ObjectiveBruton tyrosine kinase inhibitors and B-cell lymphoma 2 inhibitors are currently the new standard active agents in chronic lymphocytic leukaemia. This observational study describes the real-world use of frontline treatment in Bulgarian patients with active chronic lymphocytic leukaemia and characterises the patient population receiving these treatments.MethodsDESCRIBE was a physician-chart review study conducted at eight haematology centres across Bulgaria. Adult patients with confirmed active chronic lymphocytic leukaemia requiring frontline treatment initiation after January 2022 were considered for enrolment.ResultsA total of 90 patients were included in the study. The mean age (standard deviation) was 62.8 (11.2) years, and 58% were male. The median (range) duration of disease was 6 (0-198) months at the time of frontline treatment initiation and 19.2 (1.2-206.4) months at enrolment. Comorbidities were reported in 58 (64%) patients, with cardiovascular diseases being the most common (57%). Cytogenetic testing rates were lower, particularly for del(11q), tumour protein p53 gene and immunoglobulin heavy chain variable region gene mutation status, which were assessed in only 44%, 21% and 37% of patients, respectively. At the time of frontline treatment initiation, most patients presented with Rai stage II (44%) or Binet stage B (63%). Targeted therapy was used in 77% of cases (46% Bruton tyrosine kinase inhibitors and 31% B-cell lymphoma 2 inhibitors), while chemoimmunotherapy was used in the remaining 23%. Patients with high-risk chronic lymphocytic leukaemia were more likely to receive second-generation Bruton tyrosine kinase inhibitors (odds ratio = 5.59, p < 0.001), and each additional high-risk trait further increased the odds of its use (odds ratio = 2.35, p < 0.01).ConclusionsOur findings indicate a shift towards the adoption of novel therapies in Bulgaria, with Bruton tyrosine kinase inhibitors and B-cell lymphoma 2 inhibitors now dominating the contemporary frontline treatment landscape (2022-2023). Improving the rate of testing for specific high-risk molecular and genetic markers is vital to enhancing outcomes in patients with chronic lymphocytic leukaemia. In the era of proven efficacy of targeted agents, chemoimmunotherapy should be discouraged, in line with international guidelines.

ObjectiveDermatofibrosarcoma protuberans is a low-to-intermediate-grade malignancy with high postoperative recurrence risk. It is often misdiagnosed as superficial venous malformation due to nonspecific manifestations and clinical features similar to those of other soft tissue tumors. Ultrasound examination is crucial for dermatofibrosarcoma protuberans evaluation; however, its value in differentiating dermatofibrosarcoma protuberans from superficial venous malformation remains underinvestigated.MethodsThis retrospective study analyzed and compared the clinical and ultrasonographic features between 41 histopathologically confirmed dermatofibrosarcoma protuberans cases and 41 superficial venous malformation cases. Clinical data included sex, age, tumor size, and location. Ultrasound findings were categorized into five types, and the following features were evaluated: shape, boundary, pattern, invasion depth, and vascularity.ResultsThe dermatofibrosarcoma protuberans tissues had significantly larger maximum diameters than superficial venous malformations (p < 0.05). Anatomically, dermatofibrosarcoma protuberans predominantly occurred on the trunk, while superficial venous malformations were more common on the extremities (p < 0.05). Dermatofibrosarcoma protuberans tissues mostly invaded both dermis and hypodermis, whereas superficial venous malformations primarily involved the hypodermis (p < 0.05). Dermatofibrosarcoma protuberans tissues had clearer boundaries (p < 0.05) and were more likely to show hyperechoic cord-like structures (type 4), while superficial venous malformations frequently presented network structures (type 3) (p < 0.05).ConclusionsUltrasound can provide valuable morphological features to assist in the differential diagnosis of dermatofibrosarcoma protuberans and superficial venous malformation, improving preoperative assessment accuracy and guiding treatment planning.

Although peripheral blood flow cytometry (PBFC) can aid in the diagnosis of hematolymphoid malignancies, it is often ordered in clinical situations for which it is not useful. We hypothesized that patient clinical data could be used to design an algorithm to guide better test utilization and performance.

Patient records for 250 consecutive PBFC orders were reviewed to determine test indication, patient demographics and history, blood count, and leukocyte differential. These variables were analyzed to determine whether they could predict the detection of hematolymphoid malignancy. Using these data, a test ordering algorithm was designed to maximize positive and minimize negative results, which was then validated on an additional set of 250 consecutive cases.

Peripheral blood flow cytometry was infrequently positive for most indications. The presence of circulating blasts, history of hematolymphoid malignancy, and lymphocytosis or pancytopenia in patients 50 years of age and older are most predictive of positive results. Application of an algorithm incorporating these criteria would substantially reduce PBFC utilization while increasing the fraction of positive cases. Similar results were seen when the algorithm was applied to an independent validation set.

An evidence-based algorithm for ordering PBFC based on 5 clinical factors can substantially reduce utilization and increase positive results.

The association between social determinants of health (SDOH) and clinical outcomes among patients with hepatocellular carcinoma (HCC) remains unclear.

We conducted a retrospective cohort study of patients with treatment-naïve HCC seen between September 2018 and July 2023 at 4 US health systems. Patients completed surveys assessing SDOH and health beliefs. We used multivariable logistic regression analysis to identify factors associated with treatment receipt and Fine-Gray subdistribution hazard analysis to identify factors associated with risk of death, with liver transplantation as a competing event.

Among 770 eligible patients (55.1% with Barcelona Clinic Liver Cancer [BCLC] stage 0/A HCC), 73.2% received HCC treatment, of whom 46.8% received curative therapy. Treatment receipt was inversely associated with alcohol-associated liver disease (ALD) etiology (adjusted odds ratio [aOR], 0.52; 95% CI, 0.28-0.98), Child-Pugh class B (aOR, 0.45; 95% CI, 0.27-0.75), medical mistrust (aOR, 0.61; 95% CI, 0.38-0.98), and patient-reported discrimination (aOR, 0.80; 95% CI, 0.76-0.83). After adjusting for tumor stage and type of HCC treatment, Child-Pugh class B cirrhosis was associated with a higher risk of mortality (subdistribution hazard ratio [sHR], 1.41; 95% CI, 1.05-1.89), whereas patient-reported discrimination was associated with a lower risk of mortality (sHR, 0.96; 95% CI, 0.94-0.99). Among follow-up survey respondents (n=475), those who reported barriers to treatment had lower treatment receipt (aOR, 0.79; 95% CI, 0.65-0.93), whereas those who reported better patient-provider communication had lower mortality (sHR, 0.95; 95% CI, 0.92-0.99).

Patient-reported medical mistrust, experienced discrimination, and barriers to treatment are associated with treatment receipt and survival, underscoring the importance of addressing SDOH and health beliefs to improve outcomes in patients with HCC.

Intraoperative localization of ground-glass nodules (GGNs) is challenging. This study evaluates a CT-guided protocol that innovatively combines a glucose solution test with tissue adhesive marking to enhance safety and efficacy. The standardized procedure involves preoperative thin-slice CT (≤1 mm) with a 5 × 5 cm grid for planning, followed by percutaneous puncture to a shallow (5 mm) subpleural depth. A key safety innovation is the injection of 0.3 mL of 5% glucose solution to confirm extra-bronchial needle position via cough reflex testing before depositing 0.3 mL of 2-octyl cyanoacrylate to create a palpable marker. This protocol not only achieves precise localization of pulmonary nodules but also significantly reduces the incidence of pneumothorax by minimizing the number of required puncture attempts. The method is readily reproducible and integrates seamlessly into standard preoperative workflows. This approach establishes a safer, non-radioactive alternative for GGN localization, with its core innovations -- the glucose confirmation step and shallow subpleural injection -- serving as key mechanisms for complication prevention.

Germline loss-of-function folliculin (FLCN) gene mutations cause Birt-Hogg-Dubé (BHD) syndrome, in which pulmonary cysts are present in up to 90% of the patients. The pathogenic mechanisms underlying lung cyst development in BHD are almost entirely unknown because of the limited availability of BHD patient lung samples and the lack of authentic BHD lung disease models. We generated lung mesenchyme-specific and lung epithelium-specific Flcn-knockout mice using a Cre/loxP approach. We found that deletion of Flcn in lung mesenchymal cells, but not in lung epithelial cells, resulted in alveolar enlargement starting from early postnatal life, with evidence of cyst formation in adult mice, resembling the pulmonary disease in human BHD. These changes were associated with increased mechanistic target of rapamycin complex 1 (mTORC1) activity in the lungs of both patients with BHD and Flcn-knockout mice. Attenuation of mTORC1 activity by knocking out Raptor gene (Rptor) or pharmacologic inhibition using rapamycin substantially rescued the pulmonary pathology caused by Flcn deletion in mice. Taken together, these human and mouse data support a model in which mTORC1 hyperactivation drives pulmonary cystic pathology in BHD.

Clonal hematopoiesis (CH) results from the acquisition and expansion of somatic mutations in hematopoietic stem and progenitor cells and is associated with age-related clinical sequelae, including an increased risk for cardiovascular disease, myeloid neoplasms and complications related to cancer therapy. Chemotherapy and radiation can accelerate CH expansion and further elevate the risk of adverse events, including cardiotoxicity and therapy-related myeloid neoplasms. Although CH is increasingly recognized as a clinically relevant precursor state and predictive biomarker, the long-term dynamics of CH expansion in humans remain poorly understood. Longitudinal data are often collected but not integrated with mathematical prediction. Mathematical modeling is essential for characterizing CH evolution, estimating clone fitness, inferring stem cell pool dynamics and enabling patient-level predictions. This study summarizes the current evidence on CH dynamics in humans, compares mathematical models used to predict CH progression, assesses the validity of model assumptions and discusses the implications for clinical management of individuals with these precursor conditions.

BackgroundHypopharyngeal cancer is increasingly emerging as a disease that threatens global health, with poor prognosis and survival rates. However, clinical strategies and effective therapies remain limited.MethodsThe inhibitory effect of liensinine on tumor cells was detected through cell cycle, colony formation, and apoptosis assays. Changes in the expression levels of relevant proteins were detected and enrichment analysis of signaling pathways was performed through in vitro and RNA sequencing experiments. The transcription levels of relevant genes were further verified using reverse transcription polymerase chain reaction.ResultsWe previously discovered that the natural compound, liensinine, is effective in treating hypopharyngeal cancer. In this study, we found through in vitro and RNA sequencing experiments that liensinine can activate the Ras homolog family member B protein, thereby inhibiting the mitogen-activated protein kinase signaling pathway. Additionally, liensinine activates the nuclear factor kappa B signaling pathway and releases downstream inflammatory factors, effectively exerting its antitumor effects.ConclusionLiensinine induces cell death and inhibits hypopharyngeal cancer cell growth through multiple pathways, indicating that it is a potential chemotherapeutic agent for the treatment of hypopharyngeal cancer.

Both primary optic nerve sheath meningiomas (pONSMs) and secondary optic nerve sheath meningiomas (sONSMs) pose clinical challenges because standard treatments such as surgical debulking and radiation therapy can further damage the optic nerve, producing permanent visual loss. The molecular pathology of primary skull base meningiomas is becoming clearer. However, by comparison, pONSMs and sONSMs have not been studied adequately with contemporary high-throughput molecular genetic techniques, which is the primary aim of this study. This is a crucial issue because these tumors may harbor distinct genetic alterations that render them susceptible to targeted therapy, allowing for vision preservation or even visual improvement.

A total of 18 optic nerve sheath meningiomas, of which 11 were pONSMs and 7 were sONSMs, were obtained from 3 different institutions and underwent next-generation sequencing.

We found that pONSMs and sONSMs harbor gene variants previously identified in other meningiomas but also distinct alterations in genes implicated in cell signaling, transcriptional regulation, and DNA damage repair.

These findings expand our understanding of a relatively understudied specific meningioma with unique therapeutic challenges.

Immune checkpoint inhibitors have transformed the therapeutic landscape of classic Hodgkin lymphoma (cHL), leading to significant improvement in patient outcomes in the modern era. This review provides an overview of the established and evolving roles of PD-1 inhibitors in the management of cHL. We highlight the pivotal trials of nivolumab and pembrolizumab in relapsed/refractory cHL and discuss subsequent studies combining these agents with chemotherapy in the second-line setting, which have led to improved cure rates following autologous stem cell transplant (ASCT). In the frontline setting, the SWOG S1826 trial established nivolumab in combination with doxorubicin, vinblastine, and dacarbazine (AVD) as the new standard of care for advanced-stage cHL in North America, improving progression-free survival and tolerability compared with brentuximab vedotin with AVD. In early-stage cHL, PD-1 inhibitors are being explored as part of treatment strategies to omit bleomycin and/or radiotherapy. PD-1 inhibitor-based regimens have also become a new standard for older adults with cHL, leading to improved overall survival in this population with historically poorer outcomes compared with younger patients. We address the challenging scenario of managing patients with disease relapse after PD-1 inhibitor therapy, including novel combination strategies aimed at restoring sensitivity to checkpoint blockade. Finally, we highlight emerging directions in the field, including efforts to develop predictive biomarkers and to incorporate circulating tumor DNA-based strategies to monitor response and personalize therapy, with the potential to abbreviate chemotherapy or omit ASCT in a subset of patients. As PD-1 inhibitors are increasingly incorporated across treatment regimens for cHL, ongoing studies aim to refine patient selection, identify those most likely to benefit from therapy escalation or de-escalation, and optimize therapeutic combinations to maximize cure rates, tolerability, and survivorship.