Background/Objectives: The mitochondrial unfolded protein response (UPRmt) is one of the mitochondrial quality control mechanisms that is responsible for reparation and removal of damaged proteins in mitochondria. Methods: Here we investigated the role of the UPRmt in the myocardium of humans with and without heart failure and in the cell culture model. Results: The analysis of myocardial samples by ELISA from patients with ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), as well as healthy donors, revealed a significantly reduced expression of the UPRmt proteins HSP10, CLPP, LONP1, OMA1, and SPG7 in patients with DCM and ICM. Furthermore, patients with DCM and ICM exhibited elevated levels of myocardial reactive oxygen species (ROS, tested by 4-hydroxynonenal) compared to controls, and a positive correlation between ROS production and mt-HSP70, OMA1, and SPG7 protein expression. The correlation analysis indicated a negative correlation between cardiomyocyte hypertrophy and the expression of several UPRmt genes. The inhibition of four tested UPRmt effector proteins exacerbated the injury of cultured cells under oxidative stress. The patients with ICM, DCM, or both, who showed lower myocardial expression of HSP10, HSP60, HTRA2, OMA1, SPG7, and YME1L, underwent heart transplantation or implantation of a left ventricular assist device earlier in life compared to those with the higher protein expression. Conclusions: In conclusion, our findings indicate that the reduced expression of several UPRmt effector proteins is associated with accelerated heart failure in patients, which, together with other results, indicates that impaired UPRmt may contribute to the pathogenesis of heart failure in humans.

Introduction: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, often exhibiting loss of pan-T-cell markers such as CD2, CD3, CD5, and CD7. While these immunophenotypic alterations assist in diagnosis, their prognostic relevance in early-stage MF remains uncertain. This study aimed to determine whether immunohistochemical loss of T-cell markers CD2, CD3, CD5, and CD7 in patients with early-stage mycosis fungoides is associated with overall survival and progression-free survival. Methods: This retrospective included 83 patients with stage IA–IIA MF diagnosed between 2003 and 2012 at a single institution. Immunohistochemical staining of archived biopsy specimens was performed for CD2, CD3, CD5, and CD7. Loss of marker expression was defined as absence in ≥30% of lymphocytes. Clinical and histopathological data were correlated with survival and progression outcomes using Kaplan–Meier curves and log-rank tests. Results: Loss of at least one T-cell marker was identified in 66% of patients, most commonly CD7 (72%), followed by CD5 (11%) and CD2 (11%). No cases showed loss of CD3 expression. CD7 loss was significantly associated with shorter progression-free survival (p < 0.05), but not with overall survival. No significant associations were found between CD2 or CD5 loss and either survival or disease progression. Conclusions: CD7 loss was the only immunohistochemical abnormality significantly associated with earlier disease progression in early-stage MF, suggesting a potential prognostic role. In contrast, loss of CD2 and CD5 did not affect survival or progression, and CD3 was preserved in all cases. These findings highlight the value of incorporating CD7 status into prognostic assessment, although larger studies are needed to confirm its utility.

Primary cutaneous lymphomas (PCLs), especially mycosis fungoides (MF), pose significant diagnostic and therapeutic challenges. This study aims to correlate initial histological features with the disease course and survival in MF patients. A retrospective–prospective cohort study was conducted on 83 patients diagnosed with early-stage MF at the Departments of Dermatovenerology and Pathology, UHC Zagreb, from January 2003 to December 2012. The analyzed histopathological parameters included lichenoid dermal lymphocyte infiltrate, Pautrier microabscesses, and lymphocyte atypia. Patients with more than 30 guardian lymphocytes per 100 keratinocytes exhibited worse overall and progression-free survival. Furthermore, those with over 50% atypical lymphocytes demonstrated a faster progression rate. A dense lichenoid dermal infiltrate and a high count of lymphocyte “keepers” significantly increased the mortality risk within five years of diagnosis. This study did not fully confirm the hypothesis regarding the prognostic value of large Pautrier microabscesses but highlighted the importance of dense lichenoid infiltrates. The study identified new potential histopathological prognostic factors in early-stage MF, suggesting the need for larger studies to confirm these findings. The identification of such predictors could enhance the prognostic stratification and guide more tailored therapeutic approaches for MF patients.

Chronic kidney dysfunction is associated with increased mortality in multiple cancer types. Preliminary evidence suggests the same to be true for B-large cell lymphomas (B-LCL). To analyze the relationship of glomerular filtration rate (GFR) and outcome of B-LCL in detail we collected data on outcomes of 285 consecutive patients with newly diagnosed B-LCL treated at our institution with standard rituximab-containing regimens who did not have preexisting kidney disease or urinary tract obstruction at presentation. Median age was 59, range 18 to 87, 145 were male and 140 females. Forty-four had GFR < 60 mL/min, 123 had 60 to 90 mL/min, and 118 > 90 mL/min. Median follow-up of surviving patients was 49 months and estimated 3-year survival 76%. In univariate analysis age (P < .001), GFR (P = .014), stage (P < .001), performance status (P = .044), chemotherapy regimen (P < .01), and international prognostic index (IPI) (P < .001) were statistically significant prognostic factors. In multivariate analysis, age and GFR remained the only independent prognostic factors. Subtracting 1 from the IPI score of patients who had GFR > 90 mL/min and IPI > 1 resulted in a prognostic index that divides patients into 3 prognostic groups (low risk = 0–1, intermediate risk = 2–3 and high risk = 4–5) with an acceptable patient distribution frequency (38%, 39%, and 23%, respectively) and improved statistical significance and separation in comparison to IPI (5-year survival rates of 92%, 74%, and 42%, respectively). GFR is an important independent prognostic factor for B-LCL that should be taken into account in clinical decision making and data analysis and probably be incorporated in prognostic indices.