Background Cutaneous manifestations of COVID-19 may be useful disease markers and prognostic indicators. Recently, post-infectious telogen effluvium and trichodynia have also been reported. Objective To evaluate the presence of trichodynia and telogen effluvium in patients with COVID-19 and describe their characteristics in relation to other signs and symptoms of the disease. Methods Patients with a history of COVID-19 presenting to the clinics of a group of hair experts because of telogen effluvium and/or scalp symptoms, were questioned with regards about their hair signs and symptoms in relation to the severity of COVID-19 and associated symptoms. Results Data from 128 patients were collected. Telogen effluvium was observed in 66.3% of patients and trichodynia in 58.4%. Trichodynia was associated to telogen effluvium in 42.4% of cases and was associated to anosmia and ageusia in 66.1% and 44.1% of cases, respectively. In the majority of patients (62.5%), hair signs and symptoms started within the first month post-COVID-19 diagnosis and in 47.8% of patients after 12 weeks or more. Limitations Recruitment of patient in specialized hair clinics, lack of a control group, and lack of recording of patient comorbidities. Conclusion The severity of the post-viral telogen effluvium observed in patients with a history of COVID-19 infection is influenced by COVID-19 severity. We identified an early onset (<4 weeks) and a late onset (>12 weeks) telogen effluvium.

MTA and Z-100 composite were biocompatible at 4 and 12 weeks in this experimental model.

Colorectal cancer is a worldwide health burden, with high incidence and mortality, especially in the advanced stages of the disease. Preclinical models are very important and valuable to discover and validate early and specific biomarkers as well as new therapeutic targets. In order to accomplish that, the animal models must replicate the clinical evolution of the disease in all of its phases. In this article, we review the existent mouse models, with their strengths and weaknesses in the replication of human cancer disease progression, with major focus on orthotopic models. K E Y W O R D Scolorectal cancer, mouse model, orthotopic model

Hepatocellular carcinoma (HCC) has a worldwide high incidence and mortality. For this reason, it is essential to invest in new therapies for this type of cancer. Our team already proved that human amniotic membrane (hAM) is able to inhibit the metabolic activity of several human cancer cell lines, including HCC cell lines. Taking into account the previously performed work, this experimental study aimed to investigate the pathways by which hAM protein extracts (hAMPEs) act on HCC. Our results showed that hAMPE reduce the metabolic activity, protein content and DNA content in a dose- and time-dependent manner in all HCC cell lines. This therapy presents selective cytotoxicity, since it was not able to inhibit a non-tumorigenic human cell line. In addition, hAMPE induced cell morphology alterations in all HCC cell lines, but death type is cell line dependent, as proved by in vitro and in vivo studies. In conclusion, hAMPE have a promising role in HCC therapy, since it is capable of inducing HCC cytotoxicity and cell death.

Cholangiocarcinoma (CCA) mortality rates are increasing as a result of rising incidence and limited curative treatment(s) for patients with advanced disease. NOTCH pathway reactivation has been reported in biliary malignancies to conflicting degrees, hindering prioritization of key therapeutic targets within the network and identification of candidate responder patients for NOTCH‐directed therapies. We analyzed genomic data from 341 patients with CCA and identified NOTCH1 significantly increased in a subgroup characterized by distinct stromal infiltration. Network‐wide imbalance of the NOTCH pathway was seen in CCA, including correlation of NOTCH1 with NOTCH3 and NOTCH ligands. Given the diversity of observed NOTCH receptor engagement, γ‐secretase modulation was rationalized as a therapeutic option. Indeed, subcutaneous transplantation of sensitive and resistant CCA cell lines pretreated with a γ‐secretase inhibitor (GSi) cocktail demonstrated the antineoplastic effects of GSi in a subset of CCA and led to the development of a 225‐gene responder signature. This signature was validated in an independent cohort of 119 patients. Further, this signature was enriched in liver tumors initiated by hydrodynamic injections of activated‐NOTCH as compared with the AKT‐RAS‐driven tumors. Candidate GSi‐responder patients were characterized by distinct transcriptomes overlapping with previous hepatobiliary metastasis and stemness, unique stromal properties, and dysfunctional intratumoral immune infiltration. Pan‐cancer analysis identified 41.9% of cancer types to harbor prospective GSi‐responder patients, which was adapted into a 20‐gene GSi‐sensitivity score metric capable of discriminating nanomolar versus micromolar sensitivity to a cell‐permeable GSi (Z‐LLNle‐CHO) across 60 diverse tumor lines (area under the curve = 1). Conclusion: We have established a GSi‐responder signature with evidence across several patient cohorts, as well as in vitro and in vivo models, to enable precision medicine application of NOTCH‐directed therapy in CCA as well as prospectively across diverse malignancies.