Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma-An Update from the Pathologist's Point of View.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequently occurring non-melanocytic skin cancers. The objective of our study is to present the pathophysiology of BCC and cSCC and its direct relationship with the histopathological diagnostics and the differential diagnostics of these types of cancer, based on the morphological characteristics, immunohistochemical profile, and genetic alterations. The qualitative study was based on emphasizing the morphological characteristics and immunohistochemistry profiles of BCC and cSCC and the differential diagnostics based on the tissue samples from the Clinical Pathology Department of Mures Clinical County Hospital between 2020 and 2022. We analyzed the histopathological appearances and immunohistochemical profiles of BCC and cSCC in comparison with those of Bowen disease, keratoacanthoma, hyperkeratotic squamous papilloma, metatypical carcinoma, pilomatricoma, trichoblastoma, Merkel cell carcinoma, pleomorphic dermal sarcoma (PDS), and melanoma. Our study showed the importance of the correct histopathological diagnosis, which has a direct impact on the appropriate treatment and outcome for each patient. The study highlighted the histopathological and morphological characteristics of NMSCs and the precursor lesions in HE and the immunohistochemical profile for lesions that may make the differential diagnosis difficult to establish.

H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.

Human Placenta and Evolving Insights into Pathological Changes of Preeclampsia: A Comprehensive Review of the Last Decade.

The placenta, the foremost and multifaceted organ in fetal and maternal biology, is pivotal in facilitating optimal intrauterine fetal development. Remarkably, despite its paramount significance, the placenta remains enigmatic, meriting greater comprehension given its central influence on the health trajectories of both the fetus and the mother. Preeclampsia (PE) and intrauterine fetal growth restriction (IUGR), prevailing disorders of pregnancy, stem from compromised placental development. PE, characterized by heightened mortality and morbidity risks, afflicts 5-7% of global pregnancies, its etiology shrouded in ambiguity. Pertinent pathogenic hallmarks of PE encompass inadequate restructuring of uteroplacental spiral arteries, placental ischemia, and elevated levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also recognized as soluble FMS-like tyrosine kinase-1 (sFlt-1). During gestation, the placental derivation of sFlt-1 accentuates its role as an inhibitory receptor binding to VEGF-A and placental growth factor (PlGF), curtailing target cell accessibility. This review expounds upon the placenta's defining cellular component of the trophoblast, elucidates the intricacies of PE pathogenesis, underscores the pivotal contribution of sFlt-1 to maternal pathology and fetal safeguarding, and surveys recent therapeutic strides witnessed in the past decade.

Predictive Performances of Blood-Count-Derived Inflammatory Markers for Liver Fibrosis Severity in Psoriasis Vulgaris.

Psoriasis is an immune-mediated, chronic disorder that significantly alters patients' quality of life and predisposes them to a higher risk of comorbidities, including liver fibrosis. Various non-invasive tests (NITs) have been validated to assess liver fibrosis severity, while blood-count-derived inflammatory markers have been proven to be reliable in reflecting inflammatory status in psoriatic disease. The fibrosis-4 (FIB-4) index became part of the newest guideline for monitoring psoriasis patients undergoing systemic treatment. Patients with psoriasis vulgaris and fulfilling inclusion criteria were enrolled in this study, aiming to assess for the first time in the literature whether such inflammatory markers are useful in predicting liver fibrosis. Based on internationally validated FIB-4 index values, patients were divided into two study groups: a low risk of significant fibrosis (LR-SF) and a high risk of significant fibrosis (HR-SF). Patients from HR-SF were significantly older and had higher values of the monocyte-to-lymphocyte ratio (MLR) (p < 0.001), which further significantly correlated with fibrosis severity (p < 0.001). Platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), platelet-to-white blood cell ratio (PWR), and aggregate index of systemic inflammations (AISI) significantly correlated negatively with liver fibrosis (p < 0.001). PWR proved to be the most reliable inflammatory predictor of fibrosis severity (AUC = 0.657). MLR, PWR, and AISI were independent inflammatory markers in multivariate analysis (p < 0.001), while the AST to platelet ratio index (APRI) and AST to ALT ratio (AAR) can be used as additional NITs for significant liver fibrosis (p < 0.001). In limited-resources settings, blood-count-derived inflammatory markers such as MLR, PWR, and AISI, respectively, and hepatic indexes APRI and AAR prove to be of particular help in predicting significant liver fibrosis.

The Approach of Artificial Intelligence in Neuroendocrine Carcinomas of the Breast: A Next Step towards Precision Pathology?-A Case Report and Review of the Literature.

Primary neuroendocrine tumors (NETs) of the breast are considered a rare and undervalued subtype of breast carcinoma that occur mainly in postmenopausal women and are graded as G1 or G2 NETs or an invasive neuroendocrine carcinoma (NEC) (small cell or large cell). To establish a final diagnosis of breast carcinoma with neuroendocrine differentiation, it is essential to perform an immunohistochemical profile of the tumor, using antibodies against synaptophysin or chromogranin, as well as the MIB-1 proliferation index, one of the most controversial markers in breast pathology regarding its methodology in current clinical practice. A standardization error between institutions and pathologists regarding the evaluation of the MIB-1 proliferation index is present. Another challenge refers to the counting process of MIB-1's expressiveness, which is known as a time-consuming process. The involvement of AI (artificial intelligence) automated systems could be a solution for diagnosing early stages, as well. We present the case of a post-menopausal 79-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). The purpose of this paper is to expose the interpretation of MIB-1 expression in our patient' s case of breast neuroendocrine carcinoma, assisted by artificial intelligence (AI) software (HALO-IndicaLabs), and to analyze the associations between MIB-1 and common histopathological parameters.

VISTA, PDL-L1, and BRAF-A Review of New and Old Markers in the Prognosis of Melanoma.

Melanoma is currently known as one of the most aggressive malignant tumors. The prognostic factors and particularities of this neoplasm are a persistent hot topic in the medical field. This review has multiple purposes. First, we aim to summarize the known data regarding the histological and immunohistochemical appearance of this versatile tumor and to look further into the analysis of several widely used prognostic markers, such as B-Raf proto-oncogene, serine/threonine kinase BRAF. The second purpose is to analyze the data on the new prognostic markers, V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) and Programmed death-ligand 1 (PD-L1). VISTA is a novel target that is considered to be highly important in determining the invasive potential and treatment response of a melanoma, and there are currently only a limited number of studies describing its role. PD-L1 is a marker with whose importance has been revealed in multiple types of malignancies, but its exact role regarding melanoma remains under investigation. In conclusion, the gathered data highlights the importance of correlations between these markers toward providing patients with a better outcome.

Oxidative-Stress Related Gene Polymorphism in Endometriosis-Associated Infertility.

Background and Objectives: Endometriosis is a benign inflammatory disease associated with infertility and chronic pelvic pain, estimated to affect 7−10% of reproductive-age women, with the possibility of malignant transformation. Recent studies focus on oxidative stress and genetic mutations as risk factors in the pathophysiology of endometriosis-associated infertility. Materials and Methods: This case-control study is the first in Eastern European women that aimed to investigate four genes' genetic polymorphisms that encode antioxidant enzymes involved in oxidative stress (glutathione peroxidase 1, GPX1 198Pro > Leu, catalase CAT-262C > T, glutathione S-transferase M1, and T1 null genotype) and their association with endometriosis-related infertility. We compared 103 patients with endometriosis-associated infertility with 102 post-partum women as the control group. Results: The endometriosis group had a mean age of 34.5 +/− 6.12 years, while the control group's mean age was 35.03 +/− 5.95 years. For CAT-262C > T polymorphism, the variant genotypes were significantly more frequent in the endometriosis group. Moreover, for the GPX1 198Pro > Leu, the endometriosis group had significantly more frequent CT and TT genotypes. The null genotype of GSTM1 was detected significantly higher in the endometriosis group. No significant differences were found in the frequency of GSTT1 between the two groups. This study suggests that GPX1 198Pro > Leu, CAT-262C > T, and GSTM1 polymorphisms may be risk factors and that the association between the GSTM1-GSTT1 null genotype may play a significant role in endometriosis-associated infertility. Moreover, this study suggests that the GSTT1 null genotype does not influence the disease. Visual identification of endometriotic lesions with microscopic confirmation is the accepted gold standard for diagnosing endometriosis, but general anesthesia and laparoscopy are required. Conclusions: In this regard, a panel of genetic or laboratory markers is needed for the early diagnostics of this prevalent disease, especially in the case of young patients with future pregnancy intention.

Scientific Research Directions on the Histopathology and Immunohistochemistry of the Cutaneous Squamous Cell Carcinoma: A Scientometric Study.

Introduction: Cutaneous squamous cell carcinoma (cSCC) is one of the most frequently occurring types of cancer in humans. Scientometric research is an innovative method for analyzing the research trends in various domains, with great implications in the field of medicine. Materials and Methods: We searched the Web of Science database with the following established query terms: "Squamous cell carcinoma", "skin", and "immunohistochemistry". After applying the inclusion and exclusion criteria, a total of 76 articles were selected. The present study aims to analyze, based on the frequency of use of keywords with scientometric algorithms and map-based distributions, the trends of the research concerning cSCCs in 2017-2022. Results: A graphical representation based on 11 scientometric maps presented the division of the keywords into seven clusters, from which seven categories of research interest were defined. The clusters represent a multidisciplinary approach to the diagnosis and treatment of cSCCs, cancer diagnostics, patient outcomes, histopathological importance, management of cSCCs, role of progression, and adequate treatment of and importance of immunohistochemistry for cSCCs. The distribution of the citations shows the importance of the available research on cSCCs by analyzing the first five most-cited articles included in our study in direct concordance with the seven defined clusters. Conclusion: The scientometric research method reveals the interest of research in the multidisciplinary approach used to obtain the best outcomes for the patient, including a targeted investigation, as well as diagnostic and treatment options. The trends in the research reveal that histopathological diagnostics and immunohistochemistry, combined with molecular techniques, are the most important tools used to establish a personalized diagnosis, thus increasing the quality of life and life expectancy for patients with cSCCs.

The Impact of and Adaptations Due to the COVID-19 Pandemic on the Histopathological Diagnosis of Skin Pathologies, Including Non-Melanocyte and Melanoma Skin Cancers-A Single-Center Study in Romania.

Background and Objectives: The COVID-19 pandemic has globally affected health systems and services. Non-melanoma skin cancers (NMSCs) are the most common malignancies around the world. This study aimed to analyze the differences in the benign and malignant histopathological diagnoses performed on radical excision skin tumors and skin biopsies in the dermatopathology ward in Mures Clinical County Hospital, Targu Mures, Romania, 1 year prior to and during the COVID-19 pandemic, to emphasize the changes in the diagnostic process as per the new regulations. Materials and Methods: A total of 1168 histopathological diagnoses were included in the study-302 from the COVID-19 period and 866 from the non-COVID-19 period-considering the number, type, and frequency of the histopathological diagnoses as variables to be analyzed. Results: In the COVID-19 period, out of the 55 NMSC and melanoma histopathological diagnoses, 50.9% (n = 28) were BCCs, 20% (n = 11) were SCCs, 10.9% (n = 6) were basosquamous cell carcinomas, and 18.18% (n = 10) were melanoma cases. Regarding the non-COVID-19 period, out of the 173 NMSC and melanoma histopathological diagnoses, 46.82% (n = 81) were BCCs, 22.54% (n = 39) were SCCs, 7.51% (n = 13) were basosquamous cell carcinomas, and 23.12% (n = 40) were melanoma cases. Conclusions: During the COVID-19 pandemic, a decrease in histopathological diagnoses at the dermatopathology ward in our hospital was observed, for both benign and malignant pathologies, especially for NMSCs and melanomas, compared to the same period 1 year prior to the pandemic.

The importance of combined HPV and CINtec® PLUS genotyping testing for p16 in women with cervical squamous cell carcinoma.

INTRODUCTION: Immunohistochemistry (IHC) for p16INK4A (p16) is a reliable surrogate test for the presence of a high-risk, potentially transformative human papillomavirus (HPV) infection in precursor and malignant lesions of the cervix. The purpose of this study was to evaluate changes in cervical cells caused by persistent HPV infection, by IHC (p16 protein) by comparison with HPV genotyping. PATIENTS, MATERIALS AND METHODS: The study included female patients aged between 26 and 57 years who presented to a public hospital, with complaints related to the genital area, namely vaginal bleeding and dyspareunia. After selecting the patients, samples were subjected to cytological testing and IHC for p16 and for the determination of HPV types. RESULTS: The relationship between HPV status and p16 status was statistically significant (p=0.0001), of the 41 patients, 53.7% were HPV positive, respectively 56.1% were p16 positive, the agreement relationship between the two indicators was very high (weighted kappa: 0.951). The clinical performance of CINtec® PLUS triage for p16 shows a high positive predictive value (PPV) and a high negative predictive value (NPV) of 95.7% and 100%, respectively, as regards HPV. CONCLUSIONS: The p16 marker (CINtec® PLUS) can be used as a prognostic biomarker and provides clinical usefulness through increased sensitivity (Se) and specificity (Sp) in the triage of women at risk of developing precancerous lesions, compared to cytology that is based on morphology, but has a rather low Se and high Sp, while HPV testing is very sensitive but slightly more specific.

The Role of Artificial Intelligence in Early Diagnosis and Molecular Classification of Head and Neck Skin Cancers: A Multidisciplinary Approach.

Cancer remains a significant global health concern, with increasing genetic and metabolic irregularities linked to its onset. Among various forms of cancer, skin cancer, including squamous cell carcinoma, basal cell carcinoma, and melanoma, is on the rise worldwide, often triggered by ultraviolet (UV) radiation. The propensity of skin cancer to metastasize highlights the importance of early detection for successful treatment. This narrative review explores the evolving role of artificial intelligence (AI) in diagnosing head and neck skin cancers from both radiological and pathological perspectives. In the past two decades, AI has made remarkable progress in skin cancer research, driven by advances in computational capabilities, digitalization of medical images, and radiomics data. AI has shown significant promise in image-based diagnosis across various medical domains. In dermatology, AI has played a pivotal role in refining diagnostic and treatment strategies, including genomic risk assessment. This technology offers substantial potential to aid primary clinicians in improving patient outcomes. Studies have demonstrated AI's effectiveness in identifying skin lesions, categorizing them, and assessing their malignancy, contributing to earlier interventions and better prognosis. The rising incidence and mortality rates of skin cancer, coupled with the high cost of treatment, emphasize the need for early diagnosis. Further research and integration of AI into clinical practice are warranted to maximize its benefits in skin cancer diagnosis and treatment.

Shared Pathogenic and Therapeutic Characteristics of Endometriosis, Adenomyosis, and Endometrial Cancer: A Comprehensive Literature Review.

Endometriosis and adenomyosis behave similarly to cancer. No current treatments represent a cure, even if there are several options, including hormonal and surgical therapy. In advanced or recurrent pathologies, however, personalized treatment is necessary. We have found that due to the multiple common features, various therapeutic options have been used or studied for all three pathologies, with varying results. The objective of this review is to extract from the relevant literature the compounds that are used for endometriosis and adenomyosis characterized by malignant behavior, with some of these drugs being studied first in the treatment of endometrial cancer. Special attention is needed in the pathogenesis of these pathologies. Despite the multiple drugs that have been tested, only a few of them have been introduced into clinical practice. An unmet need is the cure of these diseases. Long-time treatment is necessary because symptoms persist, and surgery is often followed by postoperative recurrence. We emphasize the need for new, effective, long-term treatments based on pathogeny while considering their adverse effects.

Understanding the Pathophysiology of Preeclampsia: Exploring the Role of Antiphospholipid Antibodies and Future Directions.

Preeclampsia (PE) is a hypertensive disorder in pregnancy associated with significant fetal and maternal complications. Antiphospholipid syndrome (APS) is an acquired form of thrombophilia characterized by recurrent venous or arterial thrombosis and obstetric complications that significantly increases morbidity and mortality rates. While preeclampsia may not be the most prevalent obstetric complication in APS, it significantly impacts the long-term health of both mother and child. The treatment of preeclampsia in antiphospholipid syndrome is different from the treatment of preeclampsia as an independent disease. Despite current treatments involving anticoagulants, antiplatelet agents, and antihypertensive drugs, obstetric complications may persist, underscoring the need for cohesive management and effective treatments. The objective of our review is to briefly present knowledge about the physiopathology of preeclampsia and the role of antiphospholipid antibodies in this process. Based on the existing literature, our review aims to identify future directions in molecular pathology toward the discovery of biomarkers and targeted treatments. The application of multidisciplinary approaches and prognostic models, including new biomarkers, could be beneficial in the prediction of PE.

Impact of Blood-Count-Derived Inflammatory Markers in Psoriatic Disease Progression.

Psoriasis is a chronic immune-mediated disease, linked to local and systemic inflammation and predisposing patients to a higher risk of associated comorbidities. Cytokine levels are not widely available for disease progression monitoring due to high costs. Validated low-cost and reliable markers are needed for assessing disease progression and outcome. This study aims to assess the reliability of blood-count-derived inflammatory markers as disease predictors and to identify prognostic factors for disease severity. Patients fulfilling the inclusion criteria were enrolled in this study. Patients were divided into three study groups according to disease severity measured by the Body Surface Area (BSA) score: mild, moderate, and severe psoriasis. White blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic immune index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) positively were correlated with disease severity (p < 0.005). d-NLR, NLR, and SII are independent prognostic factors for mild and moderate psoriasis (p < 0.05). d-NLR is the only independent prognostic factor for all three study groups. Moderate psoriasis is defined by d-NLR values between 1.49 and 2.19. NLR, PLR, d-NLR, MLR, SII, SIRI, and AISI are useful indicators of systemic inflammation and disease severity in psoriasis.

Short-term S100A8/A9 Blockade Promotes Cardiac Neovascularization after Myocardial Infarction.

Acute-phase inhibition of the pro-inflammatory alarmin S100A8/A9 improves cardiac function post-myocardial infarction (MI), but the mechanisms underlying the long-term benefits of this short-term treatment remain to be elucidated. Here, we assessed the effects of S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 on myocardial neovascularization in mice with induced MI. The treatment significantly reduced S100A9 and increased neovascularization in the myocardium, assessed by CD31 staining. Proteomic analysis by mass-spectrometry showed strong myocardial upregulation of the pro-angiogenic proteins filamin A (~ 10-fold) and reticulon 4 (~ 5-fold), and downregulation of the anti-angiogenic proteins Ras homolog gene family member A (RhoA, ~ 4.7-fold), neutrophilic granule protein (Ngp, ~ 4.0-fold), and cathelicidin antimicrobial peptide (Camp, ~ 4.4-fold) versus controls. In-vitro, ABR-238901 protected against apoptosis induced by recombinant human S100A8/A9 in human umbilical vein endothelial cells (HUVECs). In conclusion, S100A8/A9 blockade promotes post-MI myocardial neovascularization by favorably modulating pro-angiogenic proteins in the myocardium and by inhibiting endothelial cell apoptosis.

Epidermal Barrier Parameters in Psoriasis: Implications in Assessing Disease Severity.

Psoriasis is characterized by an aberrant immune response due to myeloid dendritic cells and T helper cells intertwining with keratinocyte hyperproliferation. Skin integrity alterations may predispose patients to physiological imbalances, such as xerosis, reduced elasticity, and increased friability. This study aims to assess the epidermal barrier dysfunction in chronic plaque psoriasis and gain a comprehensive view of the dynamic changes in the epidermal barrier during various topical therapies. Adult patients with chronic plaque psoriasis were enrolled in this observational study. For each patient, skin barrier parameters, stratum corneum hydration (SCH), transepidermal water loss (TEWL), elasticity, erythema, and melanin levels were measured in lesional and non-lesional skin. Two extensions of the initial study design, with subsequent epidermal barrier determinations, were made as follows: one in which patients with moderate psoriasis were treated with clobetasol propionate 0.5% and the second one in which mild psoriasis was treated with either clobetasol propionate 0.5% or clobetasol propionate 0.5% with 10% urea. TEWL and erythema were found to be higher in the sites affected by psoriatic lesions than the unaffected sites, while SCH and elasticity were decreased. Severe psoriasis presented with higher TEWL (p = 0.032), erythema (p = 0.002), and lower SCH (p < 0.001) compared with the mild and moderate forms. SCH significantly improved during clobetasol propionate 0.5% treatment (p = 0.015). Clobetasol propionate 0.5% with 10% urea was found to be superior to clobetasol propionate 0.5% in improving TEWL and SCH in psoriasis.

Predicting Factors and Clinical Characteristics of Pruritus in Psoriasis: A Cross-Sectional Survey.

Pruritus is an important symptom among patients affected by psoriasis. To date, no general agreement has been established regarding pruritus as a measure of psoriasis severity. This study aims to assess psoriatic pruritis prevalence and characteristics using a comprehensive itch questionnaire. A semi-structured questionnaire consisting of 48 questions was applied to patients diagnosed with psoriasis and admitted to the Dermatology Department of Mures Clinical County Hospital, Romania. A total of 163 patients were enrolled, out of which 115 (70.55%) reported itch. Patients with itch had higher PASI (p = 0.003) and DLQI scores (p < 0.001). The itch was most frequently described as a crawling sensation, mainly located in the lesional skin and aggravated by stress and temperature variation. It had a moderate intensity (6.18 ± 2.46). Emollients were the treatment preferred by most patients in alleviating itch, while biologics exerted a protective effect on itch development (OR = -0.24; p < 0.0001) and negatively correlated with itch intensity (r = -0.23; p < 0.0001). Advanced age, high BMI, and PASI scores were indicators of itch presence, while female gender, high PASI score, and frequent itch episodes indicate highly intense pruritus (≥7 on the VAS). A better understanding of itch and its clinical features will guide physicians toward the best treatment option and would, ultimately, benefit the patient.

Blood-Count-Derived Inflammatory Markers as Predictors of Response to Biologics and Small-Molecule Inhibitors in Psoriasis: A Multicenter Study.

Background: Psoriasis is an immune-mediated chronic disorder associated with various comorbidities. Even though biologics and small-molecule inhibitors are the mainstay treatment for moderate-to-severe psoriasis, there is no current consensus regarding which agent should be used for a specific type of patient. This paper aims to test the reliability of blood-count-derived inflammatory markers in assessing treatment response to biologics and small-molecule inhibitors in psoriasis. Material and Methods: Bio-naïve adult patients diagnosed with chronic plaque psoriasis fulfilling the inclusion criteria were enrolled. They were divided into study subgroups based on treatment of choice, and blood-count-derived inflammatory markers were analyzed at baseline, three-month, six-month, and at twelve-month visits. Results: A total of 240 patients were included. The highest number of patients underwent treatment with ixekizumab. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-monocyte ratio (PMR), monocyte-to-lymphocyte ratio (MLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), and aggregate index of systemic inflammation (AISI) all varied significantly (p < 0.005) between the four visits. The psoriasis area severity index (PASI) score correlated with PLR, d-NLR, and SII, while the psoriasis scalp severity index (PSSI) score correlated with AISI and SIRI. More than half of patients reached the target goal of PASI90 at the six-month visit. A total of 77 patients were super-responders, with the highest number undergoing treatment with ixekizumab. Higher baseline values of d-NLR and SIRI are independent predictors of the super-responder status. Conclusions: Blood-count-derived inflammatory markers can serve as indicators of treatment response to biologics in psoriasis, while d-NLR and SIRI were independent predictors of super-responders in our study.

Cancer Cachexia: New Insights and Future Directions.

Cancer remains a major health problem and is associated with cachexia in up to 80% of cases, leading to decreased survival and quality of life. Cachexia involves complex metabolic disturbances in both protein and energy balance, muscle wasting phenomena, weight loss, systemic inflammation, overall decreased performance status, and tolerability to treatment. The clinical impact of cancer cachexia is very complex, with early detection of cachectic patients and identification of predictive biomarkers being two key factors for improving survival. Thus, a better understanding of the complexity of cancer cachexia phenomena and its main pathophysiological mechanism is much needed. Our review highlights the most important information about cancer cachexia, aiming to disseminate updated research findings about this highly deadly condition.

The Importance of Immunohistochemistry in the Evaluation of Tumor Depth of Primary Cutaneous Melanoma.

Primary cutaneous melanoma (PCM) is the most aggressive skin malignancy, with an increasing incidence and significant mortality. Tumoral invasion, expressed as Breslow thickness, is routinely assessed on hematoxylin and eosin (HE), although this stain may sometimes underestimate the tumoral depth. The aim of this study was to compare the efficiency of the immunohistochemical (IHC) markers S-100, SOX10, Melan-A, and HMB-45 with HE for the evaluation of the Breslow thickness and staging of PCM. This retrospective study included 46 cases of PCM diagnosed between 2015 and 2022; for each case, the Breslow thickness using HE, S-100, SOX10, Melan-A, and HMB-45 was measured and the appropriate T category was recorded. The highest values of the Breslow thickness were observed for S-100. However, S-100, SOX10, and Melan-A provided statistically significant higher values of the Breslow thickness compared to HE, but no difference was noted between HMB-45 and HE. S-100 was most frequently involved in increasing the T category (26.1%), the majority of cases being upstaged from T1a to T1b. The IHC markers S-100, SOX10, and Melan-A contributed to better evaluation of the melanoma invasion, especially in thin melanomas, but their impact on staging and consecutive treatment remains to be confirmed by future studies.