Diseases

18 pages, 2074 KiB

Open AccessReview

Targeting Solute Carrier Transporters (SLCs) as a Therapeutic Target in Different Cancers

by Ravi Bharadwaj, Swati Jaiswal, Erandi E. Velarde de la Cruz and Ritesh P. Thakare

Diseases 2024, 12(3), 63; https://doi.org/10.3390/diseases12030063 - 21 Mar 2024

Cited by 7 | Viewed by 4456

Solute carrier (SLC) transporters constitute a vast superfamily of transmembrane proteins tasked with regulating the transport of various substances such as metabolites, nutrients, ions, and drugs across cellular membranes. SLC transporters exhibit coordinated expression patterns across normal tissues, suggesting a tightly regulated regulatory [...] Read more.

Solute carrier (SLC) transporters constitute a vast superfamily of transmembrane proteins tasked with regulating the transport of various substances such as metabolites, nutrients, ions, and drugs across cellular membranes. SLC transporters exhibit coordinated expression patterns across normal tissues, suggesting a tightly regulated regulatory network governing normal cellular functions. These transporters are crucial for the transport of various metabolites, including carbohydrates, proteins, lipids, and nucleic acids. However, during tumor development, metabolic changes drive an increased demand for energy and nutrients. Consequently, tumor cells alter the expression of SLC transporters to meet their heightened nutrient requirements. Targeting SLCs through inhibition or activation presents a promising therapeutic approach in cancer treatment. Certain SLCs also serve as intriguing chemo-sensitizing targets, as modulating their activity can potentially alter the response to chemotherapy. This review underscores the significance of various SLCs in tumor progression and underscores their potential as both direct and indirect targets for cancer therapy. Full article

(This article belongs to the Section Oncology)

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10 pages, 741 KiB

Open AccessArticle

Papillary Thyroid Cancer Trends in the Wake of the COVID-19 Pandemic: Is There a Shift toward a More Aggressive Entity?

by Iyad Hassan, Lina Hassan, Farooq Bacha, Mohammad Al Salameh, Omran Gatee and Wiam Hassan

Diseases 2024, 12(3), 62; https://doi.org/10.3390/diseases12030062 - 20 Mar 2024

Cited by 3 | Viewed by 4110

Abstract

Background: Globally, the incidence of papillary thyroid cancer (PTC) has been increasing over the last few decades and it has become the second most common cancer in women in the UAE. There is some evidence to suggest that COVID-19 infection might be directly [...] Read more.

Background: Globally, the incidence of papillary thyroid cancer (PTC) has been increasing over the last few decades and it has become the second most common cancer in women in the UAE. There is some evidence to suggest that COVID-19 infection might be directly linked to the development of aggressive variants of PTC. The primary goal of this study was to compare the clinical and pathologic characteristics of thyroid cancer patients treated at the largest endocrine surgery center in Abu Dhabi before and after the COVID-19 pandemic outbreak. Methods: This retrospective cohort analysis included patients who underwent elective thyroid surgery at Burjeel Hospital between January 2018 and December 2022. Patients were divided into two groups based on when the COVID-19 outbreak started: group one, comprising patients who had surgery between January 2018 and December 2019 (the “pre-pandemic group”), and group two, comprising patients who had surgery between January 2021 and December 2022 (the “post-pandemic group”). In addition to demographic data, clinicopathological factors, such as aggressive cell type, multifocality, tumor size and location, laterality, lympho-vascular invasion, and extrathyroidal extension, were assessed. We utilized the t-paired test for parametric variables and the Chi-square test for the cross-table analysis. Results: During the study, 1141 people had thyroid surgery, with an annual average of 285 procedures. PTC cases recorded in the final histopathological samples rose from 111 in the pre-pandemic era to 182 in the post-pandemic era. Neither the female-to-male gender ratio, which was 90:21 in the pre-pandemic group and 142:40 in the post-pandemic group (p = 0.532), nor the median age, which was 39.1 and 40.1 years, respectively, varied significantly between the two groups. However, there was a significant increase between pre-pandemic and post-pandemic in the aggressive PTC variants (3% vs. 11.5%, p = 0.001), increased poor prognostic factors such as bilateral multifocality (10.8% vs. 32.4%, p = 0.000), as well as increased capsule–vascular tumor invasion (19.8% vs. 27%); on the other hand, the size of the single foci was 17 mm in the pre-pandemic group compared to 13 mm in the post-pandemic group (p = 0.001). Conclusions: A significant rise in unfavorable prognostic markers and aggressive subtypes of PTC was seen post-pandemic in thyroidectomy patients operated on at a leading endocrine surgery center in the United Arab Emirates. Full article

(This article belongs to the Special Issue COVID-19 and Global Chronic Disease 2023)

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13 pages, 4899 KiB

Open AccessArticle

Exploratory Evaluation of Pre-Treatment Inflammation Profiles in Patients with Colorectal Cancer

by Catalin Vladut Ionut Feier, Calin Muntean, Sorana D. Bolboacă and Sorin Olariu

Diseases 2024, 12(3), 61; https://doi.org/10.3390/diseases12030061 - 20 Mar 2024

Cited by 2 | Viewed by 2086

Abstract

In light of the elevated incidence and consequential prognostic implications associated with colorectal cancer, a comprehensive investigation into the impact exerted by inflammatory status on patient management becomes imperative. A retrospective study spanning 7 years was conducted, involving the retrospective collection of data [...] Read more.

In light of the elevated incidence and consequential prognostic implications associated with colorectal cancer, a comprehensive investigation into the impact exerted by inflammatory status on patient management becomes imperative. A retrospective study spanning 7 years was conducted, involving the retrospective collection of data on colorectal cancer patients undergoing surgical intervention. We evaluated six inflammation ratios derived from complete peripheral blood counts. A thorough analysis of these markers’ prognostic capacity was conducted, revealing that patients who died postoperatively displayed significantly higher preoperative Aggregate Index of Systemic Inflammation—AISI (p = 0.014) and Systemic Inflammation Response Index—SII (p = 0.0197) levels compared to those with successful discharge. Noteworthy variations in neutrophil-to-lymphocyte ratio (p = 0.0103), platelet-to-lymphocyte ratio (p = 0.0041), AISI (p < 0.001), and SII (p = 0.0045) were observed in patients necessitating postoperative Intensive Care Unit (ICU) monitoring. Furthermore, patients with complications, such as an intestinal fistula, exhibited significantly elevated AISI (p = 0.0489). Inflammatory biomarkers stand out as valuable prognostic tools for colorectal cancer patients, offering potential assistance in predicting their prognosis. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Upper and Lower Gastrointestinal Malignancies: Current Advances and Future Prospects)

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17 pages, 2257 KiB

Open AccessArticle

Clinical Research into Central Nervous System Inflammatory Demyelinating Diseases Related to COVID-19 Vaccines

by Mei-Yun Cheng, Hsuan-Chen Ho, Jung-Lung Hsu, Yi Wang, Linyi Chen, Siew-Na Lim, Ming-Feng Liao and Long-Sun Ro

Diseases 2024, 12(3), 60; https://doi.org/10.3390/diseases12030060 - 20 Mar 2024

Viewed by 3259

Abstract

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin [...] Read more.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and a literature review of another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine types (viral vector, mRNA, and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccine-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines, and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including fifteen patients (19%) with anti-MOG, eleven (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than those receiving other types. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. This research suggests potential associations between COVID-19 vaccine-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific types. Full article

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24 pages, 1859 KiB

Open AccessReview

Collateral Damage in the Placenta during Viral Infection in Pregnancy: A Possible Mechanism for Vertical Transmission and an Adverse Pregnancy Outcome

by Victor Javier Cruz-Holguín, Luis Didier González-García, Manuel Adrián Velázquez-Cervantes, Haruki Arévalo-Romero, Luis Adrián De Jesús-González, Addy Cecilia Helguera-Repetto, Guadalupe León-Reyes, Ma. Isabel Salazar, Leticia Cedillo-Barrón and Moisés León-Juárez

Diseases 2024, 12(3), 59; https://doi.org/10.3390/diseases12030059 - 20 Mar 2024

Viewed by 3273

Abstract

In mammals, the placenta is a connection between a mother and a new developing organism. This tissue has a protective function against some microorganisms, transports nutrients, and exchanges gases and excretory substances between the mother and the fetus. Placental tissue is mainly composed [...] Read more.

In mammals, the placenta is a connection between a mother and a new developing organism. This tissue has a protective function against some microorganisms, transports nutrients, and exchanges gases and excretory substances between the mother and the fetus. Placental tissue is mainly composed of chorionic villi functional units called trophoblasts (cytotrophoblasts, the syncytiotrophoblast, and extravillous trophoblasts). However, some viruses have developed mechanisms that help them invade the placenta, causing various conditions such as necrosis, poor perfusion, and membrane rupture which, in turn, can impact the development of the fetus and put the mother’s health at risk. In this study, we collected the most relevant information about viral infection during pregnancy which can affect both the mother and the fetus, leading to an increase in the probability of vertical transmission. Knowing these mechanisms could be relevant for new research in the maternal–fetal context and may provide options for new therapeutic targets and biomarkers in fetal prognosis. Full article

(This article belongs to the Special Issue Recent Advances in Diseases: Featured Reviews)

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12 pages, 262 KiB

Open AccessArticle

Lifestyle Profiles of Italian Oncology Nurses according to Sex, Work Experience and Shift: An Exploratory Study

by Elsa Vitale and Alessandro Rizzo

Diseases 2024, 12(3), 58; https://doi.org/10.3390/diseases12030058 - 19 Mar 2024

Cited by 1 | Viewed by 1830

Abstract

(1) Background: Several researchers have highlighted a higher incidence of overweight and obesity among nurses, and others have analyzed the quality of nurses’ eating habits and their related physical activity levels. The present study assessed the differences in personal habits among Italian oncology [...] Read more.

(1) Background: Several researchers have highlighted a higher incidence of overweight and obesity among nurses, and others have analyzed the quality of nurses’ eating habits and their related physical activity levels. The present study assessed the differences in personal habits among Italian oncology nurses according to sex, work experience and shift. (2) Methods: A cross-sectional study was performed during September–October 2023. A Google Moduli questionnaire was created and divulgated through Facebook and Instagram “Nurseallface” social pages. (3) Results: A total of 306 Italian oncology nurses agreed to participate in this study. Significant differences were reported between sex and the nutrition dimension (p = 0.018); male nurses reported higher levels in this dimension (2.69 ± 0.43) than females (2.56 ± 0.49). By considering the role of work experience in the health-promoting lifestyle profile, significant differences were recorded in the physical activity sub-dimension (p < 0.001), especially among nurses employed for more than 30 years who reported higher levels of physical activity (5.25 ± 0.23) than the other groups. By considering the shift role in the health-promoting lifestyle profile, significant differences were recorded with a health-promoting lifestyle general score (p = 0.046), especially among nurses employed only during the morning shift who recorded higher levels in health-promoting lifestyle than the others (one shift: 2.49 ± 0.29 vs. two shifts: 2.47 ± 0.24 vs. three shifts: 2.41 ± 0.25). Additionally, significant differences were reported in the physical activity dimension (p = 0.017), since nurses employed only during the morning shift recorded higher levels of physical activity than the others (one shift: 2.96 ± 1.28 vs. two shifts: 2.55 ± 0.94 vs. three shifts: 2.48 ± 1.20). Finally, a significant difference was recorded in the nutrition dimension (p = 0.017), since nurses employed during the morning and the afternoon shifts recorded higher levels of nutrition than the others (two shifts: 2.73 ± 0.39 vs. one shift: 2.63 ± 0.43 vs. three shifts: 2.56 ± 0.51). (4) Conclusions: Nurses represent the motive of healthcare organizations. Promoting healthy lifestyles among nurses would help healthcare organizations to have a healthy workforce, and nurses themselves can be advocates for policies to improve patient lifestyles and improve chronic disease prevention. Full article

(This article belongs to the Section Oncology)

2 pages, 143 KiB

Open AccessEditorial

The COVID-19 Pandemic Is Over, but the Virus Still Lingers

by Ludovico Abenavoli

Diseases 2024, 12(3), 57; https://doi.org/10.3390/diseases12030057 - 19 Mar 2024

Cited by 1 | Viewed by 1436

Abstract

The global health emergency caused by the Coronavirus disease-19 (COVID-19) pandemic officially ended on 11 May 2023 [...] Full article

(This article belongs to the Special Issue COVID-19 and Global Chronic Disease 2023)

14 pages, 900 KiB

Open AccessSystematic Review

The Assessment of SF-36 Survey for Quality-of-Life Measurement after Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Systematic Review

by Vlad Barbos, Bogdan Feciche, Silviu Latcu, Alexei Croitor, Vlad Dema, Razvan Bardan, Flaviu Ionut Faur, Tudor Mateescu, Dorin Novacescu, Gherle Bogdan and Alin Adrian Cumpanas

Diseases 2024, 12(3), 56; https://doi.org/10.3390/diseases12030056 - 16 Mar 2024

Cited by 1 | Viewed by 2035

Abstract

This study presents a systematic review of the literature on individuals’ health-related quality of life (HRQoL) following radical cystectomy for muscle-invasive bladder cancer (MIBC), utilizing the Short Form-36 Health Survey (SF-36) as a primary assessment tool. The review was designed as an exhaustive [...] Read more.

This study presents a systematic review of the literature on individuals’ health-related quality of life (HRQoL) following radical cystectomy for muscle-invasive bladder cancer (MIBC), utilizing the Short Form-36 Health Survey (SF-36) as a primary assessment tool. The review was designed as an exhaustive literature search across three major databases including PubMed, Scopus, and Embase up to December 2023, using the PRISMA guidelines. The selection process refined 2281 identified articles down to 11 studies meeting our inclusion criteria. These studies encompassed a diverse demographic and clinical profile of 774 participants, with follow-up durations ranging from 3 to 130 months, thereby offering insights into both short-term and long-term HRQoL outcomes. The results highlighted significant alterations in individuals’ HRQoL across various domains post-radical cystectomy. Notably, the Physical Functioning (PF) and Bodily Pain (BP) domains generally scored higher, indicating a moderate to high perceived physical health status. However, the Role Physical (RP) and Role Emotional (RE) domains showed variability, reflecting the challenges in daily role fulfillment and emotional adjustment post-surgery. A marked variability in physical recovery was observed, with studies reporting significant differences in PF and RP scores between patient groups. The General Health (GH) and Vitality (VT) domains sometimes reflected perceived deteriorations, whereas the Mental Health (MH) scores suggested that many patients maintained or achieved high levels of well-being post-operatively. The conclusions drawn from this systematic review underscore the profound and multi-faceted impact of radical cystectomy on HRQoL, varying widely between studies, being influenced by geographic factors, surgical methods, and the time of evaluation. The findings emphasize the necessity for holistic patient care approaches that address both physical and emotional rehabilitation, aiming to improve HRQoL outcomes. Full article

(This article belongs to the Special Issue Multidisciplinarity and Interdisciplinary Basics in Mental Health)

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15 pages, 433 KiB

Open AccessArticle

Serum Pro-Inflammatory Cytokines and Leptin as Potential Biomarkers for Treatment Response and Toxicity in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

by Amani A. Alrehaili, Amal F. Gharib, Maha M. Bakhuraysah, Afaf Alharthi, Ohud Alsalmi, Fouzeyyah Ali Alsaeedi, Reem Ali Alhakami, Kamilah Ali Alasmari, Nuha Mohammed and Wael H. Elsawy

Diseases 2024, 12(3), 55; https://doi.org/10.3390/diseases12030055 - 11 Mar 2024

Cited by 1 | Viewed by 1980

Abstract

Squamous cell carcinoma of the head and neck (HNSCC) is a globally prevalent form of cancer with significant morbidity and mortality rates. The present study examines the relationship of serum pro-inflammatory cytokines and leptin levels with the effectiveness of therapy in individuals with [...] Read more.

Squamous cell carcinoma of the head and neck (HNSCC) is a globally prevalent form of cancer with significant morbidity and mortality rates. The present study examines the relationship of serum pro-inflammatory cytokines and leptin levels with the effectiveness of therapy in individuals with HNSCC and their potential role as biomarkers for treatment response and toxicity. Induction chemotherapy and concomitant chemoradiotherapy were evaluated for efficacy and safety in 52 individuals with HNSCC. Both response and toxicity were evaluated, and serum levels of pro-inflammatory cytokines Interlukin-1 beta (IL-1β), Interlukin-2 (IL-2), Interlukin-6 (IL-6), and Tumor Necrosis Factor-Alpha (TNF-α) and leptin were measured using enzyme-linked immunoassay before and after treatment. Before treatment, these measurements were made in comparison with a control group with 50 healthy people. The results showed that serum cytokines and leptin levels varied depending on the response to treatment, with patients who had a complete or partial response (PR) showing significant decreases in IL-1 β, IL-6, and TNF-α levels and significant increases in IL-2 and leptin levels after treatment, with an improvement in cachexia. These results imply that variations in serum pro-inflammatory cytokines and leptin levels are likely related to the therapeutic effectiveness in HNSCC and may act as biomarkers for treatment response. Full article

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11 pages, 504 KiB

Open AccessArticle

Association between Dietary Practice and Gait Speed in Community-Dwelling Older Adults with Overweight and Obesity: A Cross-Sectional Study

by Leila Itani, Massimo Pellegrini, Dana Saadeddine, Hanen Samouda, Dima Kreidieh, Hana Tannir and Marwan El Ghoch

Diseases 2024, 12(3), 54; https://doi.org/10.3390/diseases12030054 - 8 Mar 2024

Cited by 1 | Viewed by 1996

Abstract

Slow gait speed is associated with poorer clinical outcomes and higher rates of functional limitation and mortality in older adults, especially when combined with overweight or obesity. Aging is also associated with nutritional deficits. The aim of our study was to assess the [...] Read more.

Slow gait speed is associated with poorer clinical outcomes and higher rates of functional limitation and mortality in older adults, especially when combined with overweight or obesity. Aging is also associated with nutritional deficits. The aim of our study was to assess the potential association between dietary practice and gait speed performance in community-dwelling older adults with overweight and obesity. Participants underwent body composition measurement with the Tanita MC-780MA Bioimpedance Analyzer (BIA). Dietary patterns were assessed with the Mini Nutritional Assessment (MNA) questionnaire, and a dietary adequacy (DA) score system was constructed. The four-meter gait speed test was performed in order to assess gait speed. Of 222 participants, aged 67.6 ± 6.6 years, with a body mass index (BMI) of 31.9 ± 4.5 kg/m², 34.7% had reduced gait speed and lower DA compared to those with normal gait speed (2.99 ± 1.12 vs. 3.37 ± 1.07; p < 0.05). The DA score of participants with slower gait speed was more likely to fall below the median than that of participants with normal gait speed (70.1% vs. 51.7%; p < 0.05). Participants with slower gait speed were more likely to be nutritionally at risk of low DA (22.1% vs. 10.3%; p < 0.05). Logistic regression analysis, after adjustment for confounders, showed that the risk of having a slow gait speed was 75% lower among those with a higher DA score (OR = 0.25; 95% CI = 0.11–0.53). Older adults with overweight or obesity in community dwellings might need to be supported with nutritional interventions that can improve their gait speed. Full article

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14 pages, 533 KiB

Open AccessArticle

Pre-Stroke Antihypertensive Therapy Affects Stroke Severity and 3-Month Outcome of Ischemic MCA-Territory Stroke

by Lehel-Barna Lakatos, Manuel Bolognese, Mareike Österreich, Laura Weichsel and Martin Müller

Diseases 2024, 12(3), 53; https://doi.org/10.3390/diseases12030053 - 3 Mar 2024

Cited by 1 | Viewed by 1955

Abstract

Objectives: Whether different antihypertensive drug classes in high blood pressure (HBP) pre-stroke treatment affect dynamic cerebral autoregulation (dCA), stroke severity, and outcome. Methods: Among 337 consecutive ischemic stroke patients (female 102; median age 71 years [interquartile range, [IQR 60; 78]; NIHSS median 3 [...] Read more.

Objectives: Whether different antihypertensive drug classes in high blood pressure (HBP) pre-stroke treatment affect dynamic cerebral autoregulation (dCA), stroke severity, and outcome. Methods: Among 337 consecutive ischemic stroke patients (female 102; median age 71 years [interquartile range, [IQR 60; 78]; NIHSS median 3 [IQR 1; 6]) with assessment of dCA, 183 exhibited the diagnosis of HBP. dCA parameters’ gain and phase were determined by transfer function analysis of spontaneous oscillations of blood pressure and cerebral blood flow velocity. Results: Patients used beta-blockers (n = 76), calcium channel blockers (60), diuretics (77), angiotensin-converting enzyme inhibitors (59), or angiotensin-1 receptor blockers (79), mostly in various combinations of two or three drug classes. dCA parameters did not differ between the non-HBP and the different HBP medication groups. Multinomial ordinal logistic regression models revealed that the use of diuretics decreased the likelihood of a less severe stroke (odds ratio 0.691, 95% CI 0.493; 0.972; p = 0.01) and that beta-blockers decreased the likelihood of a better modified Rankin score at 3 months (odds ratio 0.981, 95% CI 0.970; 0.992; p = 0.009). Other independent factors associated with stroke outcome were penumbra and infarct volume, treatment with mechanical thrombectomy, and the initial National Institute of Health Stroke Scale score. Interpretation: In this cohort of ischemic minor to moderate stroke patients, pre-stroke antihypertensive treatment with diuretics was associated with a more severe neurological deficit on admission and pre-stroke treatment with beta-blockers with a poorer 3-month outcome. The antihypertensive drug class used pre-stroke did not impact dCA. Full article

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12 pages, 532 KiB

Open AccessBrief Report

Wild-Type AmpC Beta-Lactamase-Producing Enterobacterales Are a Risk Factor for Empirical Treatment Failure in Patients with Bloodstream Infection

by Matteo Vassallo, Roxane Fabre, Laurene Lotte, Sabrina Manni and Christian Pradier

Diseases 2024, 12(3), 52; https://doi.org/10.3390/diseases12030052 - 2 Mar 2024

Cited by 1 | Viewed by 1938

Abstract

Introduction: Beta-lactamases are frequently prescribed for Gram-negative bloodstream infections (BSIs). However, chromosomally encoded AmpC-producing Enterobacterales (AE) could overproduce beta-lactamases when exposed to third-generation cephalosporins (3GCs), with a risk of clinical failure. There are few available in vivo data on the subject. Our goal [...] Read more.

Introduction: Beta-lactamases are frequently prescribed for Gram-negative bloodstream infections (BSIs). However, chromosomally encoded AmpC-producing Enterobacterales (AE) could overproduce beta-lactamases when exposed to third-generation cephalosporins (3GCs), with a risk of clinical failure. There are few available in vivo data on the subject. Our goal was to assess the potential role of AE as a predictive factor for clinical failure in patients with BSIs. Materials and Methods: We retrospectively analyzed patients admitted to Cannes hospital between 2021 and 2022 for BSIs due to Enterobacterales. Patient demographics, comorbidities, and main clinical and laboratory parameters during hospitalization were collected. The risk factors for clinical instability after 48 h or death, as well as for ineffective initial empirical therapy, were assessed using univariate and multivariate analyses. Results: From January 2021 to December 2022, 101 subjects were included (mean age 79 years, 60% men, 97% with comorbidities, 17% with healthcare-associated infection, 13% with septic shock, 82% with qPitt severity score < 2, 58% with urinary tract infection, and 18% with AE). Septic shock [adjusted odds ratio (OR_adj) = 5.30, 95% confidence interval (CI): 1.47–22.19, p = 0.014] and ineffective initial empirical therapy [OR_adj 5.54, 95% CI: 1.95–17.01, p = 0.002] were independent predictive factors for clinical instability or death. Extended-spectrum beta-lactamases [OR_adj 9.40, 95% CI: 1.70–62.14, p = 0.012], AE group [OR_adj 5.89, 95% CI: 1.70–21.40, p = 0.006], and clinical instability or death [OR_adj 4.71, 95% CI: 1.44–17.08, p = 0.012] were independently associated with ineffective empirical therapy. Conclusions: Infection with AE was associated with treatment failure. Empirical therapy may result in failure if restricted to 3GC. Full article

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12 pages, 5435 KiB

Open AccessArticle

Expression Patterns of GATA3 in Classical Hodgkin Lymphoma: A Clinico-Pathological Study

by Alexandra Papoudou-Bai, Epameinondas Koumpis, Georgia Karpathiou, Eleftheria Hatzimichael and Panagiotis Kanavaros

Diseases 2024, 12(3), 51; https://doi.org/10.3390/diseases12030051 - 29 Feb 2024

Viewed by 3513

Abstract

GATA3 is a transcription factor involved in T-cell maturation and has been previously shown to be aberrantly overexpressed in malignant Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). However, the immunophenotypes of the cell types expressing GATA3 have not been precisely [...] Read more.

GATA3 is a transcription factor involved in T-cell maturation and has been previously shown to be aberrantly overexpressed in malignant Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). However, the immunophenotypes of the cell types expressing GATA3 have not been precisely characterized so far in cHL tissues. In this single-center retrospective cohort study we analyzed the expression patterns of GATA3 alone and in combination with B, T, NK or macrophage-associated markers in 73 cases with newly diagnosed cHL and investigated for a possible correlation with clinical and laboratory parameters. Immunohistochemistry (single and double) was performed using GATA3 alone and in combination with CD20, CD3, CD56, CD68, CD30 or CD15. Clinical and laboratory parameters were collected and correlated with the expression of GATA 3. GATA3 nuclear expression was found in HRS cells in 39/73 (54%) cases of cHL. The Nodular Sclerosis (NS) subtype showed the highest positivity rate (35/56, 63%), followed by mixed cellularity (MC; 4/14, 29%) and lymphocyte rich (LR; 0/3). Double immunostainings showed that GATA3 was expressed by CD30+ or CD15+ HRS cells and a few CD3+ T-cells, whereas GATA3 expression was not detected in CD20, CD56 or CD68+ cells. GATA3-negative cHL was significantly associated with unfavorable prognostic factors such as older age at diagnosis and increased levels of serum β2-microglobulin. The heterogenous expression patterns of GATA3 in HRS cells that were observed in a substantial proportion of cHL, mainly in the NS subtype, further support the biological heterogeneity of cHL. Full article

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16 pages, 1398 KiB

Open AccessReview

The Role of Oxidative Stress in TB Meningitis and Therapeutic Options

by John Dawi, Aishvaryaa Shree Mohan, Yura Misakyan, Scarlet Affa, Edgar Gonzalez, Karim Hajjar, David Nikoghosyan, Sabrina Fardeheb, Christopher Tuohino and Vishwanath Venketaraman

Diseases 2024, 12(3), 50; https://doi.org/10.3390/diseases12030050 - 29 Feb 2024

Viewed by 3038

Abstract

Meningitis is an inflammatory condition affecting the meninges surrounding the brain and spinal cord. Meningitis can be triggered by various factors, including infectious agents like viruses and bacteria and non-infectious contributors such as cancer or head injuries. The impact of meningitis on the [...] Read more.

Meningitis is an inflammatory condition affecting the meninges surrounding the brain and spinal cord. Meningitis can be triggered by various factors, including infectious agents like viruses and bacteria and non-infectious contributors such as cancer or head injuries. The impact of meningitis on the central nervous system involves disruptions in the blood–brain barrier, cellular infiltrations, and structural alterations. The clinical features that differentiate between tuberculous meningitis (TBM) and non-tuberculous meningitis (NTM) are discussed in this review and aid in accurate diagnosis. The intricate interplay of reactive oxygen species, ferroptosis, and reactive nitrogen species within the central nervous system reveals a promising field of research for innovative therapeutic strategies tailored to TBM. This review highlights the alternative treatments targeting oxidative stress-induced TBM and ferroptosis, providing potential avenues for intervention in the pathogenesis of this complex condition. Full article

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11 pages, 266 KiB

Open AccessArticle

Protective Effects of Propolis and Chitosan Nanoparticles against Ibuprofen-Induced Hepatotoxicity in Albino Rats

by Fajer M. AlKandari, Hussein S. Mohamed, Sayed A. Ahmed, Basant Mahmoud and Asmaa M. Mahmoud

Diseases 2024, 12(3), 49; https://doi.org/10.3390/diseases12030049 - 29 Feb 2024

Cited by 4 | Viewed by 2320

Abstract

Post-marketing hepatotoxicity findings are more common or occur much later. NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen are consumed in large quantities around the world. NSAIDs have a low incidence of hepatotoxicity but their wide use makes them a major contributor to drug-induced liver [...] Read more.

Post-marketing hepatotoxicity findings are more common or occur much later. NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen are consumed in large quantities around the world. NSAIDs have a low incidence of hepatotoxicity but their wide use makes them a major contributor to drug-induced liver injury. Hepatitis is linked to systemic oxidative stress which results in cellular necrosis and fibrosis, as well as tissue lipoprotein peroxidation and glutathione depletion. Given the lack of safe and effective anti-hepatitis drugs in medicine today, natural substances appear to be a promising and safe alternative. Propolis and chitosan are considered natural substances that have a protective effect on the hepatocytes. The purpose of this study was to validate the protective effect of propolis/chitosan nanoparticle extracts on ibuprofen-induced hepatotoxicity. Thirty (30) albino rats were used for the experiment. Animals were exposed to ibuprofen (400 mg/kg body weight/day) for 4 weeks (7 days/week) followed by treatment with propolis (200 mg/kg body weight/day) and chitosan extract (200 mg/kg body weight/day) separately and also in combination for consecutive 4 weeks. This study revealed a significant increase in serum transaminases, alkaline phosphatase, albumin, and total bilirubin in serum, as well as an increase in lipid peroxidation (MDA) and nitric oxide (NO). Furthermore, GSH, GST, and SOD decreased significantly in the group that was exposed to ibuprofen. Furthermore, there was a significant increase in pro-inflammatory parameters such as IL-1β and NF-ĸB, as well as low levels of anti-inflammatory parameters such as IL-6 and BCl-2. These alterations were improved by propolis and chitosan extracts, which was further confirmed in experimental animals. This study demonstrated that propolis and chitosan nanoparticle extracts have the potential to protect against hepatotoxicity induced by ibuprofen, due to their ability to regulate anti-inflammatory and anti-oxidative defense activities. Full article

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12 pages, 2156 KiB

Open AccessReview

Pediatric Hemangiomas in the Female Genital Tract: A Literature Review

by Lucia Merlino, Agnese Immacolata Volpicelli, Franco Anglana, Giulia D’Ovidio, Mattia Dominoni, Marianna Francesca Pasquali, Barbara Gardella, Paolo Inghirami, Pietro Lippa and Roberto Senatori

Diseases 2024, 12(3), 48; https://doi.org/10.3390/diseases12030048 - 28 Feb 2024

Viewed by 1909

Abstract

Background: Hemangiomas are aberrant proliferations of blood vessels and the most frequent benign pediatric soft tissue tumors. Although they are common, genital localization is rare. This study aimed to assist doctors in the diagnosis, management, and treatment of pediatric vulvovaginal hemangiomas by conducting [...] Read more.

Background: Hemangiomas are aberrant proliferations of blood vessels and the most frequent benign pediatric soft tissue tumors. Although they are common, genital localization is rare. This study aimed to assist doctors in the diagnosis, management, and treatment of pediatric vulvovaginal hemangiomas by conducting a review of the literature. Methods: We conducted a literature review including papers published between August 2009 and May 2023. Results: While most hemangiomas are usually indolent and resolve with time, in some cases, especially cervicovaginal and uterine ones, they might present with severe symptoms like heavy bleeding and need further instrumental investigation for diagnosis, like CT or MRI. As for the treatment, many options are available, with medical therapy or expectant management being the first choice. Conclusions: Vulvovaginal pediatric hemangiomas are rare and require more research on how to detect and manage these lesions, especially the symptomatic and the psychologically impacting ones. For the time being, treatment should be personalized based on the patient’s situation and clinician’s expertise. Full article

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9 pages, 1251 KiB

Open AccessCase Report

The Conundrum of Cancer-Associated Thrombosis: Lesson Learned from Two Intriguing Cases and Literature Review

by Simona Laurino, Sabino Russi, Ludmila Carmen Omer, Alberto D’Angelo, Giovanni Bozza, Giuseppina Gallucci, Geppino Falco, Giandomenico Roviello and Anna Maria Bochicchio

Diseases 2024, 12(3), 47; https://doi.org/10.3390/diseases12030047 - 28 Feb 2024

Cited by 1 | Viewed by 2248

Abstract

The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. [...] Read more.

The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. A 75-year-old man with advanced rectal cancer treated with fluoropyrimidines suffered two catheter-related VTE events managed according to current guidelines. There was no indication for “extended” anticoagulant therapy for him, but during antithrombotic wash-out and fluoropyrimidines plus panitumumab regimen, he suffered a massive right coronary artery (RCA) thrombosis. Another patient with no cardiovascular (CV) risk factors and affected by advanced bladder cancer was treated with a platinum-containing regimen and suffered an acute inferior myocardial infarction 2 days after chemotherapy administration. He was successfully treated with primary Percutaneous Transluminal Coronary Angioplasty of RCA, discontinuing platinum-based therapy. Our observations raise the issue of cancer-associated thrombosis (CAT) complexity and the potential correlation between arterial and venous thrombotic events. Moreover, physicians should be aware of the thrombotic risk associated with anticancer therapies, suggesting that an appropriate prophylaxis should be considered. Full article

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13 pages, 1575 KiB

Open AccessArticle

SARS-CoV-2 Infection Is an Independent Risk Factor for Decompensation in Cirrhosis Patients

by Mark Ayoub, Julton Tomanguillo, Carol Faris, Nadeem Anwar, Harleen Chela and Ebubekir Daglilar

Diseases 2024, 12(3), 46; https://doi.org/10.3390/diseases12030046 - 25 Feb 2024

Cited by 3 | Viewed by 2015

Abstract

Background: SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2’s impact on decompensation in previously compensated cirrhotic patients. Methods: We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across [...] Read more.

Background: SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2’s impact on decompensation in previously compensated cirrhotic patients. Methods: We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across sixteen countries, using TriNetX’s deidentified research database. Compensated cirrhosis patients were split into two groups: one with SARS-CoV-2-positive patients and another testing negative. Using a 1:1 propensity score matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then assessed decompensation, mortality, and GI bleed at 1 and 3 months. Results: Out of 252,631 identified compensated cirrhosis patients, 27.3% (69,057) tested SARS-CoV-2-positive, while 72.6% (183,574) remained negative. Post PSM, 61,963 patients were in each group. SARS-CoV-2-positive patients showed significantly higher decompensation rates (4.4% vs. 1.9% at 1 month; 6% vs. 2.6% overall). Rates of complications, like ascites, SBP, HE, and HRS, increased notably. Mortality (2.5% vs. 1.7% at 1 month; 3.6% vs. 2.7% at 3 months) and GI bleed (1.3% vs. 0.9% at 1 month; 1.9% vs. 1.2% at 3 months) were also elevated in SARS-CoV-2 patients. Conclusions: SARS-CoV-2 increases decompensation over 2-fold in compensated cirrhosis patients and raises mortality and increases rates of complications at 1 and 3 months. Full article

(This article belongs to the Section Gastroenterology)

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16 pages, 1197 KiB

Open AccessArticle

Investigating the Incidence of Dyslipidemia among Brazilian Children and Adolescents Diagnosed with Type 1 Diabetes Mellitus: A Cross-Sectional Study

by Rafael Fagundes Melo, Lucas Fornari Laurindo, Katia Portero Sloan, Lance Alan Sloan, Adriano Cressoni Araújo, Piero Bitelli, Tereza Laís Menegucci Zutin, Rodrigo Haber Mellen, Luciano Junqueira Mellen, Elen Landgraf Guiguer, João Paulo Cera Albarossi, Márcia Rocha Gabaldi, Patricia Cincotto dos S. Bueno, Jesselina Francisco dos Santos Haber, Sandra Maria Barbalho and Eduardo Federighi Baisi Chagas

Diseases 2024, 12(3), 45; https://doi.org/10.3390/diseases12030045 - 24 Feb 2024

Cited by 2 | Viewed by 2297

Abstract

The treatment of Type 1 Diabetes Mellitus (T1DM) has always been a challenge for health professionals in relation to glycemic control. Increased body fat has been related to a worsening of the lipid profile and increased prevalence of dyslipidemia in this population, leading [...] Read more.

The treatment of Type 1 Diabetes Mellitus (T1DM) has always been a challenge for health professionals in relation to glycemic control. Increased body fat has been related to a worsening of the lipid profile and increased prevalence of dyslipidemia in this population, leading to negative repercussions on the control of cardiovascular risk. We aimed to investigate the distribution of lipid levels and the presence of dyslipidemia in children and adolescents with T1DM. A cross-sectional observational study was conducted with 81 individuals of both sexes (4–19 years) diagnosed with T1DM. Anthropometric and biochemical data were collected, in addition to data on physical activity level, sexual maturation stage, and insulin administration regimen. Lipid levels were categorized as normal, borderline, and elevated, and the presence of dyslipidemia was diagnosed by the presence of one or more altered lipid parameter. We noted a prevalence of dyslipidemia in 65.4% of the participants when considering borderline lipid values. Of those, 23.5% had one altered lipid level, and 42.0% had two or more. The main altered lipid levels were total cholesterol and triglycerides, followed by non-HDL-c. The main factor associated with the worsening of lipid levels was the increase in HbA1c. Sex had a significant effect on the levels of TC, HDL-c, and ApoA-I. The results of this study reinforce the need to monitor lipid profile in children and adolescents with T1DM, as well as the importance of early intervention in treating dyslipidemia, especially in patients with poor glycemic control. Full article

(This article belongs to the Special Issue Epidemiology of Noncommunicable Diseases)

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15 pages, 1537 KiB

Open AccessArticle

Clinical Practice Guidelines for the Diagnosis and Management of Hereditary Fructose Intolerance

by Félix Úbeda, Sonia Santander and María José Luesma

Diseases 2024, 12(3), 44; https://doi.org/10.3390/diseases12030044 - 23 Feb 2024

Cited by 1 | Viewed by 4319

Abstract

Introduction: Hereditary fructose intolerance or hereditary fructosemia is an autosomal recessive metabolic disorder caused by a loss of function in the aldolase B gene. This disorder affects 1 in 20,000 people, constituting a rare disease with a favorable prognosis through adherence to a [...] Read more.

Introduction: Hereditary fructose intolerance or hereditary fructosemia is an autosomal recessive metabolic disorder caused by a loss of function in the aldolase B gene. This disorder affects 1 in 20,000 people, constituting a rare disease with a favorable prognosis through adherence to a fructose-free diet. Despite dietary management, chronic pathology may manifest, underscoring the importance of early diagnosis to mitigate adverse effects. However, early detection of the disease poses significant challenges. Aim: Our aim was to compile pertinent information on the differential diagnosis of this pathology based on patient symptoms, facilitating the development of a diagnostic algorithm for early identification. Methodology: A systematic review adhering to PRISMA guidelines was conducted on empirical studies from PubMed, encompassing a total of 35 studies. Results: Individuals with fructose intolerance may acutely experience postprandial symptoms such as hypoglycemia, vomiting, and abdominal distension. Despite proper treatment, chronic complications such as fatty liver, Fanconi syndrome, growth deficiency, and irritable bowel syndrome may arise. The proposed diagnostic algorithm aims to minimize these adverse processes. Conclusions: Understanding the pathogenesis enables prompt diagnosis and prevention of chronicity. Establishing continuity of care from pediatric to adult medicine is crucial, and disseminating information to non-pediatric endocrinologists is imperative for managing this rare disease. Full article

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12 pages, 715 KiB

Open AccessReview

Amino Acid Metabolism in Leukocytes Showing In Vitro IgG Memory from SARS-CoV2-Infected Patients

by Giuseppina Fanelli, Veronica Lelli, Sara Rinalducci and Anna Maria Timperio

Diseases 2024, 12(3), 43; https://doi.org/10.3390/diseases12030043 - 23 Feb 2024

Cited by 1 | Viewed by 2346

Abstract

The immune response to infectious diseases is directly influenced by metabolic activities. COVID-19 is a disease that affects the entire body and can significantly impact cellular metabolism. Recent studies have focused their analysis on the potential connections between post-infection stages of SARS-CoV2 and [...] Read more.

The immune response to infectious diseases is directly influenced by metabolic activities. COVID-19 is a disease that affects the entire body and can significantly impact cellular metabolism. Recent studies have focused their analysis on the potential connections between post-infection stages of SARS-CoV2 and different metabolic pathways. The spike S1 antigen was found to have in vitro IgG antibody memory for PBMCs when obtaining PBMC cultures 60–90 days post infection, and a significant increase in S-adenosyl homocysteine, sarcosine, and arginine was detected by mass spectrometric analysis. The involvement of these metabolites in physiological recovery from viral infections and immune activity is well documented, and they may provide a new and simple method to better comprehend the impact of SARS-CoV2 on leukocytes. Moreover, there was a significant change in the metabolism of the tryptophan and urea cycle pathways in leukocytes with IgG memory. With these data, together with results from the literature, it seems that leukocyte metabolism is reprogrammed after viral pathogenesis by activating certain amino acid pathways, which may be related to protective immunity against SARS-CoV2. Full article

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11 pages, 256 KiB

Open AccessArticle

Impact of COVID-19 Pandemic on Cardiovascular Healthcare in Croatia: A Comprehensive Nationwide Survey

by Josip Lukenda and Josip Andelo Borovac

Diseases 2024, 12(3), 42; https://doi.org/10.3390/diseases12030042 - 22 Feb 2024

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Abstract

The impact of the COVID-19 pandemic on cardiovascular healthcare in Croatia remains largely unexplored. This study aimed to compare the utilization and provision of cardiovascular services during the pre-pandemic (2017–2019) and pandemic (2020–2021) periods, leveraging nationwide data from the Croatian Health Insurance Fund, [...] Read more.

The impact of the COVID-19 pandemic on cardiovascular healthcare in Croatia remains largely unexplored. This study aimed to compare the utilization and provision of cardiovascular services during the pre-pandemic (2017–2019) and pandemic (2020–2021) periods, leveraging nationwide data from the Croatian Health Insurance Fund, which covers 95% of all insurance claims in the country. Our findings reveal that while the use of coronary angiographies decreased during the pandemic, there was a notable increase in the utilization of advanced heart failure treatment modalities and percutaneous coronary interventions, particularly in the context of acute myocardial infarction. Additionally, transcatheter aortic valve implantations saw a significant rise during the pandemic period. Furthermore, laboratory diagnostic testing for troponin and natriuretic peptides experienced a marked increase, while the utilization of most other cardiovascular services remained stable or showed only minor declines compared to the pre-pandemic era. These observations suggest that the Croatian cardiovascular healthcare system displayed resilience during the COVID-19 pandemic, successfully maintaining and even expanding access to various diagnostic and interventional procedures despite facing widespread societal and logistical challenges. Full article

(This article belongs to the Section Cardiology)

11 pages, 1030 KiB

Open AccessSystematic Review

Safety and Efficacy of Convalescent Plasma Combined with Other Pharmaceutical Agents for Treatment of COVID-19 in Hospitalized Patients: A Systematic Review and Meta-Analysis

by Massimo Franchini, Daniele Focosi, Mario Cruciani, Michael J. Joyner, Liise-anne Pirofski, Jonathon W. Senefeld, Shmuel Shoham, David J. Sullivan and Arturo Casadevall

Diseases 2024, 12(3), 41; https://doi.org/10.3390/diseases12030041 - 21 Feb 2024

Cited by 6 | Viewed by 2165

Abstract

Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such [...] Read more.

Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such interaction has never been investigated systematically. To assess the safety and efficacy of CCP combined with other agents for treatment of patients hospitalized for COVID-19, a systematic literature search using appropriate Medical Subject Heading (MeSH) terms was performed through PubMed, EMBASE, Cochrane central, medRxiv and bioRxiv. The main outcomes considered were mortality and safety of CCP combined with other treatments versus CCP alone. This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Measure of treatment effect was the risk ratio (RR) together with 95% confidence intervals (CIs). A total of 11 studies (8 randomized controlled trials [RCTs] and 3 observational) were included in the systematic review, 4 studies with CCP combined with remdesivir and 6 studies with CCP combined with corticosteroids, all involving hospitalized patients. One RCT reported information on both remdesivir and steroids use with CCP. The use of CCP combined with remdesivir was associated with a significantly reduced risk of death (RR 0.74; 95% CI 0.56–0.97; p = 0.03; moderate certainty of evidence), while the use of steroids with CCP did not modify the mortality risk (RR 0.72; 95% CI 0.34–1.51; p = 0.38; very low certainty of evidence). Not enough safety data were retrieved form the systematic literature analysis. The current evidence from the literature suggests a potential beneficial effect on mortality of combined CCP plus remdesivir compared to CCP alone in hospitalized COVID-19 patients. No significant clinical interaction was found between CCP and steroids. Full article

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Diseases, Volume 12, Issue 3 (March 2024) – 23 articles

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