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Diseases, Volume 12, Issue 5 (May 2024) – 29 articles

Cover Story (view full-size image): The interaction between bile acids, bilirubin and the cardiovascular system has attracted the interest of researchers in the last few years. Several reports suggested that bile acids enhance the absorption of antioxidant vitamins, directly protect proteins and lipids from peroxidation, and exert anti-inflammatory effects, while safeguarding the endothelium from chemical injuries, even if their effects on the CV system are still under debate. Bilirubin acts as an endogenous oxygen radical scavenger, providing anti-inflammatory and vasodilatory benefits. These effects could explain the reduced CV risk observed in individuals with moderately elevated serum bilirubin levels who do not have liver diseases. This also underscores the need for further research into the relationship between bile acids and bilirubin serum levels and vascular health. View this paper
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13 pages, 318 KiB  
Article
Eating Attitudes, Stress, Anxiety, and Depression in Dietetic Students and Association with Body Mass Index and Body Fat Percent: A Cross-Sectional Study
by Olga Magni, Paraskevi Detopoulou, Evangelia Fappa, Anastasia Perrea, Despoina Levidi, Vasilios Dedes, Milia Tzoutzou, Aristea Gioxari and Georgios Panoutsopoulos
Diseases 2024, 12(5), 108; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050108 - 20 May 2024
Viewed by 859
Abstract
University students face challenges impacting psychology and dietary choices. The present work examined the association between eating attitudes, stress, anxiety, and depression to body mass index (BMI) and body fat percentage in Dietetics students. Respondents completed the Eating Attitudes Test-26 (EAT-26), the Depression [...] Read more.
University students face challenges impacting psychology and dietary choices. The present work examined the association between eating attitudes, stress, anxiety, and depression to body mass index (BMI) and body fat percentage in Dietetics students. Respondents completed the Eating Attitudes Test-26 (EAT-26), the Depression Anxiety Stress Scales (DASS), a validated Food Frequency Questionnaire, and the Hellenic Physical Activity Questionnaire (HPAQ). Anthropometry and a bioimpedance analysis were performed. The EAT-26 score was 11 (8–16) and the DASS score was 20 (11–36) (medians and interquartile ranges). Disordered eating was detected in 20% of men and 15% of women. Depressive symptomatology was detected in 30% of males and 23% of females, anxiety in 35% of males and 40% of females, and stress in 29% of males and 35% of females. EAT-26 and DASS scores were highly correlated (r = 0. 0.221, p = 0.001). The EAT-26 oral control subscale (B = 0.430, SE = 0.184, p = 0.026) was positively correlated with BMI in men in the models, adjusted for age, physical activity, and Mediterranean Diet Score, while no association was documented for % body fat. The DASS depression score was not related to BMI in multi-adjusted models. In conclusion, disordered eating, depression, stress, and anxiety are present in this sample of university students. The relationship between disordered eating and BMI needs consideration in programs targeting overweight or underweight in Dietetics students. Full article
10 pages, 234 KiB  
Article
Clinical Outcomes among Hospitalized COVID-19 Patients Who Received Baricitinib or Tocilizumab in Addition to Standard of Care
by Cucnhat P. Walker, Natalie P. Hurlock and Subrata Deb
Diseases 2024, 12(5), 107; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050107 - 20 May 2024
Viewed by 615
Abstract
COVID-19 infection is caused by the novel severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2). This novel virus has transformed into different resistant variants (e.g., omicron; delta; alpha; epsilon) since its first emergence in 2019. The National Institutes of Health and Infectious Diseases Society [...] Read more.
COVID-19 infection is caused by the novel severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2). This novel virus has transformed into different resistant variants (e.g., omicron; delta; alpha; epsilon) since its first emergence in 2019. The National Institutes of Health and Infectious Diseases Society of America guidelines currently recommend adding either baricitinib or tocilizumab to the standard of care for severe COVID-19 treatment. An outcome comparison between baricitinib and tocilizumab is needed to determine which agent is more appropriate and safer in clinical practice when deciding treatment. We aimed to compare mortality and clinical outcomes between tocilizumab and baricitinib in the management of severe COVID-19 infection. A total of 5638 adult patients from 16 acute care hospitals in a large healthcare system in Texas were included in this multicentered retrospective cohort study. The median age of the patients was 56 years and 46.67% of them were female. Severe COVID-19 patients were treated with standard of care and either tocilizumab or baricitinib. The primary outcome of hospital admission mortality rates was found to be higher with tocilizumab (odd ratio (OR) of 1.56; p = 0.001; 95% CI 1.19 to 2.008) compared to that with baricitinib (OR 0.65; p = 0.001; 95% CI 0.50 to 0.84). For one of the secondary outcomes, patients who received tocilizumab were 3.75 times more likely to be admitted to the ICU than those receiving baricitinib (p = 0.001; 95% CI 2.89 to 4.85). Among the 1199 COVID-19 patients who were admitted to the ICU, the ICU length of stay was shorter among patients receiving baricitinib with a mean difference of 4.42 days and a median difference of 2.54 days, compared to those receiving tocilizumab (p < 0.0001; 95% CI −5.97 to −2.62) as another secondary outcome. Our large retrospective observational study showed that baricitinib reduced mortality; the likelihood of ICU admission; and the ICU length of stay compared to tocilizumab in patients with severe COVID-19 infection. Full article
12 pages, 603 KiB  
Article
Frequency of the Main Human Leukocyte Antigen A, B, DR, and DQ Loci Known to Be Associated with the Clearance or Persistence of Hepatitis C Virus Infection in a Healthy Population from the Southern Region of Morocco: A Preliminary Study
by Safa Machraoui, Khaoula Errafii, Ider Oujamaa, Moulay Yassine Belghali, Abdelmalek Hakmaoui, Saad Lamjadli, Fatima Ezzohra Eddehbi, Ikram Brahim, Yasmine Haida and Brahim Admou
Diseases 2024, 12(5), 106; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050106 - 16 May 2024
Viewed by 710
Abstract
Hepatitis C Virus (HCV) infection represents a significant global health challenge, with its natural course largely influenced by the host’s immune response. Human Leukocyte Antigen (HLA) molecules, particularly HLA class I and II, play a crucial role in the adaptive immune response against [...] Read more.
Hepatitis C Virus (HCV) infection represents a significant global health challenge, with its natural course largely influenced by the host’s immune response. Human Leukocyte Antigen (HLA) molecules, particularly HLA class I and II, play a crucial role in the adaptive immune response against HCV. The polymorphism of HLA molecules contributes to the variability in immune response, affecting the outcomes of HCV infection. This study aims to investigate the frequency of HLA A, B, DR, and DQ alleles known to be associated with HCV clearance or persistence in a healthy Moroccan population. Conducted at the University Hospital Center Mohammed VI, Marrakech, this study spanned from 2015 to 2022 and included 703 healthy Moroccan individuals. HLA class I and II typing was performed using complement-dependent cytotoxicity and polymerase chain reaction-based methodologies. The results revealed the distinct patterns of HLA-A, B, DRB1, and DQB1 alleles in the Moroccan population. Notably, alleles linked to favorable HCV outcomes, such as HLA-DQB1*0301, DQB1*0501, and DRB1*1101, were more prevalent. Conversely, alleles associated with increased HCV susceptibility and persistence, such as HLA-DQB1*02 and DRB1*03, were also prominent. Gender-specific variations in allele frequencies were observed, providing insights into genetic influences on HCV infection outcomes. The findings align with global trends in HLA allele associations with HCV infection outcomes. The study emphasizes the role of host genetics in HCV infection, highlighting the need for further research in the Moroccan community, including HCV-infected individuals. The prevalence of certain HLA alleles, both protective and susceptibility-linked, underscores the potential for a national HLA data bank in Morocco. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology 2024)
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6 pages, 1044 KiB  
Case Report
Electrical Storm Induced by Cardiac Resynchronization: Efficacy of the Multipoint Pacing Stimulation
by Anna Gonella, Carmelo Casile, Endrj Menardi and Mauro Feola
Diseases 2024, 12(5), 105; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050105 - 15 May 2024
Viewed by 493
Abstract
Although cardiac resynchronization therapy (CRT) reduces morbidity and mortality and reverses left ventricular (LV) remodeling in heart failure patients with LV electrical dyssynchrony, induced proarrhythmia has been reported. The mechanism of CRT-induced proarrhythmia remains under debate. In this case report, a description of [...] Read more.
Although cardiac resynchronization therapy (CRT) reduces morbidity and mortality and reverses left ventricular (LV) remodeling in heart failure patients with LV electrical dyssynchrony, induced proarrhythmia has been reported. The mechanism of CRT-induced proarrhythmia remains under debate. In this case report, a description of how LV pacing induced polymorphic ventricular tachycardia immediately after the initiation of CRT has been reported. By changing the pacing configuration using a multipoint pacing stimulation, we can assume that induced ventricular tachycardia is related to the reentry mechanism facilitated by the unidirectional block. As a result, a multipoint pacing (MPP) configuration near the scar area can avoid the onset of a unidirectional block with the establishment of the reentry phenomenon, thus avoiding induced VTs. Full article
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16 pages, 899 KiB  
Review
Dystrophic Epidermolysis Bullosa (DEB): How Can Pregnancy Alter the Course of This Rare Disease? An Updated Literature Review on Obstetrical Management with an Additional Italian Experience
by Antonella Vimercati, Gerardo Cazzato, Lucia Lospalluti, Stefania Foligno, Cristina Taliento, Katarzyna Beata Trojanowska, Ettore Cicinelli, Domenico Bonamonte, Dario Caliandro, Amerigo Vitagliano and Pierpaolo Nicolì
Diseases 2024, 12(5), 104; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050104 - 15 May 2024
Viewed by 701
Abstract
Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner mucous membranes, occurring after mild friction or trauma, or even spontaneously. Within the spectrum of EB forms, dystrophic [...] Read more.
Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner mucous membranes, occurring after mild friction or trauma, or even spontaneously. Within the spectrum of EB forms, dystrophic EB (DEB) represents the most intriguing and challenging in terms of clinical management, especially with regard to pregnancy, due to the highly disabling and life-threatening phenotype. Disappointingly, in the literature little focus has been directed towards pregnancy and childbirth in DEB patients, resulting in a lack of sound evidence and guidance for patients themselves and clinicians. The current study aims to contribute to the DEB literature with an updated summary of the existing evidence regarding the obstetrical and anesthesiological management of this rare disease. Furthermore, this literature review sought to answer the question of whether, and if so, in which way, the pregnancy condition may alter the course of the underlying dermatologic skin disease. Having all this information is indispensable when counseling a patient with DEB who desires a child or is expecting one. Finally, we reported own experience with a pregnant woman with a recessive DEB whom we recently managed, with a favorable outcome. Full article
(This article belongs to the Section Rare Syndrome)
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19 pages, 11534 KiB  
Review
Bile Acids and Bilirubin Role in Oxidative Stress and Inflammation in Cardiovascular Diseases
by Angela Punzo, Alessia Silla, Federica Fogacci, Matteo Perillo, Arrigo F. G. Cicero and Cristiana Caliceti
Diseases 2024, 12(5), 103; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050103 - 14 May 2024
Viewed by 914
Abstract
Bile acids (BAs) and bilirubin, primarily known for their role in lipid metabolism and as heme catabolite, respectively, have been found to have diverse effects on various physiological processes, including oxidative stress and inflammation. Indeed, accumulating evidence showed that the interplay between BAs [...] Read more.
Bile acids (BAs) and bilirubin, primarily known for their role in lipid metabolism and as heme catabolite, respectively, have been found to have diverse effects on various physiological processes, including oxidative stress and inflammation. Indeed, accumulating evidence showed that the interplay between BAs and bilirubin in these processes involves intricate regulatory mechanisms mediated by specific receptors and signaling pathways under certain conditions and in specific contexts. Oxidative stress plays a significant role in the development and progression of cardiovascular diseases (CVDs) due to its role in inflammation, endothelial dysfunction, hypertension, and other risk factors. In the cardiovascular (CV) system, recent studies have suggested that BAs and bilirubin have some opposite effects related to oxidative and inflammatory mechanisms, but this area of research is still under investigation. This review aims to introduce BAs and bilirubin from a biochemical and physiological point of view, emphasizing their potential protective or detrimental effects on CVDs. Moreover, clinical studies that have assessed the association between BAs/bilirubin and CVD were examined in depth to better interpret the possible link between them. Full article
(This article belongs to the Section Cardiology)
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12 pages, 687 KiB  
Article
The Effect of Fabry Disease Therapy on Bone Mineral Density
by Tess Aitken, Mark K. Tiong, Andrew S. Talbot, Irene Ruderman and Kathleen M. Nicholls
Diseases 2024, 12(5), 102; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050102 - 13 May 2024
Viewed by 599
Abstract
Fabry disease (FD) is an X-linked lysosomal storage disorder, characterised by the cellular accumulation of globotriaosylceramide due to impaired alpha-galactosidase A enzyme activity. FD may manifest with multisystem pathology, including reduced bone mineral density (BMD). Registry data suggest that the introduction of Fabry-specific [...] Read more.
Fabry disease (FD) is an X-linked lysosomal storage disorder, characterised by the cellular accumulation of globotriaosylceramide due to impaired alpha-galactosidase A enzyme activity. FD may manifest with multisystem pathology, including reduced bone mineral density (BMD). Registry data suggest that the introduction of Fabry-specific therapies (enzyme replacement therapy or chaperone therapy) has led to significant improvements in overall patient outcomes; however, there are limited data on the impact on bone density. The aim of this study was to describe the effect of Fabry-specific therapies on longitudinal changes in bone mineral density (BMD) in FD. We performed a retrospective observational study analysing bone densitometry (DXA) in patients with genetically confirmed FD. Patients were grouped based on the use of Fabry-specific therapies. The between-group longitudinal change in BMD Z-score was analysed using linear mixed effects models. A total of 88 FD patients were analysed (50 untreated; 38 treated). The mean age at first DXA was 38.5 years in the untreated group (84% female) and 43.7 years in the treated group (34% female). There was no significant longitudinal between-group difference in the BMD Z-score at the lumbar spine. However, the Z-score per year at the total hip (β = −0.105, p < 0.001) and femoral neck (β = −0.081, p = 0.001) was significantly lower over time in the treated than the untreated group. This may reflect those receiving therapy having a more severe underlying disease. Nevertheless, this suggests that Fabry-specific therapies do not reverse all disease mechanisms and that the additional management of BMD may be required in this patient population. Full article
(This article belongs to the Collection Lysosomal Storage Diseases)
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14 pages, 1588 KiB  
Review
Molecular Diagnostics of Cryptococcus spp. and Immunomics of Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome
by Irina Vlasova-St. Louis and Hesham Mohei
Diseases 2024, 12(5), 101; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050101 - 13 May 2024
Viewed by 799
Abstract
Cryptococcal infection poses a significant global public health challenge, particularly in regions near the equator. In this review, we offer a succinct exploration of the Cryptococcus spp. genome and various molecular typing methods to assess the burden and genetic diversity of cryptococcal pathogens [...] Read more.
Cryptococcal infection poses a significant global public health challenge, particularly in regions near the equator. In this review, we offer a succinct exploration of the Cryptococcus spp. genome and various molecular typing methods to assess the burden and genetic diversity of cryptococcal pathogens in the environment and clinical isolates. We delve into a detailed discussion on the molecular pathogenesis and diagnosis of immune reconstitution inflammatory syndrome (IRIS) associated with cryptococcosis, with a specific emphasis on cryptococcal meningitis IRIS (CM-IRIS). Our examination includes the recent literature on CM-IRIS, covering host cellulomics, proteomics, transcriptomics, and genomics. Full article
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26 pages, 413 KiB  
Review
John Cunningham Virus and Progressive Multifocal Leukoencephalopathy: A Falsely Played Diagnosis
by Dimitra S. Mouliou
Diseases 2024, 12(5), 100; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050100 - 13 May 2024
Viewed by 1069
Abstract
Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple [...] Read more.
Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple Sclerosis (MS) cases treated with natalizumab (Tysabri). However, there are conflicting literature data on its pathology and diagnosis, whereas some misdiagnosed reports exist, giving rise to further questions towards the topic. In reality, the so-called PML and the supposed JCPyV are not what they seem to be. In addition, novel and more frequent PML-like conditions may be reported, especially after the Coronavirus Disease 2019 (COVID-19) pandemic. Full article
11 pages, 790 KiB  
Article
Evaluation of the Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantations in ALS Patients by Investigating Patients’ Specific Immunological and Biochemical Biomarkers
by Zahraa Alkhazaali-Ali, Sajad Sahab-Negah, Amir Reza Boroumand, Najmeh Kaffash Farkhad, Mohammad Ali Khodadoust and Jalil Tavakol-Afshari
Diseases 2024, 12(5), 99; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050099 - 12 May 2024
Viewed by 714
Abstract
Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell [...] Read more.
Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell (MSC) therapy cohort as a promising novel treatment modality by estimating some additional new parameters, such as immunological and biochemical factors. Methods: This study was designed as an open-label, one-arm cohort retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous-bone marrow-derived mesenchymal stem cells (BM-MSCs) in 15 confirmed patients with ALS, administered at a dose of 1 × 106 cells/kg BW with a one-month interval, in equal amounts in both an intravenous (IV) and intrathecal (IT) capacity simultaneously, via various biochemical (iron (Fe), ferritin, total-iron-binding capacity (TIBC), transferrin, and creatine kinase (CK)) and immunological parameters (tumor necrosis factor-alpha (TNF-α), neurofilament light chain (NFL), and glial-cell-derived neurotrophic factor (GDNF) levels, evaluated during the three-month follow-up period in serum and cerebrospinal fluid (CSF). Results: Our study indicated that, in the case of immunological biomarkers, TNF-α levels in the CSF showed a significant decrease at month three after transplantation compared with levels at month zero, and the p-value was p < 0.01. No statistically significant changes were observed for other immunological as well as biochemical parameters and a p-value of p > 0.05. Conclusions: These results can indicate the potential benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results. Full article
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12 pages, 600 KiB  
Article
A Single-Center Experience in Combined Oncological–Surgical Treatment for Resectable Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
by Dan Levy Faber, Abed Agbarya, Ben Caspy, Moshe Lapidot, Shoshana Keren Rosenberg, Sonia Schneer, Erez Sharoni and Ronen Galili
Diseases 2024, 12(5), 98; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050098 - 12 May 2024
Viewed by 801
Abstract
Non-small cell lung cancer (NSCLC) is the most common pulmonary malignancy, frequently diagnosed at an advanced stage (III/IV). Patients in the Locally Advanced Stage Subgroup (IIIA) are relatively few, yet compose heterogenic phenotypes, posing a diagnostic and treating challenge, leading to a lack [...] Read more.
Non-small cell lung cancer (NSCLC) is the most common pulmonary malignancy, frequently diagnosed at an advanced stage (III/IV). Patients in the Locally Advanced Stage Subgroup (IIIA) are relatively few, yet compose heterogenic phenotypes, posing a diagnostic and treating challenge, leading to a lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, patients with operable stage IIIA NSCLC who underwent surgery between 2013 and 2020 were evaluated on several aspects, including the initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, and overall survival at 2 years and 5 years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 19 patients, of which 25% of cases were defined as a complete pathological response. The 2-year overall survival rate was 65% and the 5-year overall survival rate was 62%. The main pattern of disease recurrence was distant metastasis. Full article
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16 pages, 685 KiB  
Article
Association of Calf Circumference with Clinical and Biochemical Markers in Older Adults with COVID-19 Admitted at Intensive Care Unit: A Retrospective Cross-Sectional Study
by Vanessa A. Araújo, Jefferson S. Souza, Bruna M. Giglio, Patrícia C. B. Lobo and Gustavo D. Pimentel
Diseases 2024, 12(5), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050097 - 8 May 2024
Viewed by 739
Abstract
Background: COVID-19 is an infectious disease characterized by a severe catabolic and inflammatory state, leading to loss of muscle mass. The assessment of muscle mass can be useful to identify nutritional risk and assist in early management, especially in older adults who have [...] Read more.
Background: COVID-19 is an infectious disease characterized by a severe catabolic and inflammatory state, leading to loss of muscle mass. The assessment of muscle mass can be useful to identify nutritional risk and assist in early management, especially in older adults who have high nutritional risks. The aim of this study was to evaluate the association of calf circumference (CC) with clinical and biochemical markers and mortality in older adults with COVID-19 admitted to the intensive care unit (ICU). Methods: A retrospective cross-sectional study was conducted in a public hospital. CC was adjusted for body mass index (BMI), reducing 3, 7, or 12 cm for a BMI of 25–29.9, 30–39.9, and ≥40 kg/m2, respectively, and classified as reduced when <33 cm for women and <34 cm for men. Pearson’s correlation between BMI and CC was performed to assess the association between variables. Regression analysis was adjusted for sex, age, and BMI variables. Cox regression was used to assess survival related to CC. Results: A total of 208 older adults diagnosed with COVID-19 admitted to ICU were included, of which 84% (n = 176) were classified as having reduced CC. These patients were older, with lower BMI, higher nutritional risk, malnourished, and higher concentration of urea and urea–creatinine ratio (UCR) compared with the group with normal CC. There was an association between edematous patients at nutritional risk and malnourished with reduced CC in the Cox regression, either adjusted or not for confounding. Conclusions: CC was not associated with severity, biochemical markers, or mortality in older adults with COVID-19 admitted to the ICU, but it was associated with moderately malnourished patients assessed by subjective global assessment (SGA). Full article
(This article belongs to the Section Infectious Disease)
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14 pages, 236 KiB  
Article
Factors Affecting Survival Outcomes in Neuroendocrine Tumor of the Appendix over the Past Two Decades
by Vignesh Krishnan Nagesh, Izage Kianifar Aguilar, Daniel Elias, Charlene Mansour, Hadrian Hoang-Vu Tran, Ruchi Bhuju, Tanni Sethi, Paranjyothy Rao Pirangi Sanjeeva, Marco Gonzalez Rivas, Emelyn Martinez, Auda Auda, Nazir Ahmed, Shawn Philip, Simcha Weissman, John Sotiriadis and Ayrton Bangolo
Diseases 2024, 12(5), 96; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050096 - 8 May 2024
Viewed by 968
Abstract
Background: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Methods: [...] Read more.
Background: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Methods: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. Results: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Conclusion: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs. Full article
(This article belongs to the Section Gastroenterology)
54 pages, 1074 KiB  
Review
Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach
by Valeria Calcaterra, Sara Zanelli, Andrea Foppiani, Elvira Verduci, Beatrice Benatti, Roberto Bollina, Francesco Bombaci, Antonio Brucato, Selene Cammarata, Elisa Calabrò, Giovanna Cirnigliaro, Silvia Della Torre, Bernardo Dell’osso, Chiara Moltrasio, Angelo Valerio Marzano, Chiara Nostro, Maurizio Romagnuolo, Lucia Trotta, Valeria Savasi, Valeria Smiroldo and Gianvincenzo Zuccottiadd Show full author list remove Hide full author list
Diseases 2024, 12(5), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050095 - 6 May 2024
Cited by 1 | Viewed by 2221
Abstract
Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing [...] Read more.
Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions. Full article
(This article belongs to the Special Issue COVID-19 and Global Chronic Disease 2024: The Post-pandemic Era)
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11 pages, 3880 KiB  
Case Report
Lichen Amyloidosis in an Atopic Patient Treated with Dupilumab: A New Therapeutic Option
by Benedetta Tirone, Gerardo Cazzato, Francesca Ambrogio, Caterina Foti and Marco Bellino
Diseases 2024, 12(5), 94; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050094 - 6 May 2024
Viewed by 810
Abstract
Lichen amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm, or thigh. It is associated with itching and atopic dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been [...] Read more.
Lichen amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm, or thigh. It is associated with itching and atopic dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, the available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids, and phototherapy, but, in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, who had been suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with the induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved to be effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in the LA related to AD and led to clinical and quality of life improvements in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in the skin lesions after discontinuation, and the safety of long-term application. Full article
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18 pages, 1056 KiB  
Review
Unravelling the Triad of Lung Cancer, Drug Resistance, and Metabolic Pathways
by Pratik Mohanty, Babita Pande, Rakesh Acharya, L V K S Bhaskar and Henu Kumar Verma
Diseases 2024, 12(5), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050093 - 6 May 2024
Viewed by 1106
Abstract
Lung cancer, characterized by its heterogeneity, presents a significant challenge in therapeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumor’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer [...] Read more.
Lung cancer, characterized by its heterogeneity, presents a significant challenge in therapeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumor’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article explores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. This review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small-cell lung cancer and small-cell lung cancer, underlining the need for subtype-specific treatments. Key signaling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. This review article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. This review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies. Full article
(This article belongs to the Section Respiratory Diseases)
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11 pages, 1385 KiB  
Article
The Effect of Trabecular Aspiration on Intraocular Pressure, Medication and the Need for Further Glaucoma Surgery in Eyes with Pseudoexfoliation Glaucoma
by Verena Prokosch, Sarah B. Zwingelberg, Desislava V. Efremova, Francesco Buonfiglio, Norbert Pfeiffer and Adrian Gericke
Diseases 2024, 12(5), 92; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050092 - 6 May 2024
Viewed by 692
Abstract
Purpose: To investigate whether trabecular aspiration (TA) has an effective medium-term intraocular pressure (IOP)-lowering and medication-saving effect in patients with pseudoexfoliation glaucoma (PEG). In addition, a subgroup analysis of patients with or without a previous trabeculectomy was performed. Methods: Records of 290 consecutive [...] Read more.
Purpose: To investigate whether trabecular aspiration (TA) has an effective medium-term intraocular pressure (IOP)-lowering and medication-saving effect in patients with pseudoexfoliation glaucoma (PEG). In addition, a subgroup analysis of patients with or without a previous trabeculectomy was performed. Methods: Records of 290 consecutive eyes with PEG that underwent TA between 2006 and 2012 at the Department of Ophthalmology, Mainz, Germany, were retrospectively analyzed with a follow-up period of 3 years. The main outcomes were IOP and the need for further medical treatment. Results: Of the 290 eyes with PEG that received TA, 167 eyes from 127 patients met the inclusion criteria. Among these eyes, 128 received TA and cataract surgery (Phaco-TA) without having had a trabeculectomy (group I) before, 29 had Phaco-TA after a previous trabeculectomy (group II) and 10 underwent stand-alone TA after a previous trabeculectomy (group III). In the whole cohort, the median IOP decreased immediately after TA and remained significantly lower compared to the baseline throughout the period of 36 months. Likewise, the median number of antiglaucoma drugs was reduced over the whole period. At the same time, in group I, the median IOP and the number of antiglaucoma drugs were reduced over 36 months. In contrast, in the post-trabeculectomy groups (group II and III), the median IOP and the number of antiglaucoma drugs could not be reduced. While most of the patients that received Phaco-TA with or without a previous trabeculectomy (group I and II) did not require further surgical intervention during the follow-up period, almost all patients receiving stand-alone TA after a previous trabeculectomy (group III) needed surgical therapy, most of them between the second and the third year following TA. Conclusions: Phaco-TA has an effective medium-term pressure-lowering and medication-saving effect, especially in patients without a previous trabeculectomy. In trabeculectomized eyes, the effect of TA is limited but still large enough to delay more invasive surgical interventions in some patients. Full article
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7 pages, 15380 KiB  
Case Report
Giant Sublingual, Submental, and Lingual Dermoid Cyst Restricting Tongue Movement Undiagnosed for Several Years
by Jakub Bargiel, Michał Gontarz, Krzysztof Gąsiorowski, Tomasz Marecik, Paweł Szczurowski, Jan Zapała and Grażyna Wyszyńska-Pawelec
Diseases 2024, 12(5), 91; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050091 - 6 May 2024
Viewed by 824
Abstract
(1) Background: Dermoid cysts occurring in the sublingual space are uncommon, typically manifesting as painless, gradually enlarging masses, usually not exceeding 3 cm in diameter. These cysts can resemble various conditions due to their clinical presentation, with a relatively low occurrence rate in [...] Read more.
(1) Background: Dermoid cysts occurring in the sublingual space are uncommon, typically manifesting as painless, gradually enlarging masses, usually not exceeding 3 cm in diameter. These cysts can resemble various conditions due to their clinical presentation, with a relatively low occurrence rate in the oral cavity, accounting for about 1.6% of all dermoid cysts. (2) Methods: We present the case of a 17-year-old female with a giant dermoid cyst involving the submental, sublingual, and lingual areas, undiagnosed for several years. Diagnosis was achieved through MRI and fine-needle aspiration, leading to the decision for surgical removal through a cervical approach. (3) Results: The healing process was uneventful. From the first day post-surgery, the patient began myofunctional therapy, successfully regaining proper tongue functions. Throughout a 24-month follow-up, the patient remained symptom-free. (4) Conclusions: A cervical approach can successfully treat giant oral dermoid cysts involving submental, sublingual, and lingual spaces. Tongue function can be successfully regained through myofunctional therapy after surgical treatment. Full article
(This article belongs to the Section Rare Syndrome)
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21 pages, 1029 KiB  
Review
A Review of the CACNA Gene Family: Its Role in Neurological Disorders
by Oliwia Szymanowicz, Artur Drużdż, Bartosz Słowikowski, Sandra Pawlak, Ewelina Potocka, Ulyana Goutor, Mateusz Konieczny, Małgorzata Ciastoń, Aleksandra Lewandowska, Paweł P. Jagodziński, Wojciech Kozubski and Jolanta Dorszewska
Diseases 2024, 12(5), 90; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050090 - 5 May 2024
Viewed by 1032
Abstract
Calcium channels are specialized ion channels exhibiting selective permeability to calcium ions. Calcium channels, comprising voltage-dependent and ligand-gated types, are pivotal in neuronal function, with their dysregulation is implicated in various neurological disorders. This review delves into the significance of the CACNA genes, [...] Read more.
Calcium channels are specialized ion channels exhibiting selective permeability to calcium ions. Calcium channels, comprising voltage-dependent and ligand-gated types, are pivotal in neuronal function, with their dysregulation is implicated in various neurological disorders. This review delves into the significance of the CACNA genes, including CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1G, and CACNA1H, in the pathogenesis of conditions such as migraine, epilepsy, cerebellar ataxia, dystonia, and cerebellar atrophy. Specifically, variants in CACNA1A have been linked to familial hemiplegic migraine and epileptic seizures, underscoring its importance in neurological disease etiology. Furthermore, different genetic variants of CACNA1B have been associated with migraine susceptibility, further highlighting the role of CACNA genes in migraine pathology. The complex relationship between CACNA gene variants and neurological phenotypes, including focal seizures and ataxia, presents a variety of clinical manifestations of impaired calcium channel function. The aim of this article was to explore the role of CACNA genes in various neurological disorders, elucidating their significance in conditions such as migraine, epilepsy, and cerebellar ataxias. Further exploration of CACNA gene variants and their interactions with molecular factors, such as microRNAs, holds promise for advancing our understanding of genetic neurological disorders. Full article
(This article belongs to the Section Rare Syndrome)
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15 pages, 461 KiB  
Article
Factors Affecting Sleep Quality among University Medical and Nursing Students: A Study in Two Countries in the Mediterranean Region
by Fadila Bousgheiri, Ali Allouch, Karima Sammoud, Rut Navarro-Martínez, Vanessa Ibáñez-del Valle, Meftaha Senhaji, Omar Cauli, Nisrin El Mlili and Adil Najdi
Diseases 2024, 12(5), 89; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050089 - 5 May 2024
Viewed by 1216
Abstract
Poor sleep quality, a global public health concern, poses a significant burden on individuals, particularly health care university students facing intense academic stress. A three-center cross-sectional study was conducted at the Higher Institute of Nursing and Health Sciences in Tetouan (Morocco), Faculty of [...] Read more.
Poor sleep quality, a global public health concern, poses a significant burden on individuals, particularly health care university students facing intense academic stress. A three-center cross-sectional study was conducted at the Higher Institute of Nursing and Health Sciences in Tetouan (Morocco), Faculty of Medicine in Tangier (Morocco) and Faculty of Nursing in Valencia (Spain). We collected various data using a sociodemographic questionnaire, the Pittsburgh sleep quality questionnaire, the international physical activity questionnaire (IPAQ) and the smartphone addiction questionnaire short-version (SAS-SV). A total of 1210 students were included in our study (mean age 20.4 years, 67.2% female, nursing students (66.2%) and medical students (33.8%), 76.1% students from Morocco and 33.9% from Spain). Analysis revealed a higher prevalence of poor sleep quality among Moroccans students compared to Spanish ones (p < 0.001), that nursing students showed less favorable sleep quality than medical students (p < 0.011) and that living with a chronic disease was linked to less favorable sleep quality (p < 0.001). Lastly, intense or weak physical activity and smartphone addiction were correlated with poor sleep quality (p < 0.001). In the multivariate analysis, an association persisted between poor sleep quality and factors such as the country of study (Odds ratio (OR): 6.25 [95% Confidence Interval (CI): 4.34–9.09]), involvement in nursing studies (OR: 3.50 [95% CI: 2.36–5.27]), and the presence of chronic diseases (OR: 2.70 [95% CI: 1.72–4.16]), (p < 0.01 each). Our findings highlight the multifaceted factors affecting sleep quality in young university students. The implications underscore the imperative of interventions tailored to this demographic group. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
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11 pages, 1335 KiB  
Article
Elevated IL-6 and Tumor Necrosis Factor-α in Immune Checkpoint Inhibitor Myocarditis
by Abdelrahman Ali, Rebecca Caldwell, Gaspar Pina, Noah Beinart, Garrett Jensen, Syed Wamique Yusuf, Efstratios Koutroumpakis, Ihab Hamzeh, Shaden Khalaf, Cezar Iliescu, Anita Deswal and Nicolas L. Palaskas
Diseases 2024, 12(5), 88; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050088 - 3 May 2024
Viewed by 875
Abstract
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 [...] Read more.
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
(This article belongs to the Section Cardiology)
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22 pages, 1758 KiB  
Review
Innovative Drug Modalities for the Treatment of Advanced Prostate Cancer
by Maurizio Capuozzo, Mariachiara Santorsola, Monica Ianniello, Francesco Ferrara, Andrea Zovi, Nadia Petrillo, Rosa Castiello, Maria Rosaria Fantuz, Alessandro Ottaiano and Giovanni Savarese
Diseases 2024, 12(5), 87; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050087 - 2 May 2024
Viewed by 935
Abstract
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 [...] Read more.
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
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12 pages, 26201 KiB  
Case Report
Surgical Treatment of Lithiasis of the Main Pancreatic Duct: A Challenging Case and a Literature Review
by Dan Brebu, Cătălin Prodan-Bărbulescu, Vlad Braicu, Paul Pașca, George Borcean, Sabrina Florea, Clarisa Bîrlog, Amadeus Dobrescu, Mărioara Cornianu, Fulger Lazăr, Bogdan Totolici, Ciprian Duță and Flaviu Ionuț Faur
Diseases 2024, 12(5), 86; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050086 - 30 Apr 2024
Viewed by 1258
Abstract
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 [...] Read more.
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
(This article belongs to the Section Gastroenterology)
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15 pages, 2889 KiB  
Article
Effects of High-Dose Cyclophosphamide on Ultrastructural Changes and Gene Expression Profiles in the Cardiomyocytes of C57BL/6J Mice
by Takuro Nishikawa, Emiko Miyahara, Ieharu Yamazaki, Kazuro Ikawa, Shunsuke Nakagawa, Yuichi Kodama, Yoshifumi Kawano and Yasuhiro Okamoto
Diseases 2024, 12(5), 85; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050085 - 27 Apr 2024
Viewed by 798
Abstract
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 [...] Read more.
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
(This article belongs to the Section Oncology)
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8 pages, 1176 KiB  
Brief Report
Immunohistochemistry as a Reliable Tool for the Diagnosis of Cystic Echinococcosis in Patients from Sardinia, Italy—A Confirmatory Study
by Cinzia Santucciu, Angela Peruzzu, Antonella Maria Fara, Antonio Cossu, Philipp A. Kronenberg, Peter Deplazes and Giovanna Masala
Diseases 2024, 12(5), 84; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050084 - 26 Apr 2024
Viewed by 847
Abstract
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 [...] Read more.
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
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12 pages, 846 KiB  
Article
Ocular Tics and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)
by Stefano Dore, Daniele Satta, Angelo Zinellu, Giacomo Boscia, Arturo Carta, Mario Fruschelli, Rita Serra and Antonio Pinna
Diseases 2024, 12(5), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050083 - 25 Apr 2024
Viewed by 762
Abstract
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 [...] Read more.
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
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13 pages, 506 KiB  
Systematic Review
The Influence of Personality Traits on Postpartum Depression: A Systematic Review Based on the NEO-FFI Scale
by Oana Neda-Stepan, Cătălina Giurgi-Oncu, Andreea Sălcudean, Elena Bernad, Brenda-Cristiana Bernad and Virgil Radu Enătescu
Diseases 2024, 12(5), 82; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050082 - 25 Apr 2024
Viewed by 946
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Multidisciplinarity and Interdisciplinary Basics in Mental Health)
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20 pages, 636 KiB  
Review
Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis
by Diana I. Salnikova, Nikita G. Nikiforov, Anton Y. Postnov and Alexander N. Orekhov
Diseases 2024, 12(5), 81; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050081 - 25 Apr 2024
Viewed by 1174
Abstract
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 [...] Read more.
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
(This article belongs to the Topic Inflammation: The Cause of all Diseases 2.0)
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13 pages, 2366 KiB  
Communication
Role of B Cells beyond Antibodies in HBV-Induced Oncogenesis: Fulminant Cancer in Common Variable Immunodeficiency—Clinical and Immunotransplant Implications with a Review of the Literature
by Przemyslaw Zdziarski and Andrzej Gamian
Diseases 2024, 12(5), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases12050080 - 23 Apr 2024
Viewed by 1117
Abstract
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 [...] Read more.
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
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