Endocrine Immune-Related Adverse Events Are Independent Predictors of Survival in Patients with Lung Cancer.

Lung cancer (LC) is a serious health problem worldwide. Survival outcomes have improved over time due to the widespread use of novel therapeutic agents, including immune checkpoint inhibitors (ICIs). Endocrine immune-related adverse events (e-irAEs) are common in LC patients treated with ICIs. We performed a retrospective study of patients with LC who received treatment with ICIs at a tertiary referral center between January 2014 and October 2023. In total, 983 LC patients were included in the study. E-irAEs presented at a median time of 4.1 months and included hypothyroidism (15.6%), hyperthyroidism (4.3%), adrenal insufficiency (0.4%), hypophysitis (0.4%), and diabetes mellitus (0.2%). These toxicities were not related to the duration of treatment or the type of ICIs. Most (97.6%) e-irAEs were mild (grade 1-2). Median overall survival (OS) was higher in LC patients who experienced e-irAEs (31.6 months) compared to those who did not (10.8 months). The difference remained statistically significant in the 3-month (HR: 0.42) and 6-month landmark analysis (HR: 0.51). The OS advantage was observed in both patients with NSCLC (HR: 0.36) and SCLC (HR: 0.27). Additional research is needed to validate the role of e-irAEs as an independent predictor of survival outcomes in patients with LC.

Real-World Data and Evidence in Lung Cancer: A Review of Recent Developments.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. The distinction between RWD and data derived from randomized clinical trials lies in the method of data collection, as RWD by definition are obtained at the point of care. Experimental designs resembling those used in traditional clinical trials can be utilized to generate RWD, thus offering multiple benefits including increased efficiency and a more equitable balance between internal and external validity. Real-world data can be utilized in the field of pharmacovigilance to facilitate the understanding of disease progression and to formulate external control groups. By utilizing prospectively collected RWD, it is feasible to conduct pragmatic clinical trials (PCTs) that can provide evidence to support randomized study designs and extend clinical research to the patient's point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly and patients with poor performance status (PS), hepatitis, or human immunodeficiency virus, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

Lung NETs and GEPNETs: One Cancer with Different Origins or Two Distinct Cancers?

Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, the role of EGFR in carcinogenesis, the presence of transcription factors, and the immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may improve our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.

Use of Dermoscopy among Greek Dermatologists in Everyday Clinical Practice: A National Questionnaire-Based Study.

Background: Dermatoscopy has been established as an important diagnostic tool for a wide range of skin diseases. This study aims to evaluate the use of dermatoscopy in clinical practice among Greek dermatologists. Methods: A nationwide questionnaire-based survey was conducted collecting data on the frequency of dermatoscopic examinations, the types of lesions examined, training and educational resources, as well as factors influencing the choice to incorporate dermatoscopy into daily clinical routines. Results: A total of 366 Greek dermatologists participated in the survey. Most of the respondents reported the daily use of dermatoscopy in their practice. Pigmented and non-pigmented lesions, inflammatory diseases, cutaneous infectious, hair disorders, and nail lesions were the most common indications for dermatoscopy. Factors influencing the utilization of dermatoscopy included increased diagnostic accuracy, enhanced patient care, better patient communication and general compliance, and improved satisfaction among dermatologists. Conclusions: This national questionnaire-based study demonstrates that dermatoscopy has become an integral part of daily dermatological practice in Greece. The findings highlight the significance of structured training and education to promote dermoscopy's effective and routine use. Incorporating dermatoscopy into clinical practice not only improves diagnostic precision but also enhances patient care, contributing to the overall quality of dermatological services in Greece.

Real-Life Utility of Basophil Activation Test in the Diagnosis of Immediate Hypersensitivity Drug Reactions.

INTRODUCTION: The basophil activation test (BAT) is a flow cytometry laboratory technique that assesses the level of activation indicators expressed on the surface of basophils. We conducted a real-life study in a prospective cohort of patients with reported drug hypersensitivity reactions to determine the true relevance of BAT as a diagnostic tool for assessing immediate hypersensitivity reactions to medicines. METHODS: We prospectively assessed individuals with clinical suspicion of immediate hypersensitivity reactions to drugs over a 2-year period. The allergological evaluation was carried out in accordance with European Academy of Allergy and Clinical Immunology (EAACI) guidance. All patients underwent BAT using the activation marker CD63. RESULTS: In total 13 patients with 54 reported immediate drug hypersensitivity reactions to medications were included in this study. Twelve were female (92.3%) and one was male (7.70%). The mean ± SD age of the patients was 47.31 ± 19.94 years. Antibiotics were tested in 35.2% (19/54) of patients, corticosteroids in 24.1% (13/54), iodinated contrast medium in 14.8% (8/54), and NSAIDs in 5.6% (3/54). There was no correlation between the BAT results and the age of patients, gender, type of medication, or time interval between the allergic reaction and BAT procedure. The sensitivity of BAT 5% CD63+ basophils to drugs was 97.6%, specificity was 96% for drug allergies, positive predictive value (PPV) was 94.3%, and negative predictive value (NPV) was 95.2%. CONCLUSIONS: The sensitivity of BAT for drug allergies is limited, but it can nevertheless be very helpful before contemplating provocation testing in cases of life-threatening drug allergies where patients cannot be rechallenged or in cases of medications for which no other tests are available or their results are ambiguous.

Perioperative characteristics, histologic diagnosis, complications, and outcomes of dogs undergoing percutaneous drainage, sclerotherapy or surgical management of intrarenal cystic lesions: 18 dogs (2004-2021).

BACKGROUND: Canine intrarenal cystic lesions (ICLs) are infrequently reported in the veterinary literature. Several treatment options have been described including cyst fenestration (partial nephrectomy/deroofing) +/- omentalization, sclerotherapy using alcohol as a sclerosing agent, percutaneous cyst drainage (PCD), and ureteronephrectomy. Information regarding presenting clinical signs, physical examination findings, histologic diagnosis and outcomes of dogs with ICLs treated by different methods is limited. Medical records of 11 institutions were retrospectively reviewed to identify dogs that underwent PCD, sclerotherapy, surgical deroofing +/- omentalization, or ureteronephrectomy for management of ICLs from 2004 to 2021. Six weeks postoperative/post-procedural follow-up was required. Cases suspected to represent malignancy on preoperative imaging were excluded. The study objective was to provide information regarding perioperative characteristics, complications, and outcomes of dogs undergoing treatment of ICLs. RESULTS: Eighteen dogs were included, with 24 ICLs treated. Ten had bilateral. There were 15 males and 3 females, with crossbreeds predominating. PCD, sclerotherapy, deroofing and ureteronephrectomy were performed in 5 (5 ICLs treated), 7 (11 ICLs), 6 (6), and 7 (7) dogs, respectively, with 5 dogs undergoing > 1 treatment. Seven dogs experienced 8 complications, with requirement for additional intervention commonest. PCD, sclerotherapy and deroofing resulted in ICL resolution in 0/5, 3/11 and 3/6 treated ICLs, respectively. Histopathology identified renal cysts (RCs) in 7/13 dogs with histopathology available and neoplasia in 6/13 (4 malignant, 2 benign). Of 5 dogs diagnosed histopathologically with neoplasia, cytology of cystic fluid failed to identify neoplastic cells. Among 7 dogs with histologically confirmed RCs, 4 had concurrent ICLs in ipsilateral/contralateral kidney, compared with 2/6 dogs with histologically confirmed neoplasia. CONCLUSIONS: Benign and neoplastic ICLs were approximately equally common and cystic fluid cytology failed to differentiate the 2. Among renal-sparing treatments, deroofing most commonly resulted in ICL resolution. Presence of concurrent ICLs in ipsilateral/contralateral kidney does not appear reliable in differentiating benign from malignant ICLs.

Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer.

BACKGROUND: Accurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days. METHODS: Using a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients. RESULTS: The resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days. CONCLUSIONS: We conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.

Willingness to pay and quality of life in patients with pruritic skin disorders.

Pruritic dermatosis is a frequent and burdensome disease. The objectives of this study were (1) to assess the willingness to pay (WTP) and the health-related quality of life (HRQoL) in patients with pruritic dermatoses and (2) to compare the results with data on socio-demographic data, and clinical features/symptoms of the patients. One hundred and three patients with pruritic dermatosis had participated in a non-interventional, cross-sectional study. Socio-demographic data, clinical features/symptoms, a health-related quality of life (HRQoL)-based and a dermatology-specific instrument (SF-6D and DLQI, respectively), and two utility indicators such as rating scale (RS) and time-trade-off (TTO) as well as willingness to pay (WTP) were recorded. In our study, there was a significant correlation between DLQI scores and WTP (p < 0.001). Time-trade-off (TTO) was also statistically correlated with SF-6D (p = 0.001). Regression models showed that daily duration and pruritus intensity were associated with lower HRQoL. Furthermore, WTP was the only measure revealing demographic and socio-economic characteristics such as age, education level, family status and income as predicting factors. No significant differences between groups of varying skin diseases were observed. HRQoL and WTP proved to be valid tools to assess the burden of disease in patients with pruritic dermatosis. However, further research with a larger number of patients is needed to validate the present findings.

Botulinum toxin type A--treatment of a patient with multiple cutaneous piloleiomyomas.

BACKGROUND: Treatment of multiple cutaneous piloleiomyomas which are rare, frequently painful, benign tumors originating from the arrector pilorum muscle of hair follicles is difficult. OBJECTIVE: To determine the efficiency of botulinum toxin type A (BT-A) treatment for pain relief of cutaneous piloleiomyomas. METHODS: A patient with multiple painful piloleiomyomas was treated with local injections of 200 units of BT-A. RESULTS: There was a rapid and sustained decrease in pain. Treatment was repeated every 3 months for 2 years with the same efficacy. CONCLUSION: BT-A may be a promising new treatment option for multiple painful cutaneous piloleiomyomas.