Diseases, Volume 12, Issue 5 (May 2024) – 9 articles

Introduction: The impact of peripheral cytokine levels on the prognosis and treatment of immune checkpoint inhibitor (ICI) myocarditis has not been well studied. Objectives: This study aimed to identify cytokines that can prognosticate and direct the treatment of ICI myocarditis. Methods: This was a single-center, retrospective cohort study of patients with ICI myocarditis who had available peripheral cytokine levels between January 2011 and May 2022. Major adverse cardiovascular events (MACEs) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis, life-threatening arrhythmias, pulmonary embolism, and sudden cardiac death. Results: In total, 65 patients with ICI myocarditis had cytokine data available. Patients were mostly males (70%), with a mean age of 67.8 ± 12.7 years. Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were the most common cytokines to be elevated with 48/65 (74%) of patients having a peak IL-6 above normal limits (>5 pg/mL) and 44/65 (68%) of patients with peak TNF-α above normal limits (>22 pg/mL). Patients with elevated peak IL-6 had similar 90-day mortality and MACE outcomes compared to those without (10.4% vs. 11.8%, p = 0.878 and 8.8% vs. 17.7%, p = 0.366, respectively). Similarly, those with elevated peak TNF-α had similar 90-day mortality and MACEs compared to those without (29.6% vs. 14.3%, p = 0.182 and 13.6% vs. 4.8%, p = 0.413, respectively). Kaplan–Meier survival analysis also showed that there was not a significant difference between MACE-free survival when comparing elevated and normal IL-6 and TNF-α levels (p = 0.182 and p = 0.118, respectively). MACEs and overall survival outcomes were similar between those who received infliximab and those who did not among all patients and those with elevated TNF-α (p-value 0.70 and 0.83, respectively). Conclusion: Peripheral blood levels of IL-6 and TNF-α are the most commonly elevated cytokines in patients with ICI myocarditis. However, their role in the prognostication and guidance of immunomodulatory treatment is currently limited. Full article

Prostate cancer, a prevalent malignancy affecting the prostate gland, is a significant global health concern. Androgen-deprivation therapy (ADT) has proven effective in controlling advanced disease, with over 50% of patients surviving at the 10-year mark. However, a diverse spectrum of responses exists, and resistance to ADT may emerge over time. This underscores the need to explore innovative treatment strategies for effectively managing prostate cancer progression. Ongoing research endeavors persist in unraveling the complexity of prostate cancer and fostering the development of biologic and innovative approaches, including immunotherapies and targeted therapies. This review aims to provide a valuable synthesis of the dynamic landscape of emerging drug modalities in this context. Interestingly, the complexities posed by prostate cancer not only present a formidable challenge but also serve as a model and an opportunity for translational research and innovative therapies in the field of oncology. Full article

Pancreaticolithiasis represents a rare phenomenon, being superimposed most of the time on a form of chronic pancreatitis of multifactorial etiology. Pancreaticolithiasis is a late complication of the phenomenon of chronic pancreatitis. The reverberant inflammatory process, followed by the fibrotic degeneration of the pancreatic parenchyma, and pancreatic fluid stasis at the ductal level are factors that contribute to the phenomenon of calcium precipitation. This article describes the case of a patient with a diagnosis of pancreaticolithiasis (Wirsung duct lithiasis), a phenomenon superimposed on chronic pancreatitis of ethanolic cause (Rosemont classification). It was decided to perform surgery via the classical approach with the perfection of corporeo-caudal pancreatectomy and preservation of the splenic vessels (Kimura procedure) with pancreatico-jejunal anastomosis on the Roux-en-Y loop. The aim of this study is to identify the best method of treatment for pancreaticolithiasis. To enhance the case and provide a basis for standardization, a literature review was carried out, which included a total of six articles. The results of this study highlight that, currently, the management of symptomatic pancreaticolithiasis encompasses medical therapy (enzyme replacement therapy), interventional therapy (ESWL (extracorporeal shock wave lithotripsy) ± ERCP (endoscopic retrograde cholangiopancreatography), ERCP + sphincterotomy + stent insertion, and POP (oral pancreatoscopy)), and surgical treatment. In conclusion, based on the analysis conducted in this study, the size of the calculi present determines which is the suitable therapeutic care. Unlike stones over 0.5 cm, when surgery is explicitly advised for therapeutic purposes in the absence of endoscopic techniques, stones under 0.5 cm should be treated using endoscopic procedures. Full article

The pathogenesis of cyclophosphamide (CY)-induced cardiotoxicity remains unknown, and methods for its prevention have not been established. To elucidate the acute structural changes that take place in myocardial cells and the pathways leading to myocardial damage under high-dose CY treatments, we performed detailed pathological analyses of myocardial tissue obtained from C57BL/6J mice subjected to a high-dose CY treatment. Additionally, we analysed the genome-wide cardiomyocyte expression profiles of mice subjected to the high-dose CY treatment. Treatment with CY (400 mg/kg/day intraperitoneally for two days) caused marked ultrastructural aberrations, as observed using electron microscopy, although these aberrations could not be observed using optical microscopy. The expansion of the transverse tubule and sarcoplasmic reticulum, turbulence in myocardial fibre travel, and a low contractile protein density were observed in cardiomyocytes. The high-dose CY treatment altered the cardiomyocyte expression of 1210 genes (with 675 genes upregulated and 535 genes downregulated) associated with cell–cell junctions, inflammatory responses, cardiomyopathy, and cardiac muscle function, as determined using microarray analysis (|Z-score| > 2.0). The expression of functionally important genes related to myocardial contraction and the regulation of calcium ion levels was validated using real-time polymerase chain reaction analysis. The results of the gene expression profiling, functional annotation clustering, and Kyoto Encyclopedia of Genes and Genomes pathway functional-classification analysis suggest that CY-induced cardiotoxicity is associated with the disruption of the Ca²⁺ signalling pathway. Full article

Cystic Echinococcosis (CE) is a zoonotic disease caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s.l.). This study aims to investigate the use of two monoclonal antibodies (mAbEmG3 and mAbEm2G11) by immunohistochemistry (IHC) to confirm the diagnosis of CE in human patients, in particular in those cases in which other techniques fail to provide a correct or conclusive diagnosis. For this purpose, a survey on 13 patients was performed. These subjects were referred to Sardinian hospitals (Italy) from 2017 to 2022 and were suspected to be affected by CE. Our findings from these 13 patients showed the detection of E. granulosus sensu stricto by IHC in 12 of 13 echinococcal cysts, as one sample was of a non-parasitological origin. The results confirmed that IHC, by means of the mAbEmG3 and mAbEm2G11, is a reliable diagnostic tool that showed a very high performances when tested on strain of E. granulosus s.l. from Sardinia. Full article

Little is known about ocular tics in Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections (PANDAS). In this retrospective study, we examined the clinical records of children with motor tics referred to the Ophthalmology Unit, Azienda Ospedaliero-Universitaria di Sassari, Italy, in 2010–2019. The presence of ocular tics was investigated. Data about antistreptolysin O (ASO) and anti-DNase B antibody titers, erythrocyte sedimentation rate (ESR), plasma C-reactive protein (CRP), and antibiotic use were recorded. Forty children (thirty-four boys and six girls; mean age: 7.65 ± 2.5 years) with motor tics were identified; thirty-three (82.5%) showed ocular tics. Children with ocular tics had significantly higher titers of anti-DNase B antibodies (p = 0.04) and CRP (p = 0.016) than those with extraocular tics. A diagnosis of PANDAS was made in 24 (60%) children. PANDAS children with oculomotor tics had significantly higher titers of anti-DNase B antibodies (p = 0.05) than those with extraocular tics. Oral antibiotics were given to 25/33 (76%) children with ocular tics and 21/24 (87.5%) with PANDAS. All treated patients showed marked improvement/complete resolution of symptoms. Results suggest that higher titers of anti-DNase B antibodies may be implicated in the pathogenesis of ocular tics in PANDAS. Oral antibiotics may be beneficial in improving ocular tics. Further research is necessary to confirm our findings. Full article

Postpartum depression (PPD) is a significant global health concern with profound implications for mothers, families, and societies. This systematic review aims to synthesize current research findings to understand better how personality traits, as assessed by the NEO Five-Factor Inventory (NEO-FFI), contribute to the development and progression of PPD. Conducted in January 2024, this review searched major databases like PubMed, PsycINFO, and Scopus up to December 2023, focusing on the NEO-FFI’s role in evaluating PPD. Following PRISMA guidelines, studies were selected based on strict criteria, including the exclusive use of NEO-FFI for personality assessment and a focus on postpartum women. A total of seven studies were included after a rigorous two-step screening process, and their data were qualitatively synthesized. The review covered a total of 4172 participants, with a prevalence of clinically significant postpartum depression symptoms ranging from 10.6% to 51.7%. Notably, Neuroticism emerged as a significant predictor of PPD, with odds ratios ranging from 1.07 (95% CI: 0.96–1.20) in some studies to as high as 1.87 (95% CI: 1.53–2.27) in others. In contrast, traits like Extraversion and Conscientiousness generally showed protective effects, with lower scores associated with reduced PPD risk. For instance, Extraversion scores correlated negatively with PPD risk (Beta = −0.171) in one study. However, the impact of other traits such as Openness and Agreeableness on PPD risk was less clear, with some studies indicating negligible effects. The review highlights Neuroticism as a consistent and significant predictor of PPD risk, with varying impacts from other personality traits. The findings suggest potential pathways for targeted interventions in maternal mental health care, emphasizing the need for comprehensive personality evaluations in prenatal and postnatal settings. Full article

Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory autoimmune condition characterized by synovitis, pannus formation (with adjacent bone erosion), and joint destruction. In the perpetuation of RA, fibroblast-like synoviocytes (FLSs), macrophages, B cells, and CD4⁺ T-cells—specifically Th1 and Th17 cells—play crucial roles. Additionally, dendritic cells, neutrophils, mast cells, and monocytes contribute to the disease progression. Monocytes, circulating cells primarily derived from the bone marrow, participate in RA pathogenesis. Notably, CCR2 interacts with CCL2, and CX3CR1 (expressed by monocytes) cooperates with CX3CL1 (produced by FLSs), facilitating the migration involved in RA. Canonical “classical” monocytes predominantly acquire the phenotype of an “intermediate” subset, which differentially expresses proinflammatory cytokines (IL-1β, IL-6, and TNF) and surface markers (CD14, CD16, HLA-DR, TLRs, and β1- and β2-integrins). However, classical monocytes have greater potential to differentiate into osteoclasts, which contribute to bone resorption in the inflammatory milieu; in RA, Th17 cells stimulate FLSs to produce RANKL, triggering osteoclastogenesis. This review aims to explore the monocyte heterogeneity, plasticity, antigenic expression, and their differentiation into macrophages and osteoclasts. Additionally, we investigate the monocyte migration into the synovium and the role of their cytokines in RA. Full article

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially affected by oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted a previously introduced clinical model of host–virus interaction (i.e., infectious process in immunodeficiency) for analysis of B cells and the specific IgG role (an observational study of a CVID patient who received intravenous immunoglobulin (IVIG). Suddenly, the patient deteriorated and a positive results of for HBs and HBV-DNA (369 × 10⁶ copies) were detected. Despite lamivudine therapy and IVIG escalation (from 0.3 to 0.4 g/kg), CT showed an 11 cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs were positive in time-lapse analysis (range 111–220 IU/mL). Replacement therapy intensification was complicated by an immune complex disease with renal failure. Fulminant HCC in CVID and the development of a tumor as the first sign is of interest. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HB substitution has not been proven to be effective, oncoprotective, nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, and patient selection more precise with the exclusion of HBV-positive donors. Our clinical model showed an HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g., chronic hepatitis). The lack of cell cooperation as well as B cell deficiency observed in CVID play a crucial role in high HBV replication, especially in carcinogenesis. Full article