Causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomisation study.

Background: Hepatocellular carcinoma (HCC), the predominant malignancy of the digestive tract, ranks as the third most common cause of cancer-related mortality globally, significantly impeding human health and lifespan. Emerging immunotherapeutic approaches have ignited fresh optimism for patient outcomes. This investigation probes the link between 731 immune cell phenotypes and HCC through Mendelian Randomization and single-cell sequencing, aiming to unearth viable drug targets and dissect HCC's etiology. Methods: We conducted an exhaustive two-sample Mendelian Randomization analysis to ascertain the causal links between immune cell features and HCC, utilizing publicly accessible genetic datasets to explore the causal connections of 731 immune cell traits with HCC susceptibility. The integrity, diversity, and potential horizontal pleiotropy of these findings were rigorously assessed through extensive sensitivity analyses. Furthermore, single-cell sequencing was employed to penetrate the pathogenic underpinnings of HCC. Results: Establishing a significance threshold of pval_Inverse.variance.weighted at 0.05, our study pinpointed five immune characteristics potentially elevating HCC risk: B cell % CD3- lymphocyte (TBNK panel), CD25 on IgD+ (B cell panel), HVEM on TD CD4+ (Maturation stages of T cell panel), CD14 on CD14+ CD16- monocyte (Monocyte panel), CD4 on CD39+ activated Treg ( Treg panel). Conversely, various cellular phenotypes tied to BAFF-R expression emerged as protective elements. Single-cell sequencing unveiled profound immune cell phenotype interactions, highlighting marked disparities in cell communication and metabolic activities. Conclusion: Leveraging MR and scRNA-seq techniques, our study elucidates potential associations between 731 immune cell phenotypes and HCC, offering a window into the molecular interplays among cellular phenotypes, and addressing the limitations of mono-antibody therapeutic targets.

Digital Remote Monitoring Using an mHealth Solution for Survivors of Cancer: Protocol for a Pilot Observational Study.

BACKGROUND: Healthy lifestyle interventions have a positive impact on multiple disease trajectories, including cancer-related outcomes. Specifically, appropriate habitual physical activity, adequate sleep, and a regular wholesome diet are of paramount importance for the wellness and supportive care of survivors of cancer. Mobile health (mHealth) apps have the potential to support novel tailored lifestyle interventions. OBJECTIVE: This observational pilot study aims to assess the feasibility of mHealth multidimensional longitudinal monitoring in survivors of cancer. The primary objective is to test the compliance (user engagement) with the monitoring solution. Secondary objectives include recording clinically relevant subjective and objective measures collected through the digital solution. METHODS: This is a monocentric pilot study taking place in Bangor, Wales, United Kingdom. We plan to enroll up to 100 adult survivors of cancer not receiving toxic anticancer treatment, who will provide self-reported behavioral data recorded via a dedicated app and validated questionnaires and objective data automatically collected by a paired smartwatch over 16 weeks. The participants will continue with their normal routine surveillance care for their cancer. The primary end point is feasibility (eg, mHealth monitoring acceptability). Composite secondary end points include clinically relevant patient-reported outcome measures (eg, the Edmonton Symptom Assessment System score) and objective physiological measures (eg, step counts). This trial received a favorable ethical review in May 2023 (Integrated Research Application System 301068). RESULTS: This study is part of an array of pilots within a European Union funded project, entitled "GATEKEEPER," conducted at different sites across Europe and covering various chronic diseases. Study accrual is anticipated to commence in January 2024 and continue until June 2024. It is hypothesized that mHealth monitoring will be feasible in survivors of cancer; specifically, at least 50% (50/100) of the participants will engage with the app at least once a week in 8 of the 16 study weeks. CONCLUSIONS: In a population with potentially complex clinical needs, this pilot study will test the feasibility of multidimensional remote monitoring of patient-reported outcomes and physiological parameters. Satisfactory compliance with the use of the app and smartwatch, whether confirmed or infirmed through this study, will be propaedeutic to the development of innovative mHealth interventions in survivors of cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52957.

Tele-Monitoring of Cancer Patients' Rhythms during Daily Life Identifies Actionable Determinants of Circadian and Sleep Disruption.

The dichotomy index (I < O), a quantitative estimate of the circadian regulation of daytime activity and sleep, predicted overall cancer survival and emergency hospitalization, supporting its integration in a mHealth platform. Modifiable causes of I < O deterioration below 97.5%-(I < O)low-were sought in 25 gastrointestinal cancer patients and 33 age- and sex-stratified controls. Rest-activity and temperature were tele-monitored with a wireless chest sensor, while daily activities, meals, and sleep were self-reported for one week. Salivary cortisol rhythm and dim light melatonin onset (DLMO) were determined. Circadian parameters were estimated using Hidden Markov modelling, and spectral analysis. Actionable predictors of (I < O)low were identified through correlation and regression analyses. Median compliance with protocol exceeded 95%. Circadian disruption-(I < O)low-was identified in 13 (52%) patients and four (12%) controls (p = 0.002). Cancer patients with (I < O)low had lower median activity counts, worse fragmented sleep, and an abnormal or no circadian temperature rhythm compared to patients with I < O exceeding 97.5%-(I < O)high-(p < 0.012). Six (I < O)low patients had newly-diagnosed sleep conditions. Altered circadian coordination of rest-activity and chest surface temperature, physical inactivity, and irregular sleep were identified as modifiable determinants of (I < O)low. Circadian rhythm and sleep tele-monitoring results support the design of specific interventions to improve outcomes within a patient-centered systems approach to health care.

Lesson of the month 2: Oncology, obstetrics and orthopaedics: an unusual partnership.

Breast cancer diagnosed during pregnancy is a relatively uncommon event. This challenging situation presents clinicians with difficult decisions, often requiring a multidisciplinary approach at a time of heightened anxiety for the patient and their family. This paper describes the case of a young woman with metastatic breast cancer diagnosed in early pregnancy, and outlines how this complex clinical situation was managed.

Mucocutaneous manifestations of helminth infections: Nematodes.

In the 21st century, despite increased globalization through international travel for business, medical volunteerism, pleasure, and immigration/refugees into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on the cutaneous manifestations of helminth infections and is divided into 2 parts: part I focuses on nematode infections, and part II focuses on trematode and cestode infections. This review highlights the clinical manifestations, transmission, diagnosis, and treatment of helminth infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus.

Cystacanths of Oncicola venezuelensis (Acanthocephala: Oligacanthorhynchidae) in Caribbean termites and various paratenic hosts in the U.S. Virgin Islands.

Cystacanths of Oncicola venezuelensis (Acanthocephala: Oligacanthorhynchidae) were discovered in the hemocoel of Caribbean termites (Nasutitermes acajutlae) on St. Thomas and St. John islands in the U.S. Virgin Islands. In addition to occurring in the insect intermediate host, cystacanths were present in subcutaneous nodules of lizards (Anolis cristatellus and Anolis stratulus), in the greater omentum of small Indian mongooses (Herpestes auropunctatus), and embedded in mesenteries of pearly-eyed thrashers (Margarops fuscatus). These vertebrates likely are paratenic hosts, although a definitive host in the Virgin Islands is yet to be discovered. Cystacanths from intermediate and paratenic hosts agree fully with the original description of proboscis armature, including size and shape of hooks and their roots, of the species. Qualitative features of developing and growing structures agree with the original description of the species, but the sizes are smaller.