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Introduction: Targeting of the proinflammatory cytokine interleukin 17A (IL-17A) or tumor necrosis factor alpha (TNFα) with the monoclonal antibodies (mAbs) ixekizumab or adalimumab, respectively, is a successful therapy for chronic plaque psoriasis. The effects of these treatments on immune cell populations in the skin are largely unknown., Methods: In this study, we compared the composition of cutaneous, lesional and non-lesional immune cells and blood immune cells in ixekizumab- or adalimumab-treated patients with psoriasis., Results: Our data reveal that both treatments efficiently downregulate T cells, macrophages and different subsets of dendritic cells (DCs) in lesional skin towards levels of healthy skin. In contrast to lesional skin, non-lesional areas in patients harbor only few or no detectable DCs compared to the skin of healthy subjects. Treatment with neither ixekizumab nor adalimumab reversed this DC imbalance in non-lesional skin of psoriatic patients., Conclusion: Our study shows that anti-IL-17A and anti-TNFα therapy rebalances the immune cell repertoire of lesional skin in psoriatic patients but fails to restore the disturbed immune cell repertoire in non-lesional skin., (© 2024. The Author(s).)

Iron uptake via the transferrin receptor (CD71) is a pivotal mechanism for T cell proliferation. Yet, it is incompletely understood if targeting of CD71 also affects the differentiation and functional polarization of primary human T cells. In this study, we demonstrate that inhibition of iron ingestion with blocking mAbs against CD71 induces nonproliferating T cells, which release high amounts of IL-2. Targeting of CD71 with blocking or nonblocking mAbs did not alter major signaling pathways and the activation of the transcription factors NF-κB, NFAT, or AP-1 as analyzed in Jurkat T cells. Growth arrest in iron-deficient (Fe-def) T cells was prevented upon addition of exogenous iron in the form of ferric ammonium citrate but was not reversible by exogenous IL-2. Surprisingly, protein synthesis was found to be intact in Fe-def T cells as demonstrated by comparable levels of CD69 upregulation and cytokine production with iron-sufficient T cells upon stimulation with CD3 plus CD28 mAbs. Indeed, high amounts of IL-2 were detectable in the supernatant of Fe-def T cells, which was accompanied with a reduced cell surface expression of IL-2R. When we used such Fe-def T cells in allogeneic MLRs, we observed that these cells acquired an accessory cell function and stimulated the proliferation of bystander T cells by providing IL-2. Thus, the results of our study demonstrate that iron deprivation causes nonproliferating, altruistic T cells that can help and stimulate other immune cells by providing cytokines such as IL-2., (Copyright © 2020 The Authors.)

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer in the United States, second only to basal cell carcinoma. While majority of patients have a favorable outcome after surgical resection, a subset of patients carry a higher risk of local recurrence, distant metastasis, and mortality. In this article, we present an unusual case of a 54-year-old male who had trunk cSCC at the site of burn wound that recurred after surgical resection and radiotherapy. Interestingly the cSCC disease recurrence presented with respiratory symptoms secondary to malignant pleural effusion from direct invasion of pleura as the tumor eroded through the chest wall. The patient died within a few weeks from progressive disease. Despite the high incidence rate of cSCC, there is a paucity of randomized controlled trials to guide evidence-based management of cSCC in recurrent and metastatic disease., Competing Interests: The authors have declared that no competing interests exist.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of neurotoxic chemotherapies. No therapies are available to prevent CIPN. The small number of positive randomized clinical trials (RCTs) evaluating preventive therapies for CIPN provide little guidance to inform the design of future trials. Moreover, the lack of consensus regarding major design features in this area poses challenges to development of new therapies. An Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION)-Consortium on Clinical Endpoints and Procedures for Peripheral Neuropathy Trials (CONCEPPT) meeting attended by neurologists, oncologists, pharmacists, clinical trialists, statisticians, and regulatory experts was convened to discuss design considerations and provide recommendations for CIPN prevention trials. This article outlines considerations related to design of RCTs that evaluate preventive therapies for CIPN including (1) selection of eligibility criteria (e.g., cancer types, chemotherapy types, inclusion of preexisting neuropathy); (2) selection of outcome measures and endpoints, including those that incorporate alterations in chemotherapy dosing, which may affect the rate of CIPN development and its severity; (3) potential effects of the investigational therapy on the efficacy of chemotherapy; and (4) sample size estimation. Our hope is that attention to the design considerations and recommendations outlined in this article will improve the quality and assay sensitivity of CIPN prevention trials and thereby accelerate the identification of efficacious therapies., (© 2018 American Academy of Neurology.)

There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for "precision medicine" or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.

Background: Based on an increasing number of outpatient treatments, an extensive demand planning is necessary to ensure the quality of medical care. University outpatient clinics are special parts of this sector and therefore it is necessary that a research demonstrates the nearly uninvestigated position of a paediatric outpatient clinic., Patients: The research at the university hospital for children and adolescents in Leipzig started in 2009 to survey 2283 of in total 9391 patients and the physicians., Methods: Sociodemographic data as well as economic and medical facts were determined by using questionnaires. In each case a questionnaire was answered by the children or their accompanying persons and a separate one was completed by the respective doctor., Results: The results created a foundation, on the basis of patient volume per day and per daytime. Less than 20% of the children admitted to consult the clinic for their first time. The majority of patients visit them because of a letter of referral. Most of the patients (58%) were younger than 6 years old. Approximately 35% of patients did not come from the city region of Leipzig., Conclusion: The investigation evidenced the necessity of a day and night operating institution for children in the region of Leipzig as well as the high specialisation of the outpatient clinic. In need of further investigation is the cooperation between several physicians to find out if this lots of medical examination are necessary or if there took place overlapping., (© Georg Thieme Verlag KG Stuttgart · New York.)

Context: Few studies have examined the prevalence and severity of treatment-induced neuropathic symptoms in patients across different cancer types., Objectives: This study aimed to report the prevalence of numbness/tingling (N/T) and neuropathic pain in patients with colorectal cancer (CRC) vs. other cancers, describe the prevalence of moderate-to-severe N/T by specific clinical variables, and examine factors associated with the presence of these symptoms., Methods: A total of 3106 outpatients with colorectal (n = 718), breast (n = 1544), lung (n = 524), or prostate (n = 320) cancer were enrolled at any point in their treatment. Assessments were conducted at the initial visit and 28-35 days later. Patients reported pain and N/T; clinicians reported mechanism of pain and ranked the top three symptoms causing difficulties., Results: Moderate-to-severe N/T was higher in patients with CRC relative to other cancer types (25.8% vs. 17.1%, P < 0.001); 25% vs. 10.5% of clinicians rated N/T as a top three symptom for patients with CRC relative to other cancers (P < 0.001). The prevalence of neuropathic pain was comparable between patients with CRC and other cancers (P = 0.654). Patients with CRC, longer duration of cancer, prior therapy, on current therapy, older patients, and patients of black race experienced worse N/T., Conclusion: Patients with CRC experience significantly higher rates of N/T but comparable neuropathic pain, relative to patients with other cancers. Awareness of the prevalence and severity of neuropathic symptoms and their associated risk factors in this patient population is critical for both clinicians and patients., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated how treatment-induced neuropathic symptoms are associated with patients' quality of life (QOL) and clinician-reported difficulty in caring for patients., Methods: Data were obtained from 3,106 outpatients with colorectal, breast, lung, or prostate cancer on numbness/tingling (N/T), neuropathic pain, and QOL. Clinicians reported the degree of difficulty in caring for patients' physical and psychological symptoms., Results: For all patients, moderate to severe N/T was associated with poor QOL (OR = 1.82, 95% CI = 1.47-2.26, P < 0.001) but neuropathic pain was not (OR = 1.31, 95% CI = 0.94-1.83, P = 0.114). Moderate to severe N/T and neuropathic pain were associated with increased care difficulty (OR = 1.49, 95% CI = 1.27-1.74, P < 0.001 for N/T, and OR = 1.46, 95% CI = 1.15-1.84, P = 0.002 for neuropathic pain). The association of neuropathic pain with care difficulty was most significant in patients with colorectal cancer (CRC) (OR = 2.32, 95% CI = 1.41-3.83, P = 0.001). Baseline neuropathic pain was associated with declining QOL in CRC patients (OR = 2.08, 95% CI = 1.21-3.58, P = 0.008)., Conclusions: Clinicians may experience increased care difficulty for patients of all cancer types with moderate to severe N/T or neuropathic pain; care difficulty due to neuropathic pain may be higher for CRC patients. Nearly half the patients of all cancer types with moderate to severe N/T may expect poor short-term QOL; CRC-but not other-patients with baseline neuropathic pain are likely to experience declining QOL., Implications for Cancer Survivors: About half of patients with moderate to severe N/T (any cancer type) may expect poor QOL in the short term; CRC patients with baseline neuropathic pain in particular may experience declining QOL.

Background: Src, EphA2, and platelet-derived growth factor receptors α and β are dysregulated in pancreatic ductal adenocarcinoma (PDAC)., Methods: Dasatinib is an oral multitarget tyrosine kinase inhibitor that targets BCR-ABL, c-Src, c-KIT, platelet-derived growth factor receptor β, and EphA2. We conducted a phase II, single-arm study of dasatinib as first-line therapy in patients with metastatic PDAC., Methods: Dasatinib (100 mg twice a day, later reduced to 70 mg twice a day because of toxicities) was orally administered continuously on a 28-day cycle. The primary endpoint was overall survival (OS). Response was measured using the Response Evaluation Criteria in Solid Tumors. Circulating tumor cells (CTCs) were also collected., Results: Fifty-one patients enrolled in this study. The median OS was 4.7 months (95% confidence interval [CI]: 2.8-6.9 months). Median progression-free survival was 2.1 months (95% CI: 1.6-3.2 months). In 34 evaluable patients, the best response achieved was stable disease in 10 patients (29.4%). One patient had stable disease while on treatment for 20 months. The most common nonhematologic toxicities were fatigue and nausea. Edema and pleural effusions occurred in 29% and 6% of patients, respectively. The number of CTCs did not correlate with survival., Conclusion: Single-agent dasatinib does not have clinical activity in metastatic PDAC.

Purpose: Advanced cancers of the bile duct and gallbladder carry an ominous prognosis. Rebeccamycin analogue (RA) is a novel antitumor antibiotic where phase I trials suggested clinical efficacy in patients with biliary cancers., Methods: The primary objective was to determine the response rate to RA in patients with advanced gallbladder and bile duct tumors. Secondary endpoints were survival and pharmacokinetic characterization. RA was given at a dose 165 mg/(m(2) day) x 5 days every 3 weeks., Results: Forty-six patients were enrolled. Nine patients were removed from study before their first planned imaging study for response. Two patients had partial responses and 16 had stable disease. On an intent-to-treat analysis the median survival was 6.3 months. A >20% drop in CA19.9 was seen in 43% of patients with initial high levels. Grade 4 neutropenia and thrombocytopenia were seen in 35 and 5% of patients, respectively. Febrile neutropenia occurred in 16% of patients. The pharmacokinetic profile of this trial closely resembles those of prior phase I trials. Measured biliary concentrations of RA were as much as 100x greater than simultaneous plasma concentration., Conclusion: Although RA has a response rate of 5% in advanced biliary cancers, it is associated with significant numbers of patients experiencing prolonged stable disease. Biliary concentrations of RA are significantly greater than plasma concentrations.

Validated data from which conclusions may be drawn about the management of leukemia during pregnancy are sparse. Cytotoxic agents should generally be avoided during the first trimester, when there is an approximately 17% chance of fetal malformation, particularly with folate antagonists. However, acute leukemias demand prompt institution of cytotoxic chemotherapy to maximize the chances of maternal survival. Treatment beyond the first trimester is generally safe if appropriate monitoring and obstetric care are available. Treatment of chronic leukemias can usually be delayed until delivery without compromising maternal health. Treatment of leukemia during pregnancy does not appear to have a significant impact on the future growth and development of the child.