The Prognostic Value of Histopathological Features in Early-Stage Mycosis Fungoides: Insights from a Retrospective-Prospective Cohort Study.

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.

Reduced Corticosteroid Exposure Is Safe and Does Not Reduce Disease Control among Hodgkin Lymphoma Patients Treated with Escalated BEACOPP (eBEACOPP).

Background and Objectives: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with significant toxicities. The 14-day/cycle prednisone course contributes to side effects, including osteoarticular events like avascular bone necrosis (AVN). Our center has been using eBEACOPP since 2009 for AS and 2014 for EU patients. In 2016, we reduced prednisone treatment to 7-10 days to lessen AVN risk. We analyzed the effects of this approach. Materials and Methods: We retrospectively collected data on patients who received at least two cycles of eBEACOPP for first-line HL treatment. Results: A total of 162 patients (33 EU, 129 AS) were included. Their median age was 31 (range 19-59 years), and 88 were males. A total of 94 patients received full corticosteroid courses, and 68 received reduced corticosteroid courses. The overall response rate (ORR) was 98%. Different corticosteroid dosings had no significant effect on ORR, febrile neutropenia episodes, or hospital admissions. After a median follow-up (mFU) of 58 months, the 5yPFS for the entire cohort was 98% vs. 95% for the standard course vs. the short corticosteroids course, respectively (p = 0.37), while the 5yOS was 98% vs. 99% for the standard course vs. short corticosteroids course, respectively (p = 0.87). In AS patients intended to be treated with six eBEACOPP cycles, 5yPFS and 5yOS were 100% vs. 97% and 100% vs. 99% for standard vs. short corticosteroid courses, respectively (p = 0.56 and p = 0.17). In EU patients, 5yPFS was 97% (standard) vs. 95% (short) (p = 0.98) and 5yOS 100% vs. 93.3% (p = 0.87). Osteoarticular events were numerically lower in patients receiving the shorter prednisone course, both in the whole cohort and in the subgroup of patients treated with six cycles of eBEACOPP, but this difference failed to reach statistical significance. Conclusions: eBEACOPP provides excellent and durable first-line disease control. Shortening the corticosteroid course does not compromise efficacy, potentially reducing toxicity. However, longer follow-ups and larger studies are needed for confirmation.

Successful clinical approach to the metastatic uterine leiomyosarcoma to the epicardium-a case report.

BACKGROUND: Uterine leiomyosarcoma is a rare and aggressive tumour with a poor prognosis. Its metastases to the heart are even rarer, especially to the epicardium. The majority of reported cardiac metastases of uterine leiomyosarcoma were in the cardiac chambers or intramyocardial. Surgical resection of the uterine leiomyosarcoma in the early stages is the only definitive treatment for this disease. However, in the cases of cardiac metastasis, surgery is recommended only in emergencies and patients with expected beneficial outcomes. CASE PRESENTATION: Our patient was a 49-year-old female referred to the Department of Cardiac Surgery for scheduled surgery of pericardial neoplasia. The patient underwent a hysterectomy and adnexectomy three years prior owing to the uterine leiomyosarcoma. A regular follow-up magnetic resonance imaging of the abdomen and pelvis discovered neoplasia in the diaphragmic portion of the pericardium. No other signs of primary disease relapse or metastases were found. The patient was asymptomatic. The multidisciplinary team concluded that the patient is a candidate for surgery. Surgery included diastolic cardiac arrest achievement and resection of the tumour. Macroscopically, a parietal layer of the pericardium was completely free from the tumour that invaded only the apical myocardium of the left ventricle. Completed histopathology confirmed the diagnosis of leiomyosarcoma of the uterine origin. Three months after surgery, the patient received adjuvant chemotherapy with doxorubicin and dacarbazine. One year after surgery, there are no signs of new metastases. CONCLUSIONS: Strict surveillance of patients with uterine leiomyosarcoma after successful treatment of the early stage of the disease is of utmost importance to reveal metastatic disease to the heart in a timely manner and to treat it with beneficial outcomes. Surgery with adjuvant chemotherapy might be a good approach in patients with a beneficial prognosis. From a surgical point of view, it is challenging to assess the appropriate width of the resection edges to be radical enough and, at the same time, sufficiently conservative to ensure the satisfactory postoperative function of the remaining myocardium and avoid repetitive tumour growth. Therefore, intraoperative histopathology should always be performed.

Student satisfaction and academic efficacy during online learning with the mediating effect of student engagement: A multi-country study.

The COVID-19 pandemic caused unprecedented changes to educational institutions, forcing their closure and a subsequent shift to online education to cater to student learning requirements. However, successful online learning depends on several factors and may also vary between countries. As such, this cross-sectional study sought to investigate how engagement of university students, a major driver of online learning, was influenced by course content, online interaction, student acceptance, and satisfaction with online learning, as well as self-efficacy across nine countries (China, India, Iran, Italy, Malaysia, Portugal, Serbia, Turkey, and the United Arab Emirates) during the COVID-19 pandemic. Using a questionnaire-based approach, data collected from 6,489 university students showed that student engagement was strongly linked to perception of the quality of the course content and online interactions (p < .001). The current study also indicated that online interactions are a major determinant of academic efficacy but only if mediated by engagement within the online learning context. A negative correlation between student engagement and satisfaction with online learning was found, demonstrating the importance of students being engaged behaviorally, emotionally, and cognitively to feel satisfied with learning. Academic efficacy and student satisfaction were explained by course content, online interaction, and online learning acceptance, being mediated by student engagement. Student satisfaction and, to a lesser degree academic efficacy, were also associated with online learning acceptance. Overall, the structural equation model was a good fit for the data collected from all nine countries (CFI = .947, TLI = .943; RMSEA = .068; SRMR = .048), despite differences in the percentage variations explained by each factor (no invariance), likely due to differences in levels of technology use, learning management systems, and the preparedness of teachers to migrate to full online instruction. Despite limitations, the results of this study highlight the most important factors affecting online learning, providing insight into potential approaches for improving student experiences in online learning environments.

Glomerular filtration rate is an independent prognostic factor in patients with B-large cell lymphoma.

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.

Atopic Dermatitis: Disease Features, Therapeutic Options, and a Multidisciplinary Approach.

The latest findings regarding AD pathogenesis point to an impaired function of the epidermal barrier, changed immune response, colonization of the skin by microorganisms, and certain psychological factors among other causes/triggers. The inflammatory response of AD patients is mainly associated with the activation of T cells (Th2 cells predominate), dendritic cells, macrophages, keratinocytes, mast cells, and eosinophils. Therapy usually involves medical evaluations and adequate management including treatment of concomitant diseases (e.g., allergies and infections), patient education and nursing care, psychological support, and nutritional consultations, which are organized through specific programs and structured educational groups. Systemic AD therapy includes conventional systemic treatment (cyclosporine, methotrexate, azathioprine) and new, specific drugs, interleukin inhibitors (e.g., dupilumab) and JAK inhibitors (baricitinib, abrocitinib, upadacitinib, etc.). Since many AD patients are affected by various psychological factors and comorbidities, they should be assessed and managed through a multidisciplinary approach, involving different professions (psychologists, ear-nose-throat specialists, pulmonologists, allergologists, immunologists, nutritionists, pediatricians, gastroenterologists, psychiatrists (when necessary), and others). A multidisciplinary approach provides better coping strategies and improves control over the disease, patient adherence to therapy, and quality of life. It also has a positive influence on family quality of life while at the same time making more efficient use of dermatology healthcare resources, reducing the economic burden on both patients and society.

Alteration of Collagen Content and Macrophage Distribution in White Adipose Tissue under the Influence of Maternal and Postnatal Diet in Male Rat Offspring.

Background and Objectives: The extracellular matrix is important for adipose tissue growth, and numerous interactions between adipocytes and extracellular matrix components occur during adipose tissue development. The main objective of this study was to investigate the interaction and influence of maternal and postnatal diet on adipose tissue remodeling in Sprague Dawley offspring. Materials and Methods: 10 Sprague Dawley females were randomly divided into two groups at nine weeks of age and fed a standard laboratory diet or high-fat diet for six weeks. Then, they were mated, and after birth, their male rat offspring were divided into four subgroups according to diet. After euthanizing the offspring at 22 weeks of age, samples of subcutaneous, perirenal and epididymal adipose tissue were collected. Sections were stained with Mallory's trichrome and analyzed by immunohistochemistry for CD68+ and CD163+ cells. Results: Staining of extracellular components showed higher collagen deposition in the perirenal and epididymal depot of offspring fed a high-fat diet. The number of CD163/CD68+ cells in the perirenal adipose tissue was lower in the CD-HFD group compared with other groups, and in the subcutaneous fat pad when the groups with modified diet were compared with those on non-modified diet. Conclusion: Morphological changes in adipose tissue, increased collagen deposition, and changes in macrophage polarization may be related to intergenerational changes in diet.

Clinical and histopathological investigation of symmetrical alopecia with associated chronic pruritus in tufted capuchin monkeys (Sapajus apella apella).

BACKGROUND: Symmetrical alopecia is a common symptom of endocrine and autoimmune diseases, which are rarely manifested with pruritus. Increased levels of stress in primates have been presented with increased levels of pruritus and alopecia appearance. METHODS: A pruritic and alopecic disease was investigated in a group of tufted capuchin monkeys (N = 12), but due to ethical reasons, four random animals were further investigated by numerous diagnostic methods. The impact of food and enclosure enrichment was assessed and observed over a 2-year period. RESULTS: Histopathology of four random tufted capuchin monkeys revealed lymphocytic perifolliculitis, with an appearance of a "swarm of bees" which was suggestive of alopecia areata. Etiological classification of pruritus excluded dermatological, systemic, and neurological causes, making it behavioral. Enclosure and food enrichment had a beneficial impact on pruritus (12/12) and alopecia (10/12). CONCLUSION: The findings were suggestive of alopecia areata, while the pruritus was considered behavioral in origin. Alopecia and pruritus improved upon enclosure and food enrichment.

A Novel Three-Dimensional Approach Towards Evaluating Endomyocardial Biopsies for Follow-Up After Heart Transplantation: X-Ray Phase Contrast Imaging and Its Agreement With Classical Histopathology.

Endomyocardial biopsies are the gold standard for surveillance of graft rejection following heart transplantation, and are assessed by classical histopathology using a limited number of previously stained slices from several biopsies. Synchrotron propagation-based X-ray phase contrast imaging is a non-destructive method to image biological samples without tissue preparation, enabling virtual 2D and 3D histopathology. We aimed to show the feasibility of this method to assess acute cellular rejection and its agreement to classical histopathology. Right ventricular biopsies were sampled from 23 heart transplantation recipients (20 males, mean age 54±14 years) as part of standard follow-up. The clinical diagnosis of potential rejection was made using classical histopathology. One additional study sample was harvested and imaged by X-ray phase contrast imaging, producing 3D datasets with 0.65 µm pixel size, and up to 4,320 images per sample. An experienced pathologist graded both histopathological and X-ray phase contrast images in a blinded fashion. The agreement between methods was assessed by weighted kappa, showing substantial agreement (kappa up to 0.80, p < 0.01) between X-ray phase contrast imaging and classical histopathology. X-ray phase contrast imaging does not require tissue processing, allows thorough analysis of a full myocardial sample and allows identification of acute cellular rejection.

Subepidermal Basal Cell carcinoma Following Laser Treatment of Congenital Capillary Malformation: A Case Report.

While basal cell carcinoma is the most common type of skin cancer in humans, its subepidermal presentation is extremely rare. The risk factors for basal cell carcinoma development are well-known, but it remains unclear in which setting the tumor restricts itself to the dermal compartment. We present the fifth known case of subepidermal basal cell carcinoma. However, this particular presentation is unique due to arising beneath a capillary malformation. The patient had previously undergone multiple laser treatments which yielded no success. Initially, the vascular malformation was removed and sent for histopathological diagnosis. After the discovery of basal cell carcinoma, wide surgical resection was performed. The patient had no recurrence up to the last follow-up at 18 months postoperatively. This case demonstrates a new presentation of a very rare condition, but also highlights the importance of histopathological examination and the need for future research on any possible association between laser therapy and carcinogenesis.

Mycosis fungoides with large cell transformation (CD30+) and B-cell chronic lymphocytic leukemia.

Mycosis fugnoides (MF) is an indolent cutaneous T-cell lymphoma (CTLC) and is the most common of all cutaneous lymphomas. An increased risk for developing a second primary malignancy in patients with CTCL has been described in several studies, with a range from 1.04 to 2.4 (1-4). Caucasian males are at higher risk for MF development. MF is often diagnosed at ages between 55 and 67 years, and second malignancy usually occurs 5 or 6 years after the diagnosis of MF was established (5). The most common second primary malignancies include non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), lung carcinoma, bladder carcinoma, and melanoma. Even though a higher incidence rate of all NHL was described in patients with MF (15/1000) in comparison with the general population (0.32/1000), there are still only a few cases of B-cell NHL following MF described in the literature (6,7). We describe a rare case of a patient with MF and simultaneous large cell transformation (LCT) and a small B-cell lymphocytic lymphoma/chronic lymphocytic leukemia (B-CLL). In 2017, an 82-year-old man previously treated for MF presented with two fast growing tumorous lesions with ulceration on the right tight (Figure 1). A biopsy was performed, and a diagnosis of MF with LCT was established (Figure 2). During hospitalization, mild leukocytosis (12.2 x109 L-1), lymphocytosis (64%, total count of 7.81 x109 L-1), and anemia were found. Bone marrow biopsy was not performed due to low pain threshold. Bone marrow aspirate showed 70% of atypical lymphocytes and few "smudged" cells. Immunophenotyping by flow cytometry detected 49% monoclonal kappa+ B-cells with phenotypic features typical for B-CLL (CD5+, CD23+, kappa +). Of overall bone marrow cells, the ratio of monoclonal kappa + B-cells with the B-CLL phenotype was 21%. Immunophenotyping of peripheral blood showed up to 50% monoclonal kappa+ B-cells with phenotypic features typical for B-CLL (CD5+, CD23+, kappa +). Of overall peripheral blood cells, the ratio of monoclonal kappa+ B-cells with the B-CLL phenotype was 28%. Multi-sliced computed tomography was within normal ranges. A flow cytometry showed lymphocytes with phenotypic findings for CD20+ B-CLL. A diagnosis of MF with LCT (CD30+) clinical grade IIB (T3, N0, M0) and B-CLL was established. The patient was treated with fractionated superficial irradiation that resulted in applanation and regression of the tumorous lesions. No hematologic treatment was indicated other than regular follow-up. On dermatologic follow up for 2 years, the patient was stable, with no active skin lesions and no progression of MF. The patient was subsequently lost to follow-up. This is a rare case of MF with LCT and B-CLL occurring simultaneously. Large cell transformation in patients with MF can occur in 20-55% of advanced MF, as in our case, and this something physicians must be aware of, so repeated biopsies are advised (8). We also should keep in mind that patients with MF are at higher risk of developing a second malignancy. Of those second malignancies, a coexistence of lymphoproliferative disorders in two lineages, T-cell and B-cell, such as CTCL and B-CLL, is very uncommon, and only a few cases have been published (6,7,10). In most of these cases, CTCL preceded B-CLL, and with the only established explanation being increased risk of second malignancy in patients with CTCL (3,5,10). Other explanatory hypotheses include neoplastic stem cells, a genetic predisposition to malignancy, the use of immunosuppressive agents for the treatment for a first neoplasm, viral agents, and modulation of the B-cell system by monoclonal T-cell proliferation (1,5,6,9,10). Regular follow-up is mandatory for all patients with CTCL as well as MF, in order to identify the disease progression but for the timely detection of second malignancies.

Adapting to an enhanced color gamut - implications for color vision and color deficiencies.

One strategy for aiding color deficiencies is to use three narrow passbands to filter the light spectrum to increase the saturation of colors. This filtering is analogous to the narrow emission bands used in wide gamut lighting or displays. We examined how perception adapts to the greater color gamut area produced by such devices, testing color-normal observers and simulated environments. Narrowband spectra increased chromatic contrasts but also increased contrast adaptation, partially offsetting the perceived contrast enhancements. Such adaptation adjustments are important for understanding the perceptual consequences of exposure to naturally or artificially enhanced color gamut areas for both color-deficient and color-normal observers.

Optimization of a plastic optical fiber based sensor for dye sensing coupled with an adapted neuro-fuzzy inference system.

In this study, estimation capacities and optimization of a dye concentration sensing model by an adapted neuro-fuzzy inference system (ANFIS) as well as central composite design coupled with response surface methodology using a plastic optical fiber (POF) based sensor were investigated. Various diameters d of POF were used for sensing different concentrations of Remazol Black B (RBB), which acts as a sensing medium of the process. The efficiency of sensing was studied as a function of three independent variables: diameter of POF, concentration of RBB dye, and initial temperature of the solution. First, the independent parameters were fed as inputs to an ANFIS, and the output of the system was the output intensity of dye ratio to output the intensity of distilled water. ANFIS showed that this established model is reliable for a dye concentration sensing process and is mainly influenced by its diameter.

Comprehensive assessment of myocardial remodeling in ischemic heart disease by synchrotron propagation based X-ray phase contrast imaging.

Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in detail. The objective was to use X-PCI to comprehensively quantify ischemic remodeling of different myocardial structures, from cell to organ level, in a rat model of myocardial infarction. Myocardial infarction-induced remodeling was recreated in a well-established rodent model. Ex vivo rodent hearts were imaged by propagation based X-PCI using two configurations resulting in 5.8 µm and 0.65 µm effective pixel size images. The acquired datasets were used for a comprehensive assessment of macrostructural changes including the whole heart and vascular tree morphology, and quantification of left ventricular myocardial thickness, mass, volume, and organization. On the meso-scale, tissue characteristics were explored and compared with histopathological methods, while microstructural changes were quantified by segmentation of cardiomyocytes and calculation of cross-sectional areas. Propagation based X-PCI provides detailed visualization and quantification of morphological changes on whole organ, tissue, vascular as well as individual cellular level of the ex vivo heart, with a single, non-destructive 3D imaging modality.

Early Childhood Fat Tissue Changes-Adipocyte Morphometry, Collagen Deposition, and Expression of CD163+ Cells in Subcutaneous and Visceral Adipose Tissue of Male Children.

Childhood obesity is a complex health problem, and not many studies have been done on adipose tissue remodeling in early childhood. The aim of this study was to examine extracellular matrix remodeling in the adipose tissue of healthy male children depending on their weight status. Subcutaneous and visceral adipose tissue was obtained from 45 otherwise healthy male children who underwent elective surgery for hernia repairs or orchidopexy. The children were divided into overweight/obese (n = 17) or normal weight groups (n = 28) depending on their body mass index (BMI) z-score. Serum was obtained for glucose, testosterone, triglyceride, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) measurements. Sections of adipose tissue were stained with hematoxylin and eosin to determine the adipocytes' surface area, and Masson's trichrome stain was used to detect the adipocytes' collagen content. Immunohistochemistry for CD163+ cells was also performed. The results showed that male children in the overweight group had higher serum triglyceride levels, greater adipocyte surface area and collagen content in their subcutaneous adipose tissue, more crown-like structures in fat tissues, and more CD163+ cells in their visceral adipose tissue than males in the normal weight group. In conclusion, in male children, obesity can lead to the hypertrophy of adipocytes, increased collagen deposition in subcutaneous adipose tissues, and changes in the polarization and accumulation of macrophages.

R-CHOEP14 in younger high-risk patients with large B cell lymphoma: an effective front-line regimen with cardiac toxicity: a real-life, single-center experience.

Currently, there is no consensus regarding optimal front-line treatment for younger high-risk patients with large B cell lymphoma. American recommendations list only R-CHOP as standard, while European also include R-ACVBP and R-CHOEP14. We have been routinely using the latter regimen at our institution since 2011 and performed this retrospective real-life single-center study to analyze outcomes. Between September 2011 and April 2019, 66 newly diagnosed patients aged 18 to 60 years with B-large cell lymphoma and high-risk age-adjusted International Prognostic Index score were scheduled to receive 6 or 8 cycles of bi-weekly chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, etoposide, steroids, and rituximab (R-CHOEP14). After a median follow-up of 4.7 years, the estimated 3-year progression-free survival was 87% (95% CI 80-96%) and 3-year overall survival 90% (95% CI 83-98%). Grade ≥ 3 hematological side effects occurred in 83% and infectious in 41% of patients; one patient died of toxicity. Grade ≥ 2 cardiac toxicity occurred in 21% of patients, more frequently than previously reported. The cumulative 5-year risk of congestive heart failure with all-cause mortality as the competing risk was 17%. R-CHOEP14 is a very effective and manageable regimen for younger high-risk patients with B-large cell lymphoma, but the risk of cardiotoxicity warrants further investigations.