The limited ability of Convolutional Neural Networks to generalize to images from previously unseen domains is a major limitation, in particular, for safety-critical clinical tasks such as dermoscopic skin cancer classification. In order to translate CNN-based applications into the clinic, it is essential that they are able to adapt to domain shifts. Such new conditions can arise through the use of different image acquisition systems or varying lighting conditions. In dermoscopy, shifts can also occur as a change in patient age or occurrence of rare lesion localizations (e.g. palms). These are not prominently represented in most training datasets and can therefore lead to a decrease in performance. In order to verify the generalizability of classification models in real world clinical settings it is crucial to have access to data which mimics such domain shifts. To our knowledge no dermoscopic image dataset exists where such domain shifts are properly described and quantified. We therefore grouped publicly available images from ISIC archive based on their metadata (e.g. acquisition location, lesion localization, patient age) to generate meaningful domains. To verify that these domains are in fact distinct, we used multiple quantification measures to estimate the presence and intensity of domain shifts. Additionally, we analyzed the performance on these domains with and without an unsupervised domain adaptation technique. We observed that in most of our grouped domains, domain shifts in fact exist. Based on our results, we believe these datasets to be helpful for testing the generalization capabilities of dermoscopic skin cancer classifiers.
To explore the interaction of real-world patients with a chatbot in a clinical setting, investigating key aspects of medical information provided by large language models (LLMs). The study enrolled 300 patients seeking urological counselling between February and July 2024. First, participants voluntarily conversed with a Generative Pre-trained Transformer 4 (GPT-4) powered chatbot to ask questions related to their medical situation. In the following survey, patients rated the perceived utility, completeness, and understandability of the information provided during the simulated conversation as well as user-friendliness. Finally, patients were asked which, in their experience, best answered their questions: LLMs, urologists, or search engines. A total of 292 patients completed the study. The majority of patients perceived the chatbot as providing useful, complete, and understandable information, as well as being user-friendly. However, the ability of human urologists to answer medical questions in an understandable way was rated higher than of LLMs. Interestingly, 53% of participants rated the question-answering ability of LLMs higher than search engines. Age was not associated with preferences. Limitations include social desirability and sampling biases. This study highlights the potential of LLMs to enhance patient education and communication in clinical settings, with patients valuing their user-friendliness and comprehensiveness for medical information. By addressing preliminary questions, LLMs could potentially relieve time constraints on healthcare providers, enabling medical personnel to focus on complex inquiries and patient care.
This rare case report describes the diagnosis and treatment of an isolated left-sided orbital floor fracture with a complete dislocation of the globe into the maxillary sinus and briefly discusses the indications of surgery and recovery for orbital floor fractures in general. Complete herniation of the globe through an orbital blow-out fracture is uncommon. However, the current case illustrates that such an occurrence should be in the differential diagnosis and should be considered, especially following high speed/impact injuries involving a foreign object. In these rare cases, surgical intervention is required.
Multiple interventions are available for the treatment of actinic keratosis (AK). However, most randomized clinical trials and meta-analyses focus on short-term efficacy outcomes.To investigate and synthesize the long-term efficacy (≥12 months) of interventions for AK from parallel-arm randomized clinical trials.Searches in MEDLINE, Embase, and Central were conducted from inception until April 6, 2020. The reference lists of the included studies and pertinent trial registers were hand searched. The study was completed February 27, 2021.Two reviewers screened the titles and abstracts of 2741 records. Finally, 17 published reports (original studies and follow-up reports) referring to 15 independent randomized clinical trials with an overall sample size of 4252 patients were included.Two reviewers independently extracted data on study, patient, and intervention characteristics. Network meta-analysis (NMA) of each outcome was conducted with a frequentist approach. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidance for NMA was used to assess the certainty of evidence. The revised Cochrane risk-of-bias tool for randomized clinical trials was used to evaluate the methodologic quality.Participant complete clearance, participant partial clearance, and lesion-specific clearance were the outcomes, with each assessed at least 12 months after the end of treatment.Data from 15 independent randomized clinical trials including 4252 patients were extracted and synthesized. Ten studies were included in an NMA for the outcome of participant complete clearance, with photodynamic therapy with aminolevulinate (ALA-PDT) showing the most favorable risk ratio (RR) compared with placebo (RR, 8.06; 95% CI, 2.07-31.37; GRADE, moderate), followed by imiquimod, 5% (RR, 5.98; 95% CI, 2.26-15.84; GRADE, very low), photodynamic therapy with methyl aminolevulinate (MAL-PDT) (RR, 5.95; 95% CI, 1.21-29.41; GRADE, low), and cryosurgery (RR, 4.67; 95% CI, 1.36-16.66; GRADE, very low). Similarly, ALA-PDT had the highest RR in the NMA for lesion-specific clearance (RR, 5.08; 95% CI, 2.49-10.33; GRADE, moderate). No NMA was possible for participant partial clearance owing to poor reporting of this outcome.This systematic review and network meta-analysis found that therapy including ALA-PDT, imiquimod, 5%, MAL-PDT, and cryosurgery was associated with significant long-term efficacy in the NMA. This study provides data for a possible use in an evidence-based framework for selecting interventions with sustained lesion clearance.
Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) is a key genetic feature which should be tested in every patient with colorectal cancer (CRC) according to medical guidelines. Artificial intelligence (AI) methods can detect MSI/dMMR directly in routine pathology slides, but the test performance has not been systematically investigated with predefined test thresholds.
<div>Abstract<p>Patients with melanoma resistant to RAF/MEK inhibitors (RMi) are frequently resistant to other therapies, such as immune checkpoint inhibitors (ICI), and individuals succumb to their disease. New drugs that control tumor growth and favorably modulate the immune environment are therefore needed. We report that the small-molecule CX-6258 has potent activity against both RMi-sensitive (RMS) and -resistant (RMR) melanoma cell lines. Haspin kinase (HASPIN) was identified as a target of CX-6258. HASPIN inhibition resulted in reduced proliferation, frequent formation of micronuclei, recruitment of cGAS, and activation of the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway. In murine models, CX-6258 induced a potent cGAS-dependent type-I IFN response in tumor cells, increased IFNγ-producing CD8<sup>+</sup> T cells, and reduced Treg frequency <i>in vivo</i>. HASPIN was more strongly expressed in malignant compared with healthy tissue and its inhibition by CX-6258 had minimal toxicity in <i>ex vivo</i>–expanded human tumor-infiltrating lymphocytes (TIL), proliferating TILs, and <i>in vitro</i> differentiated neurons, suggesting a potential therapeutic index for anticancer therapy. Furthermore, the activity of CX-6258 was validated in several Ewing sarcoma and multiple myeloma cell lines. Thus, HASPIN inhibition may overcome drug resistance in melanoma, modulate the immune environment, and target a vulnerability in different cancer lineages.</p>Significance:<p>HASPIN inhibition by CX-6258 is a novel and potent strategy for RAF/MEK inhibitor–resistant melanoma and potentially other tumor types. HASPIN inhibition has direct antitumor activity and induces a favorable immune microenvironment.</p></div>
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