Advances in the pharmacological management of cutaneous T-cell lymphoma.

INTRODUCTION: Current treatment guidelines for cutaneous T cell lymphoma (CTCL) advocate a stage-driven approach, considering clinical presentation, symptom burden, and patient comorbidities. Therapy selection hinges on factors like disease subtype, severity, and treatment availability. The primary goal is to enhance the quality of life by mitigating symptoms, as achieving lasting complete remission is infrequent. AREAS COVERED: Over the past decade (2013-2023), the therapeutic landscape of CTCL has experienced substantial transformation with the introduction of innovative therapies. This review explores the main pivotal developments in traditional treatment schedules and recently introduced drugs, aiming to offer clinicians and researchers a thorough perspective on the decade's progress in the field. EXPERT OPINION: Despite the progress made in CTCL therapeutics, ranging from topical chemotherapeutics to immunomodulatory agents, several unmet needs persist. Firstly, there is a pressing need for the incorporation of readily available predictors for treatment response, encompassing clinical, pathological, and molecular features. Secondly, a more profound comprehension of the tumor microenvironment is imperative to optimize the landscape of targetable molecules. Lastly, the undertaking of studies on combination regimens should be encouraged as it enhances therapy efficacies by synergistically combining agents with diverse modes of action.

Is blinding in studies of manual soft tissue mobilisation of the back possible? A feasibility randomised controlled trial with Swiss graduate students.

STUDY DESIGN: Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility. BACKGROUND: Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment. METHODS: On 7-8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from -1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating 'random guessing'-balanced 'active' and 'control' perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis. RESULTS: 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, -0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (-0.12 to 0.30) and -0.10 (-0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment. CONCLUSIONS: Blinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05822947 (retrospectively registered).

What Is New in Cutaneous T Cell Lymphoma?

PURPOSE OF REVIEW: This review focuses on updates in prognosis, pathogenesis, and treatment of cutaneous T cell lymphoma (CTCL). RECENT FINDINGS: Cohort studies indicate imaging may be necessary in early-stage CTCL. Risk factors for progression of CTCL have been identified. Interactions between malignant cells and the tumor microenvironment (TME) and the skin microbiome advance the understanding of pathogenesis and tumor cell dissemination. Studies support a hypothesis of circulating malignant tumor cells. MicroRNA (miR) influence tumor progression and prognosis; the IL22-STAT3-CCL20 cascade may be a novel target. IL-4, IL-5, and IL-31 cytokines are relevant for pruritus and could be targets for therapeutic interventions. Systemic therapies, such as JAK inhibitors, targeted antibodies, and checkpoint inhibitors, show promise in advanced stages. Allogenic hematopoietic stem cell transplantation provides a potential curative option for patients. Further investigations of prognosis and translational research are necessary to improve stratification of patients for treatment.

Association between vertebral bone mineral density, myocardial perfusion, and long-term cardiovascular outcomes: A sex-specific analysis.

BACKGROUND: Sexual dimorphism in the manifestation of coronary artery disease (CAD) has unleashed a call to reconsider cardiovascular risk assessment. Alterations of bone mineral density (BMD) have been associated with congestive heart failure and appear to be modified by sex. However, the sex-specific association between BMD, myocardial perfusion, and cardiovascular outcomes is currently unknown. METHODS: A total number of 491 patients (65.9 ± 10.7 years, 32.4% women) underwent 13N-ammonia positron emission tomography/computed tomography for evaluation of CAD, and were tracked for major adverse cardiac events (MACEs). RESULTS: Event-free survival (median follow-up time of 4.3 ± 2.0 years) was significantly reduced in patients with low (≤ 100 Hounsfield units) compared to those with higher BMD (log-rank P = .037). Accordingly, reduced BMD was chosen as significant predictor of MACE in a fully adjusted proportional hazards regression model (P = .015). Further, a first-order interaction term consisting of sex and BMD was statistically significant (P = .007). BMD was significantly lower in patients with abnormal myocardial perfusion or impaired left ventricular ejection fraction (P < .05). This difference, however, was noticed in men, but not in women. CONCLUSIONS: The association between low BMD and cardiovascular disease is sex dependent. Our data suggest that quantification of BMD during myocardial perfusion imaging for evaluation of CAD may be particularly useful in men.

Sex-dependent association between inflammation, neural stress responses, and impaired myocardial function.

PURPOSE: Evidence to date has failed to reveal unique female determinants of cardiovascular disease. However, a strong association was recently observed between increased metabolic activity in the amygdala, a neural centre involved in the processing of emotions, and impaired myocardial function in women, but not in men. Given the stronger immune responses in females, we sought to retrospectively investigate the interaction between inflammation, perceived stress, and myocardial injury. METHODS: Overall, 294 patients (mean age 66.9 ± 10.0 years, 28.6% women) underwent both, 99mTc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography for the assessment of cardiac function, bone marrow metabolism (surrogate marker of inflammation), and resting amygdalar activity. RESULTS: A positive association was found between amygdalar metabolism and 18F-FDG bone marrow uptake in women (r = 0.238, p = 0.029), but not in men (r = 0.060, p = 0.385). Linear regression models selected both, abnormal left ventricular ejection fraction (LVEF) and abnormal myocardial perfusion, as significant indicators of an increased amygdalar activity in women (B-coefficient LVEF, - 0.096; p = 0.021; abnormal myocardial perfusion, 3.227; p = 0.043), but not in men (bone marrow p = 0.076; abnormal myocardial perfusion p = 0.420). Accordingly, an interaction term consisting of sex and LVEF/abnormal myocardial perfusion was significant (p = 0.043 and p = 0.015, respectively). CONCLUSIONS: Upregulated amygdalar metabolism is associated with an enhanced inflammatory state in female patients with impaired cardiac function. Given that enhanced activity of the limbic system is associated with worse cardiovascular outcomes, our study suggests that a focus on inflammatory markers and indicators of distress might help to tailor cardiovascular risk assessment and therapy towards the female cardiovascular phenotype.

Metabolic Activity in Central Neural Structures of Patients With Myocardial Injury.

Background Increasing evidence suggests a psychosomatic link between neural systems and the heart. In light of the growing burden of ischemic cardiovascular disease across the globe, a better understanding of heart-brain interactions and their implications for cardiovascular treatment strategies is needed. Thus, we sought to investigate the interaction between myocardial injury and metabolic alterations in central neural areas in patients with suspected or known coronary artery disease. Methods and Results The association between resting metabolic activity in distinct neural structures and cardiac function was analyzed in 302 patients (aged 66.8±10.2 years; 70.9% men) undergoing fluor-18-deoxyglucose positron emission tomography and 99mTc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging. There was evidence for reduction of callosal, caudate, and brainstem fluor-18-deoxyglucose uptake in patients with impaired left ventricular ejection fraction (<55% versus ≥55%: P=0.047, P=0.022, and P=0.013, respectively) and/or in the presence of myocardial ischemia (versus normal perfusion: P=0.010, P=0.013, and P=0.016, respectively). In a sex-stratified analysis, these differences were observed in men, but not in women. A first-order interaction term consisting of sex and impaired left ventricular ejection fraction or myocardial ischemia was identified as predictor of metabolic activity in these neural regions (left ventricular ejection fraction: P=0.015 for brainstem; myocardial ischemia: P=0.004, P=0.018, and P=0.003 for callosal, caudate, or brainstem metabolism, respectively). Conclusions Myocardial dysfunction and injury are associated with reduced resting metabolic activity of central neural structures, including the corpus callosum, the caudate nucleus, and the brainstem. These associations differ in women and men, suggesting sex differences in the pathophysiological interplay of the nervous and cardiovascular systems.

Sex Differences in the Association between Inflammation and Ischemic Heart Disease.

BACKGROUND: Inflammation plays a fundamental role in mediating all stages of atherosclerosis. Given the higher prevalence of inflammatory rheumatologic conditions in women and the female propensity towards worse cardiovascular outcomes, refined strategies are needed to better identify the high-risk female cardiovascular phenotype. OBJECTIVES: This article aims to assess sex-specific links between inflammatory processes and the development and progression of ischemic heart disease. PATIENTS AND METHODS: The relationship between vertebral bone marrow metabolism-a marker of inflammation-and myocardial injury was retrospectively assessed in 294 patients (28.6% women, mean age: 66.9 ± 10.0 years) who underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 99mTc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). RESULTS: A significant increase in 18F-FDG bone marrow uptake was observed in women with impaired myocardial perfusion (SPECT-MPI) as compared to women with normal myocardial perfusion (standardized uptake value [SUV]: 2.2 ± 1.2 vs. 1.7 ± 0.5, p = 0.013), while no such difference was observed in men (SUV: 1.6 ± 0.8 vs. 1.6 ± 0.4, p = 0.372). Furthermore, a significant inverse correlation between left ventricular ejection fraction (LVEF) and bone marrow metabolism was seen in women (r = -0.229, p = 0.037), but not in men (r = -0.075, p = 0.289). Accordingly, in women, but not in men, bone marrow activity was identified as an independent predictor of both, reduced LVEF (ß-coefficient, -4.537; p = 0.040) and impaired myocardial perfusion (ß-coefficient, 0.138; p = 0.014). CONCLUSION: A strong link between bone marrow metabolism and impaired myocardial function and perfusion was observed in women, but not in men. Our data suggest that novel biomarkers of inflammation might help to identify women at risk for ischemic cardiomyopathy and to tailor disease management to the female cardiovascular phenotype.

Association between resting amygdalar activity and abnormal cardiac function in women and men: a retrospective cohort study.

AIMS: Cardiovascular outcomes of women with coronary artery disease (CAD) are perceived as relatively worse when compared to men. Amygdalar metabolic activity has recently been shown to independently predict cardiovascular events in patients without known cardiovascular disease. Given that traditional algorithms for risk prediction perform worse in women than in men, we sought to assess sex-specific associations between amygdalar metabolic activity and cardiac dysfunction with suspected or known CAD. METHODS AND RESULTS: This retrospective study included 302 patients (mean age 66.8 ± 10.2 years, 29.1% women) selected for evaluation of CAD, malignant, or inflammatory disease. All patients had undergone both, myocardial perfusion imaging by single photon emission computed tomography (MPI-SPECT) and whole-body fluoro-18-deoxyglucose (18F-FDG) positron emission tomography (PET), within 6 months. 18F-FDG resting amygdalar uptake was significantly increased in women with abnormal MPI scans (standardized uptake value 33.4 ± 6.5 vs. 30.4 ± 4.7, P = 0.043), while no such difference was observed in men (P = 0.808). In women, but not in men, a negative association between 18F-FDG resting amygdalar activity and left ventricular ejection fraction (LVEF) was observed (Pearson r = -0.308, P = 0.004). Accordingly, either LVEF [B-coefficient (standard error, SE) = -0.232 (0.109), P = 0.045] or abnormal MPI [B-coefficient (SE) = 8.264 (2.449), P = 0.003] were selected as significant predictors of high amygdalar 18F-FDG uptake in a fully adjusted linear regression model in women, and a first order interaction term consisting of sex and LVEF or sex and abnormal MPI was significant (P = 0.035 and P = 0.001, respectively). CONCLUSION: Resting amygdalar metabolic activity is associated with abnormal cardiac function and perfusion in women, suggesting a link between emotional stress and cardiovascular disease in women.