Journal of Clinical Medicine

30 pages, 13009 KiB

Open AccessReview

Natural Bioactives: Back to the Future in the Fight against Human Papillomavirus? A Narrative Review

by Silvia Massa, Riccardo Pagliarello, Francesca Paolini and Aldo Venuti

J. Clin. Med. 2022, 11(5), 1465; https://doi.org/10.3390/jcm11051465 - 07 Mar 2022

Cited by 3 | Viewed by 3991

Human papillomavirus (HPV) still represents an important threat to health worldwide. Better therapy in terms of further improvement of outcomes and attenuation of related side-effects is desirable. The pharmaceutical industry has always targeted natural substances—phytochemicals in particular—to identify lead compounds to be clinically [...] Read more.

Human papillomavirus (HPV) still represents an important threat to health worldwide. Better therapy in terms of further improvement of outcomes and attenuation of related side-effects is desirable. The pharmaceutical industry has always targeted natural substances—phytochemicals in particular—to identify lead compounds to be clinically validated and industrially produced as antiviral and anticancer drugs. In the field of HPV, numerous naturally occurring bioactives and dietary phytochemicals have been investigated as potentially valuable in vitro and in vivo. Interference with several pathways and improvement of the efficacy of chemotherapeutic agents have been demonstrated. Notably, some clinical trials have been conducted. Despite being endowed with general safety, these natural substances are in urgent need of further assessment to foresee their clinical exploitation. This review summarizes the basic research efforts conducted so far in the study of anti-HPV properties of bio-actives with insights into their mechanisms of action and highlights the variety of their natural origin in order to provide comprehensive mapping throughout the different sources. The clinical studies available are reported, as well, to highlight the need of uniformity and consistency of studies in the future to select those natural compounds that may be suited to clinical application. Full article

(This article belongs to the Special Issue Oncogenic Human Papillomaviruses)

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11 pages, 251 KiB

Open AccessArticle

Postoperative Complications and Swallowing Function after Jejunal and Skin Flap Reconstruction for Hypopharyngeal Carcinoma—A Multicenter Retrospective Study

by Kunihiko Tokashiki, Isaku Okamoto, Takuro Okada, Hiroki Sato, Taku Yamashita, Takashi Matsuki, Takahito Kondo, Chihiro Fushimi, Tatsuo Masubuchi, Kouki Miura, Go Omura and Kiyoaki Tsukahara

J. Clin. Med. 2022, 11(5), 1464; https://doi.org/10.3390/jcm11051464 - 07 Mar 2022

Cited by 3 | Viewed by 1413

Abstract

This study compared the incidence of perioperative complications and swallowing function between free jejunal flap reconstruction and cutaneous free tissue flap construction. We included 223 patients who underwent hypopharyngeal reconstruction using free flap. At discharge, +the free jejunal flap was associated with a [...] Read more.

This study compared the incidence of perioperative complications and swallowing function between free jejunal flap reconstruction and cutaneous free tissue flap construction. We included 223 patients who underwent hypopharyngeal reconstruction using free flap. At discharge, +the free jejunal flap was associated with a Functional Oral Intake Scale (FOIS) score of 1–6 in 132 cases (70%) and a score of 7 in 56 cases (30%). Regarding the cutaneous free tissue flaps, FOIS scores of 1–6 were observed in 18 cases (51%), and a score of 7 was noted in 17 cases (49%). Donor site complications occurred in 12% of the patients who underwent free jejunal flap procedures and in none of the patients who underwent cutaneous free tissue flap procedures. We found that the free jejunal flap had a regular dietary intake rate in 56 patients (30%), whereas cutaneous free tissue flaps had a regular dietary intake rate in 17 patients (49%). Cutaneous free tissue flaps had a significantly higher regular dietary intake rate at discharge and a significantly lower incidence of donor site complications than free jejunal flaps. In conclusion, free-flap reconstruction may be a better method than free jejunal flap reconstruction for the treatment of hypopharyngeal cancer. Full article

(This article belongs to the Section Otolaryngology)

7 pages, 560 KiB

Open AccessArticle

Arrhythmias in COVID-19/SARS-CoV-2 Pneumonia Infection: Prevalence and Implication for Outcomes

by Andrea Denegri, Matteo Sola, Marianna Morelli, Francesco Farioli, Alberto Tosetti, Matteo D’Arienzo, Fulvio Savorani, Giuseppe Stefano Pezzuto, Giuseppe Boriani, Lukasz Szarpak and Giulia Magnani

J. Clin. Med. 2022, 11(5), 1463; https://doi.org/10.3390/jcm11051463 - 07 Mar 2022

Cited by 6 | Viewed by 1704

Abstract

Arrhythmias (ARs) are potential cardiovascular complication of COVID-19 but may also have a prognostic role. The aim of this study was to explore the prevalence and impact of cardiac ARs in hospitalized COVID-19 patients. All-comer patients admitted to the emergency department of Modena [...] Read more.

Arrhythmias (ARs) are potential cardiovascular complication of COVID-19 but may also have a prognostic role. The aim of this study was to explore the prevalence and impact of cardiac ARs in hospitalized COVID-19 patients. All-comer patients admitted to the emergency department of Modena University Hospital from 16 March to 31 December 2020 and diagnosed with COVID-19 pneumonia infection were included in the study. The primary endpoint was 30-day mortality. Out of 902 patients, 637 (70.6%) presented a baseline 12-lead ECG registration; of these, 122 (19.2%) were diagnosed with ARs. Atrial fibrillation (AF, 40.2%) was the most frequent AR detected. The primary endpoint (30-day mortality) occurred in 33.6% (p < 0.001). AR-patients presented an almost 3-fold risk of mortality compared to non-AR-patients at 30d (Adj. OR = 2.8, 95%CI: 1.8–4.3, p < 0.001). After adjustment for significant baseline characteristics selected by a stepwise backward selection, AR-patients remained at increased risk of mortality (Adj. HR = 2.0, 95%CI: 1.9–2.3, p < 0.001). Sub-group analysis revealed that among ARs patients, those with AF at admission presented the highest risk of 30-day mortality (Adj. HR = 3.1, 95%CI: 2.0–4.9, p < 0.001). In conclusion, ARs are a quite common manifestation in COVID-19 patients, who are burdened by even worse prognosis. AR patients with AF presented the highest risk of mortality; thus, these patients may benefit from a more aggressive secondary preventive therapy and a closer follow up. Full article

(This article belongs to the Special Issue Recent Updates in the Management of Pneumonia and COVID-19)

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12 pages, 1851 KiB

Open AccessArticle

The Gut Microbiome, Seleno-Compounds, and Acute Myocardial Infarction

by Fu-Chun Chiu, Chin-Feng Tsai, Pang-Shuo Huang, Ching-Yu Shih, Mong-Hsun Tsai, Juey-Jen Hwang, Yi-Chih Wang, Eric Y. Chuang, Chia-Ti Tsai and Sheng-Nan Chang

J. Clin. Med. 2022, 11(5), 1462; https://doi.org/10.3390/jcm11051462 - 07 Mar 2022

Cited by 6 | Viewed by 1885

Abstract

Background: Gut microbiome alterations might be considered a metabolic disorder. However, the relationship between the microbiome and acute myocardial infarction (AMI) has not been properly validated. Methods: The feces of 44 subjects (AMI: 19; control: 25) were collected for fecal genomic DNA extraction. [...] Read more.

Background: Gut microbiome alterations might be considered a metabolic disorder. However, the relationship between the microbiome and acute myocardial infarction (AMI) has not been properly validated. Methods: The feces of 44 subjects (AMI: 19; control: 25) were collected for fecal genomic DNA extraction. The variable region V3–V4 of the 16S rRNA gene was sequenced using the Illumina MiSeq platform. The metabolite amounts were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways. Results: The bacteria were more enriched in the AMI group both in the observed operational taxonomic units (OTUs) and faith phylogenetic diversity (PD) (p-value = 0.01 and <0.001 with 95% CI, individually). The Selenomonadales were less enriched in the AMI group at the family, genus, and species levels (all linear discriminant analysis (LDA) scores > 2). Seleno-compounds were more abundant in the AMI group at the family, genus, and species levels (all LDA scores > 2). Conclusions: This is the first study to demonstrate the association of Selenomonadales and seleno-compounds with the occurrence of AMI. Our findings provide an opportunity to identify a novel approach to prevent and treat AMI. Full article

(This article belongs to the Section Cardiology)

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18 pages, 353 KiB

Open AccessReview

Large Cell Neuroendocrine Carcinoma of the Lung: Current Understanding and Challenges

by Elisa Andrini, Paola Valeria Marchese, Dario De Biase, Cristina Mosconi, Giambattista Siepe, Francesco Panzuto, Andrea Ardizzoni, Davide Campana and Giuseppe Lamberti

J. Clin. Med. 2022, 11(5), 1461; https://doi.org/10.3390/jcm11051461 - 07 Mar 2022

Cited by 20 | Viewed by 6326

Abstract

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare and highly aggressive type of lung cancer, with a complex biology that shares similarities with both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). The prognosis of LCNEC is poor, with [...] Read more.

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare and highly aggressive type of lung cancer, with a complex biology that shares similarities with both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). The prognosis of LCNEC is poor, with a median overall survival of 8–12 months. The diagnosis of LCNEC requires the identification of neuroendocrine morphology and the expression of at least one of the neuroendocrine markers (chromogranin A, synaptophysin or CD56). In the last few years, the introduction of next-generation sequencing allowed the identification of molecular subtypes of LCNEC, with prognostic and potential therapeutic implications: one subtype is similar to SCLC (SCLC-like), while the other is similar to NSCLC (NSCLC-like). Because of LCNEC rarity, most evidence comes from small retrospective studies and treatment strategies that are extrapolated from those adopted in patients with SCLC and NSCLC. Nevertheless, limited but promising data about targeted therapies and immune checkpoint inhibitors in patients with LCNEC are emerging. LCNEC clinical management is still controversial and standardized treatment strategies are currently lacking. The aim of this manuscript is to review clinical and molecular data about LCNEC to better understand the optimal management and the potential prognostic and therapeutic implications of molecular subtypes. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors: Clinical Challenges)

11 pages, 1742 KiB

Open AccessArticle

Angiotensin Converting Enzyme Inhibitors versus Receptor Blockers in Patients with Ventricular Tachyarrhythmias

by Tobias Schupp, Michael Behnes, Mohammad Abumayyaleh, Kathrin Weidner, Kambis Mashayekhi, Thomas Bertsch and Ibrahim Akin

J. Clin. Med. 2022, 11(5), 1460; https://doi.org/10.3390/jcm11051460 - 07 Mar 2022

Cited by 2 | Viewed by 1780

Abstract

Data investigating the prognostic value of treatment with angiotensin converting enzyme inhibitors (ACEi) and receptor blockers (ARB) usually focusses on patients presenting with heart failure (HF) or acute myocardial infarction (AMI). However, by preventing adverse cardiac remodeling, ACEi/ARB may also decrease the risk [...] Read more.

Data investigating the prognostic value of treatment with angiotensin converting enzyme inhibitors (ACEi) and receptor blockers (ARB) usually focusses on patients presenting with heart failure (HF) or acute myocardial infarction (AMI). However, by preventing adverse cardiac remodeling, ACEi/ARB may also decrease the risk of ventricular tachyarrhythmias and sudden cardiac death (SCD). Although ventricular tachyarrhythmias are associated with significant mortality and morbidity, only limited data are available focusing on the prognostic role of ACEi/ARB, when prescribed for secondary prevention of SCD. Therefore, this study comprehensively investigates the role of ACEi versus ARB in patients with ventricular tachyarrhythmias. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. The primary prognostic outcome was all-cause mortality at three years, secondary endpoints comprised a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, ICD therapies and sudden cardiac death) and cardiac rehospitalization. A total of 1236 patients were included (15% treated with ARB and 85% with ACEi) and followed for a median of 4.0 years. At three years, ACEi and ARB were associated with comparable long-term mortality (20% vs. 17%; log rank p = 0.287; HR = 0.965; 95% CI 0.689–1.351; p = 0.835) and comparable risk of the composite arrhythmic endpoint (HR = 1.227; 95% CI 0.841–1.790; p = 0.288). In contrast, ACEi was associated with a decreased risk of cardiac rehospitalization at three years (HR = 0.690; 95% CI 0.490–0.971; p = 0.033). Within the propensity score matched cohort (i.e., 158 patients with ACEi and ARB), ACEi and ARB were associated with comparable long-term outcomes at three years. In conclusion, ACEi and ARB are associated with comparable risk of long-term outcomes in patients presenting with ventricular tachyarrhythmias. Full article

(This article belongs to the Special Issue Sudden Cardiac Death: Clinical Updates and Perspectives)

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14 pages, 584 KiB

Open AccessArticle

Safety of Obtaining an Extra Biobank Kidney Biopsy Core

by Sheila Bermejo, Clara García-Carro, Richard Mast, Ander Vergara, Irene Agraz, Juan Carlos León, Monica Bolufer, Maria-Alejandra Gabaldon, Daniel Serón, Oriol Bestard and Maria Jose Soler

J. Clin. Med. 2022, 11(5), 1459; https://doi.org/10.3390/jcm11051459 - 07 Mar 2022

Viewed by 1811

Abstract

Background and objectives: Kidney biopsy (KB) is the “gold standard” for the diagnosis of nephropathies and it is a diagnostic tool that presents a low rate of complications. Nowadays, biobank collections of renal tissue of patients with proven renal pathology are essential for [...] Read more.

Background and objectives: Kidney biopsy (KB) is the “gold standard” for the diagnosis of nephropathies and it is a diagnostic tool that presents a low rate of complications. Nowadays, biobank collections of renal tissue of patients with proven renal pathology are essential for research in nephrology. To provide enough tissue for the biobank collection, it is usually needed to obtain an extra kidney core at the time of kidney biopsy. The objective of our study is to evaluate the complications after KB and to analyze whether obtaining an extra core increases the risk of complications. Material and methods: Prospective observational study of KBs performed at Vall d’Hebron Hospital between 2019 and 2020. All patients who accepted to participate to our research biobank of native kidney biopsies were included to the study. Clinical and laboratory data were reviewed and we studied risk factors associated with complications. Results: A total of 221 patients were included, mean age 56.6 (±16.8) years, 130 (58.8%) were men, creatinine was 2.24 (±1.94) mg/dL, proteinuria 1.56 (0.506–3.590) g/24 h, hemoglobin 12.03 (±2.3) g/dL, INR 0.99 (±0.1), and prothrombin time (PT) 11.86 (±1.2) s. A total of 38 patients (17.2%) presented complications associated with the procedure: 13.1% were minor complications, 11.3% (n = 25) required blood transfusion, 1.4% (n = 3) had severe hematomas, 2.3% (n = 5) required embolization, and 0.5% (n = 1) presented arterio-venous fistula. An increased risk for complication was independently associated with obtaining a single kidney core (vs. 2 and 3 cores) (p = 0.021). Conclusions: KB is an invasive and safe procedure with a low percentage of complications. Obtaining an extra kidney core for research does not increase the risk of complications during the intervention, which remains low in concordance with previously published reports. Full article

(This article belongs to the Section Nephrology & Urology)

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14 pages, 1228 KiB

Open AccessArticle

Association of Visual Impairment with Psychological Distress in Older Adults: A Survey of 105,092 Older People in Taiwan

by Chu-Yu Yen, I-Mo Fang, Hsiao-Yun Hu and Shih-Han Weng

J. Clin. Med. 2022, 11(5), 1458; https://doi.org/10.3390/jcm11051458 - 07 Mar 2022

Viewed by 1554

Abstract

This study aimed to evaluate the association between visual impairment (VI) and psychological distress (PD) among older adults in Taiwan. The present cohort study included participants aged >65 years who participated in a physical examination program. Participants were divided into two groups on [...] Read more.

This study aimed to evaluate the association between visual impairment (VI) and psychological distress (PD) among older adults in Taiwan. The present cohort study included participants aged >65 years who participated in a physical examination program. Participants were divided into two groups on the basis of whether they had PD at baseline. The association between PD and VI with other variables was compared using the two-sample t-test for continuous variables and chi-squared test for discrete variables. Cox regression analyses were used to calculate the hazard ratio (HR). Cumulative incidence of PD was analyzed using the Kaplan-Meier method, and differences among participants with different severities of VI were analyzed using the two-tailed log-rank test. Subgroup analyses were performed to calculate the HR for PD among participants with different severities of VI. The PD group showed a significantly high percentage of VI. In addition, participants with VI showed a significantly higher HR and seven-year cumulative incidence rate of PD than those without VI. VI was independently and significantly associated with a higher incidence of PD among older Asian people. Therefore, identifying and treating correctible VI is important to prevent PD and improve the overall quality of life. Full article

(This article belongs to the Section Mental Health)

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10 pages, 239 KiB

Open AccessArticle

Adverse Pregnancy Outcomes and Maternal Chronic Diseases in the Future: A Cross-Sectional Study Using KoGES-HEXA Data

by Geum Joon Cho, Jiae Kim, Ji Young Kim, Sung Won Han, Soo Bin Lee, Min-Jeong Oh, Sa Jin Kim and Jae Eun Shin

J. Clin. Med. 2022, 11(5), 1457; https://doi.org/10.3390/jcm11051457 - 07 Mar 2022

Cited by 2 | Viewed by 2134

Abstract

Adverse pregnancy outcomes (APOs) are associated with an increased risk of chronic diseases, including cardiovascular disease (CVD) and metabolic syndrome (MS), in the future. We designed a large-scale cohort study to evaluate the influence of APOs (preeclampsia, gestational diabetes mellitus (GDM), stillbirth, macrosomia, [...] Read more.

Adverse pregnancy outcomes (APOs) are associated with an increased risk of chronic diseases, including cardiovascular disease (CVD) and metabolic syndrome (MS), in the future. We designed a large-scale cohort study to evaluate the influence of APOs (preeclampsia, gestational diabetes mellitus (GDM), stillbirth, macrosomia, and low birth weight) on the incidence of chronic diseases, body measurements, and serum biochemistry in the future and investigate whether combinations of APOs had additive effects on chronic diseases. We used health examinee data from the Korean Genome and Epidemiology Study (KoGES-HEXA) and extracted data of parous women (n = 30,174; mean age, 53.02 years) for the analysis. Women with APOs were more frequently diagnosed with chronic diseases and had a family history of chronic diseases compared with women without APOs. Composite APOs were associated with an increased risk of hypertension, diabetes mellitus, hyperlipidemia, angina pectoris, stroke, and MS (adjusted odds ratio: 1.093, 1.379, 1.269, 1.351, 1.414, and 1.104, respectively) after adjustment for family history and social behaviors. Preeclampsia and GDM were associated with an increased risk of some chronic diseases; however, the combination of preeclampsia and GDM did not have an additive effect on the risk. APOs moderately influenced the future development of maternal CVD and metabolic derangements, independent of family history and social behaviors. Full article

(This article belongs to the Special Issue Cardiovascular Disease: Risk Factors, Comorbidities, and Prevention)

21 pages, 2207 KiB

Open AccessReview

HIPEC in Peritoneal Metastasis of Gastric Origin: A Systematic Review of Regimens and Techniques

by Felix Gronau, Linda Feldbruegge, Frauke Oberwittler, Santiago Gonzalez-Moreno, Laurent Villeneuve, Clarisse Eveno, Olivier Glehen, Shigeki Kusamura and Beate Rau

J. Clin. Med. 2022, 11(5), 1456; https://doi.org/10.3390/jcm11051456 - 07 Mar 2022

Cited by 11 | Viewed by 2753

Abstract

(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC [...] Read more.

(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC that makes it difficult to weigh different results obtained in the literature. In order to enable standardization and development of HIPEC, we here present a systematic review of different drug regimens and technical approaches. (2) Methods: PubMed, Embase, and the Cochrane Library were systematically searched on 26 May 2021 using the mesh terms “intraperitoneal chemotherapy AND gastric cancer”. Under consideration of systematic review guidelines, articles reporting on HIPEC in combination with CRS were selected. Data on duration, drugs, dosage, and other application parameters as well as morbidity and long term survival data were extracted for subsequent statistical analysis, tabulation, and descriptive synthesis. We assessed the risk of bias due to inhomogeneity of the patient cohort and incompleteness of report of HIPEC parameters. (3) Results: Out of 1421 screened publications, 42 publications presenting data from 1325 patients met the criteria. Most of the publications were single institutional retrospective cohort studies. The most common HIPEC regimen is performed after gastrointestinal anastomosis and consists of 50–200 mg/m² cisplatinum and 30–40 mg/m² mytomycin C at 42–43 °C for 60–90 min in a closed abdomen HIPEC system with three tubes. Almost every study reported incompletely on HIPEC parameters. Lower rates of anastomotic leakage were reported in studies that performed HIPEC after gastrointestinal anastomosis. Studies that performed open HIPEC and integrated a two-drug regimen indicated better overall survival rates. (4) Discussion: This is an exhaustive overview of the use of drug regimens and techniques for HIPEC after CRS for gastric cancer peritoneal metastasis. Other indications and application modes of intraperitoneal chemotherapy such as prophylactic or palliative HIPEC apart from CRS were not addressed. (5) Conclusion: Complete report of HIPEC parameters should be included in every publication. A consensus for dose expression either per BSA or as flat dose is desirable for comparison of the drug regimens. Despite numerous variations, we identified the most common regimens and techniques and their advantages and disadvantages according to the data in the literature. More phase I/II studies are needed to identify the best approach for HIPEC. (6) Other: This review was not supported by third parties. Full article

(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)

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12 pages, 256 KiB

Open AccessEditor’s ChoiceReview

Rethinking Resistant Hypertension

by Gabrielle Bourque and Swapnil Hiremath

J. Clin. Med. 2022, 11(5), 1455; https://doi.org/10.3390/jcm11051455 - 07 Mar 2022

Cited by 11 | Viewed by 4311

Abstract

Resistant hypertension is common and known to be a risk factor for cardiovascular events, including stroke, myocardial infarction, heart failure, and cardiovascular mortality, as well as adverse renal events, including chronic kidney disease and end-stage kidney disease. This review will discuss the definition [...] Read more.

Resistant hypertension is common and known to be a risk factor for cardiovascular events, including stroke, myocardial infarction, heart failure, and cardiovascular mortality, as well as adverse renal events, including chronic kidney disease and end-stage kidney disease. This review will discuss the definition of resistant hypertension as well as the most recent evidence regarding its diagnosis, evaluation, and management. The issue of medication non-adherence and its association with apparent treatment-resistant hypertension will be addressed. Non-pharmacological interventions for the treatment of resistant hypertension will be reviewed. Particular emphasis will be placed on pharmacological interventions, highlighting the role of mineralocorticoid receptor antagonists and sodium-glucose cotransporter-2 inhibitors and device therapy, including renal denervation, baroreceptor activation or modulation, and central arteriovenous fistula creation. Full article

(This article belongs to the Collection Hypertension: Etiology, Risk Factors, Associated Symptoms and Treatment)

15 pages, 682 KiB

Open AccessReview

Formulations of Topical Steroids in Eosinophilic Esophagitis—Current Treatment and Emerging Possibilities

by Adam Główczewski and Aneta Krogulska

J. Clin. Med. 2022, 11(5), 1454; https://doi.org/10.3390/jcm11051454 - 07 Mar 2022

Cited by 3 | Viewed by 8682

Abstract

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder characterised by eosinophilic inflammation and esophageal dysfunction symptoms. The recommended first-line treatment options are proton pump inhibitors and swallowed topical steroids (STS). However, current recommendations regarding STS are based on relatively few studies employing various [...] Read more.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder characterised by eosinophilic inflammation and esophageal dysfunction symptoms. The recommended first-line treatment options are proton pump inhibitors and swallowed topical steroids (STS). However, current recommendations regarding STS are based on relatively few studies employing various doses and formulations. Our aim was to review the STS formulations currently used in the treatment of eosinophilic esophagitis, to demonstrate in a practical way the variety of exiting application methods, and to present emerging options for STS delivery to the esophagus. After the literature review, we established that the three most commonly used STS formulations include mist from an inhaler, viscous suspensions compounded with vehicles for oral use, and a recently introduced proprietary medication in the form of orodispersible tablets. Several drug delivery technologies with potential use in EoE are under investigation. To ensure optimal adherence, the choice of formulation should be based on efficacy, patient preferences and experience of the clinician, as well as current recommendations. Further studies are needed to compare the efficacy and acceptability of existing STS types, and to develop new, well-tolerated and effective drug formulations. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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10 pages, 537 KiB

Open AccessArticle

Prognostic Factors Associated with Recovery from Recurrent Idiopathic Sudden Sensorineural Hearing Loss: Retrospective Analysis and Systematic Review

by So Young Jeon, Dae Woong Kang, Sang Hoon Kim, Jae Yong Byun and Seung Geun Yeo

J. Clin. Med. 2022, 11(5), 1453; https://doi.org/10.3390/jcm11051453 - 07 Mar 2022

Cited by 5 | Viewed by 2547

Abstract

Although idiopathic sudden sensorineural hearing loss (ISSNHL) is uncommon, recurrent ISSNHL is even rarer. The knowledge about factors associated with patient recovery from recurrent episodes is needed to counsel and treat the patients. Medical records of patients admitted for high dose oral steroid [...] Read more.

Although idiopathic sudden sensorineural hearing loss (ISSNHL) is uncommon, recurrent ISSNHL is even rarer. The knowledge about factors associated with patient recovery from recurrent episodes is needed to counsel and treat the patients. Medical records of patients admitted for high dose oral steroid therapy for recurrent ISSNHL between January 2009 and December 2021 were reviewed. Their demographic and clinical characteristics, co-morbid symptoms, and audiologic results were analyzed. The 38 patients admitted for treatment of recurrent ISSNHL included 14 men and 24 women. Recovery rates after the first and recurrent episodes of ISSNHL were 78.9% and 63.2%, respectively. Patients who recovered after recurrent episodes showed significantly higher rates of ear fullness symptoms and early treatment onset than those who did not recover (p < 0.05 each). Of the 30 patients who recovered after the first episode, those who had ear fullness symptoms (p < 0.05, odds ratio (OR) 0.1, 95% confidence interval (CI) 0.01–0.76) and who showed a lower initial hearing threshold (p < 0.05, OR 1.06, 95% CI 1.01–1.12) during the recurrent episode showed significantly better or similar recovery than after the first episode. Ear fullness symptoms and less initial hearing loss were associated with a more favorable prognosis after intial than after recurrent ISSNHL. Full article

(This article belongs to the Special Issue Hearing Disorders: Diagnosis, Management, and Future Opportunities)

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12 pages, 535 KiB

Open AccessArticle

Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients

by Pasquale Ambrosino, Paolo Parrella, Roberto Formisano, Giovanni Perrotta, Silvestro Ennio D’Anna, Marco Mosella, Antimo Papa and Mauro Maniscalco

J. Clin. Med. 2022, 11(5), 1452; https://doi.org/10.3390/jcm11051452 - 07 Mar 2022

Cited by 14 | Viewed by 2653

Abstract

Background: Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial [...] Read more.

Background: Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial dysfunction and the reduced CPET performance in COVID-19 survivors. Methods: 36 consecutive COVID-19 survivors underwent symptom-limited incremental CPET and assessment of endothelium-dependent flow-mediate dilation (FMD) according to standardized protocols. Results: A significantly higher FMD was documented in patients with a preserved, as compared to those with a reduced, exercise capacity (4.11% ± 2.08 vs. 2.54% ± 1.85, p = 0.048), confirmed in a multivariate analysis (β = 0.899, p = 0.038). In the overall study population, FMD values showed a significant Pearson’s correlation with two primary CPET parameters, namely ventilation/carbon dioxide production (VE/VCO₂) slope (r = −0.371, p = 0.026) and end-tidal carbon dioxide tension (P_ETCO₂) at peak (r = 0.439, p = 0.007). In multiple linear regressions, FMD was the only independent predictor of VE/VCO₂ slope (β = −1.308, p = 0.029) and peak P_ETCO₂ values (β = 0.779, p = 0.021). Accordingly, when stratifying our study population based on their ventilatory efficiency, patients with a ventilatory class III-IV (VE/VCO₂ slope ≥ 36) exhibited significantly lower FMD values as compared to those with a ventilatory class I-II. Conclusions: The alteration of endothelial barrier properties in systemic and pulmonary circulation may represent a key pathogenic mechanism of the reduced CPET performance in COVID-19 survivors. Personalized pharmacological and rehabilitation strategies targeting endothelial function may represent an attractive therapeutic option. Full article

(This article belongs to the Special Issue Post-COVID Symptoms in Long-Haulers: Definition, Identification, Mechanisms, and Management)

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9 pages, 1732 KiB

Open AccessArticle

Low Incidence of Hepatocellular Carcinoma after Antiviral Therapy in Patients with Chronic Hepatitis C and Hemophilia

by In Jung Kim, Sung Hwan Yoo, Sora Kim, Young Youn Cho, Ki Young Yoo, Hyung Joon Kim and Hyun Woong Lee

J. Clin. Med. 2022, 11(5), 1451; https://doi.org/10.3390/jcm11051451 - 07 Mar 2022

Viewed by 1383

Abstract

Background: Hepatocellular carcinoma (HCC) rarely develops in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). We assessed the incidence of HCC in CHC patients with hemophilia after treatment with pegylated interferon plus ribavirin (PegIFN/RBV) and direct-acting antivirals (DAAs). Methods: [...] Read more.

Background: Hepatocellular carcinoma (HCC) rarely develops in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). We assessed the incidence of HCC in CHC patients with hemophilia after treatment with pegylated interferon plus ribavirin (PegIFN/RBV) and direct-acting antivirals (DAAs). Methods: Patients (n = 202) were enrolled between March 2007 and July 2019. A total of 139 patients were treated with PegIFN/RBV (genotype 1, n = 98; genotype 2, n = 41). Sixty-three patients were treated with DAAs (genotype 1, n = 44; genotype 2, n = 19). The cumulative incidence rates of HCC were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: For genotype 1, SVR was achieved in 78.6% (77/98) and 90.9% (40/44) of patients in the PegIFN/RBV and DAAs groups, respectively. For genotype 2, SVR was achieved in 95.1% (39/41) and 94.7% (18/19) of patients in the PegIFN/RBV and DAAs groups, respectively. Six HCC cases were identified. The cumulative incidence of HCC was 4.1% at 14 years in PegIFN/RBV and 1.7% at 5 years in DAAs. The 14-year cumulative incidence of HCC was 1.9% in the SVR group and 21.7% in the no-SVR group in the PegIFN/RBV group (p < 0.001). Conclusions: Treatment with PegIFN/RBV led to stable SVR and a low incidence of HCC. Although the follow-up period was short, DAAs led to more stable SVR than PegIFN/RBV and a low incidence of HCC in CHC patients with hemophilia. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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10 pages, 844 KiB

Open AccessArticle

Cardioprotective Properties of Humoral Factors Released after Remote Ischemic Preconditioning in CABG Patients with Propofol-Free Anesthesia—A Translational Approach from Bedside to Bench

by Katharina Feige, Carolin Torregroza, Milena Gude, Patrick Maddison, Martin Stroethoff, Sebastian Roth, Giovanna Lurati Buse, Markus W. Hollmann and Ragnar Huhn

J. Clin. Med. 2022, 11(5), 1450; https://doi.org/10.3390/jcm11051450 - 07 Mar 2022

Cited by 2 | Viewed by 1575

Abstract

The cardioprotective effect of remote ischemic preconditioning (RIPC) is well detectable in experimental studies but not in clinical trials. Propofol, a commonly used sedative, is discussed to negatively influence the release of humoral factors after RIPC. Further, results from experimental and clinical trials [...] Read more.

The cardioprotective effect of remote ischemic preconditioning (RIPC) is well detectable in experimental studies but not in clinical trials. Propofol, a commonly used sedative, is discussed to negatively influence the release of humoral factors after RIPC. Further, results from experimental and clinical trials suggest various comorbidities interact with inducible cardioprotective properties of RIPC. In the present study, we went back from bedside to bench to investigate, in male patients undergoing CABG surgery, whether (1) humoral factors are released after RIPC during propofol-free anesthesia and/or (2) DM interacts with plasma factor release. Blood samples were taken from male patients with and without DM undergoing CABG surgery before (control) and after RIPC (RIPC). To investigate the release of cardioprotective humoral factors into the plasma, isolated perfused hearts of young rats (n = 5 per group) were used as a bioassay. The hearts were perfused with patients’ plasma without (Con) and with RIPC (RIPC) for 10 min (1% of coronary flow) before global ischemia and reperfusion. In additional groups, the plasma of patients with DM was administered (Con DM, RIPC DM). Infarct size was determined by TTC staining. Propofol-free RIPC plasma of male patients without DM showed an infarct size of 59 ± 5% compared to 61 ± 13% with Con plasma (p = 0.973). Infarct sizes from patients with DM showed similar results (RIPC DM: 55 ± 3% vs. Con DM: 56 ± 4%; p = 0.995). The release of humoral factors into the blood after RIPC in patients receiving propofol-free anesthesia undergoing CABG surgery did not show any cardioprotective properties independent of a pre-existing diabetes mellitus. Full article

(This article belongs to the Section Anesthesiology)

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14 pages, 465 KiB

Open AccessArticle

Associations of Depressive Symptoms and Cognition in the FINGER Trial: A Secondary Analysis of a Randomised Clinical Trial

by Elisa Neuvonen, Jenni Lehtisalo, Tiia Ngandu, Esko Levälahti, Riitta Antikainen, Tuomo Hänninen, Tiina Laatikainen, Jaana Lindström, Teemu Paajanen, Hilkka Soininen, Timo Strandberg, Jaakko Tuomilehto, Miia Kivipelto and Alina Solomon

J. Clin. Med. 2022, 11(5), 1449; https://doi.org/10.3390/jcm11051449 - 07 Mar 2022

Cited by 1 | Viewed by 1903

Abstract

Depression and cognition are associated, but the role of depressive symptoms in lifestyle interventions to prevent dementia needs further study. We investigated the intervention effect on depressive symptoms and their associations with cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment [...] Read more.

Depression and cognition are associated, but the role of depressive symptoms in lifestyle interventions to prevent dementia needs further study. We investigated the intervention effect on depressive symptoms and their associations with cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER; NCT01041989), a two-year multidomain lifestyle trial. One thousand two-hundred and sixty individuals (60–77 years) at risk for dementia were randomised into a multidomain intervention (diet, exercise, cognitive training, and vascular/metabolic risk monitoring) or control group (regular health advice). Depressive symptoms (Zung scale) and cognition (modified Neuropsychological Test Battery) were evaluated at baseline, 12, and 24 months. One thousand one-hundred and twenty-five participants had baseline Zung data. Mean Zung score decreased 0.73 (SD 5.6) points in the intervention and 0.36 (5.6) points in the control group, with nonsignificant between-group difference (group × time coefficient −0.006, 95% CI −0.019 to 0.007). Overall, higher baseline Zung score was associated with less improvement in global cognition (−0.140, p = 0.005) and memory (−0.231, p = 0.005). Participants with clinically significant baseline depressive symptoms (Zung ≥ 40 points) had less intervention benefit to executive functioning (group × time × Zung −0.096, 95% CI −0.163 to −0.028). Change in Zung score was not associated with change in cognition. Clinically significant depressive symptoms warrant more attention when designing dementia-prevention interventions. Full article

(This article belongs to the Section Mental Health)

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15 pages, 2157 KiB

Open AccessReview

Comparison between Prehospital Mechanical Cardiopulmonary Resuscitation (CPR) Devices and Manual CPR for Out-of-Hospital Cardiac Arrest: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis

by Cheng-Ying Chiang, Ket-Cheong Lim, Pei Chun Lai, Tou-Yuan Tsai, Yen Ta Huang and Ming-Jen Tsai

J. Clin. Med. 2022, 11(5), 1448; https://doi.org/10.3390/jcm11051448 - 07 Mar 2022

Cited by 10 | Viewed by 5057

Abstract

In pre-hospital settings, efficient cardiopulmonary resuscitation (CPR) is challenging; therefore, the application of mechanical CPR devices continues to increase. However, the evidence of the benefits of using mechanical CPR devices in pre-hospital settings for adult out-of-hospital cardiac arrest (OHCA) is controversial. This meta-analysis [...] Read more.

In pre-hospital settings, efficient cardiopulmonary resuscitation (CPR) is challenging; therefore, the application of mechanical CPR devices continues to increase. However, the evidence of the benefits of using mechanical CPR devices in pre-hospital settings for adult out-of-hospital cardiac arrest (OHCA) is controversial. This meta-analysis compared the effects of mechanical and manual CPR applied in the pre-hospital stage on clinical outcomes after OHCA. Cochrane Library, PubMed, Embase, and ClinicalTrials.gov were searched from inception until October 2021. Studies comparing mechanical and manual CPR applied in the pre-hospital stage for survival outcomes of adult OHCA were eligible. Data abstraction, quality assessment, meta-analysis, trial sequential analysis (TSA), and grading of recommendations, assessment, development, and evaluation were conducted. Seven randomized controlled and 15 observational studies were included. Compared to manual CPR, pre-hospital use of mechanical CPR showed a positive effect in achieving return of spontaneous circulation (ROSC) and survival to admission. No difference was found in survival to discharge and discharge with favorable neurological status, with inconclusive results in TSA. In conclusion, pre-hospital use of mechanical CPR devices may benefit adult OHCA in achieving ROSC and survival to admission. With low certainty of evidence, more well-designed large-scale randomized controlled trials are needed to validate these findings. Full article

(This article belongs to the Special Issue Cardiopulmonary Resuscitation: Clinical Updates and Perspectives)

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10 pages, 239 KiB

Open AccessReview

HIV-Associated Lymphomas: Progress and New Challenges

by Georgios N. Pongas and Juan C. Ramos

J. Clin. Med. 2022, 11(5), 1447; https://doi.org/10.3390/jcm11051447 - 07 Mar 2022

Cited by 6 | Viewed by 2345

Abstract

The association of human immunodeficiency virus (HIV) and aggressive lymphomas was first reported in 1982. Before the development of effective HIV antiviral therapy, the incidence and the mortality of these lymphomas was high, with patients frequently succumbing to the disease. More lately, the [...] Read more.

The association of human immunodeficiency virus (HIV) and aggressive lymphomas was first reported in 1982. Before the development of effective HIV antiviral therapy, the incidence and the mortality of these lymphomas was high, with patients frequently succumbing to the disease. More lately, the combination of cART with chemoimmunotherapy significantly improved the survival outcome of the HIV-lymphomas. In this review, we discuss on describing the incidence of HIV-associated lymphomas, their clinical features, and the latest advances in the management of the various lymphoma subtypes. Full article

(This article belongs to the Special Issue Advances in the Management of Aggressive Lymphomas)

14 pages, 1038 KiB

Open AccessArticle

Comparing the Occurrence of Healthcare-Associated Infections in Patients with and without COVID-19 Hospitalized during the Pandemic: A 16-Month Retrospective Cohort Study in a Hospital Intensive Care Unit

by Claudia Isonne, Valentina Baccolini, Giuseppe Migliara, Mariateresa Ceparano, Francesco Alessandri, Giancarlo Ceccarelli, Guglielmo Tellan, Francesco Pugliese, Maria De Giusti, Corrado De Vito, Carolina Marzuillo, Paolo Villari, Lavinia Camilla Barone, Dara Giannini, Daniela Marotta, Mattia Marte, Elena Mazzalai, Irma Germani, Arianna Bellini, Andrea Bongiovanni, Marta Castellani, Ludovica D’Agostino, Andrea De Giorgi, Chiara De Marchi, Elisa Mazzeo, Shadi Orlandi, Matteo Piattoli, Eleonora Ricci, Leonardo Maria Siena, Alessandro Territo and Stefano Zanni Show full author list Hide full author list

J. Clin. Med. 2022, 11(5), 1446; https://doi.org/10.3390/jcm11051446 - 07 Mar 2022

Cited by 9 | Viewed by 2394

Abstract

The COVID-19 pandemic has increased the healthcare-associated infection (HAI) risk in intensive care unit (ICU) patients. However, a comparison between patients with and without COVID-19 in terms of HAI incidence has been rarely explored. In this study, we characterized the occurrence of HAI [...] Read more.

The COVID-19 pandemic has increased the healthcare-associated infection (HAI) risk in intensive care unit (ICU) patients. However, a comparison between patients with and without COVID-19 in terms of HAI incidence has been rarely explored. In this study, we characterized the occurrence of HAI among patients with and without COVID-19 admitted to the ICU of the Umberto I hospital of Rome during the first 16 months of the pandemic and also identified risk factors for HAI acquisition. Patients were divided into four groups according to their ICU admission date. A multivariable conditional risk set regression model for multiple events was constructed for each admission period. Adjusted hazard ratios and 95% confidence intervals were calculated. Overall, 352 COVID-19 and 130 non-COVID-19 patients were included, and a total of 361 HAIs were recorded. We found small differences between patients with and without COVID-19 in the occurrence and type of HAI, but the infections in the two cohorts mostly involved different microorganisms. The results indicate that patient management was likely an important factor influencing the HAI occurrence during the pandemic. Effective prevention and control strategies to reduce HAI rates should be implemented. Full article

(This article belongs to the Special Issue COVID-19 in the Intensive Care Unit)

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10 pages, 285 KiB

Open AccessArticle

Hyperuricemia Is Associated with Significant Liver Fibrosis in Subjects with Nonalcoholic Fatty Liver Disease, but Not in Subjects without It

by Pei-Chia Yen, Yu-Tsung Chou, Chung-Hao Li, Zih-Jie Sun, Chih-Hsing Wu, Yin-Fan Chang, Feng-Hwa Lu, Yi-Ching Yang, Chih-Jen Chang and Jin-Shang Wu

J. Clin. Med. 2022, 11(5), 1445; https://doi.org/10.3390/jcm11051445 - 07 Mar 2022

Cited by 9 | Viewed by 2980

Abstract

Liver fibrosis is associated with liver-related outcomes, yet often remains underdiagnosed in primary care settings. Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD), but the relationship between hyperuricemia and liver fibrosis remains unclear. Data on individuals without NAFLD is also limited. We [...] Read more.

Liver fibrosis is associated with liver-related outcomes, yet often remains underdiagnosed in primary care settings. Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD), but the relationship between hyperuricemia and liver fibrosis remains unclear. Data on individuals without NAFLD is also limited. We investigated the association between hyperuricemia and liver fibrosis in subjects with and without NAFLD. This study recruited 11,690 relevant participants from a health-checkup center. NAFLD was based on ultrasonography. Hyperuricemia was defined as serum uric acid > 6.0 mg/dL in women and >7.0 mg/dL in men. Significant liver fibrosis was diagnosed with the aspartate aminotransferase to platelet ratio index ≥0.5. The following were positively associated with significant liver fibrosis: hyperuricemia (p = 0.001), age ≥ 65 years (p < 0.001), male gender (p < 0.001), obesity (p = 0.009), hypertension (p = 0.002), diabetes (p < 0.001), and NAFLD (p < 0.001) in the logistic regression. The positive association of hyperuricemia with significant liver fibrosis remained in subjects with NAFLD (p = 0.001), but not in subjects without NAFLD. In conclusion, hyperuricemia increased the associated risk of significant liver fibrosis. The positively associated risk existed in subjects with NAFLD, but not in those without it. Full article

(This article belongs to the Topic Liver Fibrosis and Cirrhosis)

8 pages, 932 KiB

Open AccessArticle

Efficacy of Lenvatinib and Sorafenib in the Real-World First-Line Treatment of Advanced-Stage Hepatocellular Carcinoma in a Taiwanese Population

by Shou-Wu Lee, Sheng-Shun Yang, Han-Chung Lien, Yen-Chun Peng, Chung-Wang Ko and Teng-Yu Lee

J. Clin. Med. 2022, 11(5), 1444; https://doi.org/10.3390/jcm11051444 - 06 Mar 2022

Cited by 12 | Viewed by 2470

Abstract

Aim: Currently, atezolizumab combined with bevacizumab is the standard first-line treatment for unresectable hepatocellular carcinoma (HCC), but lenvatinib or sorafenib are still recommended for these patients for some reasons. The aim of the study was to determine the outcomes of Taiwanese patients with [...] Read more.

Aim: Currently, atezolizumab combined with bevacizumab is the standard first-line treatment for unresectable hepatocellular carcinoma (HCC), but lenvatinib or sorafenib are still recommended for these patients for some reasons. The aim of the study was to determine the outcomes of Taiwanese patients with advanced-stage HCC who received lenvatinib or sorafenib. Methods: Data on patients with BCLC stage C HCC who were receiving lenvatinib or sorafenib as the first-line therapy from May 2018 to August 2020 was collected. The individuals with lenvatinib and sorafenib were propensity score-matched at a ratio of 1:2. Results: A total of 22 patients with lenvatinib and 44 patients with sorafenib were enrolled. The ORR (36.4% vs. 11.4%, p = 0.023) and DCR (81.9% vs. 56.9%, p = 0.039) were both higher in the lenvatinib group compared with the sorafenib group. The median overall survival (OS) of the lenvatinib group and the sorafenib group was 9.36 months and 8.36 months, respectively. The best median OS was detected in patients receiving lenvatinib and having an objective tumor response (11.29 months), with a significant difference (p = 0.031) compared with the other groups. Conclusion: Lenvatinib, compared to sorafenib, had better ORR and DCR, but similar OS, in Taiwanese patients with advanced-stage HCC. The patients with an objective tumor response had a better OS. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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9 pages, 1221 KiB

Open AccessArticle

OCT Angiography Fractal Analysis of Choroidal Neovessels Secondary to Central Serous Chorioretinopathy, in a Caucasian Cohort

by Rita Serra, Antonio Pinna, Francine Behar-Cohen and Florence Coscas

J. Clin. Med. 2022, 11(5), 1443; https://doi.org/10.3390/jcm11051443 - 06 Mar 2022

Cited by 5 | Viewed by 1777

Abstract

Central serous chorioretinopathy (CSCR) can be complicated by different types of choroidal neovascularization (CNV). The purpose of this study was to investigate the incidence and quantitative optical coherence tomography angiography (OCT-A) features of CSCR-related CNVs. Methods: This was a retrospective multicenter study including [...] Read more.

Central serous chorioretinopathy (CSCR) can be complicated by different types of choroidal neovascularization (CNV). The purpose of this study was to investigate the incidence and quantitative optical coherence tomography angiography (OCT-A) features of CSCR-related CNVs. Methods: This was a retrospective multicenter study including 102 eyes of 102 Caucasian patients with acute or complex CSCR. All patients underwent a comprehensive ophthalmological examination. Quantitative OCT-A parameters, including vascular perfusion density (VPD), fractal dimension (FD), and lacunarity (LAC), were measured in CNV eyes. Results: Forty eyes (39.2%) had acute CSCR, whereas the remaining sixty-two (60.8%) had complex CSCR. CNV was observed in 37 (36.27%) eyes, all of which had the complex form. CNVs were classified as type 1 CNV in 11/37 (29.73%) cases and as polypoidal choroidal vasculopathy (PCV) in the remaining 26/37 (70.27%). Overall, the mean VPD, FD, and LAC of CSCR-related CNVs were 0.52 ± 0.20%, 1.44 ± 0.12, and 2.40 ± 1.1, respectively. No significant difference between type 1 CNV and PCV was found. Conclusion: Complex CSCR is often complicated by type 1 CNV and PCV with similar neovascular architecture and branching complexity, a finding supporting the idea that they might be different stages of the same neovascular process. Future OCT-A fractal analysis-based studies that also include other relevant parameters, such as demographics, presentation, morphology on multimodal imaging, and response to treatment, are necessary before drawing any definitive conclusions. Full article

(This article belongs to the Special Issue Optical Coherence Tomography Imaging: Advances in Ophthalmology)

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15 pages, 3425 KiB

Open AccessArticle

A Computational Text Mining-Guided Meta-Analysis Approach to Identify Potential Xerostomia Drug Targets

by Micaela F. Beckman, Elizabeth J. Brennan, Chika K. Igba, Michael T. Brennan, Farah B. Mougeot and Jean-Luc C. Mougeot

J. Clin. Med. 2022, 11(5), 1442; https://doi.org/10.3390/jcm11051442 - 05 Mar 2022

Cited by 4 | Viewed by 3112

Abstract

Xerostomia (subjective complaint of dry mouth) is commonly associated with salivary gland hypofunction. Molecular mechanisms associated with xerostomia pathobiology are poorly understood, thus hampering drug development. Our objectives were to (i) use text-mining tools to investigate xerostomia and dry mouth concepts, (ii) identify [...] Read more.

Xerostomia (subjective complaint of dry mouth) is commonly associated with salivary gland hypofunction. Molecular mechanisms associated with xerostomia pathobiology are poorly understood, thus hampering drug development. Our objectives were to (i) use text-mining tools to investigate xerostomia and dry mouth concepts, (ii) identify associated molecular interactions involving genes as candidate drug targets, and (iii) determine how drugs currently used in clinical trials may impact these genes and associated pathways. PubMed and PubMed Central were used to identify search terms associated with xerostomia and/or dry mouth. Search terms were queried in pubmed2ensembl. Protein–protein interaction (PPI) networks were determined using the gene/protein network visualization program search tool for recurring instances of neighboring genes (STRING). A similar program, Cytoscape, was used to determine PPIs of overlapping gene sets. The drug–gene interaction database (DGIdb) and the clinicaltrials.gov database were used to identify potential drug targets from the xerostomia/dry mouth PPI gene set. We identified 64 search terms in common between xerostomia and dry mouth. STRING confirmed PPIs between identified genes (CL = 0.90). Cytoscape analysis determined 58 shared genes, with cytokine–cytokine receptor interaction representing the most significant pathway (p = 1.29 × 10⁻²³) found in the Kyoto encyclopedia of genes and genomes (KEGG). Fifty-four genes in common had drug interactions, per DGIdb analysis. Eighteen drugs, targeting the xerostomia/dry mouth PPI network, have been evaluated for xerostomia, head and neck cancer oral complications, and Sjögren’s Syndrome. The PPI network genes IL6R, EGFR, NFKB1, MPO, and TNFSF13B constitute a possible biomarker signature of xerostomia. Validation of the candidate biomarkers is necessary to better stratify patients at the genetic and molecular levels to facilitate drug development or to monitor response to treatment. Full article

(This article belongs to the Special Issue Diseases of the Salivary Glands—Part II)

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12 pages, 1274 KiB

Open AccessSystematic Review

How Is Spinal Cord Function Measured in Degenerative Cervical Myelopathy? A Systematic Review

by Khadija H. Soufi, Tess M. Perez, Alexis O. Umoye, Jamie Yang, Maria Burgos and Allan R. Martin

J. Clin. Med. 2022, 11(5), 1441; https://doi.org/10.3390/jcm11051441 - 05 Mar 2022

Cited by 10 | Viewed by 2308

Abstract

Degenerative cervical myelopathy (DCM) is a prevalent condition in which spinal degeneration causes cord compression and neurological dysfunction. The spinal cord is anatomically complex and operates in conjunction with the brain, the musculoskeletal system, and numerous organs to control numerous functions, including simple [...] Read more.

Degenerative cervical myelopathy (DCM) is a prevalent condition in which spinal degeneration causes cord compression and neurological dysfunction. The spinal cord is anatomically complex and operates in conjunction with the brain, the musculoskeletal system, and numerous organs to control numerous functions, including simple and coordinated movement, sensation, and autonomic functions. As a result, accurate and comprehensive measurement of spinal cord function in patients with DCM and other spinal pathologies is challenging. This project aimed to summarize the neurological, functional, and quality of life (QoL) outcome measures currently in use to quantify impairment in DCM. A systematic review of the literature was performed to identify prospective studies with at least 100 DCM subjects that utilized one or more quantitative neurological, functional, or QoL outcome measures. A total of 148 studies were identified. The most commonly used instruments were subjective functional scales including the Japanese Orthopedic Association (JOA) (71 studies), modified JOA (mJOA) (66 studies), Neck Disability Index (NDI) (54 studies), and Nurick (39 studies), in addition to the QoL measure Short-Form-36 (SF-36, 52 studies). A total of 92% (320/349) of all outcome measures were questionnaires, whereas objective physical testing of neurological function (strength, gait, balance, dexterity, or sensation) made up 8% (29/349). Studies utilized an average of 2.36 outcomes measures, while 58 studies (39%) utilized only a single outcome measure. No studies were identified that specifically assessed the dorsal column sensory pathway or respiratory, bowel, or sexual function. In the past five years, there were no significant differences in the number of total, functional, or QoL outcome measures used, but physical testing of neurological function has increased (p = 0.005). Prior to 2017, cervical spondylotic myelopathy (CSM) was the most frequently used term to describe the study population, whereas in the last five years, DCM has become the preferred terminology. In conclusion, clinical studies of DCM typically utilize limited data to characterize impairment, often relying on subjective, simplistic, and non-specific measures that do not reflect the complexity of the spinal cord. Although accurate measurement of impairment in DCM is challenging, it is necessary for early diagnosis, monitoring for deterioration, and quantifying recovery after therapeutic interventions. Clinical decision-making and future clinical studies in DCM should employ a combination of subjective and objective assessments to capture the multitude of spinal cord functions to improve clinical management and inform practice guidelines. Full article

(This article belongs to the Special Issue Management of Degenerative Cervical Myelopathy and Spinal Cord Injury)

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9 pages, 599 KiB

Open AccessArticle

A Retrospective Study of Postictal Suppression during Electroconvulsive Therapy

by Virginie Moulier, Julien Guehl, Emilie Evêque-Mourroux, Pierre Quesada and Maud Rothärmel

J. Clin. Med. 2022, 11(5), 1440; https://doi.org/10.3390/jcm11051440 - 05 Mar 2022

Cited by 3 | Viewed by 1592

Abstract

Background: electroconvulsive therapy (ECT) is the most effective treatment in treatment-resistant depression (TRD), but its response remains partial. Identifying useful indicators to guide decision making for treatment and improve clinical response remains a major issue. The objective of the present retrospective study was [...] Read more.

Background: electroconvulsive therapy (ECT) is the most effective treatment in treatment-resistant depression (TRD), but its response remains partial. Identifying useful indicators to guide decision making for treatment and improve clinical response remains a major issue. The objective of the present retrospective study was to determine if clinical response—early (after 5 ECT sessions) or longer-term (after 12 ECT sessions)—was associated with postictal suppression during the first ECT course and/or with postictal suppression frequency during the whole ECT course. Methods: in a retrospective study, the data of 42 patients suffering from treatment-resistant depression and receiving at least 5 ECT sessions were collected. Two sessions per week of bitemporal brief-pulse ECT sessions were administered to patients. Each of the electroencephalography (EEG) recordings were assessed to determine the presence of postictal suppression. Results: the postictal suppression from the first ECT session predicted a better long-term clinical response (after 12 ECT sessions), but not early clinical response (after only 5 ECT sessions). The postictal suppression frequency was associated with neither the short- nor the long-term clinical response. In addition, postictal suppression and short-term cognitive performances were not associated. Conclusions: this EEG indicator is clinically useful if it appears in the first ECT sessions, but it is no longer relevant in the following sessions. Full article

(This article belongs to the Collection Advances in Neurostimulation: Understanding of the Mechanisms and Clinical Applications)

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13 pages, 2390 KiB

Open AccessArticle

Expression of Macrophage Scavenger Receptor (MSR1) in Peripheral Blood Cells from Patients with Different Respiratory Diseases: Beyond Monocytes

by Selene Baos, Lucía Cremades-Jimeno, María López-Ramos, María Ángeles de Pedro, Silvia A. Uriarte, Joaquín Sastre, Nicolás González-Mangado, María Jesús Rodríguez-Nieto, Germán Peces-Barba and Blanca Cárdaba

J. Clin. Med. 2022, 11(5), 1439; https://doi.org/10.3390/jcm11051439 - 05 Mar 2022

Cited by 7 | Viewed by 2314

Abstract

Background: Macrophage scavenger receptor 1 (MSR1) has mostly been described in macrophages, but we previously found a significant gene expression increase in peripheral blood mononuclear cells (PBMCs) of asthmatic patients. Objective: To confirm those results and to define its cellular origin in PBMCs. [...] Read more.

Background: Macrophage scavenger receptor 1 (MSR1) has mostly been described in macrophages, but we previously found a significant gene expression increase in peripheral blood mononuclear cells (PBMCs) of asthmatic patients. Objective: To confirm those results and to define its cellular origin in PBMCs. Methods: Four groups of subjects were studied: healthy controls (C), nonallergic asthmatic (NA), allergic asthmatic (AA), and chronic obstructive pulmonary disease (COPD) patients. RNA was extracted from PBMCs. MSR1 gene expression was analyzed by RT-qPCR. The presence of MSR1 on the cellular surface of PBMC cellular subtypes was analyzed by confocal microscopy and flow cytometry. Results: MSR1 gene expression was significantly increased in the three clinical conditions compared to the healthy control group, with substantial variations according to disease type and severity. MSR1 expression on T cells (CD4⁺ and CD8⁺), B cells, and monocytes was confirmed by confocal microscopy and flow cytometry. In all clinical groups, the four immune cell subtypes studied expressed MSR1, with a greater expression on B lymphocytes and monocytes, exhibiting differences according to disease and severity. Conclusions: This is the first description of MSR1’s presence on lymphocytes’ surfaces and reinforces the potential role of MSR1 as a player in asthma and COPD. Full article

(This article belongs to the Section Pulmonology)

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7 pages, 487 KiB

Open AccessArticle

Elective Neck Dissection during Salvage Total Laryngectomy: Personal Experience

by Jacopo Galli, Giovanni Di Cintio, Stefano Settimi, Antonio Salvati, Claudio Parrilla, Giovanni Almadori and Gaetano Paludetti

J. Clin. Med. 2022, 11(5), 1438; https://doi.org/10.3390/jcm11051438 - 05 Mar 2022

Cited by 1 | Viewed by 1499

Abstract

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to [...] Read more.

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to evaluate the survival rate and the main oncologic outcomes of cN0 patients who underwent salvage total laryngectomy and elective bilateral neck dissection. In this retrospective observational study, we enrolled 80 cN0 patients affected by recurrent laryngeal cancer and who underwent salvage total laryngectomy and bilateral selective elective neck dissection. Several parameters were collected in order to find prognostic factors; finally, postoperative complications were reviewed and survival analysis was performed. Occult lymph node metastases were reported in 18 out of 80 patients (22.5%). Significant statistical correlation between lymphovascular invasion (p = 0.007), perineural invasion (p = 0.025) and occult nodal metastasis was found. Other variables (glottic subsite of recurrence, clinical T, pathological T, previous chemotherapy) were not significantly predictive of occult nodal metastasis. The 5-year OS, DSS, and RFS were 50.4%, 64.7%, and 63.4%, respectively. In conclusion, our single-institution data on a large cohort of patients, suggest performing routinely elective selective bilateral neck dissection during salvage total laryngectomy in cN0 patients due to the biological attitude of the tumor to spread to cervical nodes, considering an acceptable complications rate. Full article

(This article belongs to the Section Otolaryngology)

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13 pages, 913 KiB

Open AccessArticle

Clinical Characteristics of COVID-19 Patients and Application to an Artificial Intelligence System for Disease Surveillance

by Ying-Chuan Wang, Dung-Jang Tsai, Li-Chen Yen, Ya-Hsin Yao, Tsung-Ta Chiang, Chun-Hsiang Chiu, Te-Yu Lin, Kuo-Ming Yeh and Feng-Yee Chang

J. Clin. Med. 2022, 11(5), 1437; https://doi.org/10.3390/jcm11051437 - 05 Mar 2022

Cited by 1 | Viewed by 2083

Abstract

During the coronavirus disease (COVID-19) pandemic, we admitted suspected or confirmed COVID-19 patients to our isolation wards between 2 March 2020 and 4 May 2020, following a well-designed and efficient assessment protocol. We included 217 patients suspected of COVID-19, of which 27 had [...] Read more.

During the coronavirus disease (COVID-19) pandemic, we admitted suspected or confirmed COVID-19 patients to our isolation wards between 2 March 2020 and 4 May 2020, following a well-designed and efficient assessment protocol. We included 217 patients suspected of COVID-19, of which 27 had confirmed COVID-19. The clinical characteristics of these patients were used to train artificial intelligence (AI) models such as support vector machine (SVM), decision tree, random forest, and artificial neural network for diagnosing COVID-19. When analyzing the performance of the models, SVM showed the highest sensitivity (SVM vs. decision tree vs. random forest vs. artificial neural network: 100% vs. 42.86% vs. 28.57% vs. 71.43%), while decision tree and random forest had the highest specificity (SVM vs. decision tree vs. random forest vs. artificial neural network: 88.37% vs. 100% vs. 100% vs. 94.74%) in the diagnosis of COVID-19. With the aid of AI models, physicians may identify COVID-19 patients earlier, even with few baseline data available, and segregate infected patients earlier to avoid hospital cluster infections and to ensure the safety of medical professionals and ordinary patients in the hospital. Full article

(This article belongs to the Section Infectious Diseases)

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Open AccessArticle

Accuracy of a Computer-Aided Dynamic Navigation System in the Placement of Zygomatic Dental Implants: An In Vitro Study

by Juan Ramón González Rueda, Irene García Ávila, Víctor Manuel de Paz Hermoso, Elena Riad Deglow, Álvaro Zubizarreta-Macho, Jesús Pato Mourelo, Javier Montero Martín and Sofía Hernández Montero

J. Clin. Med. 2022, 11(5), 1436; https://doi.org/10.3390/jcm11051436 - 05 Mar 2022

Cited by 6 | Viewed by 2030

Abstract

The objective of this in vitro study was to evaluate and compare the accuracy of zygomatic dental implant (ZI) placement carried out using a dynamic navigation system. Materials and Methods: Forty (40) ZIs were randomly distributed into one of two study groups: (A) [...] Read more.

The objective of this in vitro study was to evaluate and compare the accuracy of zygomatic dental implant (ZI) placement carried out using a dynamic navigation system. Materials and Methods: Forty (40) ZIs were randomly distributed into one of two study groups: (A) ZI placement via a computer-aided dynamic navigation system (n = 20) (navigation implant (NI)); and (B) ZI placement using a conventional free-hand technique (n = 20) (free-hand implant (FHI)). A cone-beam computed tomography (CBCT) scan of the existing situation was performed preoperatively to plan the surgical approach for the computer-aided study group. Four zygomatic dental implants were placed in anatomically based polyurethane models (n = 10) manufactured by stereolithography, and a postoperative CBCT scan was performed. Subsequently, the preoperative planning and postoperative CBCT scans were added to dental implant software to analyze the coronal entry point, apical end point, and angular deviations. Results were analyzed using the Student’s t-test. Results: The results showed statistically significant differences in the apical end-point deviations between FHI and NI (p = 0.0018); however, no statistically significant differences were shown in the coronal entry point (p = 0.2617) or in the angular deviations (p = 0.3132). Furthermore, ZIs placed in the posterior region showed more deviations than the anterior region at the coronal entry point, apical end point, and angular level. Conclusions: The conventional free-hand technique enabled more accurate placement of ZIs than the computer-assisted surgical technique. In addition, placement of ZIs in the anterior region was more accurate than that in the posterior region. Full article

(This article belongs to the Special Issue Current Trends and Future Directions in Prosthetic and Implant Dentistry in the Digital Era)

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J. Clin. Med., Volume 11, Issue 5 (March-1 2022) – 317 articles

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