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Diseases, Volume 12, Issue 7 (July 2024) – 34 articles

Cover Story (view full-size image): This study introduces a first-of-its-kind novel method for designing personalized peptide vaccines for cancer, using RNA sequencing to detect prevalent mutations in patient tumors. We focused on highly mutated genes, processed RNAseq data for read alignment and variant calling using our Python tool, SCGeneID. This tool also aligns RNAseq data against the UCSC hg38 reference, identifying target genes using chromosomes and loci. We designed a personalized vaccine for pancreatic ductal adenocarcinoma (PDAC), targeting highly prevalent gene mutations in PDAC patients. Our approach involved predicting peptide–MHC binding affinity, and selecting the top epitopes based on our established vaccine design principles. Validation was achieved by matching mutated genes found in a reference study, confirming the efficacy of our vaccine design method. View this paper
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10 pages, 223 KiB  
Article
Mortality, Length of Stay and Cost of Hospitalization among Patients with Adult-Onset Still’s Disease: Results from the National Inpatient Sample 2016–2019
by Sushmita Mittal, Benjamin Schroeder and Musaab Alfaki
Diseases 2024, 12(7), 166; https://doi.org/10.3390/diseases12070166 - 22 Jul 2024
Viewed by 435
Abstract
We use this study to analyze the trends in in-hospital length of stay, total hospital charges, and mortality among adult patients with a primary diagnosis of adult-onset still’s disease (AOSD). We used the 2016–2019 National Inpatient Sample (NIS) database to conduct a retrospective [...] Read more.
We use this study to analyze the trends in in-hospital length of stay, total hospital charges, and mortality among adult patients with a primary diagnosis of adult-onset still’s disease (AOSD). We used the 2016–2019 National Inpatient Sample (NIS) database to conduct a retrospective study on adult AOSD patients (≥18 years old). We analyzed data on baseline patient and hospital characteristics and determined trends in in-hospital mortality, length of stay (LOS), and total hospital charges (TOTCHG). Univariate and multivariate linear and logistic regression analyses were performed to identify factors that independently affected these outcomes. Among the 1615 AOSD hospitalizations, the mean LOS was 7.34 days and the mean TOTCHG was 68,415.31 USD. Macrophage activating syndrome (MAS), disseminated intravascular coagulation (DIC), and a large hospital size were shown to statistically increase the LOS and TOTCHG, while a Native American background was shown to statistically decrease both. The mean in-hospital mortality was 0.929%, with age being the only independent predictor. Our findings reveal an increase in the economic burden of AOSD hospitalizations despite declining admissions and mortality rates. Complications, like MAS and DIC, were found to significantly contribute to this burden despite treatment advancements. Our study indicates the importance of investigating new strategies to prevent these complications. Full article
10 pages, 1688 KiB  
Case Report
Surgical Approach and Considerations for Compressive Thoracic Intraspinal Osteochondroma in Familial Hereditary Multiple Exostosis
by Corneliu Toader, Antonio-Daniel Corlatescu, Nicolaie Dobrin, Razvan-Adrian Covache-Busuioc, Horia Petre Costin and Alexandru Vlad Ciurea
Diseases 2024, 12(7), 165; https://doi.org/10.3390/diseases12070165 - 19 Jul 2024
Viewed by 516
Abstract
Introduction: Hereditary multiple exostosis or hereditary multiple osteochondromas is a very rare clinical condition. Usually, these lesions tend to occur in the pediatric population, remaining silent until adulthood. Moreover, current studies show a small prevalence in the male population. The osteochondromas usually occur [...] Read more.
Introduction: Hereditary multiple exostosis or hereditary multiple osteochondromas is a very rare clinical condition. Usually, these lesions tend to occur in the pediatric population, remaining silent until adulthood. Moreover, current studies show a small prevalence in the male population. The osteochondromas usually occur at sites with great bone activity and turnover, such as the diaphysis or metaphyseal plates (especially in children) of long bones. Their appearance in short bones (such as vertebrae) is very rare. Case presentation: We present a case of familial HME in a 53-year-old female patient with a very uncommon clinical description of the disease. The patient presented at our hospital with Frankel D-type paraparesis, with multiple osteochondromas (located at the right humerus, bilateral femurs, right tibia, and hip joints, besides the numerous ones over the spinal column) and urinary incontinence. She was suffering from bilateral coxarthrosis and gonarthrosis, which limited severely the range of her movements. An early menopause status was brought into consideration by the patient, being installed circa 15 years before, at 38 years old. She was currently in treatment with bisphosphonates for her concomitant osteoporosis. Conclusions: Despite the relatively rare nature of the disease, it may be an important concern for the patient’s quality of life. Intraspinal processes may trigger paraparesis or other neurological statuses, which may require a surgical treatment. The nature of the lesions is usually benign and do not require further radio- or chemotherapy. Full article
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8 pages, 5104 KiB  
Case Report
Nerve Sheath Myxoma in Pregnancy: A Case Report
by Elena De Chiara, Valerio Gaetano Vellone, Jacopo Ferro, Chiara Trambaiolo Antonelli, Liliana Piro, Stefano Avanzini, Valentina Prono, Andrea Beccaria, Monica Muraca and Ramona Tallone
Diseases 2024, 12(7), 164; https://doi.org/10.3390/diseases12070164 - 18 Jul 2024
Viewed by 487
Abstract
Nerve sheath myxoma (NSM) is a rare benign peripheral nerve sheath tumor that affects young adults. NSMs are asymptomatic, slow-growing swellings located in the upper extremities, more rarely in the lower extremities. Given the high risk of recurrence, it is recommended to perform [...] Read more.
Nerve sheath myxoma (NSM) is a rare benign peripheral nerve sheath tumor that affects young adults. NSMs are asymptomatic, slow-growing swellings located in the upper extremities, more rarely in the lower extremities. Given the high risk of recurrence, it is recommended to perform a complete exeresis. To our knowledge, the evolution and management of NMS during pregnancy have not been described yet. We report the first case of recurrent pretibial NSM in a pregnant girl and its follow-up and outcome during and after pregnancy. NSM is difficult to diagnose clinically or using imaging. The final diagnosis remains histopathological. It is known how various types of benign and malignant skin tumors can develop or change during pregnancy. With our case, however, we documented that pregnancy does not affect the growth and evolution of NSM. Given the benign nature of the lesions and their tendency to grow slowly, during pregnancy, follow-up of NSMs can be conducted through ultrasonography and surgical treatment postponed after delivery. Our case highlights the importance of careful monitoring and individualized decision making, especially in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Our case highlights the importance of a careful monitoring and a tailored treatment in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Considering the benign nature of the lesions and their tendency to grow slowly, follow-up of NSMs during pregnancy can be conducted through ultrasonography, and surgical treatment can be postponed after delivery. Full article
(This article belongs to the Section Oncology)
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9 pages, 1403 KiB  
Article
Upregulation of TET2 and Resistance to DNA Methyltransferase (DNMT) Inhibitors in DNMT1-Deleted Cancer Cells
by Angelo B. A. Laranjeira, Dat Nguyen, Lorraine C. Pelosof, James H. Doroshow and Sherry X. Yang
Diseases 2024, 12(7), 163; https://doi.org/10.3390/diseases12070163 - 18 Jul 2024
Viewed by 592
Abstract
Background: Ten-eleven-translocation (TET) 2 is a member of the TET family of proteins (TET1-3). DNMT1 gene deletion confers resistance to DNA methyltransferase (DNMT) inhibitors in colorectal, breast, and ovarian cancer cells. Currently, the effect of DNMT1 gene status on TET2 phenotype following DNMT [...] Read more.
Background: Ten-eleven-translocation (TET) 2 is a member of the TET family of proteins (TET1-3). DNMT1 gene deletion confers resistance to DNA methyltransferase (DNMT) inhibitors in colorectal, breast, and ovarian cancer cells. Currently, the effect of DNMT1 gene status on TET2 phenotype following DNMT inhibitor treatment is unclear in human malignancies. Methods: Human colorectal carcinoma HCT116 cells (DNMT+/+) and their isogenic DNMT1 knockout (DNMT1–/–) counterpart were treated with DNMT inhibitors. Expression of TET2 and tumor suppressor (p16ink4A and p15ink4B) proteins were examined by Western blot. Apoptosis and CDKN2A promoter demethylation following drug treatment were detected by Annexin-V apoptosis assay and methylation-specific PCR. Results: TET2 expression was robustly increased in DNMT1−/− cells by 0.5 µM and 5 µM decitabine and azacitidine treatment. Augmentation of TET2 expression was accompanied by re-expression of p16ink4A and p15ink4B proteins and CDKN2A promoter demethylation. TET2 upregulation and tumor suppressor re-expression were associated with resistance conferred by DNMT1 deletion. Treatment with 5-aza-4′-thio-2′-deoxycytidine at a low 0.5 µM dose only upregulated TET2 and reduced CDKN2A promoter methylation, and re-expression of p16ink4A in DNMT1−/− cells. DNMT inhibitors showed minimal effects on TET2 upregulation and re-expression of tumor suppressor proteins in cells with intact DNMT1. Conclusions: DNMT1 gene deletion made cancer cells prone to TET2 upregulation and activation of tumor suppressor expression upon DNMT inhibitor challenge. TET2 augmentation is concomitant with resistance to DNMT inhibitors in a DNMT1-deleted state. Full article
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10 pages, 1655 KiB  
Article
Enzalutamide Prolonged the Duration of Drug Use in Comparison to Abiraterone Acetate and Cabazitaxel after Upfront Docetaxel: A Large Japanese Database Study
by Katsuya Yamaguchi, Takashi Kawahara, Akihito Hashizume, Kimito Ousaka, Koichi Uemura, Yusuke Ito, Hiroki Ito, Kazuhide Makiyama and Hiroji Uemura
Diseases 2024, 12(7), 162; https://doi.org/10.3390/diseases12070162 - 18 Jul 2024
Viewed by 631
Abstract
Introduction: In the United States, a total of 268,490 men were found to have prostate cancer in 2022, thus making it the most common cancer in men, accounting for 27% of all cancers in the male population. Among all cancers in men, it [...] Read more.
Introduction: In the United States, a total of 268,490 men were found to have prostate cancer in 2022, thus making it the most common cancer in men, accounting for 27% of all cancers in the male population. Among all cancers in men, it was the fifth leading cause of death, with 34,500 deaths and a mortality rate of 11%. In 2019, the total number of cases was 94,748, making it the leading cancer in males, accounting for 11% of all male cancers. In terms of mortality, it ranked seventh, with 13,217 deaths and a mortality rate of 1.6%. However, new treatment options for metastatic castration-sensitive prostate cancer (mCSPC) have emerged. Docetaxel has been shown to be effective for both mCSPC and castration-resistant prostate cancer (CRPC). Upfront docetaxel has not been approved in Japan, nor has it been validated in large-scale studies. Furthermore, several agents can be used after docetaxel treatment, but it is unclear which is the most effective. We used a large Japanese health insurance database to determine which agent would be the most effective as a next-line therapy in patients who had received docetaxel. Materials and Methods: We used data from medical institutions using the Diagnosis Procedure Combination (DPC), which provides a comprehensive evaluation of medical classifications. The Medical Data Vision database covers approximately 23% of DPC hospitals in Japan. This study analyzed 2938 patients with mCSPC who received docetaxel, followed by CRPC, between April 2008 and December 2021. The study focused on three agents: enzalutamide, abiraterone acetate, and cabazitaxel. Other agents were excluded due to the small number of patients. The following data were analyzed: age, date of CRPC diagnosis, presence of bone metastasis, drug type, and prognosis. Results: This study included 1997 patients with CRPC after upfront docetaxel therapy for mCSPC (enzalutamide [ENZ] group, n = 998; abiraterone acetate [ABI] group, n = 617; and cabazitaxel [CBZ] group, n = 382). The overall survival (OS) time from drug initiation was 456 days in the enzalutamide group, which was significantly longer than that in the cabazitaxel group (p = 0.017, HR 0.94) (ENZ: ABI p = 0.54, HR 0.94; ABI: CBZ p = 0.14, HR 0.75). OS was also compared for the third-line drug in the group that received enzalutamide as the second-line drug, the group that used abiraterone acetate as the third-line drug (ENZ-ABI group), and the group that used abiraterone acetate as the second-line drug. OS from the start of the third-line drug was compared between the ENZ–ABI group and the ABI–ENZ group, which received enzalutamide as the third-line drug, but showed no significant difference (269 vs. 281 days, p = 0.85; HR 1.03). Conclusion: ENZ was shown to prolong OS relative to cabazitaxel after the cessation of docetaxel. ENZ was associated with a longer duration of drug use than ABI and CBZ. Full article
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12 pages, 1022 KiB  
Article
Thrombotic Long-Term Consequences of SARS-CoV-2 Infection in Patients with Compensated Cirrhosis: A Propensity Score-Matched Analysis of a U.S. Database
by Mark Ayoub, Carol Faris, Tajana Juranovic, Rafi Aibani, Morgan Koontz, Harleen Chela, Nadeem Anwar and Ebubekir Daglilar
Diseases 2024, 12(7), 161; https://doi.org/10.3390/diseases12070161 - 17 Jul 2024
Viewed by 466
Abstract
Background: Cirrhosis causes an imbalance in the coagulation pathway and leads to a tendency for both bleeding and clotting. SARS-CoV-2 has been reported to be associated with a hypercoagulable state. This study examines SARS-CoV-2’s impact on hemostasis in compensated patients with cirrhosis. Methods: [...] Read more.
Background: Cirrhosis causes an imbalance in the coagulation pathway and leads to a tendency for both bleeding and clotting. SARS-CoV-2 has been reported to be associated with a hypercoagulable state. This study examines SARS-CoV-2’s impact on hemostasis in compensated patients with cirrhosis. Methods: We analyzed the US Collaborative Network, which comprises 63 HCOs in the U.S.A. Compensated cirrhosis patients were split into two groups: SARS-CoV-2-positive and -negative. Patients’ baseline characteristics were used in a 1:1 propensity score-matched module to create comparable cohorts. We compared the risk of portal vein thrombosis (PVT), deep venous thrombosis (DVT), and pulmonary embolism (PE) at 6 months, and 1 and 3 years. Results: Of 330,521 patients, 27% tested positive and 73% remained negative. After PSM, both cohorts included 74,738 patients. Patients with SARS-CoV-2 had a higher rate of PVT compared to those without at 6 months (0.63% vs 0.5%, p < 0.05), 1 year (0.8% vs 0.6%, p < 0.05), and 3 years (1% vs. 0.7%, p < 0.05), a higher rate of DVT at 6 months (0.8% vs. 0.4%, p < 0.05), 1 year (1% vs. 0.5%, p < 0.05), and 3 years (1.4% vs. 0.8%, p < 0.05), and a higher rate of PE at 6 months (0.6% vs. 0.3%, p < 0.05), 1 year (0.7% vs. 0.4%, p < 0.05), and 3 years (1% vs. 0.6%, p < 0.05). Conclusions: The presence of SARS-CoV-2 infection in patients with compensated cirrhosis was associated with a higher rate of PVT, DVT, and PE at 6 months, and 1 and 3 years. Full article
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15 pages, 997 KiB  
Systematic Review
Prevalence of Leishmaniasis among Blood Donors: A Systematic Review and Meta-Analysis
by Maria Kantzanou, Evangelos Kostares, Georgia Kostare, Evangelia Papagiannopoulou, Michael Kostares and Athanasios Tsakris
Diseases 2024, 12(7), 160; https://doi.org/10.3390/diseases12070160 - 17 Jul 2024
Viewed by 475
Abstract
Our study seeks to provide a comprehensive assessment of leishmaniasis prevalence among blood donors, employing rigorous methodologies to inform public health initiatives and transfusion safety measures. A thorough literature search was conducted using electronic databases (Medline, Scopus, Web of Science, and Google Scholar) [...] Read more.
Our study seeks to provide a comprehensive assessment of leishmaniasis prevalence among blood donors, employing rigorous methodologies to inform public health initiatives and transfusion safety measures. A thorough literature search was conducted using electronic databases (Medline, Scopus, Web of Science, and Google Scholar) to identify the relevant studies reporting the prevalence of leishmaniasis among blood donors, gathering a wide range of studies encompassing different geographic locations and time periods. The pooled prevalence with a 95% confidence interval (CI) was estimated, and quality assessment, outlier analysis, and influential analysis were performed to ensure the robustness and validity of the findings. Our search and subsequent analyses led to the inclusion of thirty-five studies in our review. Using molecular diagnostic methods, the prevalence was estimated at 2.3% (95% CI 1–3.9%), while serological diagnostic methods indicated a higher prevalence rate of 4.5% (95% CI 2.8–6.7%). Notably, we observed significant heterogeneity among the included studies for each analysis. The observed heterogeneity highlights the need for future research to delve into the factors influencing leishmaniasis prevalence, with prospective and retrospective studies addressing the limitations identified in this review. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology 2024)
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13 pages, 635 KiB  
Review
Gestational Trophoblastic Disease: Complete versus Partial Hydatidiform Moles
by Jeffrey Gonzalez, Meagan Popp, Stephanie Ocejo, Alvaro Abreu, Hisham F. Bahmad and Robert Poppiti
Diseases 2024, 12(7), 159; https://doi.org/10.3390/diseases12070159 - 17 Jul 2024
Viewed by 613
Abstract
Hydatidiform moles, including both complete and partial moles, constitute a subset of gestational trophoblastic diseases characterized by abnormal fertilization resulting in villous hydrops and trophoblastic hyperplasia with or without embryonic development. This involves chromosomal abnormalities, where one or two sperms fertilize an empty [...] Read more.
Hydatidiform moles, including both complete and partial moles, constitute a subset of gestational trophoblastic diseases characterized by abnormal fertilization resulting in villous hydrops and trophoblastic hyperplasia with or without embryonic development. This involves chromosomal abnormalities, where one or two sperms fertilize an empty oocyte (complete hydatidiform mole (CHM); mostly 46,XX) or two sperms fertilize one oocyte (partial hydatidiform mole (PHM); mostly 69,XXY). Notably, recurrent occurrences are associated with abnormal genomic imprinting of maternal effect genes such as NLRP7 (chromosome 19q13.4) and KHDC3L (chromosome 6q1). Ongoing efforts to enhance identification methods have led to the identification of growth-specific markers, including p57 (cyclin-dependent kinase inhibitor 1C; CDKN1C), which shows intact nuclear expression in the villous cytotrophoblast and villous stromal cells in PHMs and loss of expression in CHMs. Treatment of hydatidiform moles includes dilation and curettage for uterine evacuation of the molar pregnancy followed by surveillance of human chorionic gonadotropin (HCG) levels to confirm disease resolution and rule out the development of any gestational trophoblastic neoplasia. In this review, we provide a synopsis of the existing literature on hydatidiform moles, their diagnosis, histopathologic features, and management. Full article
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13 pages, 537 KiB  
Article
Quality of Life Assessment Using the WHOQOL-BREF Survey in Hospitalized Patients with Alcohol Use Disorder from Romania
by Melania Lavinia Bratu, Dorel Sandesc, Teodora Anghel, Liana Dehelean, Mariana Bondrescu, Felix Bratosin and Raluca Tudor
Diseases 2024, 12(7), 158; https://doi.org/10.3390/diseases12070158 - 16 Jul 2024
Viewed by 510
Abstract
This cross-sectional analysis aimed to assess the quality of life (QoL) among hospitalized patients with alcohol use disorder (AUD) in Romania, utilizing the WHOQOL survey. Conducted from January to December 2023 in the Psychiatry Clinic of the “Pius Brinzeu” Emergency Clinical Hospital in [...] Read more.
This cross-sectional analysis aimed to assess the quality of life (QoL) among hospitalized patients with alcohol use disorder (AUD) in Romania, utilizing the WHOQOL survey. Conducted from January to December 2023 in the Psychiatry Clinic of the “Pius Brinzeu” Emergency Clinical Hospital in Timisoara, this study engaged 70 participants, adhering to ethical standards outlined in the Declaration of Helsinki. Employing the WHOQOL-BREF instrument, the research hypothesized that AUD patients would show significantly lower QoL scores across its domains compared to general population norms. The study focused on identifying the QoL domains most impacted by AUD, exploring correlations between QoL scores and AUD background characteristics, and pinpointing intervention areas for patient care improvement. Participants were predominantly males (88.57%) with a middle-aged average of 55.51 years. Educational backgrounds varied, with a notable percentage having attended college (44.29%) or university (17.14%). Regarding marital status, 41.43% were married. Comorbidities were present in 52.86% of the sample, with hypertension being the most common (34.29%). Results showed mean QoL scores in the physical (61.84 ± 16.05), psychological (64.11 ± 17.16), social (60.48 ± 24.85), and environmental (68.44 ± 17.34) domains, revealing a significant diversity in satisfaction levels across these areas. Statistical analyses highlighted marital status as significantly associated with a better QoL in the physical domain, with married, co-habiting, and divorced participants reporting higher scores compared to single ones. In conclusion, while AUD significantly affects the QoL of hospitalized patients in Romania, marital status emerges as a critical factor in mitigating these effects, particularly in the physical domain of QoL. These findings underscore the complexity of AUD’s impact on QoL and the importance of considering sociodemographic factors in patient care practices and interventions. The study contributes valuable insights into the nuanced relationship between AUD and QoL, proposing a foundation for enhancing care outcomes for AUD patients in Romania. Full article
(This article belongs to the Special Issue Multidisciplinarity and Interdisciplinary Basics in Mental Health)
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13 pages, 946 KiB  
Review
COVID-19 and Prostatitis: A Review of Current Evidence
by Datesh Daneshwar, Yemin Lee and Abid Nordin
Diseases 2024, 12(7), 157; https://doi.org/10.3390/diseases12070157 - 15 Jul 2024
Viewed by 867
Abstract
Coronavirus disease 2019 (COVID-19), a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a global health threat. The virus enters host cells by binding with angiotensin-converting enzyme 2 (ACE2), which is then facilitated by the protease activity [...] Read more.
Coronavirus disease 2019 (COVID-19), a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a global health threat. The virus enters host cells by binding with angiotensin-converting enzyme 2 (ACE2), which is then facilitated by the protease activity of transmembrane serine protease 2 (TMPRSS2). It triggers a cytokine storm that eventually leads to cell apoptosis, tissue damage, and organ failure. Therefore, any organs in the human body that have both receptors are highly susceptible to COVID-19 infection, potentially resulting in multiple-organ failure. The prostate has been reported to express high levels of ACE2 and TMPRSS2. While there are limited studies regarding the association between COVID-19 and prostatitis, the possibility that SARS-CoV-2 could cause prostatitis cannot be denied. Thus, through this review, a better insight into the associations of SAR-CoV-2 can be provided. Full article
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30 pages, 1188 KiB  
Systematic Review
Healthcare Professionals’ Knowledge, Attitudes, and Practices in the Assessment, and Management of Sickle-Cell Disease: A Meta-Aggregative Review
by Andrews Adjei Druye, Dorcas Frempomaa Agyare, William Akoto-Buabeng, Jethro Zutah, Frank Odonkor Offei, Bernard Nabe, Godson Obeng Ofori, Amidu Alhassan, Benjamin Kofi Anumel, Godfred Cobbinah, Susanna Aba Abraham, Mustapha Amoadu and John Elvis Hagan, Jr.
Diseases 2024, 12(7), 156; https://doi.org/10.3390/diseases12070156 - 14 Jul 2024
Viewed by 725
Abstract
Background: Sickle Cell Disease (SCD) presents significant health challenges globally. Despite its prevalence in diverse geographical regions, there is a paucity of literature synthesizing evidence on healthcare professionals’ knowledge, attitudes, and practices (KAP) toward SCD assessment and management. This meta-aggregative review systematically examined [...] Read more.
Background: Sickle Cell Disease (SCD) presents significant health challenges globally. Despite its prevalence in diverse geographical regions, there is a paucity of literature synthesizing evidence on healthcare professionals’ knowledge, attitudes, and practices (KAP) toward SCD assessment and management. This meta-aggregative review systematically examined and synthesized existing qualitative research to elucidate healthcare professionals’ KAP regarding SCD assessment and management. Methods: This meta-aggregative review followed Aromataris and Pearson’s guidelines and the PRISMA framework for systematic review reporting. The search was conducted in Scopus, PubMed, Embase, CINAHL Web of Science, Google Scholar, Dimensions AI, and HINARI. Quality appraisal was performed using the Joanna Briggs Institute tool. Results: Healthcare professionals (HCPs) demonstrate varying levels of KAP toward SCD assessment and management. Studies reveal low-to-moderate levels of general knowledge among HCPs, with nurses often exhibiting poorer understanding than physicians. Deficiencies in awareness of specific interventions, such as chemoprophylaxis and prenatal diagnosis, are noted, along with gaps in SCD assessment and diagnosis, particularly in pain management and premarital screening. Attitudes toward SCD patients vary, and practices reveal inconsistencies and deficiencies, including inadequate nutritional counseling and barriers in emergency departments. However, interventions aimed at improving HCPs’ KAP show promise in enhancing understanding and attitudes toward SCD, suggesting potential avenues for improvement. Conclusions: Educational initiatives targeted at both student nurses and practicing healthcare providers, coupled with the implementation of standardized protocols and guidelines, can enhance knowledge acquisition and promote consistent, high-quality care delivery. Future studies should improve the quality of their methods in this area of study. Full article
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12 pages, 890 KiB  
Article
A Randomized Controlled Trial of the Safety and Efficacy of Systemic Enzyme Supplementation on Symptoms and Quality of Life in Patients with Idiopathic Pulmonary Fibrosis
by Neha Shah
Diseases 2024, 12(7), 155; https://doi.org/10.3390/diseases12070155 - 13 Jul 2024
Viewed by 565
Abstract
Idiopathic pulmonary fibrosis (IPF) imposes a substantial symptom burden that adversely impacts patients’ quality of life. Current anti-fibrotic treatments for IPF provide limited symptomatic relief, necessitating the implementation of complementary disease management strategies to enhance health-related quality of life (HRQOL). Serracor-NK® and [...] Read more.
Idiopathic pulmonary fibrosis (IPF) imposes a substantial symptom burden that adversely impacts patients’ quality of life. Current anti-fibrotic treatments for IPF provide limited symptomatic relief, necessitating the implementation of complementary disease management strategies to enhance health-related quality of life (HRQOL). Serracor-NK® and Serra Rx260, systemic enzyme supplements, improved symptoms and HRQOL with favorable safety profiles in a proof-of-concept study in PF patients. This prospective, double-blind randomized placebo-controlled trial enrolled 100 IPF patients from six institutions. The supplement group (n = 50) received the oral systemic enzyme supplements Serracor-NK® and Serra Rx260 in addition to standard care for 6 months, while the placebo group (n = 50) received standard care alone. The primary objective was to evaluate the regimen’s impact on symptoms, QOL, and well-being using the UCSD shortness of breath (UCSD-SOB) questionnaire, St. George’s respiratory questionnaire (SGRQ), and WHO well-being index (WHO-5). Safety evaluation was a secondary objective. A significantly higher proportion of patients in the supplement group demonstrated meaningful improvement in symptoms as compared to the placebo group, as assessed by the UCSD-SOB (p < 0.05) and SGRQ questionnaires (p < 0.05). Additionally, a significantly greater proportion of patients in the supplement group showed improved QOL and well-being (p < 0.05) and reduced health impairment (p < 0.05), as assessed by SGRQ. Mental well-being (WHO-5) and physical activity (SGRQ activity domain) did not differ significantly between the groups. Safety assessments, including liver function tests and vital signs, indicated that the supplement regimen was well tolerated. To conclude, Serracor-NK® and Serra Rx260 alleviate symptoms and enhance HRQOL in IPF patients with a favorable safety profile (Clinical Trials Registry India registration number: CTRI/2020/05/025374). Full article
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18 pages, 1859 KiB  
Systematic Review
Prevalence and Species Distribution of Neonatal Candidiasis: A Systematic Review and Meta-Analysis
by Amr Molla and Muayad Albadrani
Diseases 2024, 12(7), 154; https://doi.org/10.3390/diseases12070154 - 12 Jul 2024
Cited by 1 | Viewed by 805
Abstract
Background and aim: Candida infection is a significant cause of morbidity and mortality in neonatal intensive care units (NICU) globally. We aimed to conduct a systematic review to investigate the prevalence of candida among causative organisms of neonatal sepsis and identify the distribution [...] Read more.
Background and aim: Candida infection is a significant cause of morbidity and mortality in neonatal intensive care units (NICU) globally. We aimed to conduct a systematic review to investigate the prevalence of candida among causative organisms of neonatal sepsis and identify the distribution of candida species infecting Saudi neonates. Methods: We comprehensively searched Web of Science, Scopus, PubMed, and Cochrane Library from their inception till November 2023. After screening titles, abstracts, and full texts, we ultimately included 21 eligible studies. The designs of the included studies were randomized clinical trials, cohorts, case–control, and case reports; the methodological quality was appraised using the Cochrane risk of bias assessment tool, NIH tool for observational studies, and Murad tool for assessing case reports. Results: Our systematic review and meta-analysis pooled data reported in 21 studies in the Saudi populations, which provided data on different types of candidal infections in 2346 neonates. The pooled data of ten retrospective studies enrolling 1823 neonates revealed that candida species resembled 4.2% of the causative organisms of neonatal sepsis among Saudi neonates (95%CI [2.5%; 5.9%], p = 0.000). Additionally, out of a total of 402 candida species that were identified among the included studies, C. albicans prevailed mostly among Saudi neonates, followed by C. parapsilosis, NS candida, and C. tropicalis (50.25%, 21.40%, 12.44%, and 9.45%, respectively). Conclusions: We found that candida species prevailed in 4.2% of 1823 cases of neonatal sepsis; the most common candida species was C. albicans. We could not pool data regarding risk factors or susceptibility of candida species to different treatment modalities due to insufficient data, requiring future large-scale, high-quality studies to be conducted. Full article
(This article belongs to the Section Infectious Disease)
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10 pages, 1243 KiB  
Article
STRILL: Phase I Trial Evaluating Stereotactic Body Radiotherapy (SBRT) Dose Escalation for Re-Irradiation of Inoperable Peripheral Lung Lesions
by Davide Franceschini, Mauro Loi, Antonio Marco Marzo, Luca Dominici, Ruggero Spoto, Anna Bertolini, Lorenzo Lo Faro, Francesco La Fauci, Beatrice Marini, Luciana Di Cristina and Marta Scorsetti
Diseases 2024, 12(7), 153; https://doi.org/10.3390/diseases12070153 - 12 Jul 2024
Viewed by 607
Abstract
Few data are available on the role of SBRT re-irradiation for isolated recurrences. We designed a prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation, for peripheral lung lesions. RT was delivered with a dose escalation [...] Read more.
Few data are available on the role of SBRT re-irradiation for isolated recurrences. We designed a prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation, for peripheral lung lesions. RT was delivered with a dose escalation design from 30 Gy in five fractions up to 50 Gy in five fractions. The primary end point was the definition of the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation. The dose-limiting toxicity was pneumonia ≥G3. Fifteen patients were enrolled. No cases of pneumonia ≥G3 occurred in any of our cohorts. Only one patient developed pneumonia G1 during treatment. Three patients developed acute toxicities that included dyspnea G1, cardiac failure G3, and chest wall pain. One patient developed G3 late toxicity with acute coronary syndrome. After a median follow-up of 21 months (range 3.6–29.1 months), six patients (40%) had a local relapse. Distant relapse occurred in five patients (33.3%). At the last follow-up, six patients died, all but two due to progressive disease. SBRT dose escalation for thoracic re-irradiation is an effective and well-tolerated option for patients with inoperable lung lesions after a first thoracic RT with acceptable acute and late toxicities. Full article
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16 pages, 4231 KiB  
Article
In Silico Identification of Dysregulated miRNAs Targeting KRAS Gene in Pancreatic Cancer
by Asbiel Felipe Garibaldi-Ríos, Luis E. Figuera, Guillermo Moisés Zúñiga-González, Belinda Claudia Gómez-Meda, Patricia Montserrat García-Verdín, Irving Alejandro Carrillo-Dávila, Itzae Adonai Gutiérrez-Hurtado, Blanca Miriam Torres-Mendoza and Martha Patricia Gallegos-Arreola
Diseases 2024, 12(7), 152; https://doi.org/10.3390/diseases12070152 - 12 Jul 2024
Viewed by 570
Abstract
Pancreatic cancer (PC) is highly lethal, with KRAS mutations in up to 95% of cases. miRNAs inversely correlate with KRAS expression, indicating potential as biomarkers. This study identified miRNAs targeting KRAS and their impact on PC characteristics using in silico methods. dbDEMC identified [...] Read more.
Pancreatic cancer (PC) is highly lethal, with KRAS mutations in up to 95% of cases. miRNAs inversely correlate with KRAS expression, indicating potential as biomarkers. This study identified miRNAs targeting KRAS and their impact on PC characteristics using in silico methods. dbDEMC identified dysregulated miRNAs in PC; TargetScan, miRDB, and PolymiRTS 3.0 identified miRNAs specific for the KRAS gene; and OncomiR evaluated the association of miRNAs with clinical characteristics and survival in PC. The correlation between miRNAs and KRAS was analysed using ENCORI/starBase. A total of 210 deregulated miRNAs were identified in PC (116 overexpressed and 94 underexpressed). In total, 16 of them were involved in the regulation of KRAS expression and 9 of these (hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30b-5p, hsa-miR-30e-5p, hsa-miR-377-3p, hsa-miR-495-3p, hsa-miR-654-3p, hsa-miR-877-5p and hsa-miR-885-5p) were associated with the clinical characteristics of the PC. Specifically, the overexpression of hsa-miR-30a-5p was associated with PC mortality, and hsa-miR-30b-5p, hsa-miR-377-3p, hsa-miR-495-3p, and hsa-miR-885-5p were associated with survival. Correlation analysis revealed that the expression of 10 miRNAs is correlated with KRAS expression. The dysregulated miRNAs identified in PC may regulate KRAS and some are associated with clinically relevant features, highlighting their potential as biomarkers and therapeutic targets in PC treatment. However, experimental validation is required for confirmation. Full article
(This article belongs to the Topic miRNAs in Pathophysiology of Disease)
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9 pages, 508 KiB  
Article
Influence of Meteorological Parameters on the Prevalence of TEE Detected Left Atrial Appendage Thrombi
by Franziska Lecker, Klaus Tiemann, Thorsten Lewalter and Clemens Jilek
Diseases 2024, 12(7), 151; https://doi.org/10.3390/diseases12070151 - 12 Jul 2024
Viewed by 613
Abstract
(1) Background: Meteorological factors seem to exert various effects on human health, influencing the occurrence of diseases such as thromboembolic events and strokes. Low atmospheric pressure in summer may be associated with an increased likelihood of ischemic stroke. The aim of this study [...] Read more.
(1) Background: Meteorological factors seem to exert various effects on human health, influencing the occurrence of diseases such as thromboembolic events and strokes. Low atmospheric pressure in summer may be associated with an increased likelihood of ischemic stroke. The aim of this study was to investigate the potential impact of meteorological conditions on left atrial appendage (LAA) thrombus formation. (2) Methods: A total of 131 patients were included, diagnosed with a first instance of thrombus via 3D transesophageal echocardiography (TEE) between February 2009 and February 2019. Months with frequent thrombus diagnoses of at least 10 thrombi per month were categorized as frequent months (F-months), while months with fewer than 10 thrombus diagnoses per month were labelled as non-frequent months (N-months). The analysis focused on differences in meteorological parameters in two-week and four-week periods before the diagnosis. (3) Results: F-months were predominantly observed in spring and summer (April, May, June, and July), as well as in February and November. During F-months, a higher absolute temperature difference, lower relative humidity, longer daily sunshine duration, and greater wind speed maximum were observed in the two- and four-week periods rather than for N-months. In the two-week period, average temperatures, equivalent temperatures, and temperature maxima were also significantly higher during F-months than N-months. (4) Conclusion: Thrombi in the left atrial appendage are more prevalent during periods characterized by high absolute temperature differences, low relative humidity, and long daily sunshine duration. Full article
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12 pages, 1965 KiB  
Article
An Alternative Non-Invasive Screening Model for Liver Fibrosis among US Adults at Risk of MASLD
by Hongbing Sun
Diseases 2024, 12(7), 150; https://doi.org/10.3390/diseases12070150 - 11 Jul 2024
Viewed by 514
Abstract
Background and Aims: Screening for liver fibrosis presents a clinical challenge. This study aimed to explore a useful alternative method for assessing fibrosis risk among US adults at risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A liver stiffness score (LSS) model [...] Read more.
Background and Aims: Screening for liver fibrosis presents a clinical challenge. This study aimed to explore a useful alternative method for assessing fibrosis risk among US adults at risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A liver stiffness score (LSS) model was proposed and tested using data from 3976 participants at possible risk of MASLD, obtained from the US National Health and Nutrition Examination Survey (NHANES). Results: The LSS model was developed using liver stiffness measurements, blood biochemistry, and body measurement data from 2414 NHANES participants at risk of MASLD, sampled between 2017 and 2020: LSS = exp(0.007035 × bodyweightkg − 0.1061 × raceblack1,0 + 0.183221 × diabetes1,0 + 0.008539 × ASTIU/L − 0.0018 × plateletcount1000cell/UL − 0.21011 × albuming/dL + 2.259087). The probability (P) of having fibrosis F3 + F4 is calculated as follows: P = 0.0091 × LSS2 − 0.0791 × LSS + 0.1933. The developed LSS model was tested on 1562 at-risk participants from the 2017–2018 cycle. The results showed that the LSS model achieved AUROC values of 0.79 and 0.78 for diagnosing cirrhosis (F4) and advanced fibrosis (F3 + F4) in the US population, respectively. It outperformed existing models such as NFS, FIB-4, SAFE, and FIB-3. For screening F3 + F4 fibrosis, the LSS model’s top decile outperformed the NFS and FIB-4 models by 37.7% and 42.6%, respectively. Additionally, it showed superior performance compared to the waist circumference classification method by 29.5%. Conclusions: derived from an ethnically diverse population dataset, the LSS screening model, along with its probability equation, may offer clinicians a valuable alternative method for assessing the risk of liver fibrosis in the at-risk adult population. Full article
(This article belongs to the Section Gastroenterology)
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14 pages, 4951 KiB  
Article
Novel Methodology for the Design of Personalized Cancer Vaccine Targeting Neoantigens: Application to Pancreatic Ductal Adenocarcinoma
by Kush Savsani and Sivanesan Dakshanamurthy
Diseases 2024, 12(7), 149; https://doi.org/10.3390/diseases12070149 - 11 Jul 2024
Viewed by 622
Abstract
Personalized cancer vaccines have emerged as a promising avenue for cancer treatment or prevention strategies. This approach targets the specific genetic alterations in individual patient’s tumors, offering a more personalized and effective treatment option. Previous studies have shown that generalized peptide vaccines targeting [...] Read more.
Personalized cancer vaccines have emerged as a promising avenue for cancer treatment or prevention strategies. This approach targets the specific genetic alterations in individual patient’s tumors, offering a more personalized and effective treatment option. Previous studies have shown that generalized peptide vaccines targeting a limited scope of gene mutations were ineffective, emphasizing the need for personalized approaches. While studies have explored personalized mRNA vaccines, personalized peptide vaccines have not yet been studied in this context. Pancreatic ductal adenocarcinoma (PDAC) remains challenging in oncology, necessitating innovative therapeutic strategies. In this study, we developed a personalized peptide vaccine design methodology, employing RNA sequencing (RNAseq) to identify prevalent gene mutations underlying PDAC development in a patient solid tumor tissue. We performed RNAseq analysis for trimming adapters, read alignment, and somatic variant calling. We also developed a Python program called SCGeneID, which validates the alignment of the RNAseq analysis. The Python program is freely available to download. Using chromosome number and locus data, SCGeneID identifies the target gene along the UCSC hg38 reference set. Based on the gene mutation data, we developed a personalized PDAC cancer vaccine that targeted 100 highly prevalent gene mutations in two patients. We predicted peptide-MHC binding affinity, immunogenicity, antigenicity, allergenicity, and toxicity for each epitope. Then, we selected the top 50 and 100 epitopes based on our previously published vaccine design methodology. Finally, we generated pMHC-TCR 3D molecular model complex structures, which are freely available to download. The designed personalized cancer vaccine contains epitopes commonly found in PDAC solid tumor tissue. Our personalized vaccine was composed of neoantigens, allowing for a more precise and targeted immune response against cancer cells. Additionally, we identified mutated genes, which were also found in the reference study, where we obtained the sequencing data, thus validating our vaccine design methodology. This is the first study designing a personalized peptide cancer vaccine targeting neoantigens using human patient data to identify gene mutations associated with the specific tumor of interest. Full article
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14 pages, 1182 KiB  
Article
Acute Effect of Simultaneous Exercise and Cognitive Tasks on Cognitive Functions in Elderly Individuals with Mild Cognitive Impairment
by Ines Ben Ayed, Achraf Ammar, Mohamed Ali Boujelbane, Atef Salem, Salma Naija, Sana Ben Amor, Khaled Trabelsi, Haitham Jahrami, Hamdi Chtourou, Yassine Trabelsi and Farid El Massioui
Diseases 2024, 12(7), 148; https://doi.org/10.3390/diseases12070148 - 10 Jul 2024
Viewed by 553
Abstract
The increasing prevalence of age-related cognitive decline, alongside the aging global population, underscores the urgent need for innovative and effective preventative strategies. While the advantages of combining physical and cognitive exercises have been recognized as a promising approach to address these socioeconomic challenges, [...] Read more.
The increasing prevalence of age-related cognitive decline, alongside the aging global population, underscores the urgent need for innovative and effective preventative strategies. While the advantages of combining physical and cognitive exercises have been recognized as a promising approach to address these socioeconomic challenges, the acute effects of such interventions on cognitive functions remain understudied. This study aimed to investigate whether simultaneous physical and cognitive exercise has a greater beneficial impact on the cognitive functions of older adults with mild cognitive impairment (MCI) than physical exercise alone or reading activities. A total of 44 MCI patients (75% females aged between 65 and 75 years) were randomly assigned to one of three groups: aerobic exercise alone (EG group, n = 15), aerobic combined with cognitive exercises (CEG group, n = 15), or a reading task for controls (CG group, n = 14). Attention, memory, and problem solving were assessed before and after the acute intervention using the Tower of Hanoi, Digit Span, and Stroop tasks, respectively. Statistical analysis revealed that both of the experimental interventions appeared to enhance cognitive function scores (p < 0.05), except for the number of moves in the Tower of Hanoi task, where no improvement was noted. In contrast, no significant differences in any cognitive performance measures were observed following the reading session. Notably, the CEG group exhibited a more pronounced positive impact, especially on working memory. This advantage was specifically evident in the digit span tasks, where significantly greater percentage gains were found in the CEG than in the CG (p = 0.02), while no significant difference existed between the EG and CG. Simultaneous combined exercise has proven to be a more effective method than aerobic physical exercise alone for improving cognitive function. The results of this study are recommended for inclusion in clinical practice guidelines to maintain the mental health of older adults, as simultaneous exercise seems to offer a time-efficient strategy to enhance cognitive performance in adults with MCI. Full article
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14 pages, 1419 KiB  
Article
Association of Number of Comorbid Conditions and Pain among United States Adults
by David R. Axon and Becka Eckert
Diseases 2024, 12(7), 147; https://doi.org/10.3390/diseases12070147 - 10 Jul 2024
Viewed by 526
Abstract
Studies have explored the association of particular conditions, or combinations of conditions, and pain among specific populations. However, there is limited information regarding the association of the number of comorbid conditions, as well as other demographic, economic, health, and limitation variables, with pain [...] Read more.
Studies have explored the association of particular conditions, or combinations of conditions, and pain among specific populations. However, there is limited information regarding the association of the number of comorbid conditions, as well as other demographic, economic, health, and limitation variables, with pain among adults in the United States. This cross-sectional database study aimed to examine the relationships between number of comorbid conditions (including cancer, arthritis, joint pain, stroke, heart attack, angina, coronary heart disease, high cholesterol, high blood pressure, other heart diseases, diabetes, asthma, chronic bronchitis, and emphysema), demographic, economic, health, and limitation variables with pain among United States adults using 2021 Medical Expenditure Panel Survey data. A multivariable logistic model assessed the association between the number of comorbid conditions (≥6, 5, 4, 3, 2, 1, versus 0 conditions) and quite a bit/extreme (versus little/moderate) pain, adjusting for demographic, economic, health, and limitation variables. The study found that greater numbers of comorbid conditions were associated with higher odds of quite a bit or extreme pain. In addition, age, education, employment, income, overall health, regular physical activity, and three limitation variables were each associated with pain in the multivariable model. These findings offer insight into the association between number of comorbid conditions and other variables with pain and suggest areas where interventions may be helpful to help improve pain outcomes for United States adults. Full article
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22 pages, 3817 KiB  
Systematic Review
The Association between Marital Status and Obesity: A Systematic Review and Meta-Analysis
by Tamara Nikolic Turnic, Vladimir Jakovljevic, Zulfiya Strizhkova, Nikita Polukhin, Dmitry Ryaboy, Mariia Kartashova, Margarita Korenkova, Valeriia Kolchina and Vladimir Reshetnikov
Diseases 2024, 12(7), 146; https://doi.org/10.3390/diseases12070146 - 5 Jul 2024
Viewed by 604
Abstract
Background: Obesity was included in the International Classification of Diseases in 1990 as a chronic disease characterized by the excessive accumulation of body fat and a body mass index (BMI) greater than 30 kg/m2. Aim: This systematic review was aimed to [...] Read more.
Background: Obesity was included in the International Classification of Diseases in 1990 as a chronic disease characterized by the excessive accumulation of body fat and a body mass index (BMI) greater than 30 kg/m2. Aim: This systematic review was aimed to examine the role of marital status in determining body mass index and the risk of obesity. Methods: We performed a systematic literature search using three databases (PubMed (Medline), Embase, and Google Scholar) with the search query. Results: Of the 105 studies included in the systematic review, 76 studies (72%) reported a greater risk of obesity in married individuals compared to unmarried individuals. A meta-analysis of 24 studies included a total population of 369,499 participants: 257,257 married individuals (40,896 of whom had obesity) and 112,242 comparison subjects (single, divorced, or widowed individuals, 15,084 of whom had obesity). Odds ratios for obesity found a significant pooled odds ratio for obesity in married individuals compared with controls (OR 1.70; 95% CI 1.38–2.10). The socioeconomic environment was not the same throughout the period of studies analyzed. The odds of obesity in married individuals during economic crises was greater than during the period between crises: OR 2.56 (95% CI 2.09–3.13) during crises vs. OR 1.55 (95% CI 1.24–1.95) between crises. Conclusion: The results of this review confirm the importance of considering marital status in determining the risk of obesity. Full article
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13 pages, 989 KiB  
Article
Post-Operative Radiation in Early Breast Cancer with N1 Disease: 10-Year Follow-Up
by Ee Ling Serene Tang, E-Jan Sim, Wei-Wen Ang, Jun Su, Juliana Jia Chuan Chen, Mun Yew Patrick Chan, Bok Ai Choo and Ern Yu Tan
Diseases 2024, 12(7), 145; https://doi.org/10.3390/diseases12070145 - 5 Jul 2024
Viewed by 519
Abstract
Post-operative radiotherapy for post-menopausal women with early breast cancer and N1 disease is controversial. Although locoregional control is improved, overall survival (OS) benefit is unclear. The clinical benefit of post-operative irradiation in this group of patients over 10 years was reviewed. We aimed [...] Read more.
Post-operative radiotherapy for post-menopausal women with early breast cancer and N1 disease is controversial. Although locoregional control is improved, overall survival (OS) benefit is unclear. The clinical benefit of post-operative irradiation in this group of patients over 10 years was reviewed. We aimed to evaluate the OS, disease-free survival (DFS), and factors affecting OS and DFS. A retrospective review of 191 post-menopausal women with early breast cancer and N1 disease from 2004 to 2011 was performed. Demographics, post-operative histology, adjuvant treatment, OS, and DFS were evaluated. Post-operative radiation was given to 95 of 191 women (49.7%). Younger age at diagnosis (p < 0.001), a greater number of involved nodes (p = 0.004), lymphovascular invasion (LVI), and a higher tumor grade (p = 0.001) were more likely in women who received post-operative radiation. Nodal radiation did not improve 10-year DFS (p = 0.084) or OS (p = 0.203). Post-operative nodal radiation was associated with significant improvement in 10-year OS in women who received only hormonal therapy (p = 0.047) and no other systemic therapy. Women with unfavorable risk factors were more likely to receive post-operative radiation, likely due to a perceived higher risk of recurrence. Nodal radiation did not significantly improve 10-year DFS or OS in early breast cancer patients with N1 disease, and the benefit was not clearly demonstrated. However, in those who were on hormonal therapy, radiotherapy was beneficial in improving overall survival. Full article
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16 pages, 2652 KiB  
Article
Effects of Combustible Cigarettes and Heated Tobacco Products on Systemic Inflammatory Response in Patients with Chronic Inflammatory Diseases
by Nikolina Kastratovic, Natasa Zdravkovic, Ivan Cekerevac, Vanesa Sekerus, Carl Randall Harrell, Violeta Mladenovic, Aleksandar Djukic, Ana Volarevic, Marija Brankovic, Tijana Gmizic, Marija Zdravkovic, Jelica Bjekic-Macut, Nebojsa Zdravkovic, Valentin Djonov and Vladislav Volarevic
Diseases 2024, 12(7), 144; https://doi.org/10.3390/diseases12070144 - 5 Jul 2024
Viewed by 610
Abstract
Smoke derived from combustible cigarettes (CCs) contains numerous harmful chemicals that can impair the viability, proliferation, and activation of immune cells, affecting the progression of chronic inflammatory diseases. In order to avoid the detrimental effects of cigarette smoking, many CC users have replaced [...] Read more.
Smoke derived from combustible cigarettes (CCs) contains numerous harmful chemicals that can impair the viability, proliferation, and activation of immune cells, affecting the progression of chronic inflammatory diseases. In order to avoid the detrimental effects of cigarette smoking, many CC users have replaced CCs with heated tobacco products (HTPs). Due to different methods of tobacco processing, CC-sourced smoke and HTP-derived aerosols contain different chemical constituents. With the exception of nicotine, HTP-sourced aerosols contain significantly lower amounts of harmful constituents than CC-derived smoke. Since HTP-dependent effects on immune-cell-driven inflammation are still unknown, herein we used flow cytometry analysis, intracellular staining, and an enzyme-linked immunosorbent assay to determine the impact of CCs and HTPs on systemic inflammatory response in patients suffering from ulcerative colitis (UC), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Both CCs and HTPs significantly modulated cytokine production in circulating immune cells, affecting the systemic inflammatory response in COPD, DM, and UC patients. Compared to CCs, HTPs had weaker capacity to induce the synthesis of inflammatory cytokines (IFN-γ, IL-1β, IL-5, IL-6, IL-12, IL-23, IL-17, TNF-α), but more efficiently induced the production of immunosuppressive IL-10 and IL-35. Additionally, HTPs significantly enhanced the synthesis of pro-fibrotic TGF-β. The continuous use of CCs and HTPs aggravated immune-cell-driven systemic inflammation in COPD and DM patients, but not in UC patients, suggesting that the immunomodulatory effects of CC-derived smoke and HTP-sourced aerosols are disease-specific, and need to be determined for specific immune-cell-driven inflammatory diseases. Full article
(This article belongs to the Topic Inflammation: The Cause of all Diseases 2.0)
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12 pages, 731 KiB  
Article
SARS-CoV-2 Infection Positively Correlates with Hyperglycemia and Inflammatory Markers in COVID-19 Patients: A Clinical Research Study
by Prashanth Chikkahonnaiah, Siva Dallavalasa, SubbaRao V. Tulimilli, Muskan Dubey, Shashidhar H. Byrappa, Raghavendra G. Amachawadi, SubbaRao V. Madhunapantula and Ravindra P. Veeranna
Diseases 2024, 12(7), 143; https://doi.org/10.3390/diseases12070143 - 4 Jul 2024
Viewed by 830
Abstract
Diabetes mellitus (DM) is a common comorbidity in COVID-19 subjects. Hyperglycemia at hospital admission identified as a major risk factor and is responsible for poor prognosis. Hematological and inflammatory parameters have been recognized as predictive markers of severity in COVID-19. In this clinical [...] Read more.
Diabetes mellitus (DM) is a common comorbidity in COVID-19 subjects. Hyperglycemia at hospital admission identified as a major risk factor and is responsible for poor prognosis. Hematological and inflammatory parameters have been recognized as predictive markers of severity in COVID-19. In this clinical study, we aimed to assess the impact of hyperglycemia at hospital admission on hematological and several inflammatory parameters in COVID-19 patients. A total of 550 COVID-19 subjects were primarily categorized into two major groups (normoglycemic and hyperglycemic) based on random blood sugar levels. On the first day of hospitalization, subjects’ oxygen saturation, random blood sugar, hematological variables, and inflammatory parameters were recorded. The hyperglycemic group exhibited higher levels of serum ferritin, total leukocyte count (TLC), lactate dehydrogenase (LDH), neutrophil count, and neutrophil-to-lymphocyte ratio (NLR). In contrast, oxygen saturation and lymphocyte count were lower compared to the normoglycemic group. Significantly elevated levels of hematological variables (TLC, neutrophil count, NLR) and inflammatory parameters (serum ferritin) were observed in the hyperglycemic group. Among inflammatory parameters, only serum ferritin levels showed statistical significance. This study supports the clinical association between hyperglycemia and an increased severity of COVID-19. Consequently, the identification of these parameters is a crucial and valuable prognostic indicator for assessing disease severity in hyperglycemic subjects. Full article
(This article belongs to the Section Infectious Disease)
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15 pages, 2866 KiB  
Article
SARS-CoV-2 Infection during Delivery Causes Histopathological Changes in the Placenta
by Jędrzej Borowczak, Agnieszka Gąsiorek-Kwiatkowska, Krzysztof Szczerbowski, Mateusz Maniewski, Marek Zdrenka, Marta Szadurska-Noga, Karol Gostomczyk, Paula Rutkiewicz, Katarzyna Olejnik, Wojciech Cnota, Magdalena Karpów-Greiner, Wojciech Knypiński, Marta Sekielska-Domanowska, Grzegorz Ludwikowski, Mariusz Dubiel, Łukasz Szylberg and Magdalena Bodnar
Diseases 2024, 12(7), 142; https://doi.org/10.3390/diseases12070142 - 2 Jul 2024
Viewed by 663
Abstract
Background: SARS-CoV-2 can damage human placentas, leading to pregnancy complications, such as preeclampsia and premature birth. This study investigates the histopathological changes found in COVID-19-affected placentas. Materials and Methods: This study included 23 placentas from patients with active COVID-19 during delivery and 22 [...] Read more.
Background: SARS-CoV-2 can damage human placentas, leading to pregnancy complications, such as preeclampsia and premature birth. This study investigates the histopathological changes found in COVID-19-affected placentas. Materials and Methods: This study included 23 placentas from patients with active COVID-19 during delivery and 22 samples from patients without COVID-19 infection in their medical history. The samples underwent histopathological examination for pathology, such as trophoblast necrosis, signs of vessel damage, or fetal vascular malperfusion. Results: Newborns from the research group have lower weights and Apgar scores than healthy newborns. In the COVID-19 group, calcifications and collapsed intervillous space were more frequent, and inflammation was more severe than in the healthy group. At the same time, the placenta of SARS-CoV-2-positive patients showed signs of accelerated vascular maturation. Trophoblast necrosis was found only in the placentas of the research group. The expression of CD68+ was elevated in the COVID-19 cohort, suggesting that macrophages constituted a significant part of the inflammatory infiltrate. The increase in lymphocyte B markers was associated with placental infarctions, while high levels of CD3+, specific for cytotoxic T lymphocytes, correlated with vascular injury. Conclusions: SARS-CoV-2 is associated with pathological changes in the placenta, including trophoblast necrosis, calcification, and accelerated villous maturation. Those changes appear to be driven by T cells and macrophages, whose increased expression reflects ongoing histiocytic intervillositis in the placenta. Full article
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12 pages, 237 KiB  
Article
Attitudes, Knowledge and Clinical Practice of Health Professionals towards Psychological Disorders in Cancer Patients: An Observational Study
by Maria Chiara Carriero, Antonio Leo, Alessia Lezzi, Roberto Lupo, Luana Conte, Annarita Fanizzi, Raffaella Massafra, Elsa Vitale and Antonio Carriero
Diseases 2024, 12(7), 141; https://doi.org/10.3390/diseases12070141 - 1 Jul 2024
Viewed by 712
Abstract
Background: The suffering associated with a cancer diagnosis can find different channels to express itself: sleep disorders, psychiatric disorders, sexuality. These are not always analyzed by health professionals, but they have an impact on the patient’s quality of life and on the outcome [...] Read more.
Background: The suffering associated with a cancer diagnosis can find different channels to express itself: sleep disorders, psychiatric disorders, sexuality. These are not always analyzed by health professionals, but they have an impact on the patient’s quality of life and on the outcome of the disease. Methods: An observational study was conducted in order to investigate attitudes, knowledge and clinical practice towards psychological symptoms in cancer patients. Results: A total of 132 clinicians from all Italian regions responded. In total, 99.2% (n = 131) considered the figure of the psychologist useful in the oncology field and recommended him/her in clinical practice (n = 115; 87.7%), especially in the terminal phase of the illness (58.6%; n = 99). Despite the importance given to the figure of the psychologist, psychiatric disorders are not diagnosed. Only 20.0% (n = 26) identified depressive disorder as accurate and only 33.9% (n = 43) identified demoralization syndrome as accurate. Conclusions: Results prove the need for training on psychological disorders in oncology and the emotional repercussions of cancer illness. Full article
9 pages, 6203 KiB  
Case Report
Tumor-to-Tumor Metastasis: Dissemination of Cutaneous Squamous Cell Carcinoma Involving Parotid Warthin Tumor—Case Report
by Michał Gontarz, Krystyna Gałązka, Krzysztof Gąsiorowski, Jakub Bargiel, Tomasz Marecik, Paweł Szczurowski and Grażyna Wyszyńska-Pawelec
Diseases 2024, 12(7), 140; https://doi.org/10.3390/diseases12070140 - 1 Jul 2024
Viewed by 536
Abstract
Warthin tumors (WTs) are the second most common salivary gland tumors, most commonly found in the tail of the parotid gland. The lymphoid components of a WT may also serve as a site for tumor-to-tumor metastasis. This report describes the metastasis of cutaneous [...] Read more.
Warthin tumors (WTs) are the second most common salivary gland tumors, most commonly found in the tail of the parotid gland. The lymphoid components of a WT may also serve as a site for tumor-to-tumor metastasis. This report describes the metastasis of cutaneous squamous cell carcinoma (cSCC) from the preauricular region to a parotid WT. A 68-year-old male patient was admitted to the Department of Cranio-Maxillofacial Surgery of the Jagiellonian University in Cracow, Poland, with a two-year history of a growing, painless skin tumor of the right preauricular region. The patient was eligible for surgical treatment with elective neck dissection at the Va, III, II, I levels with parotidectomy and the excision of the cSCC. In the histopathological examination of the components of the surgical specimen beside the primary cutaneous squamous cell carcinoma (cSCC), a parotid WT was found; in the majority, it was occupied and destroyed by the metastatic cSCC and radically removed. After a tumor board consultation, due to the advanced stage (pT3N2b LVI2 PNI0 R0), with three intraparotid lymph node metastases and LVI2, the patient was authorized for postoperative radiotherapy. In conclusion, tumor-to-tumor metastasis is an extremely rare entity. Surgery is the standard of care for both WTs and head and neck cSCC. In most cases, metastasis into the parotid gland can be successfully treated with superficial parotidectomy with facial nerve preservation. Dissemination into the parotid gland requires elective neck dissection, as well as adjuvant treatment. Full article
(This article belongs to the Section Oncology)
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14 pages, 3396 KiB  
Article
Machine Learning Model Construction and Testing: Anticipating Cancer Incidence and Mortality
by Yuanzhao Ding
Diseases 2024, 12(7), 139; https://doi.org/10.3390/diseases12070139 - 30 Jun 2024
Viewed by 599
Abstract
In recent years, the escalating environmental challenges have contributed to a rising incidence of cancer. The precise anticipation of cancer incidence and mortality rates has emerged as a pivotal focus in scientific inquiry, exerting a profound impact on the formulation of public health [...] Read more.
In recent years, the escalating environmental challenges have contributed to a rising incidence of cancer. The precise anticipation of cancer incidence and mortality rates has emerged as a pivotal focus in scientific inquiry, exerting a profound impact on the formulation of public health policies. This investigation adopts a pioneering machine learning framework to address this critical issue, utilizing a dataset encompassing 72,591 comprehensive records that include essential variables such as age, case count, population size, race, gender, site, and year of diagnosis. Diverse machine learning algorithms, including decision trees, random forests, logistic regression, support vector machines, and neural networks, were employed in this study. The ensuing analysis revealed testing accuracies of 62.17%, 61.92%, 54.53%, 55.72%, and 62.30% for the respective models. This state-of-the-art model not only enhances our understanding of cancer dynamics but also equips researchers and policymakers with the capability of making meticulous projections concerning forthcoming cancer incidence and mortality rates. Considering sustainability, the application of this advanced machine learning framework emphasizes the importance of judiciously utilizing extensive and intricate databases. By doing so, it facilitates a more sustainable approach to healthcare planning, allowing for informed decision-making that takes into account the long-term ecological and societal impacts of cancer-related policies. This integrative perspective underscores the broader commitment to sustainable practices in both health research and public policy formulation. Full article
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12 pages, 296 KiB  
Article
Factors Associated with Prolonged SARS-CoV-2 Viral Positivity in an Italian Cohort of Hospitalized Patients
by Simona De Grazia, Francesco Pollicino, Chiara Giannettino, Chiara Maria Errera, Nicola Veronese, Giovanni M. Giammanco, Federica Cacioppo, Giuseppa Luisa Sanfilippo, Mario Barbagallo and COMEPA Study Authors
Diseases 2024, 12(7), 138; https://doi.org/10.3390/diseases12070138 - 28 Jun 2024
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Abstract
Clinical or microbiological factors potentially associated with prolonged COVID-19 PCR positivity are still poorly underexplored, but they could be of importance for public-health and clinical reasons. The objective of our analysis is to explore demographic, clinical, and microbiological factors potentially associated with a [...] Read more.
Clinical or microbiological factors potentially associated with prolonged COVID-19 PCR positivity are still poorly underexplored, but they could be of importance for public-health and clinical reasons. The objective of our analysis is to explore demographic, clinical, and microbiological factors potentially associated with a prolonged positivity to SARS-CoV-2 among 222 hospitalized patients. Prolonged detection positivity for SARS-CoV-2 RNA in swap samples, defined as positivity more than 21 days, was the outcome of interest. The 56 cases with a prolonged positivity to SARS-CoV-2 were matched for age and sex with 156 controls. The cases reported a significantly higher presence of diabetes mellitus, autoimmune diseases, chronic kidney diseases, and acute coronary syndrome. Moreover, the viral load was significantly higher in a period of prolonged positivity compared to a normal period. In the multivariable analysis, the presence of autoimmune diseases and chronic kidney disease were significantly associated with an increased risk of prolonged positivity as well as medium viral load or high viral load, i.e., low Ct value ≤ 30 indicating high viral load. The results of this study confirmed that in a large population of hospitalized patients with COVID-19 manifestations, the prolonged positivity of SARS-CoV-2 detection with nasopharyngeal swab was mainly related to autoimmune diseases, chronic kidney disease, and to baseline viral load. Full article
14 pages, 1049 KiB  
Article
Prognostic Role of Lymphocyte-to-Monocyte Ratio (LMR) in Patients with Intermediate-Stage Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations (DEM-TACE or cTACE) of the Liver: Exploring the Link between Tumor Microenvironment and Interventional Radiology
by Roberto Minici, Massimo Venturini, Giuseppe Guzzardi, Federico Fontana, Andrea Coppola, Filippo Piacentino, Federico Torre, Marco Spinetta, Pietro Maglio, Pasquale Guerriero, Michele Ammendola, MGJR Research Team, Luca Brunese and Domenico Laganà
Diseases 2024, 12(7), 137; https://doi.org/10.3390/diseases12070137 - 27 Jun 2024
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Abstract
Inflammation-based scores are biomarkers of the crosstalk between the tumor microenvironment and the immune response. Investigating the intricate relationship between the tumor stromal microenvironment, biomarkers, and the response to transcatheter arterial chemoembolization (TACE) is essential for early identification of TACE refractoriness or failure, [...] Read more.
Inflammation-based scores are biomarkers of the crosstalk between the tumor microenvironment and the immune response. Investigating the intricate relationship between the tumor stromal microenvironment, biomarkers, and the response to transcatheter arterial chemoembolization (TACE) is essential for early identification of TACE refractoriness or failure, providing insights into tumor biology and facilitating personalized therapeutic interventions. This study addresses a dearth of recent literature exploring the prognostic significance of the preoperative LMR in individuals from western countries diagnosed with stage B hepatocellular carcinoma (HCC) undergoing drug eluting microspheres TACE (DEM-TACE) or conventional TACE (cTACE). This international multi-center retrospective analysis included consecutive patients with stage B HCC who underwent TACE from January 2017 to June 2023. The study evaluated the ability of the preoperative LMR to predict complete response (CR), objective response (OR), sustained response duration (SRD) exceeding 6 months, successful downstaging at 6 months, progression-free survival (PFS) at 6 months, and overall survival (OS) at 6 months. The study population included 109 HCC patients and it was divided into low LMR (LMR < 2.24) and high LMR (LMR ≥ 2.24) groups, according to ROC curve analysis to select the optimal LMR cut-off value. High LMR was associated with lower Hepatitis C prevalence, higher absolute lymphocyte count, and a trend toward lower alpha-fetoprotein. The group with high LMRs exhibited superior CR rates (14.9% vs. 0%), overall OR (43.2% vs. 14.3%), and better PFS at 6 months (75.7% vs. 45.7%). The LMR, specifically categorized as <2.24 and ≥2.24, emerged as a robust predictor for treatment response and short-term outcomes in patients with stage B HCC undergoing DEM- or c-TACE. Full article
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