Journal of Clinical Medicine

11 pages, 247 KiB

Open AccessArticle

Correlations between Sleep Bruxism and Temporomandibular Disorders

by Brigitte Ohlmann, Moritz Waldecker, Michael Leckel, Wolfgang Bömicke, Rouven Behnisch, Peter Rammelsberg and Marc Schmitter

J. Clin. Med. 2020, 9(2), 611; https://doi.org/10.3390/jcm9020611 - 24 Feb 2020

Cited by 34 | Viewed by 5676

Abstract

The aim of this study was to identify correlations between sleep bruxism (SB) and temporomandibular disorders (TMD) as diagnosed by means of the research diagnostic criteria for temporomandibular disorders (RDC/TMD). Sleep bruxism was diagnosed on the basis of I) validated questionnaires, II) clinical [...] Read more.

The aim of this study was to identify correlations between sleep bruxism (SB) and temporomandibular disorders (TMD) as diagnosed by means of the research diagnostic criteria for temporomandibular disorders (RDC/TMD). Sleep bruxism was diagnosed on the basis of I) validated questionnaires, II) clinical symptoms, and III) electromyographic/electrocardiographic data. A total of 110 subjects were included in the study. Fifty-eight patients were identified as bruxers and 52 as nonbruxers. A psychosocial assessment was also performed. An RDC/TMD group-I diagnosis (myofascial pain) was made for 10 out of 58 bruxers, whereas none of the nonbruxers received a diagnosis of this type. No significant differences were found between bruxers and nonbruxers with regard to RDC/TMD group-II (disc displacement) and group-III (arthralgia, arthritis, arthrosis) diagnoses. Somatization was significantly more common among bruxers than nonbruxers. Multivariate logistic regression analysis revealed that somatization was the only factor significantly correlated with the diagnosis of myofascial pain. The results of this study indicate a correlation between myofascial pain, as diagnosed using the RDC/TMD, and somatization. It seems that somatization is a stronger predictor of an RDC/TMD diagnosis of myofascial pain than sleep bruxism is. Full article

(This article belongs to the Special Issue Sleep Bruxism—The Controversial Sleep Movement Activity)

12 pages, 1321 KiB

Open AccessArticle

A Mortality Prediction Rule for Hematology Patients with Invasive Aspergillosis Based on Serum Galactomannan Kinetics

by Toine Mercier, Joachim Wera, Louis Y. A. Chai, Katrien Lagrou and Johan Maertens

J. Clin. Med. 2020, 9(2), 610; https://doi.org/10.3390/jcm9020610 - 24 Feb 2020

Cited by 11 | Viewed by 2853

Abstract

In invasive aspergillosis (IA), an early and adequate assessment of the response to the initial antifungal therapy remains problematic. We retrospectively analyzed 206 hematology patients with proven or probable IA, and collected serial serum galactomannan (sGM) values and survival status through week 6 [...] Read more.

In invasive aspergillosis (IA), an early and adequate assessment of the response to the initial antifungal therapy remains problematic. We retrospectively analyzed 206 hematology patients with proven or probable IA, and collected serial serum galactomannan (sGM) values and survival status through week 6 and week 12. We created a model for survival at week 6 based on the sGM taken at baseline and on early sGM kinetics. This resulted in a rule predicting that patients with a baseline sGM index >1.4, who failed to lower that index to <0.5 after one week, had a mortality rate of 48.1% at week 6. Conversely, patients presenting with a baseline sGM index ≤1.4 that obtained a negative sGM (<0.5) after one week, had a mortality that was almost five times lower at only 10.1% by week 6. These findings were confirmed in an external cohort from an independent prospective study. In conclusion, sGM kinetics correlate well with treatment outcomes in hematology patients with IA. We present a rule which is easy to use at the bedside and has good accuracy in predicting week 6 survival. Full article

(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)

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14 pages, 440 KiB

Open AccessArticle

Risk Factors for Postural and Functional Balance Impairment in Patients with Chronic Obstructive Pulmonary Disease

by Jaekwan K. Park, Nicolaas E. P. Deutz, Clayton L. Cruthirds, Sarah K. Kirschner, Hangue Park, Michael L. Madigan and Mariëlle P. K. J. Engelen

J. Clin. Med. 2020, 9(2), 609; https://doi.org/10.3390/jcm9020609 - 24 Feb 2020

Cited by 11 | Viewed by 3485

Abstract

Reduced balance function has been observed during balance challenging conditions in the chronic obstructive pulmonary disease (COPD) population and is associated with an increased risk of falls. This study aimed to examine postural balance during quiet standing with eyes open and functional balance [...] Read more.

Reduced balance function has been observed during balance challenging conditions in the chronic obstructive pulmonary disease (COPD) population and is associated with an increased risk of falls. This study aimed to examine postural balance during quiet standing with eyes open and functional balance in a heterogeneous group of COPD and non-COPD (control) subjects, and to identify risk factors underlying balance impairment using a large panel of methods. In COPD and control subjects, who were mostly overweight and sedentary, postural and functional balance were assessed using center-of-pressure displacement in anterior-posterior (AP) and medio-lateral (ML) directions, and the Berg Balance Scale (BBS), respectively. COPD showed 23% greater AP sway velocity (p = 0.049). The presence of oxygen therapy, fat mass, reduced neurocognitive function, and the presence of (pre)diabetes explained 71% of the variation in postural balance in COPD. Transcutaneous oxygen saturation, a history of exacerbation, and gait speed explained 83% of the variation in functional balance in COPD. Neurocognitive dysfunction was the main risk factor for postural balance impairment in the control group. This suggests that specific phenotypes of COPD patients can be identified based on their type of balance impairment. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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9 pages, 487 KiB

Open AccessArticle

Impact of Having a Planned Additional Operation at Time of Liver Transplant on Graft and Patient Outcomes

by Shirin Salimi, Keval Pandya, Vinay Sastry, Claire West, Susan Virtue, Mark Wells, Michael Crawford, Carlo Pulitano, Geoffrey W. McCaughan, Avik Majumdar, Simone I. Strasser and Ken Liu

J. Clin. Med. 2020, 9(2), 608; https://doi.org/10.3390/jcm9020608 - 24 Feb 2020

Cited by 1 | Viewed by 1922

Abstract

Advances in liver transplantation (LT) have allowed for expanded indications and increased surgical complexity. In select cases, additional surgery may be performed at time of LT rather than prior to LT due to the significant risks associated with advanced liver disease. We retrospectively [...] Read more.

Advances in liver transplantation (LT) have allowed for expanded indications and increased surgical complexity. In select cases, additional surgery may be performed at time of LT rather than prior to LT due to the significant risks associated with advanced liver disease. We retrospectively studied the characteristics and outcomes of patients who underwent an additional planned abdominal or cardiac operation at time of LT between 2011–2019. An additional operation (LT+) was defined as a planned operation performed under the same anesthetic as the LT but not directly related to the LT. In total, 547 patients were included in the study, of which 20 underwent LT+ (4%). Additional operations included 10 gastrointestinal, 5 splenic, 3 cardiac, and 2 other abdominal operations. Baseline characteristics between LT and LT+ groups were similar. The median total operating time was significantly longer in LT+ compared to LT only (451 vs. 355 min, p = 0.002). Graft and patient survival, intraoperative blood loss, transfusion of blood products, length of hospital stay, and post-operative complications were not significantly different between groups. In carefully selected patients undergoing LT, certain additional operations performed at the same time appear to be safe with equivalent short-term outcomes and liver graft survival as those undergoing LT alone Full article

(This article belongs to the Special Issue Liver Transplantation)

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11 pages, 1033 KiB

Open AccessArticle

Aortic Valve Calcium Associates with All-Cause Mortality Independent of Coronary Artery Calcium and Inflammation in Patients with End-Stage Renal Disease

by Lu Dai, Oscar Plunde, Abdul Rashid Qureshi, Bengt Lindholm, Torkel B. Brismar, Leon J. Schurgers, Magnus Söderberg, Jonaz Ripsweden, Magnus Bäck and Peter Stenvinkel

J. Clin. Med. 2020, 9(2), 607; https://doi.org/10.3390/jcm9020607 - 24 Feb 2020

Cited by 9 | Viewed by 2554

Abstract

Background: Aortic valve calcium (AVC) and coronary artery calcium (CAC) are common complications in end-stage renal disease (ESRD). We investigated the prognostic significance of overlapping presence of AVC and CAC, and whether AVC was associated with all-cause mortality independent of the presence of [...] Read more.

Background: Aortic valve calcium (AVC) and coronary artery calcium (CAC) are common complications in end-stage renal disease (ESRD). We investigated the prognostic significance of overlapping presence of AVC and CAC, and whether AVC was associated with all-cause mortality independent of the presence of CAC in ESRD. Methods: 259 ESRD patients (median age 55 years, 67% males) undergoing cardiac computed tomography were included. Framingham risk score (FRS), presence of cardiovascular disease (CVD), statin use, nutritional status and other relevant laboratory data were determined at baseline. During follow-up for median 36 months, 44 patients died, and 68 patients underwent renal transplantation. Results: The baseline overlap presence of AVC and CAC was 37%. Multivariate regression analysis showed that FRS (odds ratio (OR) 2.25; 95% confidence interval (95% CI), 1.43–3.55) and CAC score (OR (95% CI), 2.18 (1.34–3.59)) were independent determinants of AVC. In competing-risk regression models adjusted for presence of CAC, inflammation, nutritional status, CVD, FRS and statin use, AVC remained independently associated with all-cause mortality (sub-hazard ratio (95% CI), 2.57 (1.20–5.51)). Conclusions: The overlap of AVC and CAC was 37% in this ESRD cohort. AVC was associated with increased all-cause mortality independent of presence of CAC, traditional risk factors and inflammation. Full article

(This article belongs to the Section Nephrology & Urology)

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23 pages, 4151 KiB

Open AccessArticle

Characterization of Burn Eschar Pericytes

by Alexander Evdokiou, Onur Kanisicak, Stephanie Gierek, Amanda Barry, Malina J. Ivey, Xiang Zhang, Richard J. Bodnar and Latha Satish

J. Clin. Med. 2020, 9(2), 606; https://doi.org/10.3390/jcm9020606 - 24 Feb 2020

Cited by 8 | Viewed by 3671

Abstract

Pericytes are cells that reside adjacent to microvasculature and regulate vascular function. Pericytes gained great interest in the field of wound healing and regenerative medicine due to their multipotential fate and ability to enhance angiogenesis. In burn wounds, scarring and scar contractures are [...] Read more.

Pericytes are cells that reside adjacent to microvasculature and regulate vascular function. Pericytes gained great interest in the field of wound healing and regenerative medicine due to their multipotential fate and ability to enhance angiogenesis. In burn wounds, scarring and scar contractures are the major pathologic feature and cause loss of mobility. The present study investigated the influence of burn wound environment on pericytes during wound healing. Pericytes isolated from normal skin and tangentially excised burn eschar tissues were analyzed for differences in gene and protein expression using RNA-seq., immunocytochemistry, and ELISA analyses. RNA-seq identified 443 differentially expressed genes between normal- and burn eschar-derived pericytes. Whereas, comparing normal skin pericytes to normal skin fibroblasts identified 1021 distinct genes and comparing burn eschar pericytes to normal skin fibroblasts identified 2449 differential genes. Altogether, forkhead box E1 (FOXE1), a transcription factor, was identified as a unique marker for skin pericytes. Interestingly, FOXE1 levels were significantly elevated in burn eschar pericytes compared to normal. Additionally, burn wound pericytes showed increased expression of profibrotic genes periostin, fibronectin, and endosialin and a gain in contractile function, suggesting a contribution to scarring and fibrosis. Our findings suggest that the burn wound environment promotes pericytes to differentiate into a myofibroblast-like phenotype promoting scar formation and fibrosis. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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12 pages, 1553 KiB

Open AccessArticle

A Multiplex Test Assessing MiR663a_me and VIM_me in Urine Accurately Discriminates Bladder Cancer from Inflammatory Conditions

by Sara Monteiro-Reis, Ana Blanca, Joana Tedim-Moreira, Isa Carneiro, Diana Montezuma, Paula Monteiro, Jorge Oliveira, Luís Antunes, Rui Henrique, António Lopez-Beltran and Carmen Jerónimo

J. Clin. Med. 2020, 9(2), 605; https://doi.org/10.3390/jcm9020605 - 24 Feb 2020

Cited by 6 | Viewed by 2863

Abstract

Bladder cancer (BlCa) is a common malignancy with significant morbidity and mortality. Current diagnostic methods are invasive and costly, showing the need for newer biomarkers. Although several epigenetic-based biomarkers have been proposed, their ability to discriminate BlCa from common benign conditions of the [...] Read more.

Bladder cancer (BlCa) is a common malignancy with significant morbidity and mortality. Current diagnostic methods are invasive and costly, showing the need for newer biomarkers. Although several epigenetic-based biomarkers have been proposed, their ability to discriminate BlCa from common benign conditions of the urinary tract, especially inflammatory diseases, has not been adequately explored. Herein, we sought to determine whether VIM_me and miR663a_me might accurately discriminate those two conditions, using a multiplex test. Performance of VIM_me and miR663a_me in tissue samples and urines in testing set confirmed previous results (96.3% sensitivity, 88.2% specificity, area under de curve (AUC) 0.98 and 92.6% sensitivity, 75% specificity, AUC 0.83, respectively). In the validation sets, VIM_me-miR663a_me multiplex test in urine discriminated BlCa patients from healthy donors or patients with inflammatory conditions, with 87% sensitivity, 86% specificity and 80% sensitivity, 75% specificity, respectively. Furthermore, positive likelihood ratio (LR) of 2.41 and negative LR of 0.21 were also disclosed. Compared to urinary cytology, VIM_me-miR663a_me multiplex panel correctly detected 87% of the analysed cases, whereas cytology only forecasted 41%. Furthermore, high miR663a_me independently predicted worse clinical outcome, especially in patients with invasive BlCa. We concluded that the implementation of this panel might better stratify patients for confirmatory, invasive examinations, ultimately improving the cost-effectiveness of BlCa diagnosis and management. Moreover, miR663a_me analysis might provide relevant information for patient monitoring, identifying patients at higher risk for cancer progression. Full article

(This article belongs to the Special Issue Outcomes and Therapeutic Management of Bladder Cancer)

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15 pages, 2864 KiB

Open AccessArticle

Fractional Flow Reserve Derived from Coronary Computed Tomography Angiography Safely Defers Invasive Coronary Angiography in Patients with Stable Coronary Artery Disease

by Mark Rabbat, Jonathon Leipsic, Jeroen Bax, Brian Kauh, Rina Verma, Demetrios Doukas, Sorcha Allen, Gianluca Pontone, David Wilber, Verghese Mathew, Campbell Rogers and John Lopez

J. Clin. Med. 2020, 9(2), 604; https://doi.org/10.3390/jcm9020604 - 24 Feb 2020

Cited by 30 | Viewed by 5043

Abstract

Objectives: In the United States, the real-world feasibility and outcome of using fractional flow reserve from coronary computed tomography angiography (FFR_CT) is unknown. We sought to determine whether a strategy that combined coronary computed tomography angiography (CTA) and FFR_CT could [...] Read more.

Objectives: In the United States, the real-world feasibility and outcome of using fractional flow reserve from coronary computed tomography angiography (FFR_CT) is unknown. We sought to determine whether a strategy that combined coronary computed tomography angiography (CTA) and FFR_CT could safely reduce the need for invasive coronary angiography (ICA), as compared to coronary CTA alone. Methods: The study included 387 consecutive patients with suspected CAD referred for coronary CTA with selective FFR_CT and 44 control patients who underwent CTA alone. Lesions with 30–90% diameter stenoses were considered of indeterminate hemodynamic significance and underwent FFR_CT. Nadir FFR_CT ≤ 0.80 was positive. The rate of patients having ICA, revascularization and major adverse cardiac events were recorded. Results: Using coronary CTA and selective FFR_CT, 121 patients (32%) had at least one vessel with ≥50% diameter stenosis; 67/121 (55%) patients had at least one vessel with FFR_CT ≤ 0.80; 55/121 (45%) underwent ICA; and 34 were revascularized. The proportion of ICA patients undergoing revascularization was 62% (34 of 55). The number of patients with vessels with 30–50% diameter of stenosis was 90 (23%); 28/90 (31%) patients had at least one vessel with FFR_CT ≤ 0.80; 8/90 (9%) underwent ICA; and five were revascularized. In our institutional practice, compared to coronary CTA alone, coronary CTA with selective FFR_CT reduced the rates of ICA (45% vs. 80%) for those with obstructive CAD. Using coronary CTA with selective FFR_CT, no major adverse cardiac events occurred over a mean follow-up of 440 days. Conclusion: FFR_CT safely deferred ICA in patients with CAD of indeterminate hemodynamic significance. A high proportion of those who underwent ICA were revascularized. Full article

(This article belongs to the Special Issue Coronary Physiology in Clinical Practice: Fractional Flow Reserve and Beyond)

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Graphical abstract

11 pages, 984 KiB

Open AccessArticle

First Multi-Center All-Comers Study for the Aquablation Procedure

by Thorsten Bach, Peter Gilling, Albert El Hajj, Paul Anderson and Neil Barber

J. Clin. Med. 2020, 9(2), 603; https://doi.org/10.3390/jcm9020603 - 24 Feb 2020

Cited by 27 | Viewed by 6361

Abstract

Waterjet-based prostate resection (Aquablation procedure) is an increasingly recognized treatment for symptomatic benign prostatic hyperplasia (BPH). We confirmed the safety and effectiveness of the Aquablation procedure in the commercial setting in 178 men at five sites. The mean prostate volume was 59 cc. [...] Read more.

Waterjet-based prostate resection (Aquablation procedure) is an increasingly recognized treatment for symptomatic benign prostatic hyperplasia (BPH). We confirmed the safety and effectiveness of the Aquablation procedure in the commercial setting in 178 men at five sites. The mean prostate volume was 59 cc. The procedure time averaged 24 min and total anesthesia duration was 50 min. The International Prostate Symptom Score (IPSS) decreased from 21.6 at the baseline to 6.5 at the 12-month follow-up, a 15.3-point improvement (p < 0.0001). The maximum urinary flow rate increased from 10 cc/s at the baseline to 20.8 cc/s at month 12 (increase of 11.8 cc, p < 0.0001). Ejaculatory function was relatively preserved. Prostate volume assessed with transrectal ultrasound decreased 36% by month three. Five patients (2.7%) underwent a transfusion in the first week after the procedure. Real-world evidence shows that Aquablation is safe and effective for the treatment of BPH. Full article

(This article belongs to the Special Issue Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia)

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16 pages, 542 KiB

Open AccessReview

Instruments of Choice for Assessment and Monitoring Diabetic Foot: A Systematic Review

by Raúl Fernández-Torres, María Ruiz-Muñoz, Alberto J. Pérez-Panero, Jerónimo García-Romero and Manuel Gónzalez-Sánchez

J. Clin. Med. 2020, 9(2), 602; https://doi.org/10.3390/jcm9020602 - 24 Feb 2020

Cited by 11 | Viewed by 4814

Abstract

Diabetic foot is the most frequent disorder among the chronic complications of diabetes, happening in 25% of patients. Objective clinical outcome measures are tests or clinical instruments that provide objective values for result measurement. The aim of this study was to carry out [...] Read more.

Diabetic foot is the most frequent disorder among the chronic complications of diabetes, happening in 25% of patients. Objective clinical outcome measures are tests or clinical instruments that provide objective values for result measurement. The aim of this study was to carry out a systematic review of specific objective clinical outcome measures focused on the assessment and monitoring of diabetic foot disorders. The databases used were PubMed, CINAHL, Scopus, PEDro, Cochrane, SciELO and EMBASE. Search terms used were foot, ankle, diabet*, diabetic foot, assessment, tools, instruments, objective outcome measures, valid*, reliab*. Because of the current published evidence, diabetic neuropathy assessment via sudomotor analysis, cardiovascular autonomic neuropathy and peripheral vascular disease detection by non-invasive electronic devices, wound 3D dimensional measurement, hyperspectral imaging for ulcer prediction and the probe-to-bone test for osteomyelitis diagnosis were highlighted in this study. Full article

(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects-Part I)

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9 pages, 1402 KiB

Open AccessArticle

Assessing the Impact of Reduced Travel on Exportation Dynamics of Novel Coronavirus Infection (COVID-19)

by Asami Anzai, Tetsuro Kobayashi, Natalie M. Linton, Ryo Kinoshita, Katsuma Hayashi, Ayako Suzuki, Yichi Yang, Sung-mok Jung, Takeshi Miyama, Andrei R. Akhmetzhanov and Hiroshi Nishiura

J. Clin. Med. 2020, 9(2), 601; https://doi.org/10.3390/jcm9020601 - 24 Feb 2020

Cited by 129 | Viewed by 22517

Abstract

The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to [...] Read more.

The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to estimate the impact of travel reduction on three epidemiological outcome measures: (i) the number of exported cases, (ii) the probability of a major epidemic, and (iii) the time delay to a major epidemic. From 28 January to 7 February 2020, we estimated that 226 exported cases (95% confidence interval: 86,449) were prevented, corresponding to a 70.4% reduction in incidence compared to the counterfactual scenario. The reduced probability of a major epidemic ranged from 7% to 20% in Japan, which resulted in a median time delay to a major epidemic of two days. Depending on the scenario, the estimated delay may be less than one day. As the delay is small, the decision to control travel volume through restrictions on freedom of movement should be balanced between the resulting estimated epidemiological impact and predicted economic fallout. Full article

(This article belongs to the Special Issue Real Time Clinical and Epidemiological Investigations on Novel Coronavirus - Part I)

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8 pages, 1053 KiB

Open AccessArticle

Microinvasive Fungal Rhinosinusitis: Proposal of a New Subtype in the Classification

by Min Young Seo, Hyeri Seok, Seung Hoon Lee, Ji Eun Choi, Sang Duk Hong, Seung-Kyu Chung, Kyong Ran Peck and Hyo Yeol Kim

J. Clin. Med. 2020, 9(2), 600; https://doi.org/10.3390/jcm9020600 - 24 Feb 2020

Cited by 7 | Viewed by 3214

Abstract

Background: Fungal rhinosinusitis (FRS) with mucosal invasion is not classified by the current criteria, and clinical reports on the topic are limited. The aim of this study was to present our 25-year experience on fungal balls with mucosal invasion that do not appear [...] Read more.

Background: Fungal rhinosinusitis (FRS) with mucosal invasion is not classified by the current criteria, and clinical reports on the topic are limited. The aim of this study was to present our 25-year experience on fungal balls with mucosal invasion that do not appear in the FRS classification. Methods: Of 1318 patients who underwent endoscopic surgery with paranasal FRS between November 1994 and July 2019, 372 underwent mucosal biopsies. Medical chart and pathology review were performed on 13 patients diagnosed as having fungal balls with mucosal invasion without accompanying tissue invasion. Results: Histopathologic findings identified all fungi as belonging to the Aspergillus species. In 13 patients, 7 fungal balls were located in the maxillary sinus, 3 in the sphenoid sinus, and 3 in both the maxillary and ethmoid sinuses. The median age at diagnosis was 67 years (interquartile range (IQR): 62–72), and the sex ratio was 1:2 (4 men and 9 women). Five patients had comorbidities—three with diabetes mellitus and two with hematologic malignancy—all of whom received postoperative antifungal therapy. The median duration of antifungal treatment was 13 weeks (IQR: 8–17). No recurrences occurred during the median follow-up period of 30 months (IQR: 22–43). Conclusions: Patients who have been clinically diagnosed with a fungal ball and showed mucosal invasion but no vascular invasion, based on pathologic findings after surgery, may need a new FRS classification category, such as microinvasive FRS, and adjuvant antifungal treatment may be needed for immunocompromised patients with microinvasive FRS. Key points: Fungal rhinosinusitis with mucosal invasion is different from fungal ball and invasive fungal rhinosinusitis and may be classified in a separate category as microinvasive FRS. Full article

(This article belongs to the Section Otolaryngology)

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15 pages, 1097 KiB

Open AccessReview

Gestational Diabetes Mellitus and the Long-Term Risk for Glucose Intolerance and Overweight in the Offspring: A Narrative Review

by Hannah Nijs and Katrien Benhalima

J. Clin. Med. 2020, 9(2), 599; https://doi.org/10.3390/jcm9020599 - 22 Feb 2020

Cited by 55 | Viewed by 5797

Abstract

Gestational diabetes mellitus (GDM) is a common condition with increasing prevalence worldwide. GDM is associated with an increased risk for maternal and neonatal complications. In this review we provide an overview of the most recent evidence on the long-term metabolic risk associated with [...] Read more.

Gestational diabetes mellitus (GDM) is a common condition with increasing prevalence worldwide. GDM is associated with an increased risk for maternal and neonatal complications. In this review we provide an overview of the most recent evidence on the long-term metabolic risk associated with GDM in the offspring. We conducted an extensive literature search on PubMed and Embase between February 2019 and December 2019. We performed a narrative review including 20 cohort studies, one cross-sectional study, and two randomized controlled trials. Our review shows that the prevalence of overweight/obesity and glucose intolerance is higher in children exposed to GDM compared to unexposed children. Maternal overweight is an important confounding factor, but recent studies show that in general the association remains significant after correction for maternal overweight. There is limited evidence suggesting that the association between GDM and adverse metabolic profile in the offspring becomes more significant with increasing offspring age and is also more pronounced in female offspring than in male offspring. More research is needed to evaluate whether treatment of GDM can prevent the long-term metabolic complications in the offspring. Full article

(This article belongs to the Special Issue Recent Advances in Gestational Diabetes Mellitus)

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22 pages, 7463 KiB

Open AccessArticle

p53 CRISPR Deletion Affects DNA Structure and Nuclear Architecture

by Aline Rangel-Pozzo, Samuel Booth, Pak Lok Ivan Yu, Madhurendra Singh, Galina Selivanova and Sabine Mai

J. Clin. Med. 2020, 9(2), 598; https://doi.org/10.3390/jcm9020598 - 22 Feb 2020

Cited by 4 | Viewed by 3999

Abstract

The TP53 gene is a key tumor suppressor. Although the tumor suppressor p53 was one of the first to be characterized as a transcription factor, with its main function potentiated by its interaction with DNA, there are still many unresolved questions about its [...] Read more.

The TP53 gene is a key tumor suppressor. Although the tumor suppressor p53 was one of the first to be characterized as a transcription factor, with its main function potentiated by its interaction with DNA, there are still many unresolved questions about its mechanism of action. Here, we demonstrate a novel role for p53 in the maintenance of nuclear architecture of cells. Using three-dimensional (3D) imaging and spectral karyotyping, as well as super resolution microscopy of DNA structure, we observe significant differences in 3D telomere signatures, DNA structure and DNA-poor spaces as well gains or losses of chromosomes, between normal and tumor cells with CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-deleted or wild-type TP53. Additionally, treatment with Nutlin-3 results in differences in nuclear architecture of telomeres in wild-type but not in p53 knockout MCF-7 (Michigan Cancer Foundation-7) cells. Nutlin-3 binds to the p53-binding pocket of mouse double minute 2 (MDM2) and blocks the p53-MDM2 interaction. Moreover, we demonstrate that another p53 stabilizing small molecule, RITA (reactivation of p53 and induction of tumor cell apoptosis), also induces changes in 3D DNA structure, apparently in a p53 independent manner. These results implicate p53 activity in regulating nuclear organization and, additionally, highlight the divergent effects of the p53 targeting compounds Nutlin-3 and RITA. Full article

(This article belongs to the Special Issue CRISPR, Cancer, and p53)

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8 pages, 2073 KiB

Open AccessArticle

Radiosynoviorthesis after Surgery in the Treatment of Patients with Ankle Pigmented Villonodular Synovitis: A Case Series

by Ioannis Iakovou, Panagiotis Symeonidis, Dimitrios Kotrotsios, Evanthia Giannoula and Christos Sachpekidis

J. Clin. Med. 2020, 9(2), 597; https://doi.org/10.3390/jcm9020597 - 22 Feb 2020

Cited by 5 | Viewed by 3519

Abstract

Pigmented villonodular synovitis (PVNS) of the ankle is a very rare, locally aggressive, proliferative disorder. Although surgical excision represents the standard curative treatment, the PVNS relapse rate is high. We present our study of five young athletes (range 20–36 years) with a histopathological [...] Read more.

Pigmented villonodular synovitis (PVNS) of the ankle is a very rare, locally aggressive, proliferative disorder. Although surgical excision represents the standard curative treatment, the PVNS relapse rate is high. We present our study of five young athletes (range 20–36 years) with a histopathological diagnosis of PVNS of the ankle, who were treated by surgery and adjuvant radiosynoviorthesis (RSO). The operation involved either arthroscopic (four patients) or open (one patient) debridement, followed by intraarticular RSO with the radiopharmaceutical erbium-169 (¹⁶⁹Er). They were evaluated with the Foot Function Index (FFI) and a visual analog scale (VAS) for pain. At a median follow up period of 47 months (range 36–54 months), all five patients reported marked pain relief with improvements in their daily activities. In particular, the median FFI decreased from 77% (range 71.0%–84.5%) pre-treatment, to 0.5% (range 0%–6%) after treatment. The median VAS score decreased from 4 (range 3–7) to 0 (range 0–1), respectively. Throughout the follow-up period, there were no major complications regarding either therapeutic intervention (arthroscopic or open debridement, RSO). Based on these results, it can be concluded that adjuvant RSO with ¹⁶⁹Er following surgical excision is effective and safe in the treatment of PVNS of the ankle. Full article

(This article belongs to the Section Orthopedics)

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9 pages, 1630 KiB

Open AccessArticle

Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13–23, 2020

by Kimberlyn Roosa, Yiseul Lee, Ruiyan Luo, Alexander Kirpich, Richard Rothenberg, James M. Hyman, Ping Yan and Gerardo Chowell

J. Clin. Med. 2020, 9(2), 596; https://doi.org/10.3390/jcm9020596 - 22 Feb 2020

Cited by 143 | Viewed by 17970

Abstract

The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of [...] Read more.

The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic’s epicenter. Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China. Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports. Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases. Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang; however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang. Our 10-day forecasts across the three models predict an additional 65–81 cases (upper bounds: 169–507) in Guangdong and an additional 44–354 (upper bounds: 141–875) cases in Zhejiang by February 23, 2020. In the best-case scenario, current data suggest that transmission in both provinces is slowing down. Full article

(This article belongs to the Special Issue Real Time Clinical and Epidemiological Investigations on Novel Coronavirus - Part I)

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18 pages, 2839 KiB

Open AccessReview

Choroidal Vascularity Index: An In-Depth Analysis of This Novel Optical Coherence Tomography Parameter

by Claudio Iovino, Marco Pellegrini, Federico Bernabei, Enrico Borrelli, Riccardo Sacconi, Andrea Govetto, Aldo Vagge, Antonio Di Zazzo, Matteo Forlini, Lucia Finocchio, Adriano Carnevali, Giacinto Triolo and Giuseppe Giannaccare

J. Clin. Med. 2020, 9(2), 595; https://doi.org/10.3390/jcm9020595 - 21 Feb 2020

Cited by 135 | Viewed by 8277

Abstract

Remarkable improvements in optical coherence tomography (OCT) technology have resulted in highly sophisticated, noninvasive machines allowing detailed and advanced morphological evaluation of all retinal and choroidal layers. Postproduction semiautomated imaging analysis with dedicated public-domain software allows precise quantitative analysis of binarized OCT images. [...] Read more.

Remarkable improvements in optical coherence tomography (OCT) technology have resulted in highly sophisticated, noninvasive machines allowing detailed and advanced morphological evaluation of all retinal and choroidal layers. Postproduction semiautomated imaging analysis with dedicated public-domain software allows precise quantitative analysis of binarized OCT images. In this regard, the choroidal vascularity index (CVI) is emerging as a new imaging tool for the measurement and analysis of the choroidal vascular system by quantifying both luminal and stromal choroidal components. Numerous reports have been published so far regarding CVI and its potential applications in healthy eyes as well as in the evaluation and management of several chorioretinal diseases. Current literature suggests that CVI has a lesser variability and is influenced by fewer physiologic factors as compared to choroidal thickness. It can be considered a relatively stable parameter for evaluating the changes in the choroidal vasculature. In this review, the principles and the applications of this advanced imaging modality for studying and understanding the contributing role of choroid in retinal and optic nerve diseases are discussed. Potential advances that may allow the widespread adoption of this tool in the routine clinical practice are also presented. Full article

(This article belongs to the Special Issue Application of Retinal and Optic Nerve Imaging in Clinical Medicine)

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20 pages, 1148 KiB

Open AccessReview

Lysosomal Ceramide Metabolism Disorders: Implications in Parkinson’s Disease

by Silvia Paciotti, Elisabetta Albi, Lucilla Parnetti and Tommaso Beccari

J. Clin. Med. 2020, 9(2), 594; https://doi.org/10.3390/jcm9020594 - 21 Feb 2020

Cited by 28 | Viewed by 4865

Abstract

Ceramides are a family of bioactive lipids belonging to the class of sphingolipids. Sphingolipidoses are a group of inherited genetic diseases characterized by the unmetabolized sphingolipids and the consequent reduction of ceramide pool in lysosomes. Sphingolipidoses include several disorders as Sandhoff disease, Fabry [...] Read more.

Ceramides are a family of bioactive lipids belonging to the class of sphingolipids. Sphingolipidoses are a group of inherited genetic diseases characterized by the unmetabolized sphingolipids and the consequent reduction of ceramide pool in lysosomes. Sphingolipidoses include several disorders as Sandhoff disease, Fabry disease, Gaucher disease, metachromatic leukodystrophy, Krabbe disease, Niemann Pick disease, Farber disease, and GM2 gangliosidosis. In sphingolipidosis, lysosomal lipid storage occurs in both the central nervous system and visceral tissues, and central nervous system pathology is a common hallmark for all of them. Parkinson’s disease, the most common neurodegenerative movement disorder, is characterized by the accumulation and aggregation of misfolded α-synuclein that seem associated to some lysosomal disorders, in particular Gaucher disease. This review provides evidence into the role of ceramide metabolism in the pathophysiology of lysosomes, highlighting the more recent findings on its involvement in Parkinson’s disease. Full article

(This article belongs to the Special Issue Lysosomal Storage Disorders: Causes, Symptoms, Diagnosis, and Treatment)

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29 pages, 944 KiB

Open AccessReview

Role of Non-Coding RNAs in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia

by Felice Pepe and Veronica Balatti

J. Clin. Med. 2020, 9(2), 593; https://doi.org/10.3390/jcm9020593 - 21 Feb 2020

Cited by 13 | Viewed by 4347

Abstract

In the past decade, novel targeted therapy approaches, such as BTK inhibitors and Bcl2 blockers, and innovative treatments that regulate the immune response against cancer cells, such as monoclonal antibodies, CAR-T cell therapy, and immunomodulatory molecules, have been established to provide support for [...] Read more.

In the past decade, novel targeted therapy approaches, such as BTK inhibitors and Bcl2 blockers, and innovative treatments that regulate the immune response against cancer cells, such as monoclonal antibodies, CAR-T cell therapy, and immunomodulatory molecules, have been established to provide support for the treatment of patients. However, drug resistance development and relapse are still major challenges in CLL treatment. Several studies revealed that non-coding RNAs have a main role in the development and progression of CLL. Specifically, microRNAs (miRs) and tRNA-derived small-RNAs (tsRNAs) were shown to be outstanding biomarkers that can be used to diagnose and monitor the disease and to possibly anticipate drug resistance and relapse, thus supporting physicians in the selection of treatment regimens tailored to the patient needs. In this review, we will summarize the most recent discoveries in the field of targeted therapy and immunotherapy for CLL and discuss the role of ncRNAs in the development of novel drugs and combination regimens for CLL patients. Full article

(This article belongs to the Special Issue Immuno-Oncology: Identification of Therapeutic Targets, Development of Novel Drugs and Improvement of Treatment Approaches for Cancer)

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15 pages, 293 KiB

Open AccessArticle

Collaborating with Complementary and Alternative Medicine (CAM) Providers When Writing HPV Vaccine Review Articles

by Michael J. Deml, Léna G. Dietrich, Bernhard Wingeier, Gisela Etter, Caesar Gallmann, Christoph Berger, L. Suzanne Suggs, Benedikt M. Huber and Philip E. Tarr

J. Clin. Med. 2020, 9(2), 592; https://doi.org/10.3390/jcm9020592 - 21 Feb 2020

Cited by 5 | Viewed by 4392

Abstract

Novel strategies are needed to address vaccine hesitancy (VH), which correlates with complementary and alternative medicine (CAM). In Switzerland, CAM providers play important roles in vaccine counseling of vaccine hesitant (VH) parents, and traditional vaccination messaging tends to overlook CAM provider perspectives. In [...] Read more.

Novel strategies are needed to address vaccine hesitancy (VH), which correlates with complementary and alternative medicine (CAM). In Switzerland, CAM providers play important roles in vaccine counseling of vaccine hesitant (VH) parents, and traditional vaccination messaging tends to overlook CAM provider perspectives. In the setting of a Swiss national research program on VH, our key strategy has been to work together closely with CAM providers. To assess the feasibility of generating educational human papillomavirus (HPV) vaccine materials that would interest VH healthcare providers (HCPs), we invited four CAM providers to co-author two HPV vaccine review articles for general practitioners. We conducted thematic analysis of CAM provider comments to identify patterns that could complement and improve vaccination messaging from CAM perspectives. We identified several themes and generated an inventory of CAM provider messaging recommendations related to language use, presentation of background information, nuanced statements regarding HPV vaccine efficacy and safety, and communication tools that would be important to VH HCPs. Contrary to our initial expectations, and in an inclusive, respectful atmosphere of open dialogue, we were able to productively finalize our manuscripts. In the opinion of the CAM co-authors, the manuscripts effectively considered the communication needs and perspectives of VH HCPs. Engaging with CAM providers appears to be a feasible and innovative avenue for providing vaccine information and designing communication tools aimed at VH healthcare providers. Full article

(This article belongs to the Section Infectious Diseases)

12 pages, 224 KiB

Open AccessReview

Sleep Apnea, Hypertension and the Sympathetic Nervous System in the Adult Population

by Shreyas Venkataraman, Soumya Vungarala, Naima Covassin and Virend K. Somers

J. Clin. Med. 2020, 9(2), 591; https://doi.org/10.3390/jcm9020591 - 21 Feb 2020

Cited by 34 | Viewed by 4919

Abstract

Sleep apnea is very common in patients with cardiovascular disease, especially in patients with hypertension. Over the last few decades a number of discoveries have helped support a causal relationship between the two and even resistant hypertension. The role neurogenic mechanisms play has [...] Read more.

Sleep apnea is very common in patients with cardiovascular disease, especially in patients with hypertension. Over the last few decades a number of discoveries have helped support a causal relationship between the two and even resistant hypertension. The role neurogenic mechanisms play has gathered more attention in the recent past due to their immediate bedside utility. Several innovative discoveries in pathogenesis including those exploring the role of baroreflex gain, cardiovascular variability, chemoreceptor reflex activation and the sympathetic nervous system have emerged. In this review, we discuss the epidemiology of sleep apnea and hypertension and the pathogenic mechanisms contributing to neurogenic hypertension. Furthermore, recent management strategies in addition to continuous positive airway pressure (CPAP), such as upper airway stimulation and renal denervation that target these pathogenic mechanisms, are also discussed. Full article

(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)

16 pages, 2641 KiB

Open AccessReview

Effectiveness of Vestibular Training for Balance and Dizziness Rehabilitation in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis

by Cristina García-Muñoz, María-Dolores Cortés-Vega, Alberto Marcos Heredia-Rizo, Rocío Martín-Valero, María-Isabel García-Bernal and María Jesús Casuso-Holgado

J. Clin. Med. 2020, 9(2), 590; https://doi.org/10.3390/jcm9020590 - 21 Feb 2020

Cited by 22 | Viewed by 7325

Abstract

Postural instability and dizziness are commonly observed in people with multiple sclerosis (PwMS). The aim of this systematic review was to evaluate the evidence for the use of vestibular rehabilitation, in comparison with other exercise interventions or no intervention, to treat balance impairments [...] Read more.

Postural instability and dizziness are commonly observed in people with multiple sclerosis (PwMS). The aim of this systematic review was to evaluate the evidence for the use of vestibular rehabilitation, in comparison with other exercise interventions or no intervention, to treat balance impairments and dizziness in PwMS. An electronic search was conducted by two independent reviewers in the following databases: MEDLINE (Pubmed), Scopus, the Physiotherapy Evidence Database (PEDro), Web of Science (WOS), Lilacs, CINHAL and the Cochrane Database of Systematic Reviews (CDSR). A quality assessment was performed using the PEDro scale and the Cochrane Risk of Bias Tool. When possible, the data were pooled in a meta-analysis (95%CI). This systematic review followed the PRISMA guideline statement and was registered in the PROSPERO database (CRD42019134230). Seven studies were included, with a total of 321 participants analysed. Compared with no intervention, vestibular rehabilitation was more effective for balance development (SMD = 2.12; 95% CI = 0.49, 3.75; p = 0.01; I² = 89%) and dizziness symptoms improvement (SMD = −17.43; 95% CI = −29.99, −4.87; p= 0.007; I²= 66%). Compared with other exercise interventions, improvements in favour of the experimental group were observed, but statistical significance for the differences between groups was not reached. Full article

(This article belongs to the Section Clinical Neurology)

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21 pages, 4157 KiB

Open AccessReview

rAAV-Mediated Cochlear Gene Therapy: Prospects and Challenges for Clinical Application

by Fabian Blanc, Michel Mondain, Alexis-Pierre Bemelmans, Corentin Affortit, Jean-Luc Puel and Jing Wang

J. Clin. Med. 2020, 9(2), 589; https://doi.org/10.3390/jcm9020589 - 21 Feb 2020

Cited by 11 | Viewed by 5810

Abstract

Over the last decade, pioneering molecular gene therapy for inner-ear disorders have achieved experimental hearing improvements after a single local or systemic injection of adeno-associated, virus-derived vectors (rAAV for recombinant AAV) encoding an extra copy of a normal gene, or ribozymes used to [...] Read more.

Over the last decade, pioneering molecular gene therapy for inner-ear disorders have achieved experimental hearing improvements after a single local or systemic injection of adeno-associated, virus-derived vectors (rAAV for recombinant AAV) encoding an extra copy of a normal gene, or ribozymes used to modify a genome. These results hold promise for treating congenital or later-onset hearing loss resulting from monogenic disorders with gene therapy approaches in patients. In this review, we summarize the current state of rAAV-mediated inner-ear gene therapies including the choice of vectors and delivery routes, and discuss the prospects and obstacles for the future development of efficient clinical rAAV-mediated cochlear gene medicine therapy. Full article

(This article belongs to the Special Issue Therapies for Hearing Loss)

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15 pages, 1547 KiB

Open AccessArticle

Natural History and Management of Familial Paraganglioma Syndrome Type 1: Long-Term Data from a Large Family

by Giulia Puliani, Franz Sesti, Tiziana Feola, Nicola Di Leo, Giorgia Polti, Monica Verrico, Roberta Modica, Annamaria Colao, Andrea Lenzi, Andrea M. Isidori, Vito Cantisani, Elisa Giannetta and Antongiulio Faggiano

J. Clin. Med. 2020, 9(2), 588; https://doi.org/10.3390/jcm9020588 - 21 Feb 2020

Cited by 8 | Viewed by 2593

Abstract

Head and neck paragangliomas are the most common clinical features of familial paraganglioma syndrome type 1 caused by succinate dehydrogenase complex subunit D (SDHD) mutation. The clinical management of this syndrome is still unclear. In this study we propose a diagnostic algorithm for [...] Read more.

Head and neck paragangliomas are the most common clinical features of familial paraganglioma syndrome type 1 caused by succinate dehydrogenase complex subunit D (SDHD) mutation. The clinical management of this syndrome is still unclear. In this study we propose a diagnostic algorithm for SDHD mutation carriers based on our family case series and literature review. After genetic diagnosis, first evaluation should include biochemical examination and whole-body imaging. In case of lesion detection, nuclear medicine examination is required for staging and tumor characterization. The study summarizes the diagnostic accuracy of different functional imaging techniques in SDHD mutation carriers. 18F-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)-computed tomography (CT) is considered the gold standard. If it is not available, 123I-Metaiodobenzylguanidine (MIBG) could be used also for predicting response to radiometabolic therapy. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET-CT has a prognostic role since high uptake identifies more aggressive cases. Finally, 68Ga-peptides PET-CT is a promising diagnostic technique, demonstrating the best diagnostic accuracy in our and in other published case series, even if this finding still needs to be confirmed in larger studies. Periodic follow-up should consist of annual biochemical and ultrasonographic screening and biannual magnetic resonance examination to identify biochemical silent tumors early. Full article

(This article belongs to the Special Issue Radiation Oncology - Head and Neck Cancers)

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12 pages, 787 KiB

Open AccessArticle

Impaired Right and Left Ventricular Longitudinal Function in Patients with Fibrotic Interstitial Lung Diseases

by Agostino Buonauro, Ciro Santoro, Maurizio Galderisi, Angelo Canora, Regina Sorrentino, Roberta Esposito, Maria Lembo, Mario Enrico Canonico, Federica Ilardi, Valeria Fazio, Bruno Golia, Alessandro Sanduzzi Zamparelli and Maria Luisa Bocchino

J. Clin. Med. 2020, 9(2), 587; https://doi.org/10.3390/jcm9020587 - 21 Feb 2020

Cited by 11 | Viewed by 2666

Abstract

Background: Left ventricular (LV) and right ventricular (RV) dysfunction is recognized in idiopathic pulmonary fibrosis (IPF). Little is known about cardiac involvement in non-idiopathic pulmonary fibrosis (no-IPF). This issue can be explored by advanced echocardiography. Methods: Thirty-three clinically stable and therapy-naive fibrotic IPF [...] Read more.

Background: Left ventricular (LV) and right ventricular (RV) dysfunction is recognized in idiopathic pulmonary fibrosis (IPF). Little is known about cardiac involvement in non-idiopathic pulmonary fibrosis (no-IPF). This issue can be explored by advanced echocardiography. Methods: Thirty-three clinically stable and therapy-naive fibrotic IPF and 28 no-IPF patients, and 30 healthy controls were enrolled. Exclusion criteria were autoimmune systemic diseases, coronary disease, heart failure, primary cardiomyopathies, chronic obstructive lung diseases, pulmonary embolism, primary pulmonary hypertension. Lung damage was evaluated by diffusion capacity for carbon monoxide (DLCO_sb). All participants underwent an echo-Doppler exam including 2D global longitudinal strain (GLS) of both ventricles and 3D echocardiographic RV ejection fraction (RVEF). Results: We observed LV diastolic dysfunction in IPF and no-IPF, and LV GLS but not LV EF reduction only in IPF. RV diastolic and RV GLS abnormalities were observed in IPF versus both controls and no-IPF. RV EF did not differ significantly between IPF and no-IPF. DLCO_sb and RV GLS were associated in the pooled pulmonary fibrosis population and in the IPF subgroup (β = 0.708, p < 0.001), independently of confounders including pulmonary arterial systolic pressure. Conclusion: Our data highlight the unique diagnostic capabilities of GLS in distinguishing early cardiac damage of IPF from no-IPF patients. Full article

(This article belongs to the Section Cardiology)

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21 pages, 866 KiB

Open AccessReview

Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology

by Antonio Di Zazzo, Sang-Mok Lee, Jaemyoung Sung, Matteo Niutta, Marco Coassin, Alireza Mashaghi and Takenori Inomata

J. Clin. Med. 2020, 9(2), 586; https://doi.org/10.3390/jcm9020586 - 21 Feb 2020

Cited by 21 | Viewed by 4047

Abstract

Corneal grafts interact with their hosts via complex immunobiological processes that sometimes lead to graft failure. Prediction of graft failure is often a tedious task due to the genetic and nongenetic heterogeneity of patients. As in other areas of medicine, a reliable prediction [...] Read more.

Corneal grafts interact with their hosts via complex immunobiological processes that sometimes lead to graft failure. Prediction of graft failure is often a tedious task due to the genetic and nongenetic heterogeneity of patients. As in other areas of medicine, a reliable prediction method would impact therapeutic decision-making in corneal transplantation. Valuable insights into the clinically observed heterogeneity of host responses to corneal grafts have emerged from multidisciplinary approaches, including genomics analyses, mechanical studies, immunobiology, and theoretical modeling. Here, we review the emerging concepts, tools, and new biomarkers that may allow for the prediction of graft survival. Full article

(This article belongs to the Special Issue Corneal Transplant Immunology)

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16 pages, 3453 KiB

Open AccessArticle

Genomic Profiling of Uterine Aspirates and cfDNA as an Integrative Liquid Biopsy Strategy in Endometrial Cancer

by Carlos Casas-Arozamena, Eva Díaz, Cristian Pablo Moiola, Lorena Alonso-Alconada, Alba Ferreiros, Alicia Abalo, Carlos López Gil, Sara S. Oltra, Javier de Santiago, Silvia Cabrera, Victoria Sampayo, Marta Bouso, Efigenia Arias, Juan Cueva, Eva Colas, Ana Vilar, Antonio Gil-Moreno, Miguel Abal, Gema Moreno-Bueno and Laura Muinelo-Romay

J. Clin. Med. 2020, 9(2), 585; https://doi.org/10.3390/jcm9020585 - 21 Feb 2020

Cited by 26 | Viewed by 3736

Abstract

The incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, we combined different types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates [...] Read more.

The incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, we combined different types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates (UAs) from 60 patients with EC were obtained during surgery and analyzed by next-generation sequencing (NGS). Blood samples, collected at surgery, were used for cell-free DNA (cfDNA) and circulating tumor cell (CTC) analyses. Finally, personalized therapies were tested in patient-derived xenografts (PDXs) generated from the UAs. NGS analyses revealed the presence of genetic alterations in 93% of the tumors. Circulating tumor DNA (ctDNA) was present in 41.2% of cases, mainly in patients with high-risk tumors, thus indicating a clear association with a more aggressive disease. Accordingly, the results obtained during the post-surgery follow-up indicated the presence of ctDNA in three patients with progressive disease. Moreover, 38.9% of patients were positive for CTCs at surgery. Finally, the efficacy of targeted therapies based on the UA-specific mutational landscape was demonstrated in PDX models. Our study indicates the potential clinical applicability of a personalized strategy based on a combination of different liquid biopsies to characterize and monitor tumor evolution, and to identify targeted therapies. Full article

(This article belongs to the Special Issue Circulating Biomarkers as a Liquid Biopsy for Cancer)

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13 pages, 1852 KiB

Open AccessArticle

Impact of the Fibrosis-4 Index on Risk Stratification of Cardiovascular Events and Mortality in Patients with Atrial Fibrillation: Findings from a Japanese Multicenter Registry

by Yuki Saito, Yasuo Okumura, Koichi Nagashima, Daisuke Fukamachi, Katsuaki Yokoyama, Naoya Matsumoto, Eizo Tachibana, Keiichiro Kuronuma, Koji Oiwa, Michiaki Matsumoto, Toshihiko Nishida, Toshiaki Kojima, Shoji Hanada, Kazumiki Nomoto, Kazumasa Sonoda, Ken Arima, Fumiyuki Takahashi, Tomobumi Kotani, Kimie Ohkubo, Seiji Fukushima, Satoru Itou, Kunio Kondo, Hideyuki Ando, Yasumi Ohno, Motoyuki Onikura and Atsushi Hirayama Show full author list Hide full author list

J. Clin. Med. 2020, 9(2), 584; https://doi.org/10.3390/jcm9020584 - 21 Feb 2020

Cited by 25 | Viewed by 2981

Abstract

Background: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the [...] Read more.

Background: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. Methods: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index < 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index < 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). Results: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p < 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p < 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31–2.25) and all-cause mortality (HR 1.43; 95% CI 1.06–1.95). Adding the FIB4 index to a baseline model with CHA₂DS₂-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p < 0.05), net reclassification improvement (all p < 0.001), and integrated discrimination improvement (all p < 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS₂ scores (all p < 0.001). Conclusions: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients. Full article

(This article belongs to the Special Issue New Approaches to the Atrial Fibrillation Management)

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11 pages, 1991 KiB

Open AccessArticle

High Platelet Reactivity after Transition from Cangrelor to Ticagrelor in Hypothermic Cardiac Arrest Survivors with ST-Segment Elevation Myocardial Infarction

by Nina Buchtele, Harald Herkner, Christian Schörgenhofer, Anne Merrelaar, Roberta Laggner, Georg Gelbenegger, Alexander O. Spiel, Hans Domanovits, Irene Lang, Bernd Jilma and Michael Schwameis

J. Clin. Med. 2020, 9(2), 583; https://doi.org/10.3390/jcm9020583 - 21 Feb 2020

Cited by 6 | Viewed by 2563

Abstract

Transition from cangrelor to oral P2Y12 inhibitors after PCI carries the risk of platelet function recovery and acute stent thrombosis. Whether the recommended transition regimen is appropriate for hypothermic cardiac arrest survivors is unknown. We assessed the rate of high platelet reactivity (HPR) [...] Read more.

Transition from cangrelor to oral P2Y12 inhibitors after PCI carries the risk of platelet function recovery and acute stent thrombosis. Whether the recommended transition regimen is appropriate for hypothermic cardiac arrest survivors is unknown. We assessed the rate of high platelet reactivity (HPR) after transition from cangrelor to ticagrelor in hypothermic cardiac arrest survivors. Adult survivors of out-of-hospital cardiac arrest with ST-segment elevation myocardial infarction (STEMI), who were treated for hypothermia (33 °C ± 1) and received intravenous cangrelor during PCI and subsequent oral loading with 180mg ticagrelor were enrolled in this prospective observational cohort study. Platelet function was assessed using whole blood aggregometry. HPR was defined as AUC > 46U. The primary endpoint was the rate of HPR (%) at predefined time points during the first 24 h after cangrelor cessation. Poisson regression was used to estimate the relationship between the overlap time of cangrelor and ticagrelor co-administration and the number of subsequent HPR episodes, expressed as incidence rate ratio (IRR) with 95% confidence interval (95%CI). Between December 2017 and October 2019 16 patients (81% male, 58 years) were enrolled. On average, ticagrelor was administered 39 min (IQR 5–50) before the end of cangrelor infusion. The rate of HPR was highest 90 min after cangrelor cessation and was present in 44% (7/16) of patients. The number of HPR episodes increased significantly with decreasing overlap time of cangrelor and ticagrelor co-administration (IRR 1.03, 95%CI 1.01–1.05; p = 0.005). In this selected cohort of hypothermic cardiac arrest survivors who received cangrelor during PCI, ticagrelor loading within the recommended time frame before cangrelor cessation resulted in a substantial amount of patients with HPR. Full article

(This article belongs to the Special Issue Antithrombotic Treatment of Acute Coronary Syndrome)

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14 pages, 694 KiB

Open AccessArticle

A Population-Based Study of Diabetes during Pregnancy in Spain (2009–2015): Trends in Incidence, Obstetric Interventions, and Pregnancy Outcomes

by Ana López-de-Andrés, Napoleón Perez-Farinos, Valentín Hernández-Barrera, María A. Palomar-Gallego, David Carabantes-Alarcón, José J. Zamorano-León, Javier De Miguel-Diez and Rodrigo Jimenez-Garcia

J. Clin. Med. 2020, 9(2), 582; https://doi.org/10.3390/jcm9020582 - 21 Feb 2020

Cited by 29 | Viewed by 3155

Abstract

(1) Background: We examined trends in incidence and outcomes in women with existing type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) compared with a control group without diabetes. (2) Methods: This was an observational, retrospective epidemiological [...] Read more.

(1) Background: We examined trends in incidence and outcomes in women with existing type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) compared with a control group without diabetes. (2) Methods: This was an observational, retrospective epidemiological study using the National Hospital Discharge Database. (3) Results: There were 2,481,479 deliveries in Spain between 2009 and 2015 (5561 mothers with T1DM, 4391 with T2DM, and 130,980 with GDM). Incidence and maternal age of existing diabetes and GDM increased over time. Women with T2DM were more likely to have obstetric comorbidity (70.12%) than those with GDM (60.28%), T1DM (59.45%), and no diabetes (41.82%). Previous cesarean delivery, preeclampsia, smoking, hypertension, and obesity were the most prevalent risk factors in all types of diabetes. Women with T1DM had the highest rate of cesarean delivery (Risk Ratio (RR) 2.34; 95% Confidence Interval (CI) 2.26–2.43) and prolonged maternal length of stay. Labor induction was higher in T2DM (RR 1.99; 95% CI 1.89–2.10). Women with T1DM had more severe maternal morbidity (RR 1.97; 95% CI 1.70–2.29) and neonatal morbidity (preterm birth, RR 3.32; 95% CI 3.14–3.51, and fetal overgrowth, RR 8.05; 95% CI 7.41–8.75). (4) Conclusions: existing and GDM incidence has increased over time. We found differences in the prevalence of comorbidities, obstetric risk factors, and the rate of adverse obstetric outcomes among women with different types of diabetes. Pregnant women with diabetes have the highest risk of adverse pregnancy outcomes. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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