highlights a likely underrecognized eosinophilic pleural-fluid phenotype within pembrolizumab-associated polyserositis and supports routine differential cell counts in drained serosal fluid when immune-related serositis is suspected.

Background: National trends in sepsis-associated cancer mortality in the USA remain incompletely characterised, particularly regarding long-term structural shifts and their variation across oncologic subpopulations.Methods: We conducted a population-based time-series analysis using the CDC WONDER Multiple Cause of Death database (1999–2020). Cases were defined by an underlying cause of death of malignant neoplasm (ICD-10 codes C00–C97) and a contributing cause of sepsis (A40–A41). We calculated age-standardised mortality rates (ASMR) indexed to the 2000 US Standard Population. Temporal dynamics were assessed using segmented Poisson regression to estimate annual percent changes (APC) and identify structural breakpoints. Furthermore, we employed counterfactual modelling to quantify excess mortality by projecting pre-2010 trends forward, and performed stratified analyses by cancer type (solid vs haematological), sex, and geography.Findings: Of 14 713 914 cancer deaths, 455 369 (3·10%) involved sepsis. Crude mortality increased from 6·26 to 7·94 per 100 000. Segmented regression identified a structural acceleration in the early 2010s, with APCs increasing from 0·47% (95% CI 0·36–0·57) to 2·84% (2·54–3·13). This inflection corresponded to an estimated 31 896 excess deaths compared with historical trends. Crucially, trends diverged by cancer type: mortality declined for haematological malignancies (APC −1·97%; 95% CI −2·21 to −1·73) but surged for solid tumours (APC 2·25%; 95% CI 2·10–2·39). Population ageing accounted for 77·1% of the post-inflection increase; COVID-19 contributions were transient.Interpretation: A structural acceleration in sepsis-associated cancer mortality began in the early 2010s, driven largely by solid tumours and exceeding demographic expectations. This identifies sepsis as a critical, structural determinant of cancer outcomes, necessitating prioritisation within oncologic survivorship guidelines and health system infrastructure.

Introduction: Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small cell lung cancer (ES-SCLC), long-term survival remains limited. There is currently no available predictive biomarker to identify which patients would benefit most from this treatment. We hypothesized that pre-treatment PD-L1 expression on circulating immune cells might predict survival outcomes and toxicity. Material and methods: This prospective, multi-center observational study included patients with untreated ES-SCLC treated with first-line durvalumab plus platinum-based chemotherapy. The percentages of circulating PD-L1 ⁺ immune cells at baseline were analysed by flow cytometry to assess their association with survival outcomes and the development of immune-related adverse events (irAEs). Results: Among 41 patients with ES-SCLC, 65.9% were male, 73.2% had an ECOG-PS 1, 9.8% had central nervous system (CNS) metastases and 31.7% had liver metastases. Sixteen patients (39%) experienced irAEs. Median PFS was longer in patients with high percentages of circulating PD-L1 ⁺ monocytes compared to those with low percentages: 8.97 months (95% CI NR to NR) vs. 5.97 months (95% CI 4.65 to 7.28), p = 0.007. There was a trend toward longer median OS in patients with ES-SCLC and high percentages of circulating PD-L1 ⁺ monocytes versus low percentages: NR (95% CI NR-NR) vs. 9.13 months (95% CI 6.34 to 11.92), p = 0.092. Patients with higher circulating PD-L1 ⁺ neutrophils correlated with the development of irAES ( p = 0.007). Conclusions: Our results showed a statistically significant longer PFS in patients with ES-SCLC and high percentages of circulating PD-L1 ⁺ monocytes. This suggests PD-L1 expression on monocytes might be established as a predictive biomarker for patients with ES-SCLC treated with upfront chemo-immunotherapy. Trial registration: NCT04712903 Trial. Last registered 1 December 2025, https://www.clinicaltrials.gov/study/NCT04712903 .

Soluble immune checkpoints (sICs) have emerged as potential biomarkers in various cancers. However, their role in extensive-stage small cell lung cancer (ES-SCLC), an aggressive tumor type with limited therapeutic options and poor prognosis, remains poorly characterized. We analyzed 14 circulating sICs, leukocyte–platelet (PLT) complexes, and PD-L1 surface expression in ES-SCLC patients treated with chemoimmunotherapy (n = 41) prior to treatment and healthy donors (HD, n = 10). We assessed their associations with clinical and demographic factors and performed survival analyses using Kaplan–Meier and log-rank tests. Levels of soluble (s) PD-L1, PD-L2, BTLA, HVEM, TIM-3, and CD27 were higher in plasma from ES-SCLC patients compared to those from HD (p < 0.05). Patients with liver metastases exhibited higher sIC levels, and a multivariate model demonstrated discriminative power. Network analyses revealed distinct patterns of immune dysregulation between ES-SCLC and HD. We observed correlations among sICs and leukocyte–PLT complexes and leukocyte PD-L1 expression, indicating links between systemic immune status and tumor–immune interactions. Furthermore, increased concentrations of sTIM-3, sCD27, sHVEM and sPD-L1 were associated with a poor prognosis. Overall, sICs reflect relevant clinical, prognostic, and immunological features in ES-SCLC. Their plasma measurement could aid in non-invasive patient stratification regarding liver metastases and survival risk.