No abstract

Summary Background Cutaneous T‐cell lymphoma (CTCL) negatively impacts quality of life (QoL), but existing QoL questionnaires may not comprehensively reflect patients’ experience. Objectives To identify the aspects of QoL that are most meaningful to patients with CTCL and to evaluate existing QoL instruments in this context. Methods Semistructured interviews were conducted between May and June 2019 using purposive sampling of patients with CTCL. Data were analysed by an inductive thematic approach using Dedoose Version 8.0.35. Results One‐on‐one interviews lasting a median of 43 min were completed by 18 patients [median age 62 years (interquartile range 52–70); 39% advanced‐stage (IIB–IV)]. Itch was the most common clinical symptom reported (16 of 18 patients), followed by pain (12 of 18), skin breaks (11 of 18) and skin flaking (10 of 18). Eleven patients reported that their symptoms interfered with sleep, which impacted daily functioning. Patients also noted a lack of understanding of the disease in the community and felt uncertain (12 of 18), depressed (11 of 18), suicidal (four of 18) and hopeless (nine of 18). Nearly all patients (17 of 18) reported a sense of ‘otherness’ (not feeling ‘normal’ or ‘like themselves’), and most patients (16 of 18) specifically mentioned concern about their physical appearance. Patients also noted substantial treatment burden. Salient patient concerns, including individual clinical symptoms, concern about appearance and problems with sleep, were not adequately or consistently represented in generic, skin‐specific or CTCL‐specific QoL measures. Conclusions Incorporating the concerns and priorities that distinguish patients with CTCL from other patient populations will be of paramount importance in developing a comprehensive CTCL‐specific measure of QoL that adequately captures patients’ experience.

Background & AimsPancreatic stellate cells (PSCs) regulate the development of chronic pancreatitis (CP) and are activated by the cytokine transforming growth factor β (TGFB). Integrins of the αv family promote TGFB signaling in mice, probably by interacting with the Arg-Gly-Asp (RGD) sequence of the TGFB latency-associated peptide, which frees TGFB to bind its cellular receptors. However, little is known about the role of integrins in the development of CP. We investigated the effects of small-molecule integrin inhibitors in a mouse model of CP.MethodsWe induced CP in C57BL/6 female mice by repeated cerulein administration. An active RGD peptidomimetic compound (Center for World Health and Medicine [CWHM]-12) was delivered by continuous infusion, starting 3 days before or 5 days after cerulein administration began. Pancreata were collected and parenchymal atrophy, fibrosis, and activation of PSCs were assessed by histologic, gene, and protein expression analyses. We measured CWHM-12 effects on activation of TGFB in co-culture assays in which rat PSC cells (large T immortalized cells [LTC-14]) activate expression of a TGFB-sensitive promoter in reporter cells.ResultsPancreatic tissues of mice expressed messenger RNAs encoding subunits of RGD-binding integrins. Cerulein administration increased expression of these integrins, altered pancreatic cell morphology, and induced fibrosis. The integrin inhibitor CWHM-12 decreased acinar cell atrophy and loss, and substantially reduced fibrosis, activation of PSCs, and expression of genes regulated by TGFB. CWHM-12 also reduced established fibrosis in mice and blocked activation of TGFB in cultured cells.ConclusionsBased on studies of a mouse model of CP and cultured PSCs, integrins that bind RGD sequences activate PSCs and promote the development of pancreatic fibrogenesis in mice. Small-molecule antagonists of this interaction might be developed for treatment of pancreatic fibrotic diseases.

No abstract

provided by hair styles in women. Human papillomavirus infection and/or systemic immunosuppression are additional risk factors for SCC; however, it is unclear whether they influence SCC development differently regarding face region or sex. 2 Melanoma distribution on the face may differ by sex. In two studies, 59Á8% and 71Á8% of facial melanoma cases were distributed on the cheek in female patients as compared with 48Á8% and 43Á6%, respectively, in male patients. 6,7 Although protection from hair can help decrease melanoma occurrence on the external face in women, the higher incidence of melanoma on the cheek may involve other factors, including hormone-related UV sensitivity and habitual friction. 7,8 Larger studies with detailed anatomical mapping are needed to confirm our results.The present study was a descriptive, single-centre study that contained a limited number of patients, and did not adjust for confounders. However, the unique nonoverlapping distributions of BCC, SCC and melanoma on the face surface indicates the presence of disease-specific aetiological factors other than UV exposure.